Communication in pediatric oncology: State of the field and research agenda

Abstract

From the time of diagnosis through either survivorship or end of life, communication between healthcare providers and patients or parents can serve several core functions, including fostering healing relationships, exchanging information, responding to emotions, managing uncertainty, making decisions, and enabling patient/family self-management. We systematically reviewed all studies that focused on communication between clinicians and patients or parents in pediatric oncology, categorizing studies based on which core functions of communication they addressed. After identifying gaps in the literature, we propose a research agenda to further the field.

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VIncristine, irinotecan, and temozolomide in children and adolescents with relapsed rhabdomyosarcoma

Abstract

Background

The combination of vincristine, irinotecan, and temozolomide (VIT) is often used to treat children and adolescents with relapsed rhabdomyosarcoma (RMS); however, the outcome of these patients has not been previously described.

Procedures

We sought to determine the response rate (RR) and progression-free survival (PFS) for patients with relapsed RMS treated with VIT by retrospective review of patients treated at five tertiary care hospitals. Prior treatment with irinotecan was permitted.

Results

Among 19 patients with a median age of 8 years (range 2–17 years), 12 (63%) were males and 12 (63%) had embryonal histology. Median time to relapse from initial diagnosis was 16 months (range 2.8-45 months). VIT was used as first, second, third, or fourth line of therapy in four (21%), seven (37%), six (32%), and two (10%) patients, respectively. Four patients received VIT as adjuvant therapy following radiation and/or surgery. Therefore, among 15 evaluable patients, the best response to VIT was 0 (complete response, CR), 0 (partial response, PR), 4 (stable disease, SD), and 11 (progressive disease, PD) for an overall clinical benefit rate (CR + PR + SD) of 26.7% (95% CI: 7.8–55.1%). After a median follow-up of 8 months, 2 (10%) patients were alive without disease, 3 (16%) were alive with disease, and 14 (74%) patients died of PD. PFS at 3 months was 23% (95% CI: 5.7–46.7%).

Conclusions

VIT therapy in combination with adequate local control is associated with some disease control in patients with first relapse RMS and may be another reasonable option to offer patients as salvage therapy.

http://ift.tt/2v9YWla

Outcomes of matched sibling donor bone marrow transplantation in children using single-agent calcineurin inhibitors as prophylaxis for graft versus host disease

Abstract

Background

Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort.

Procedure

We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014.

Results

Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5–8.3) and donor age of 6 years (IQR 3–10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2–4 acute GVHD was 25.5%, grades 3–4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194–318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4–90.6%) and event-free survival was 78.9% (95% CI: 65.1–87.7%). No patient experienced graft failure.

Conclusions

Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.

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Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by constitutive activation of extracellular signal-regulated kinase (ERK). Genomic characterization has identified activating point mutations including mutually exclusive BRAFV600E and activating MAP2K1 mutations to be responsible for ERK activation in a majority of pediatric LCH patients. Here, we report the discovery of a novel BRAF kinase fusion, PACSIN2-BRAF, in a child with multisystem LCH. This is the second reported case of an activating BRAF kinase fusion and indicates a recurrent pathologic mechanism. Genomic evaluation for activating kinase fusions should be strongly considered in pediatric LCH patients lacking more common mutations.

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Management of chemotherapy-induced febrile neutropenia in pediatric oncology patients: A North American survey of pediatric hematology/oncology and pediatric infectious disease physicians

ABSTRACT

Background

Chemotherapy-induced febrile neutropenia (FN) is traditionally managed with hospital admission for parenteral antibiotics until neutropenia resolves. Recent studies have explored risk stratification and the safety of managing "low-risk" patients as outpatients. Few studies have directly assessed pediatric provider preferences for managing FN.

Procedure

We conducted a survey of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric infectious disease (PID) physicians to assess their FN management preferences using case scenarios with varying risk profiles.

Results

Twenty-one percent (n = 186) of PHO and 32% (n = 123) of PID physicians completed the survey. Overall, both groups of providers agreed regarding which patients with FN could be managed outpatient. For a child with acute lymphoblastic leukemia receiving maintenance chemotherapy with an absolute neutrophil count (ANC) of 400 cells/μl, 35% (n = 66) of PHO and 49% (n = 60) of PID physicians would consider outpatient management (P = 0.02). Of those physicians selecting inpatient management, 41% (n = 49) of PHO and 52% (n = 33) of PID physicians would be willing to discharge the patient without an increase in ANC, if afebrile with a negative blood culture (P = 0.16). For a similar patient with an ANC of 100 cells/μl, only 23% (n = 35) of PHO and 42% (n = 39) of PID physicians would consider discharge without an increase in ANC (P = 0.002).

Conclusions

Despite the lack of established guidelines for low-risk pediatric FN, a significant proportion of North American physicians report willingness to modify traditional management. This reinforces the need for evidence-based low-risk criteria and outpatient management guidelines to optimize consistency of care for these patients.

http://ift.tt/2w2Creo

Reliable assessment of the incidence of childhood autoimmune hemolytic anemia

Abstract

Background

Childhood autoimmune hemolytic anemia (AIHA) is a rare and severe disease characterized by hemolysis and positive direct antiglobulin test (DAT). Few epidemiologic indicators are available for the pediatric population. The objective of our study was to reliably estimate the number of AIHA cases in the French Aquitaine region and the incidence of AIHA in patients under 18 years old.

Procedure

In this retrospective study, the capture–recapture method and log-linear model were used for the period 2000–2008 in the Aquitaine region from the following three data sources for the diagnosis of AIHA: the OBS'CEREVANCE database cohort, positive DAT collected from the regional blood bank database, and the French medico-economic information system.

Results

A list of 281 different patients was obtained after cross-matching the three databases; 44 AIHA cases were identified in the period 2000–2008; and the total number of cases was estimated to be 48 (95% confidence interval [CI]: 45–55). The calculated incidence of the disease was 0.81/100,000 children under 18 years old per year (95% CI 0.76–0.92).

Conclusion

Accurate methods are required for estimating the incidence of AIHA in children. Capture–recapture analysis corrects underreporting and provides optimal completeness. This study highlights a possible under diagnosis of this potentially severe disease in various pediatric settings. AIHA incidence may now be compared with the incidences of other hematological diseases and used for clinical or research purposes.

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Rethinking reconsent when minors reach adult age in minimal risk studies

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Transverse myelitis as an unexpected complication following treatment with dinutuximab in pediatric patients with high-risk neuroblastoma: A case series

Abstract

Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high-risk neuroblastoma and is now considered part of standard of care in this patient population. To date, transverse myelitis as a result of dinutuximab therapy has not been reported in clinical trials or in the published literature. We describe three patients with clinical symptoms of transverse myelitis, confirmed via magnetic resonance imaging, shortly following initiation of dinutuximab. All patients were discontinued from dinutuximab treatment and received urgent treatment, with rapid improvement in symptoms and resultant functional recovery.

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The relationship between coping style and psychological distress in people with head and neck cancer: a systematic review

Abstract

Objective

Individuals diagnosed with head and neck cancer (HNC) are at an elevated risk of experiencing psychological distress and a reduced quality of life. The aim of this review was to systematically examine and assess the quality of empirical evidence on the associations between coping mechanisms and psychological distress among people with HNC.

Methods

CINAHL, MEDLINE, PsycINFO, EMBASE and Web of Science were accessed to conduct this review. Studies were included if they used reliable and valid measures to investigate the relationship between coping style and psychological distress. Study quality was assessed and rated according to pre-set criteria, and showed variability in relation to selection methods.

Results

12 studies (nine cross-sectional and three prospective designs) involving 1281 patients were reviewed. There was considerable heterogeneity in study samples and coping measures. Moderate to large associations between disengagement coping mechanisms (e.g. avoidance) and psychological distress were observed. Engagement coping strategies (e.g. direct action) were not consistently associated with psychological distress across studies.

Conclusions

Several studies observed a significant relationship between coping styles aimed at disengaging and distancing from cancer and increased psychological distress. To understand directionality of these associations and further develop an understanding of temporal features of the relationship between coping styles and distress, longitudinal designs could be used in future research.

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Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis

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miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis

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Breast cancer family history leads to early breast cancer detection and optimal management

Abstract

Purpose

We investigated whether the relationship between family history (FH) of breast cancer and survival of women with breast cancer is related to the quality of care received, once adjusted for other prognostic variables using data from the Geneva population-based cancer registry and quality of care indicators defined by the European Society of breast cancer specialists (EUSOMA).

Methods

We included non-metastatic malignant breast tumor patients who had their surgery between 2001 and 2010. We assessed the association between FH and patient and tumor characteristics on one hand, and each quality of care indicator and an overall score of quality of care, on the other hand, through logistic regression. We assessed the impact of FH and the quality of care-score on 5-year survival with Cox regression adjusting for patient and tumor characteristics.

Results

2,672 patients were included in the study. Women with a positive FH were younger, more likely from Switzerland, screen detected, had positive estrogen and progesterone receptor status, and had smaller and ductal tumors. A positive FH was also associated with better management for several quality indicators. Women with a positive FH had a better crude survival (Hazard Ratio 0.61, p = 0.006). This association was not substantially affected when adjusting for quality of care. However, the effect of FH did not persist when also adjusting for patient and tumor characteristics.

Conclusions

A positive FH of breast cancer is associated with earlier breast cancer diagnosis, better tumor features, and higher quality of care. These factors explain the better survival observed among breast cancer women with a positive FH as compared to women without positive FH.

http://ift.tt/2tF6Pe5

Optimising the surgical outcome in a case of post-traumatic cataract using ultrasound biomicroscopy

A 12-year-old boy was brought with the chief complaint of diminution of vision in his left eye for the past 1 month. History revealed a blunt trauma to his left eye with a wooden stick 6âweeks ago.Visual acuity was 20/20 and hand movement close to face in right and left eye, respectively, without any relative afferent pupillarydefect. Slit-lamp examination showed a total cataractous lens with signs suggestive of suspected posterior capsular (PC) defect. The PC defect was screened initially using B-scan ultrasound of the posterior segment, followed by confirmation of the same using ultrasound biomicroscopy. Left eye lens aspiration along with limited anterior vitrectomy followed by placement of multipiece intraocular lens in the sulcus was performed. Best-corrected visual acuity at 6 months of follow-up was 20/20.

http://ift.tt/2uzPYMM

Giant oesophageal gastrointestinal stromal tumour presenting with dyspnoea and clubbed fingers

Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms of the gastrointestinal tract originating from the interstitial cells of Cajal. Giant oesophageal GISTs are rare since the oesophagus is rarely the primary site of GISTs, and they are usually diagnosed early due to complaints such as dysphagia. We present the case of a giant oesophageal GIST presenting with prominent clubbing. The case underlined the diagnostic importance of clubbing and the careful consideration of chemotherapy. Although clubbed fingers associated with GISTs are rare, our experience demonstrates the importance of physicians' recognition of clubbing as a paraneoplastic phenomenon for early diagnosis of malignancies since patients seldom notice their own clubbing by themselves. Chemotherapy using imatinib, an Bcr-Abl kinase inhibitor, is the standard option for unresectable giant GISTs. However, careful consideration must be made of the risk of complications associated with rapid mass reduction due to imatinib such as bleeding, oesophageal perforation and mediastinitis.

http://ift.tt/2vKTulV

Type I talon cusp on mandibular incisor

Description

Talon cusp is a comparably rare developmental dental anomaly assumed to arise because of evagination on the surface of a tooth crown during tooth calcification stage. Talon cusp also called as Eagle's is a well-defined extra cusp like structure located on lingual or palatal surface of deciduous or permanent anterior teeth. Its occurrence may be either unilateral or bilateral, single or multiple teeth in males or females. Prevalence of talon's cusp is reported to be between 0.06% to 7.7%. Eagle's talon is most commonly seen in maxillary lateral incisor >maxillary central incisor> maxillary canine> mandibular incisor.1

Mandibular talon cusp is a rare entity to occur. Mandibular talon cusps are more prevalent in men than women. Occurrence in talon cusp is more common in permanent dentition. Most of the mandibular talon cusp shows unilateral presentation. Talon cusp associated with permanent central incisor and primary lateral incisor...

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Between fire and ice: refractory hypothermia and warmth-induced pain in inherited erythromelalgia

Inherited erythromelalgia (IEM) is a well-described pain disorder caused by mutations of sodium channel Na_v1.7, a peripheral channel expressed within dorsal root ganglion and the sympathetic ganglion neurons. Clinically, IEM is characterised by paroxysmal attacks of severe pain, usually in the distal extremities, triggered by warmth or exercise. Pain is not adequately treated by existing pharmacological agents. Individuals with IEM classically cool their limbs for relief, in some cases resulting in tissue injury. We describe a patient from a family with IEM due to the L858F mutation of Na_v1.7 who presented with refractory hypothermia due to overcooling. This presentation of refractory hypothermia necessitating warming strategies, complicated by severe warmth-induced pain, posed a substantial therapeutic challenge. We report our experience in overcoming hypothermia lasting 3 weeks in a child with IEM, discuss possible pathophysiological mechanisms underlying this unusual complication and suggest potential therapeutic interventions.

http://ift.tt/2vKB7h1

Pseudoprogression in pediatric low-grade glioma after irradiation

Abstract

This study aimed to assess the incidence and management of pseudoprogression after radiation therapy (RT) in patients with pediatric low-grade glioma (LGG). This retrospective review included patients aged 21 years or younger with intracranial LGG treated with curative-intent RT. Pseudoprogression was defined as an increase in tumor size by ≥10% in at least two dimensions between two and three consecutive MR imaging studies. Overall survival (OS) and event-free survival (EFS) were measured from the first day of RT. EFS was defined as survival without true progression or secondary high-grade glioma. Sixty-two of 221 patients developed pseudoprogression, with a 10-year cumulative incidence of 29.0% (95% CI 23.0–35.2). Median time to pseudoprogression was 6.1 months after RT. Symptomatic pseudoprogression was managed with subtotal resection, shunt/Ommaya reservoir placement, or corticosteroids in 11 (18%), 7 (11%), and 2 patients (3%), respectively. The remaining tumors were observed (68%). Patients with pilocytic astrocytoma (PA) had 5.4-fold greater odds of developing pseudoprogression relative to tumors of other histology (odds ratio 95% CI 2.5–11.4, P < 0.0001). Among patients with PA (n = 127), the 10-year cumulative incidence of pseudoprogression was 42.9%. In this group, pseudoprogression was associated with improved 10-year EFS (84.5% vs. 58.5%, P = 0.008) and OS (98.0% vs. 91.2%, P = 0.03). Pseudoprogression after irradiation was common, especially in patients with pilocytic astrocytoma, and was associated with improved survival. Knowledge of the incidence and temporal course of pseudoprogression may help avoid unnecessary salvage therapy.

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Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators

Future Oncology, Ahead of Print.


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Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project

Purpose: The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein–Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer.

Experimental Design: Gene expression data from a TCGA cohort (n = 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts (n = 267 and 432). An integrated risk assessment model (TCGA risk score) was also developed.

Results: EBV subtype was associated with the best prognosis, and GS subtype was associated with the worst prognosis. Patients with MSI and CIN subtypes had poorer overall survival than those with EBV subtype but better overall survival than those with GS subtype (P = 0.004 and 0.03 in two cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score was an independent prognostic factor [HR, 1.5; 95% confidence interval (CI), 1.2–1.9; P = 0.001]. Patients with the CIN subtype experienced the greatest benefit from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16–0.94; P = 0.03) and those with the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95% CI, 0.36–1.89; P = 0.65).

Conclusions: Our prediction model successfully stratified patients by survival and adjuvant chemotherapy outcomes. Further development of the prediction model is warranted. Clin Cancer Res; 23(15); 1–9. ©2017 AACR.

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In Memoriam: Sidney Saltzstein, MD

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Unilateral Headache Status after Intra-Aortic Balloon Pump Placement

Introduction. Intra-aortic balloon pump (IABP) counterpulsation is a catheter-based treatment for coronary artery disease and decompensated heart failure to increase coronary blood flow and improve cardiac output. IABP is generally well tolerated, and complications are usually related to peripheral vasculature or red blood cell and platelet consumption. The usual insertion site via femoral artery renders the patient bedbound. Recently, axillary artery has been used in patients with atherosclerotic peripheral vascular disease and documented small arteries or in those awaiting transplant to ensure ambulation and prevent deconditioning. Case Report. We present a patient with ischemic cardiomyopathy and severe left ventricular dysfunction, awaiting Orthotropic Heart Transplant. His worsening intractable angina and dyspnea necessitated IABP placement via left axillary artery, significantly improving his condition. He subsequently experienced migraine-type persistent unilateral headache refractory to standard pain management. Multiple strategies were utilized to treat his pain, but the patient insisted that his pain commenced after IABP placement. Ultimately, the removal of the pump led to complete resolution with no recurrence. Conclusion. The authors hypothesize that the unilaterally directed blood flow and direct increase in cerebral perfusion from the intra-aortic balloon pump may have caused vasodilation of the extracranial arteries, leading to a persistent and debilitating headache in this susceptible patient.

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Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Tumor control and late toxicity

The benefit of upfront neck dissection (ND) in locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared disease control and toxicity between patients who were treated with and without upfront ND followed by R(C)T.

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Indel derived tumour-specific neoantigens: The Lancet Oncology: Aug 2017

Samra Turajlic discusses the contribution of small insertions and deletions to tumour-specific antigen analyses.

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In Memoriam: Sidney Saltzstein, MD

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[Comment] A step towards predicting checkpoint inhibitor response in kidney cancer

In this issue of The Lancet Oncology, Samra Turaljic and colleagues report a heroic undertaking, using whole-exome sequencing data from 5777 patients representing 19 solid tumour types.1 In their series, the presence of frameshift indels across this large pan-cancer cohort was associated with more tumour-specific neoantigens compared with non-synonymous single nucleotide variant (nsSNV) mutations. In renal cell carcinoma, frameshift indels were more prevalent compared with in other tumour types and were associated with enhanced antigen-presenting machinery and T-cell activation.

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[Corrections] Correction to Lancet Oncol 2017; 18: 917–28

Stebbing J, Baranau Y, Baryash V, et al. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol 2017; 18: 917–28—Justin Stebbing's affiliations should have read "Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, UK", and his Declaration of Interests statement should have read "JS is supported by the Biomedical Research Centre, Imperial College London, and the National Institute for Health Research." This correction has been made to the online version as of July 26, 2017.

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[Corrections] Correction to Lancet Oncol 2017; 18: 1022–39

Gatta G, Capocaccia R, Botta L, et al, for the RARECAREnet working group. Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet—a population-based study. Lancet Oncol 2017; 18: 1022–39—In the list of authors, Innos Kaire should have been Kaire Innos. In the affiliations list, I Kaire should have been K Innos. In the Results section, "but soft tissue sarcomas were treated more centrally than bone sarcoma" should have been "but soft tissue sarcomas were treated centrally less than bone sarcoma".

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[Comment] High-dose chemotherapy and autologous stem-cell transplantation for DLBCL in the rituximab era

In this issue of The Lancet Oncology, Annalisa Chiappella and colleagues1 report the results of high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment for young patients with diffuse large B-cell lymphoma with poor prognosis—patients with two or three risk factors according to the age-adjusted international prognostic index (aa-IPI). By use of a 2×2 factorial design, two questions were addressed: first, whether a dose-escalated version of a 14-day R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen, R-MegaCHOP-14, is better than R-CHOP-14; and second, whether results can be improved by switching patients in remission after four cycles of R-CHOP-14 or R-MegaCHOP-14 to a programme that includes an intensive consolidation regimen: MAD (cytarabine plus mitoxantrone plus dexamethasone), followed by high-dose chemotherapy and autologous stem-cell transplantation (transplantation group) rather than maintaining them on R-CHOP-14 or R-MegaCHOP-14 (no transplantation group).

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[Comment] FLT3 inhibition in acute myeloid leukaemia

FLT3 is a transmembrane tyrosine kinase that stimulates survival and proliferation of leukaemic blasts. The two main FLT3 mutations found in acute myeloid leukaemia are internal tandem duplications in the juxtamembrane domain (roughly 30% of mutations) and point mutations in the tyrosine kinase domain loop at the Asp835 codon (D835; roughly 7–10%).1 Patients with newly diagnosed acute myeloid leukaemia and internal tandem duplications in FLT3 who are treated with conventional chemotherapy have poorer outcomes (3-year survival <20%) than do patients without these mutations (3-year survival 45–55%), because of their increased risk of relapse and inferior event-free survival.

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[Corrections] Correction to Lancet Oncol 2017; 18: 1040–48

Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observationfor completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18: 1040–48—In figure 2 of this Article, the key for the treatment groups should have shown the Observation group in blue and the SRS group in red. The initials of Dr Paul Brown have been updated to "Paul D Brown" in the author list, affiliations, and contributors. These corrections have been made to the online version as of July 26, 2017, and the printed Article is correct.

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[Clinical Picture] Tumour d'emblee

A healthy businessman aged in his 50s presented to our outpatient clinic at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, in March 2016 with sudden eruption of multiple swellings on the scalp of 3 months' duration. The condition had been treated empirically as deep folliculitis for the past 3 months by different care providers without any improvement. Six well-defined, firm, erythematous tumours with visible telangiectasiae along with several papulonodules were noted on the fronto-parietal scalp (figure, A).

http://ift.tt/2v0aGWA

[Series] Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence

The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels.

http://ift.tt/2tE9eFN

[Series] Cardiotoxic effects of anthracycline-based therapy: what is the evidence and what are the potential harms?

Despite the known cardiotoxic effects of doxorubicin and other anthracyclines, no evidence-based guidelines exist for the surveillance and prevention of chemotherapy-induced cardiotoxicity in adult survivors of breast cancer who have had limited previous doses of anthracyclines (ie, total cumulative dose 240 mg/m2), or limited-dose anthracyclines followed by trastuzumab-based regimens. Nonetheless, some national and international cardio-oncology and cardiac-imaging organisations recommend increased cardiac surveillance during or after treatment, measurement of cardiac biomarkers and other surrogate endpoints, and in some cases initiation of cardioprotective drug therapy in asymptomatic women.

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[Correspondence] Colorectal adenomas, surveillance, and cancer – Authors' reply

The primary aim of surveillance is to reduce colorectal cancer incidence to avoid morbidity and mortality from the disease. Current guidelines stratify patients with adenomas into risk groups, but these guidelines are based on advanced adenoma detection at surveillance. Advanced adenomas vary in malignant potential and diagnosis can occur only in those attending surveillance. Data that use colorectal cancer as the endpoint are thus needed.

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[Comment] The science of precision prevention of cancer

Precision medicine has been proposed as a new frontier to tackle the emergence of non-communicable diseases. According to one definition, "Precision medicine is a revolutionary approach for disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology."1 Prevention is mentioned side-by-side with treatment. However, what is precision prevention? How can it be conceptualised? In this Comment, we raise some key considerations relating to the development of a science of precision prevention of cancer.

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[Corrections] Correction to Lancet Oncol 2017; 18: 556–57

Kotsakis A, Georgoulias V. Avelumab, an anti-PD-L1 monoclonal antibody, shows activity in various tumour types. Lancet Oncol 2017; 18: 556–57—In this Comment, the term 'immune-related' should have read 'infusion-related' in two phrases. The two affected sentences should have read as follows: "However, an important finding from these two studies was that the frequency of infusion-related reactions exceeded 20%; infusion-related reactions are uncommon with the other approved immunotherapeutic agents, with an estimated frequency of about 1–2%" and "Once again, ongoing phase 3 trials (NCT02395172, NCT02576574) might shed light on the frequency, significance, and severity of infusion-related adverse events and how best to manage them." These corrections have been made to the online version as of July 26, 2017.

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[Comment] Beyond bad luck: induced mutations and hallmarks of cancer

In March, 2017, the American Association for the Advancement of Science (AAAS) published a headline stating "Random errors in DNA replication play a major role in cancer", referring to a new paper by Tomasetti and colleagues,1 a follow-up to their first paper in 2015. Headlines subsequently appeared on many news and social media outlets reading "Most cancer cases arise from 'bad luck'" (Scientific American) or "'Bad luck' mutations increase cancer risk more than behavior, study says" (CNN). Such a message, suggesting that cancers are largely due to bad luck, is an incorrect interpretation of the authors' results, and is ultimately misleading.

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[Correspondence] Evidence-based management of adult patients with diffuse glioma – Authors' reply

We appreciate the interest of our colleagues representing the European Low-Grade Glioma Network in the updated European Association for Neuro-Oncology (EANO) guidelines.1 Such guidelines often represent a multidisciplinary consensus that aims at providing guidance also in areas where evidence from conclusive clinical studies is limited or absent. Our colleagues miss a specific reference to the value of radiological growth rates.

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[Comment] Increasing global access to cancer care: models of care with non-oncologists as primary providers

The rapidly increasing incidence of cancer in low-income and middle-income countries is compounded by a profound shortage of both oncologists and facilities with the capacity for cancer care in these settings.1,2 In a model where only oncologists treat cancer, patients—many with curable diseases—will die waiting for oncologists to be trained. Thus, it is imperative to develop innovative models of care that address the immediate needs of patients with cancer. One possibility is task-shifting, whereby general medical practitioners can be trained to deliver safe and effective oncology services.

http://ift.tt/2v0wgKn

[Series] Preventive therapy for cancer

Therapeutic cancer prevention is a developing area that can gain a lot from the successes in the prevention of cardiovascular diseases. Although weight control and physical activity are important in the prevention of both diseases, several other preventive measures exist. Low-dose aspirin for cancer prevention is often cited as the most important approach in terms of population benefit, and should be offered to those older than 50 years of age without hypertension or risk factors for gastrointestinal bleeding.

http://ift.tt/2tEt0kp

[Correspondence] Prospective radiotherapy for patients with oropharyngeal carcinoma

We read with interest the recent article in The Lancet Oncology, in which Allen M Chen and colleagues1 investigated reduced-dose radiotherapy for patients with human papillomavirus (HPV)-associated squamous-cell carcinoma of the oropharynx. Few prospective studies have specifically investigated optimum (tolerable and efficacious) reduced-dose treatment regimens for such patients. This relatively new and prospective treatment approach to oropharyngeal cancer might be potentially safer and more effective than standard radiotherapy regimens.

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[Correspondence] Evidence-based management of adult patients with diffuse glioma

Recently, Weller and colleagues1 proposed the new European Association for Neuro-Oncology (EANO) guidelines for adult gliomas. They have to be congratulated for their efforts in building recommendations based on the 2016 revision of the WHO classification, translating the integrated histomolecular diagnosis into algorithmic decision making. They confirm that maximal safe surgical resection in high-volume specialist centres has to be proposed whenever feasible, independent of the grade of malignancy and the histomolecular profile.

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[Correspondence] Prospective radiotherapy for patients with oropharyngeal carcinoma – Authors' reply

We thank Yue Wang and Long Wu for their thoughtful comments on our recently completed clinical trial for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma.1 As they astutely point out, de-escalation strategies for this disease can take the form of radiotherapy dose reduction or the attenuation or outright elimination of chemotherapy. A third approach, radiotherapy volume reduction, should also be mentioned. Although Wang and Wu suggest that use of dose-reduced radiotherapy alone for HPV-associated oropharyngeal squamous cell carcinoma holds promise, little data currently exist to support such a strategy.

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[Correspondence] Cancer in the Renaissance court of Naples

Cancer nowadays is the second most common cause of death in high-income countries. However, only five cases of malignant-soft-tissue tumours are present in the palaeopathological literature.1 The rarity of cancer in antiquity is a highly debated problem and the main reasons are apparently the short lifespan of past populations, the scarcity of mummified remains, and the technical difficulties of detecting neoplastic lesions in mummified tissues.2

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Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients

Abstract

Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2 months (95% CI [12.1–58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5). Median overall survival was 7.5 years (95% CI [4–NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.

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Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists

Purpose: Stereotactic body radiotherapy (SBRT) is often used to treat patients with oligometastases (OM). Yet, patterns of SBRT practice for OM are unknown. Therefore, we surveyed radiation oncologists internationally, to understand how and when SBRT is used for OM. Methods: A 25-question survey was distributed to radiation oncologists. Respondents using SBRT for OM were asked how long they have been treating OM, number of patients treated, organs treated, primary reason for use, doses used, and future intentions. Respondents not using SBRT for OM were asked reasons why SBRT was not used and intentions for future adoption. Data were analyzed anonymously. Results: We received 1007 surveys from 43 countries. Eighty-three percent began using SBRT after 2005 and greater than one third after 2010. Eighty-four percent cited perceived treatment response/durability as the primary reason for using SBRT in OM patients. Commonly treated organs were lung (90%), liver (75%), and spine (70%). SBRT dose/fractionation schemes varied widely. Most would offer a second course to new OM. Nearly all (99%) planned to continue and 66% planned to increase SBRT for OM. Of those not using SBRT, 59% plan to start soon. The most common reason for not using SBRT was lack of clinical efficacy (48%) or lack of necessary image guidance equipment (34%). Conclusions: Radiation oncologists are increasingly using SBRT for OM. The main reason for not using SBRT for OM is a perceived lack of evidence demonstrating clinical advantages. These data strengthen the need for robust prospective clinical trials (ongoing and in development) to demonstrate clinical efficacy given the widespread adoption of SBRT for OM.

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Oral Platelet Gel Supernatant Plus Supportive Medical Treatment Versus Supportive Medical Treatment in the Management of Radiation-induced Oral Mucositis: A Matched Explorative Active Control Trial by Propensity Analysis

Objectives: In this active control trial, the rate of radio-induced WHO grade 3/4 oral mucositis and the change in quality of life, assessed by OMWQ-HN, were measured in subjects with head and neck cancer treated by platelet gel supernatant (PGS) and supportive medical treatment versus subjects treated by supportive medical treatment alone. Materials and Methods: Eighty patients with nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy. All patients underwent supportive medical treatment and/or PGS at the beginning and during radiotherapy. Sixteen patients received PGS in association with supportive medical treatment. To obtain 2 groups virtually randomized for important clinical characteristics subjects were matched, by propensity analysis, with a group of subjects (64 patients) treated with supportive medical treatment alone. Results: Subjects treated with standard supportive treatment experienced significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the evidence that they developed later symptoms with respect to controls. The Cox proportional hazard model indicated that patients treated with standard supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95% confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS group significantly experienced higher quality of life than control groups as measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was found in the PGS group. Conclusions: These preliminary data should be interpreted with caution and could serve as a framework around which to design future trials.

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Induction Therapy for Locally Advanced, Resectable Esophagogastric Cancer: A Phase I Trial of Vandetanib (ZD6474), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiotherapy Followed by Resection

Objectives: Preoperative chemotherapy and radiation for localized esophageal cancer produces cure rates near 30% when combined with surgical resection. Vandetanib, a small molecule receptor tyrosine kinase inhibitor of VEGFR-2, VEGFR-3, RET, and EGFR, demonstrated synergy with radiation and chemotherapy in preclinical models. We conducted a phase I study to assess the safety and tolerability of vandetanib when combined with preoperative chemoradiation in patients with localized esophageal carcinoma who were surgical candidates. Methods: Patients with stage II-III esophageal and gastroesophageal junction carcinoma without prior therapy were enrolled in a 3+3 phase I design. Patients received once-daily vandetanib (planned dosing levels of 100, 200, and 300 mg) with concomitant daily radiotherapy (1.8 Gy/d, 45 Gy total) and chemotherapy, consisting of infusional 5-FU (225 mg/m2/d over 96 h, weekly), paclitaxel (50 mg/m2, days 1, 8, 15, 22, 29) and carboplatin (AUC of 5, days 1, 29). Results: A total 9 patients were enrolled with 8 having either distal esophageal or gastroesophageal junction carcinomas. All patients completed the planned preoperative chemoradiation and underwent esophagectomy. Nausea (44%) and anorexia (44%) were the most common acute toxicities of any grade. One grade 4 nonhematologic toxicity was observed (gastrobronchial fistula). One additional patient suffered a late complication, a fatal aortoenteric hemorrhage, not definitively related to the investigational regimen. Five (56%) patients achieved a pathologic complete response. Three (33%) additional patients had only microscopic residual disease. Five (56%) patients remain alive and disease free with a median follow-up of 3.7 years and median overall survival of 3.2 years. The maximum tolerated dose was vandetanib 100 mg/d. Conclusions: Vandetanib at 100 mg daily is tolerable in combination with preoperative chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy with encouraging efficacy worthy of future study.

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Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies

Purpose/Objectives: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. Materials/Methods: In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). Results: Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was 1.9×106/L in patients receiving Radium alone, versus 2.3×106/L in patients receiving concurrent therapy (P=0.77). Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone, versus 1.8 g/L in patients receiving concurrent therapy (P=0.31). Mean change from initial platelet count to nadir was 52.3×109 cells/L in patients receiving Radium alone versus 70.6×109 cells/L in patients receiving concurrent therapy (P=0.39). Individual blood counts for each measured laboratory are included in the supplemental data. PSA was stable or decreased in 22% of patients receiving Radium alone versus 35% of patients receiving combination treatment (P=0.24). Conclusions: Concurrent administration of Radium-223 and next-generation antiandrogen therapies appears to be well tolerated with similar toxicities to standard administration of Radium-223 alone. This particular cohort of patients represents a high-risk, heavily pretreated group of patients with advanced metastatic disease and significant marrow burden. Despite these risk factors, hematologic toxicity was modest and was in the range expected for this risk group based on previous trials. To date, this is the first study investigating the toxicity of combination treatment. Further studies investigating the safety and efficacy of combination treatments are warranted.

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Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130

Objectives: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC. This phase I trial evaluated the combination of AMR and cyclophosphamide in refractory solid organ malignancies and in relapsed SCLC. Materials and Methods: The primary endpoint was to determine maximum-tolerated dose and dose-limiting toxicities of the combination. Eligible patients were enrolled in sequential dose escalation cohorts in a standard 3+3 design. Treatment consisted of cyclophosphamide IV at 500 mg/m2 on day 1 with escalating doses of AMR IV on days 1 to 3 (25 to 40 mg/m2 with increments of 5 mg/m2 per cohort). Cycles were repeated every 21 days. Exploratory objectives analyzed the presence of NQO1 polymorphisms and topoisomerase IIA amplification and correlation with response. Results: Thirty-six patients were enrolled, of whom 18 patients had SCLC (50%). Maximum-tolerated dose was determined to be dose level 2 (cyclophosphamide 500 mg/m2, AMR 30 mg/m2) due to grade 4 thrombocytopenia. The main grade 3 to 4 toxicities were hematologic. Efficacy results are available for 34 patients. Partial responses, stable disease, and progressive disease rates in the overall study population were 20.6% (n=7), 38.2% (n=13), and 41.2% (n=14), respectively. Partial response, stable disease, and progressive disease rates in the SCLC patients and 1 patient with extrathoracic small cell were 36.8% (n=7), 26.3% (n=5), and 36.8% (n=7), respectively. There was no correlation between topoisomerase IIA amplification or NQO1 polymorphisms and response. Conclusions: AMR and cyclophosphamide can be safely combined with little activity observed in heavily pretreated SCLC patients.

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High-risk Prostate Cancer Treated With Dose-escalated RT: An Analysis of Hormonal Therapy Use and Duration, and Prognostic Implications of PSA Nadir ≤0.2 to Select Men for Short-term Hormonal Therapy

Objectives: To determine prognostic factors to select high-risk men receiving dose-escalated radiation therapy (RT) who will have favorable outcomes with short-term (ST) or no androgen deprivation therapy (ADT). Methods: Medical records of 458 men treated with definitive RT for high-risk, nonmetastatic prostate cancer at 3 academic referral centers from 1988 to 2009 were examined. Median dose was 76.4 Gy. Men received no ADT (n=105), STADT (0.05). Those with PSA nadir ≤0.2 ng/mL had improved outcomes. Men with GS 9 disease did poorly despite a PSA nadir ≤0.2 ng/mL and had improved CSS with LTADT (95% vs. 71%, P

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The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer

Objectives: The prognostic value of several hematologic parameters, including platelet, lymphocyte, and neutrophil counts, has been studied in a variety of solid tumors. In this study, we examined the significance of inflammatory markers and their prognostic implications in patients with colorectal cancer (CRC). Materials and Methods: Patients with stage I-III CRC who underwent surgical resection at the Stanford Cancer Institute between 2005 and 2009 were included. Patients were excluded if they did not have preoperative complete blood counts performed within 1 month of surgical resection, underwent preoperative chemotherapy or radiation, had metastatic disease at diagnosis, or had another previous malignancy. We included 129 eligible patients with available preoperative complete blood counts in the final analysis. Results: A preoperative neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a preoperative lymphocyte-to-monocyte ratio of ≤2.6 (P=0.01, 0.002). Preoperative lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048) but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS (P=0.24) or DFS (P=0.15). Conclusions: Pretreatment lymphopenia, thrombocytosis, a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to-lymphocyte ratio independently predict for worse OS in patients with CRC.

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Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of Disease After Transperineal Template-guided Mapping Biopsy

Objectives: Previous studies have evaluated whether metformin is associated with prostate cancer incidence and outcomes with conflicting conclusions. In this study, we evaluate the incidence of prostate cancer in diabetic patients treated with and without metformin compared with nondiabetic patients. Materials and Methods: One thousand thirty-four patients underwent transperineal template-guided mapping biopsy secondary to either an elevated prostate-specific antigen (PSA) or a prior biopsy finding of atypical small acinar proliferation/prostatic intraepithelial neoplasia. The cohort included 881 nondiabetic men, 65 diabetic men treated with metformin, and 88 diabetic men not receiving metformin. In metformin-treated patients, the median duration of usage was 6.0 years. Differences in prostate cancer diagnosis, histologic grade, and tumor volume were compared across the 3 cohorts. Results: There was no statistically significant differences discerned between the 3 cohorts in patient age, prebiopsy PSA, prostate volume, PSA density, PSA doubling time, PSA velocity, or the total number of prior transrectal ultrasound biopsy sessions. Five hundred eighty-four patients were diagnosed with prostate cancer. There was no difference in prostate cancer diagnosis (P=0.153), Gleason score (P=0.960), the number of positive biopsy cores (P=0.764), or risk group stratification (P=0.877) between the 3 cohorts. In multivariate analysis, only older age predicted for prostate cancer diagnosis. In terms of Gleason score ≥7, patient age, PSA velocity, and body mass index predicted for more aggressive histology. Neither diabetes, metformin use or duration was of statistical consequence. Conclusion: Metformin did not impact incidence of prostate cancer diagnosis, Gleason score distribution, or volume of disease.

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Surgery and Adjuvant Radiation for High-risk Skin Adnexal Carcinoma of the Head and Neck

Objectives: Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that arises from sebaceous and sweat glands. These carcinomas are believed to behave more aggressively than cutaneous squamous cell carcinomas (SCC) with a propensity for local recurrence. The role of adjuvant radiotherapy in SAC is undefined. Methods: We retrospectively reviewed all cases of head and neck SAC treated with surgery and adjuvant radiation from 2000 to 2012 at a single institution. Results: Nine cases were identified. Median age was 67 (range, 52 to 88) years. The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1), skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to confirm the SAC diagnosis. All patients had undergone surgery. Indications for adjuvant radiation included involved lymph nodes (n=4), perineural invasion (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5). Radiation was delivered to the primary site alone (n=3), to the draining lymphatics alone (n=2), or to both (n=4). One patient received concurrent cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50 Gy. Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3 toxicity and no greater than or equal to grade 2 late toxicities were recorded. Conclusions: Surgery and adjuvant radiation for high-risk SAC offers excellent locoregional control with acceptable toxicity.

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Stage I Lung SBRT Clinical Practice Patterns

Objectives: Stereotactic body radiation therapy (SBRT) has become increasingly utilized over the last decade in the treatment of inoperable stage I non–small cell lung cancer (NSCLC) patients, although no standardized dosing guidelines exist. In this retrospective study, we investigated the dose prescription pattern use in the United States for patients receiving SBRT. Methods: Patients with stage I NSCLC treated with SBRT between 2004 and 2011 were identified within the National Cancer Database (NCDB). Trends in SBRT use and dose prescriptions were analyzed. Results: A total of 5246 patients met criteria as receiving SBRT. The overall mean and median BED10 were 134.5 and 132 Gy, respectively. Of these patients, 94.5% were prescribed a regimen with a BED10≥100 Gy. The most common prescriptions overall were 60 Gy in 3 fractions (24.1%), 48 Gy in 4 fractions (17.8%), 50 Gy in 5 fractions (13.0%), and 54 Gy in 3 fractions (12.8%). Analysis of prescription trends revealed decreased utilization of 54 to 60 Gy in 3 fractions (47.9% in 2006 to 27.9% in 2011, combined) and increased utilization of 50 Gy in 5 fractions (3.1% in 2006 to 20.4% in 2011). Conclusions: Our findings suggest increasing use of SBRT over the last decade with a majority of patients being treated with regimens employing a BED10≥100 Gy. Since 2006, there has been a decline in the use of 54 to 60 Gy in 3 fractions, with an increase in the use of 50 Gy in 5 fractions. Possible explanations include concern for increased toxicity with higher BED regimens and increasing treatment of centrally located tumors.

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Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal

Purpose: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. Materials and Methods: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. Results: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. Conclusions: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

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The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor: A Meta-analysis of 25 RCTs

Objective: To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non–small cell lung cancer (NSCLC) patients with wild-type (WT) EGFR tumors, we performed an indirect meta-analysis to assess the treatment effects of EGFR-TKIs in such patients. Methods: We searched for randomized controlled trials in Medline, Embase, the Cochrane controlled trials register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Effect measures used were hazard ratios (HR) for progression-free survival (PFS) and overall survival. Results: Out of 2134 retrieved articles, 25 randomized controlled trials including more than 4467 patients were identified. This pooled analysis showed the inferior efficacy of TKI over chemotherapy among patients with WT EGFR NSCLC in terms of PFS (HR, 1.37; 95% confidence interval [CI]: 1.10, 1.72; P=0.006). When used as first-line treatment, TKIs have also fared worse than chemotherapy when compared with standard platinum doublet regimens in patients with WT EGFR in terms of PFS (HR, 2.15; 95% CI: 1.68, 2.76; P

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Contemporary Patterns and Survival Outcome of Adjuvant Systemic Therapy for Localized Gastrointestinal Stromal Tumors

Objectives: To describe contemporary patterns of and factors associated with adjuvant therapy use and survival outcome after resection of localized gastrointestinal stromal tumors (GISTs) using a large contemporary clinical database. Methods: We queried the National Cancer Data Base to identify localized GIST cases diagnosed from 2004 to 2011, and used descriptive and logistic regression analyses to determine patterns of and factors associated with adjuvant therapy. Kaplan-Meier and Cox proportional-hazard model were utilized to generate survival probabilities and hazard ratios (HRs). Results: Of 4694 patients, 73.5% received surgery alone, and 26.5% received adjuvant therapy during 2004 to 2011. Receipt of adjuvant therapy more than doubled between 2006 (13.2%) and 2007 (30.5%), peaked to 37.9% in 2009, and then decreased to 25.6% in 2011 (P for trend10 cm) than those with smaller tumor size (≤5 cm) (44.1% vs. 15.8%; P10 cm tumor size (HR=0.42; 95% confidence interval, 0.20-0.89; P=0.02). Conclusions: In a large nationwide dataset, we showed that the use of adjuvant therapy for localized GISTs has significantly increased over time and patients treated with adjuvant therapy have better survival than patients treated with surgery alone.

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Influence of NSAID Use Among Colorectal Cancer Survivors on Cancer Outcomes

Purpose: Colorectal cancer (CRC) is the third most common cancer diagnosed in men and women in the United States. Given the availability of effective screening, most tumors are found early enough to offer patients substantial long-term survival. Thus there is a resulting significant population of CRC survivors for whom modifiable risk factors for recurrence and survival would be of interest. Methods: We conducted a population-based retrospective cohort study among patients enrolled in 2 large Midwestern health plans for which claims data, including pharmacy fill data, and medical record data were available. Men and women who were 40 years of age or older at the time of CRC diagnosis with disease less than stage IV and no history of Crohn disease, ulcerative colitis, and irritable bowel syndrome were included. CRC cases diagnosed between January 1, 1990 and December 31, 2000 were included if they met the inclusion criteria. Adjusted Cox proportional hazard models were used with exposure modeled as a time-dependent covariate. We assessed progression-free survival, defined as an aggressive polyp or invasive disease, and overall survival. Results: After adjustment for age at diagnosis, sex, race, body mass index, stage, side of initial tumor, and tumor histology, we found that current users of nonsteroidal anti-inflammatory drugs had a 3-fold decreased risk of recurrence and a >7-fold decreased risk of death. Our results are statistically significant with P-values

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Thyroid V50 Highly Predictive of Hypothyroidism in Head-and-Neck Cancer Patients Treated With Intensity-modulated Radiotherapy (IMRT)

Objectives: Radiation-induced hypothyroidism affects a significant number of patients with head-and-neck squamous cell cancer (HNSCC). We examined detailed dosimetric and clinical parameters to better determine the risk of hypothyroidism in euthyroid HNSCC patients treated with intensity-modulated radiation therapy (IMRT). Materials and Methods: From 2006 to 2010, 75 clinically euthyroid patients with HNSCC were treated with sequential IMRT. The cohort included 59 men and 16 females with a median age of 55 years (range, 30 to 89 y) who were treated to a median dose of 70 Gy (range, 60 to 75 Gy) with concurrent chemotherapy in nearly all (95%) cases. Detailed thyroid dosimetric parameters including maximum dose, mean dose, and other parameters (eg, V50—percent volume receiving at least 50 Gy) were obtained. Freedom from hypothyroidism was evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using Cox regression. Results: After a median follow-up period of 50 months, 25 patients (33%) became hypothyroid. On univariate analysis, thyroid V50 was highly correlated with developing hypothyroidism (P=0.035). Other dosimetric paramaters including mean thyroid dose (P=0.11) and maximum thyroid dose (P=0.39) did not reach statistical significance. On multivariate analysis incorporating patient, tumor, and treatment variables, V50 remained highly statistically significant (P=0.037). Regardless of other factors, for V50>60%, the odds ratio of developing hypothyroidism was 6.76 (P=0.002). Conclusions: In HNSCC patients treated with IMRT, thyroid V50 highly predicts the risk of developing hypothyroidism. V50>60% puts patients at a significantly higher risk of becoming hypothyroid. This can be a useful dose constraint to consider during treatment planning.

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Lymph Node Burden as a Predictive Factor for Selective Chemoradiotherapy in Patients With Locally Advanced Gastric Cancer After a D2 Dissection: A Retrospective Study

Objectives: The role of adjuvant radiation in locally advanced gastric cancer after a D2 lymph node dissection is not well defined. The Adjuvant Chemoradiation Therapy in Stomach Cancer trial demonstrated a benefit in selected patients with positive lymph nodes. This study further defines lymph node burden as a predictive factor for adjuvant radiation in locally advanced gastric cancer after radical D2 lymph node dissection. Materials and Methods: One hundred eighty-six patients with locally advanced gastric cancer and D2 dissections were retrospectively investigated. Patients were divided into 2 equal and well-balanced groups based on clinicopathologic characteristics, with half receiving chemoradiation and the other half chemotherapy alone. Clinical outcomes and recurrence patterns were compared. Lymph node ratio (LNR) was defined as ratio of positive to examined nodes. Chemotherapies were fluorouracil-based regimens. Radiation was prescribed to 45 Gy (range, 45 to 50.4 Gy) using 3-dimensional conformal or intensity-modulated radiation therapy techniques. Results: There was no difference between patients treated with or without radiation in 3-year disease-free survival (DFS) (57.0% vs. 62.0%, P=0.30) or 3-year overall survival (72.8% vs. 77.4%, P=0.23). However, patients with LNR>0.65 or 3 to 6 positive nodes (N2) had improved 3-year DFS and 3-year distant metastasis-free survival (DMFS) in the chemoradiation group (LNR>0.65 vs. LNR≤0.65: 3-y DFS: 35.8% vs. 0%, P=0.052, 3-y DMFS: 75.2% vs. 0%, P=0.026; N2 vs. non-N2: 3-y DFS: 84.7% vs. 57.1%, P=0.046, 3-y DMFS: 100.0% vs. 65.3%, P=0.036). Conclusions: N2 or LNR>0.65 may be indications for adjuvant chemoradiotherapy. Further randomized studies are needed for validation.

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Long-term Outcomes and Complications in Pediatric Ewing Sarcoma

Objectives: The objective of this study was to determine treatment outcomes and long-term complications in pediatric patients with Ewing Sarcoma treated at the British Columbia Cancer Agency (BCCA). Methods: A retrospective chart review of 101 pediatric patients (

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Resection of Colorectal Cancer With Versus Without Preservation of Inferior Mesenteric Artery

Objective: To assess the clinical significance of preservation of the inferior mesenteric artery (IMA) in comparison with IMA ligation in surgery for sigmoid colon or rectal (colorectal) cancer. Methods: Consecutive patients (n=862) with colorectal cancer who underwent intended surgical resection of the main tumor between 1986 and 2011 were retrospectively analyzed. The patients were divided into 2 groups: IMA preserved (n=745) and IMA ligated (n=117). Results: No significant difference was observed in incidence of advanced stage III or IV disease between the 2 groups (P=0.56 and 0.51, respectively), whereas a longer operation time (287 [95 to 700] vs. 215 [60 to 900] min, respectively; P

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Favorable Outcome of Hurthle Cell Carcinoma of the Thyroid Treated With Total Thyroidectomy, Radioiodine, and Selective Use of External-Beam Radiotherapy

Objectives: There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era. Methods: Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient. Results: Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows: Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%. Conclusions: Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and—in selected cases—external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

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Preoperative genetic testing impacts surgical decision making in BRCA mutation carriers with breast cancer: a retrospective cohort analysis

Abstract

Background

The impact of timing of genetic testing on surgical decision making in women with breast cancer and BRCA mutation is not well known.

Methods

Women who were found to carry a deleterious BRCA mutation and had been diagnosed with breast cancer were identified from a database at Beaumont Health. Women who had received BRCA positive results at least a day prior to their index surgery were considered to be aware of their mutation status prior to surgery. Baseline characteristics and surgical choices were compared between women who were aware of their mutation status prior to surgery and those who were not. Fischer's exact test was used for categorical variables and Mann–Whitney U-Test was used for continuous variables.

Results

A total of 220 patients were included in the final analysis, 208 (94.5%) with unilateral breast cancer and 12 (5.5%) with bilateral breast cancer. Out of the 208 patients with unilateral breast cancer, 106 (51.0%) patients were aware of their mutation status prior to index surgery while 102 (49%) were not. A significantly (p < 0.05) higher proportion of women underwent contralateral prophylactic mastectomy in the group that was aware of their mutation status prior to index surgery compared to the group that was not (76.4% vs 14.7%).

Conclusions

Our study demonstrates that knowledge of BRCA mutation status impacts surgical decision making in favor of bilateral mastectomy in patients who are aware of their results prior to index surgery. This finding supports the practice of preoperative genetic testing in patients with newly diagnosed breast cancer.

http://ift.tt/2w19DDa

Hemoglobin Himeji and inconsistent hemoglobin A1c values: a case report

Hemoglobin A1c is used to evaluate the glycemic control in patients with diabetes and is a risk marker for chronic complications of diabetes. Hemoglobin variants are reported to falsely lower or increase hemog...

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Hypercapnic respiratory failure during pregnancy due to polymyositis-related respiratory muscle weakness: a case report

Polymyositis is a rare medical disorder complicating pregnancy. Ventilatory muscle weakness leading to respiratory failure is an uncommon manifestation of this autoimmune disease. We report a case of life-thre...

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Cancer donor preferences for disposition of their biospecimens after biobank closure

BACKGROUND

Biobank funding is unstable and biobank administrators are concerned about loss of funding and subsequent biobank closure. Nevertheless, only a minority of biobanks have policies regarding the distribution or destruction of tissue if the biobank were to close. To the authors' knowledge, the current study is the first to report on the preferences of oncology biospecimen donors regarding the handling of their biospecimens in the event of biobank closure.

METHODS

A total of 98 biospecimen donors who were diagnosed with cancer at the Georgia Cancer Center for Excellence at Grady Memorial Hospital or the Winship Cancer Institute were interviewed concerning their preferences for the handling of their biospecimens in the event of biobank closure.

RESULTS

The majority of biospecimen donors who expressed a preference (62 of 83 donors; 75%) wanted their biological materials transferred to another biobank, specifically an academic bank or a national bank. The most unacceptable options for the handling of tissue were transfer to a for-profit/pharmaceutical biobank (39 of 98 donors; 40%) or a biobank based outside of the United States (31 of 98 donors; 32%). Nonwhite participants were more likely to view the transfer of their tissue to a for-profit/pharmaceutical tissue bank, international tissue bank, or a national tissue bank as unacceptable compared with white participants.

CONCLUSIONS

According to these biospecimen donors, the most acceptable options for the handling of biospecimens after biobank closure were transfer to an academic or national bank. The most objectionable options were transfer to a for-profit/pharmaceutical biobank or a biobank based outside of the United States. These findings can be used as the basis for educational interventions directed at the public and can inform the policies of biobanks that serve oncology research. Cancer 2017. © 2017 American Cancer Society.

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Cytogenetic clonal evolution in myelodysplastic syndromes is associated with inferior prognosis

BACKGROUND

The karyotype of bone marrow cells at the time of diagnosis is a strong prognostic parameter for overall survival as well as acute myeloid leukemia (AML) progression in patients with myelodysplastic syndromes (MDS). However, to the authors' knowledge, few data exist regarding the prognostic impact of cytogenetic clonal evolution during the course of MDS.

METHODS

The authors evaluated follow-up karyotype analyses in 549 patients from the Dusseldorf MDS Registry.

RESULTS

Clonal evolution was detectable in 24% of the entire cohort and in 18% of 294 patients receiving best supportive care. The authors noted a clear adverse effect of clonal evolution on the risk of leukemic transformation (hazard ratio, 2.233; P = .036) and overall survival (hazard ratio, 3.677; P<.001). The authors also analyzed the prognostic influence of subclones detectable at the time of diagnosis. Again, such a finding was associated with a significantly shorter overall survival and a higher 5-year-probability of acute myeloid leukemia progression (30% vs 22%).

CONCLUSIONS

The results of the current study support the belief that follow-up karyotype analyses should be performed, especially in patients with lower-risk and intermediate-risk MDS, to identify those patients who are at higher risk of disease progression and therefore might benefit from earlier or more intensive treatment. Cancer 2017. © 2017 American Cancer Society.

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Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a-5p in renal cell carcinoma

Summary

Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of this study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKIs). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore-associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by genome-based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR-10a-5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR-10a-5p and overexpression of the SKA1 axis were deeply involved in RCC pathogenesis and resistance to TKI treatment in RCC.

This article is protected by copyright. All rights reserved.

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Overexpression of leucine-rich α2-glycoprotein-1 is a prognostic marker and enhances tumor migration in gastric cancer

Summary

Gastric cancer is one of the most common malignant tumors. Although improvement in chemotherapy has been achieved, the clinical prognosis of advanced gastric cancer remains poor. Therefore, it is increasingly important to predict the prognosis and determine whether patients should or should not receive neoadjuvant or adjuvant chemotherapy. Leucine-rich α2-glycoprotein-1 (LRG1) is overexpressed during inflammation and is associated with various malignancies. In this study, we assessed LRG1 expression in cancer specimens and in the sera of patients with cancer to clarify the usefulness of LRG1 as a biomarker in gastric cancer. This study enrolled 239 (for immunohistochemical staining; IHC) and 184 (for enzyme-linked immunosorbent assay) patients with gastric cancer. IHC showed that LRG1 expression was significantly associated with histological type, lymphatic and venous invasion, tumor and node factors, and disease stage. Overall survival was significantly worse in the high LRG1 expression group than in the low LRG1 group (p = 0.0003). Cox multivariate analysis of overall survival revealed that LRG1 expression was an independent prognostic factor (p = 0.0258). Serum LRG1 was significantly higher in gastric cancer patients than in healthy volunteers, and increased as the pathological stage progressed. Furthermore, a significant correlation was revealed between serum LRG1 level and LRG1 expression with IHC (p < 0.0001). LRG1 inhibition significantly decreased cell proliferation in vitro (migratory and invasive capacity of gastric cancer cells). The present results suggest that LRG1 expression in tumors and serum may be a useful prognostic marker in gastric cancer patients.

This article is protected by copyright. All rights reserved.

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Lack of IL-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy

Abstract

Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In this study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8⁺ T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells, and cytotoxic T cells were highly accumulated in tumor sites under the IL-6-deficient condition. In addition, higher numbers of interferon (IFN)-γ-producing T cells were present in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26 cells were enhanced under the IL-6-deficient condition in vivo and by IFN-γ stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD-L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on these findings, we speculate that a lack of IL-6 produced in tumor-bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL-6 signaling may be a promising target for the development of effective cancer immunotherapies.

This article is protected by copyright. All rights reserved.

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Association of coffee consumption with all-sites cancer incidence and mortality

Summary

The preventive effect of coffee on cancer at different sites has been reported, although the effect on all-sites cancer incidence has not been extensively investigated. We evaluated the association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality among 39,685 men and 43,124 women (age 40 to 79 years, at baseline), in the Three Prefecture Cohort Study. The association between frequency of coffee consumption and risk of all-sites cancer incidence and mortality was assessed by a Cox proportional hazards regression model, adjusted for potential confounders. During 411,341 person-years among men and 472,433 person-years among women, a total of 4,244 men and 2,601 women developed cancer at different sites and a total of 3,021 men and 1,635 women died of cancer at different sites. We showed an inverse association between frequency of coffee consumption and all-sites cancer incidence in both men and women. Comparing participants who consumed coffee with those who never drank coffee, the adjusted hazard ratios (HRs) [95% confidential interval (CI)] for all-sites cancer incidence was 0.74 (0.62–0.88) for coffee consumption of ≥5 cups/day in men (p for trend<0.001) and 0.76 (0.58–1.02) in women (p for trend=0.020). Coffee consumption frequency was inversely associated with mortality from all-sites cancer. In this population, increasing coffee consumption resulted in a decreased risk of all-sites cancer incidence and mortality.

This article is protected by copyright. All rights reserved.

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Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells

Abstract

Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death. Cytotoxicity assay was performed to determine 50% inhibitory concentration (IC50) of SAL and RES in different human breast cancer cells (HBCCs). Drug synergism and combination index (CI) were calculated using CompuSyn software and effects of synergistic combinations (CI < 1) involving lower doses of SAL and RES were selected for further studies. This combination significantly induced apoptosis in HBCCs without affecting non tumorigenic human breast epithelial cells MCF-10A. Co-treatment enhanced apoptosis in MCF-7 cells via reactive oxygen species (ROS) mediated mitochondrial dysfunction. Oxidative stress disrupt redox homeostasis which altered antioxidant enzymes viz. CuZn Superoxide dismutase (SOD), MnSOD and catalase. Additionally, combination altered nuclear morphology, enhanced PARP cleavage and led to caspase activation. SAL and RES also synergistically modulated MAPK pathway. Study suggests that SAL and RES offer a novel combination approach for the treatment of breast cancer.

http://ift.tt/2w0Dc7C

The effects of segmentation algorithms on the measurement of 18 F-FDG PET texture parameters in non-small cell lung cancer

Abstract

Background

Measures of tumour heterogeneity derived from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) scans are increasingly reported as potential biomarkers of non-small cell lung cancer (NSCLC) for classification and prognostication. Several segmentation algorithms have been used to delineate tumours, but their effects on the reproducibility and predictive and prognostic capability of derived parameters have not been evaluated. The purpose of our study was to retrospectively compare various segmentation algorithms in terms of inter-observer reproducibility and prognostic capability of texture parameters derived from non-small cell lung cancer (NSCLC) ¹⁸F-FDG PET/CT images.

Fifty three NSCLC patients (mean age 65.8 years; 31 males) underwent pre-chemoradiotherapy ¹⁸F-FDG PET/CT scans. Three readers segmented tumours using freehand (FH), 40% of maximum intensity threshold (40P), and fuzzy locally adaptive Bayesian (FLAB) algorithms. Intraclass correlation coefficient (ICC) was used to measure the inter-observer variability of the texture features derived by the three segmentation algorithms. Univariate cox regression was used on 12 commonly reported texture features to predict overall survival (OS) for each segmentation algorithm. Model quality was compared across segmentation algorithms using Akaike information criterion (AIC).

Results

40P was the most reproducible algorithm (median ICC 0.9; interquartile range [IQR] 0.85–0.92) compared with FLAB (median ICC 0.83; IQR 0.77–0.86) and FH (median ICC 0.77; IQR 0.7–0.85). On univariate cox regression analysis, 40P found 2 out of 12 variables, i.e. first-order entropy and grey-level co-occurence matrix (GLCM) entropy, to be significantly associated with OS; FH and FLAB found 1, i.e., first-order entropy. For each tested variable, survival models for all three segmentation algorithms were of similar quality, exhibiting comparable AIC values with overlapping 95% CIs.

Conclusions

Compared with both FLAB and FH, segmentation with 40P yields superior inter-observer reproducibility of texture features. Survival models generated by all three segmentation algorithms are of at least equivalent utility. Our findings suggest that a segmentation algorithm using a 40% of maximum threshold is acceptable for texture analysis of ¹⁸F-FDG PET in NSCLC.

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Interleukin-17F expression is elevated in hepatitis C patients with fibrosis and hepatocellular carcinoma

Abstract

Background

The role of interleukin (IL) 17A in chronic liver diseases had been extensively studied, but the function of IL-17F, which shares a high degree of homology with IL-17A, in the progression of chronic hepatic diseases is poorly understood. The aim of the study was to evaluate the association between IL-17F and liver diseases including, fibrosis and hepatocellular carcinoma (HCC).

Methods

Hepatic tumor samples from both hepatitis C virus (HCV) positive and negative patients (without HBV and HCV, NBNC) were examined with quantitative PCR and immunohistochemistry staining for inflammatory cytokine genes expression. In addition, 250 HCV patients naïve for interferon treatment were also subjected to enzyme-linked immunosorbent Assay (ELISA) for their serum cytokine concentrations.

Results

Serum IL-17F concentrations were significantly elevated in HCV patients with severe fibrosis stages. In accordance with serum data, IL-17F expression was also found higher in HCV-associated HCC tissues compared with NBNC HCC tissues at both the mRNA and protein levels.

Conclusions

Our data suggest that IL-17F might be used as a valuable biological marker than IL-17A during chronic fibrosis progression and HCC development in HCV patients.

http://ift.tt/2eNOAjQ

Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

British Journal of Cancer 117, 340 (25 July 2017). doi:10.1038/bjc.2017.187

Authors: Bruno Vincenzi, Silvia Stacchiotti, Paola Collini, Francesco Pantano, Carla Rabitti, Giuseppe Perrone, Michele Iuliani, Alfonso Baldi, Giuseppe Badalamenti, Roberta Sanfilippo, Daniele Santini, Andrea Onetti Muda, Alessandro Gronchi, Paolo Casali, Angelo Paolo Dei Tos & Giuseppe Tonini

http://ift.tt/2t0oYGF

Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas

Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas

British Journal of Cancer 117, 398 (25 July 2017). doi:10.1038/bjc.2017.174

Authors: Nadège Presneau, Laure Alice Duhamel, Hongtao Ye, Roberto Tirabosco, Adrienne M Flanagan & Malihe Eskandarpour

http://ift.tt/2sQXKBV

Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer

Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer

British Journal of Cancer 117, 347 (25 July 2017). doi:10.1038/bjc.2017.196

Authors: Daniele Oddo, Giulia Siravegna, Annunziata Gloghini, Claudio Vernieri, Benedetta Mussolin, Federica Morano, Giovanni Crisafulli, Rosa Berenato, Giorgio Corti, Chiara Costanza Volpi, Michela Buscarino, Monica Niger, Philip D Dunne, Giuseppe Rospo, Emanuele Valtorta, Alice Bartolini, Giovanni Fucà, Simona Lamba, Antonia Martinetti, Maria Di Bartolomeo, Filippo de Braud, Alberto Bardelli, Filippo Pietrantonio & Federica Di Nicolantonio

http://ift.tt/2seVXqz

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component

Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component

British Journal of Cancer 117, 421 (25 July 2017). doi:10.1038/bjc.2017.208

Authors: M Henar Alonso, Susanna Aussó, Adriana Lopez-Doriga, David Cordero, Elisabet Guinó, Xavier Solé, Mercè Barenys, Javier de Oca, Gabriel Capella, Ramón Salazar, Rebeca Sanz-Pamplona & Victor Moreno

http://ift.tt/2tXACT8

Characterisation of blood-derived exosomal hTERT mRNA secretion in cancer patients: a potential pan-cancer marker

Characterisation of blood-derived exosomal hTERT mRNA secretion in cancer patients: a potential pan-cancer marker

British Journal of Cancer 117, 353 (25 July 2017). doi:10.1038/bjc.2017.166

Authors: Hadar Goldvaser, Anna Gutkin, Einat Beery, Yonatan Edel, Jardena Nordenberg, Ofir Wolach, Ester Rabizadeh, Orit Uziel & Meir Lahav

http://ift.tt/2tzLdjH

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

British Journal of Cancer 117, 439 (25 July 2017). doi:10.1038/bjc.2017.180

Authors: Melanie Turner, Shona Fielding, Yuhan Ong, Chris Dibben, Zhiqianq Feng, David H Brewster, Corri Black, Amanda Lee & Peter Murchie

http://ift.tt/2t0thBM

A rare case of an ectopic pregnancy in the rudimentary tube of a patient with an isolated unicornuate uterus

Uterine anomalies are relatively uncommon and go undiagnosed in many cases. Ectopic pregnancies have been reported in such patients, although rarely, in the non-communicating rudimentary horns of unicornuate uteri. However, the case presented is of an ectopic pregnancy in the rudimentary fallopian tube related to an undescended ovary in a patient with an isolated unicornuate uterus, a phenomenon which is extremely rare.

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Migration of intraocular silicone oil into brain

Description

An 84 -year-old woman was admitted following a slight mechanical fall while she was in her garden. She had banged the back of her head followed by a brief period of nausea and vomiting which was self-limiting.

One year before, the patient underwent surgical repair for retinal detachment of left eye with involvement of the macula. She underwent a vitrectomy, endolaser therapy and injection of silicone oil into the vitreous. There was no recovery of vision in the left eye. Medical history included hypertension and bilateral glaucoma.

On examination, she looked well. She had no light perception in the left eye and the visual acuity in the right eye was N10 on the near reading chart with normal peripheral fields of vision. She was managed conservatively but died shortly due to bowel ischaemia, that was unrelated to her presentation.

A CT scan of brain at presentation revealed hyperdensity in...

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Severe asymptomatic rhabdomyolysis complicating a mycoplasma pneumonia

Rhabdomyolysis is a very rare and serious extrapulmonary manifestation of a Mycoplasma pneumoniae infection. We describe a case of a 47-year-old male patient who presented with progressive dyspnoea, hypoxaemia and cough during the last 3 days. He had no relevant muscular complaints but was diagnosed with severe rhabdomyolysis for which he was treated with hyperhydration. Molecular diagnostics confirmed M. pneumoniae as the causative agent and our patient was successfully treated with doxycycline.

Only a few cases of rhabdomyolysis complicating a M. pneumoniae infection have been described, mostly in infants. In this case, typical suggestive complaints of rhabdomyolysis were absent suggesting that the complication might be underdiagnosed.

http://ift.tt/2h2j9TN

Stroke of the inferiomedial temporal lobe causing word agnosia

A 69-year-old man presented with sudden loss of ability to recognise written words and remember the meaning of words and names. He could not name the town he lived in nor name his children. It was difficult for him to remember the meaning of concrete and abstract nouns. His speech fluency and understanding of casual talks were normal. He remembered that he had a conversation with his family that morning, but not the exact content. He was referred to the transient ischaemic attack clinic by his general practitioner as he scored low on the abbreviated mental test score. He underwent a brain MRI scan (T2 weighted, diffusion weighted and fluid-attenuated inversion recovery) which showed an acute infarction in the left medial temporal region affecting the fusiform and parahippocampal gyri. He also noticed that it was easier to retrieve numbers, for example, his mobile number. He recovered on waking up the next day.

http://ift.tt/2eNki0F

Barium aspiration through a tracheo-oesophageal fistula caused by percutaneous tracheostomy

Description

A healthy 43-year-old gravida 14, para 12+1 woman, developed Sheehan syndrome followed by disseminated intravascular coagulopathy and sepsis post-Caesarean section. Her postoperative course was further complicated by a hospital-acquired pneumonia for which she required endotracheal intubation and mechanical ventilation. Enteral feeding and medications were administered via a nasogastric tube (NGT). After three failed attempts at extubation, a tracheostomy was inserted percutaneously. Over the next 2 weeks, she improved and was successfully weaned off ventilatory support. She was transferred to a medical ward with the tracheostomy in situ with minimum oxygen requirement.

Her rehabilitation progressed slowly while the NGT was kept in situ in view of recurrent aspiration with oral intake. A barium study was performed via the NGT after she developed severe vomiting and CT of the abdomen was reported as normal. This demonstrated mild gastritis and delayed gastric emptying due to ileus. No immediate complications were apparent during...

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Discitis and Clostridium perfringens bacteraemia

The authors present a case involving an 80-year-old man with infectious T10/T11 discitis on the background of a recent Clostridium perfringens bacteraemia. This case report describes a case of probable C. perfringens discitis as further investigations failed to identify any causative agents. He was treated with intravenous piperacillin/tazobactam to good effect, achieving favourable clinical outcome. Diagnosis of discitis/osteomyelitis can often be delayed and mismanaged due to its non-specific presentations. Timing of empirical antimicrobial therapy requires careful consideration based on haemodynamic stability and neurological function to maximise microbiological yield.

http://ift.tt/2eNkexX

Muscular sarcocystosis: an index case in a native Malaysian

A previously healthy 20-year-old man presented with prolonged intermittent low grade fever and cough for 6months. He had bilateral calf pain and lower limb weakness 2days prior to admission. Physical examination revealed multiple enlarged lymph nodes with hepatomegaly. There was bilateral calf tenderness with evidence of proximal myopathy. Full blood picture showed lymphocytosis with reactive lymphocytes and eosinophilia. Creatine kinase and lactate dehydrogenase were markedly elevated. Over 2 weeks of admission, patient was treated symptomatically until the muscle biopsy of right calf revealed eosinophilic myositis with muscular sarcocystosis. He was treated with albendazole and high-dose corticosteroids. Symptoms subsided on reviewed at 2weeks and the dose of corticosteroid was tapered down slowly over a month. Due to poor compliance, he was readmitted 1month later because of relapsed. High-dose corticosteroid was restarted and duration for albendazole was prolonged for 1month. His symptom finally resolved over 2weeks.

http://ift.tt/2h2j56v