Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 20 Ιουνίου 2018
Clinical Significance of Incidental Pituitary TC-99m MIBI Uptake on Parathyroid Spect and Factors Affecting Uptake Intensity
Superior vena cava syndrome presenting as position-dependent periorbital oedema
Description
A 54-year-old woman presented to our dermatology clinic with a 2 months history of periorbital oedema, more prominent after lying down in horizontal position. Her face and throat felt swollen. She experienced dyspnoea on exertion, fatigue and had lost 6 kg of weight. Treatment with antihistamines and oral prednisone were ineffective. She smoked one pack of tobacco per week. Medical history and family history were unremarkable. She did not use any medications. Physical examination revealed prominent periorbital oedema and facial swelling (figure 1). Chest radiograph revealed a pathologically enlarged right hilum, broadened mediastinum and modest pleural effusion (figure 2). Diagnosis of superior vena cava syndrome (SVCS) was made and the patient was referred to the pulmonologist.
Figure 1
Prominent periorbital oedema and facial swelling after lying down the night before as a presenting symptom of superior vena cava syndrome.
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Acute locked superior shoulder dislocation in a patient with cuff tear arthropathy
In the field of traumatic shoulder dislocations, this report of a 61-year-old female patient discusses the case of an acute locked superior shoulder dislocation in conjunction with a chronic rotator cuff arthropathy resulting from a low-energy fall on the outstretched and abducted arm. Radiological assessment revealed a complex combination of associated bony injuries including a fracture of the upper part of the glenoid and an impaction fracture of the inferior articular surface of the humeral head. Closed reduction and immobilisation were not successful in obtaining joint stability. This unique report highlights the clinical importance of accurate management of bony injuries in traumatic shoulder dislocation.
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Renal pelvicalyceal rupture secondary to extraperitoneal pelvic packing (EPP) in the unstable trauma patient
Presented here is the case of an 86-year-old man who was found to have right-sided pelvicalyceal rupture and anuric renal failure, secondary to obstructive uropathy caused by life-saving extraperitoneal pelvic packing (EPP) in the settling of severe trauma. In efforts to control haemorrhage in this haemodynamically unstable patient, EPP placement deviated from the recognised method of three extraperitoneal packs bilaterally with seven surgical packs placed. Progress postoperative imaging revealed right-sided hydroureteronephrosis with obstruction evident at the level of the extraperitoneal pelvic packs, identified by delayed contrast excretion from the preceding CT angiography imaging. Urology performed bilateral retrograde pyelograms at his relook laparotomy, timed after removal of his extraperitoneal packs and haemostasis, which showed impression of the surgical pack on the distal ureter but no persisting obstruction or short-term complications. Anuric renal failure improved, and renal function returned to near premorbid levels on day 4 postoperatively.
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Massive faecal impaction leading to abdominal compartment syndrome and acute lower limb ischaemia
Abdominal compartment syndrome (ACS) is associated with significant morbidity and mortality requiring prompt treatment. We report a rare case of a 57-year-old man who developed acute lower limb ischaemia, severe metabolic acidosis and renal impairment from massive faecal impaction of unknown aetiology resulting in ACS causing occlusion of the right common iliac artery. This was treated with faecal disimpaction, which eventually resulted in slow but full recovery.
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Laparoscopic revisional surgery for an unusual complication of Roux-en-Y gastric bypass
With the worldwide epidemic of obesity, there has been an increase in the numbers of primary and revisional procedures of bariatric surgery such as the Roux-en-Y gastric bypass (RYGBP). Nevertheless, this type of surgery is not exempt from complications. An excessive length of non-functional Roux limb proximal to the jejunojejunostomy can cause abnormal upper gastrointestinal symptoms after laparoscopic RYGBP. We present the case of a female patient who presented these unspecific abdominal symptoms after laparoscopic RYGBP who underwent laparoscopic resection in order to reduce the length of the dilated blind loop responsible for the symptoms.
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Gorlin-Goltz syndrome: first reported case of bullae in the lungs complicated with tension pneumothorax
A 13-year-old girl was referred by her general practitioner with acute worsening exertional dyspnoea and sudden onset of left-sided chest pain. There was no associated trauma, palpitations or syncope. Clinical examination revealed that the left lung was hyper-resonant on percussion with reduced air entry on auscultation. Chest X-ray showed a left tension pneumothorax. She was treated conservatively with chest drain. Follow-up X-ray revealed multiple bullae within her left lung. Unfortunately, she redeveloped a pneumothorax and was sent to a tertiary centre. She was under the care of the paediatric cardiothoracic surgeons who organised a CT thorax and performed a lobectomy to remove the bullae. She was discharged from the tertiary centre and currently being followed up under the care of the paediatrician in the district general hospital. She have not developed any further pneumothoraxes.
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Posterior root medial meniscus reconstruction: an option in chronic posterior root meniscal injury management
Posterior root medial meniscus (PRMM) tears have shown to be biomechanically equivalent to complete meniscectomy. Drawbacks from PRMM tears repair are unsatisfactory healing rates. In this case report, we outlined a PRMM reconstruction with gracilis graft healing outcome in chronic PRMM tear case, based on clinical and MRI evaluation. A 60-year-old man reported a chief complaint of increasing pain on the right knee joint in the last 1 year after a deep-flexion injury. On MRI investigation, we confirmed the chronic PRMM tear as Osteoarthritis Kellgren-Lawrence grade II. Then, we planned to perform a PRMM reconstruction with gracilis graft per arthroscopy. At the 6-month MRI evaluation, we found healing of the attached PRMM on its footprints, with intact graft transition from the meniscus to the tibial bone tunnel.
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Symptomatic dyspnoea addressed by excision of ossified anterior longitudinal ligament
Ossification of the anterior longitudinal ligament (OALL) in cervical spine is known to cause dysphagia. However, dyspnoea and obstructive sleep apnoea (OSA) due to OALL is a rare entity. A 50-year-old man presented to our clinic 2 years after anterior cervical discectomy and fusion (ACDF) with complaints of dysphagia, dyspnoea and difficulty in sleeping supine. The clinico-neurological examination of patient was normal without any long tract signs. The diagnosis of OALL was made on plain lateral radiographs. Ultrasonic bone cutter was used to convert sessile osteophyte mass into a pedunculated mass. It was then disconnected from the anterior aspect of vertebral bodies with a chisel. The patient showed immediate relief from dysphagia and OSA. Dyspnoea improved over a week and the postoperative change in voice responded well to speech therapy. To the best of our knowledge, this is the first report of dyspnoea due to OALL after ACDF.
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Long-term control of laryngeal plasma cell mucositis with systemic immunosuppression
Plasma cell mucositis (PCM) is a rare non-neoplastic plasma cell proliferative disorder of the mucous membranes, which typically presents as soft tissue lesions involving oral, upper airway or genital mucosa. Laryngeal involvement resulting in stridor has been reported in four other cases previously, with three requiring tracheostomy. We present a case of supraglottic stenosis in a 53-year-old woman presenting with dysphonia and stridor, requiring surgical resection on three occasions accompanied by tracheostomy on two occasions; biopsy was consistent with PCM. Due to relapsing disease activity, high-dose prednisolone and mycophenolate mofetil were commenced with prednisolone eventually being ceased. After 2 years of mycophenolate mofetil therapy, the patient's disease has been controlled without need for further surgical intervention. This is the first reported case of prolonged symptomatic improvement with the use of systemic immunosuppressive therapy with mycophenolate mofetil in PCM.
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The effect of desferrioxamine chelation versus no therapy in patients with non transfusion-dependent thalassaemia: a multicenter prospective comparison from the MIOT network
Abstract
We prospectively assessed by magnetic resonance imaging (MRI) the advantages of desferrioxamine (DFO) with respect to the absence of chelation therapy in non transfusion-dependent thalassaemia (NTDT) patients. We considered 18 patients non-chelated and 33 patients who received DFO alone between the two MRI scans. Iron overload was assessed by the T2* technique. Biventricular function parameters were quantified by cine sequences. No patient treated with DFO had cardiac iron. At baseline, only one non-chelated patient showed a pathological heart T2* value (< 20 ms) and he recovered at the follow-up. The percentage of patients who maintained a normal heart T2* value was 100% in both groups. A significant increase in the right ventricular ejection fraction was detected in DFO patients (3.48 ± 7.22%; P = 0.024). The changes in cardiac T2* values and in the biventricular function were comparable between the two groups. In patients with hepatic iron at baseline (MRI liver iron concentration (LIC) ≥ 3 mg/g/dw), the reduction in MRI LIC values was significant only in the DFO group (− 2.20 ± 4.84 mg/g/dw; P = 0.050). The decrease in MRI LIC was comparable between the groups. In conclusion, in NTDT patients, DFO therapy showed no advantage in terms of cardiac iron but its administration allowed an improvement in right ventricular function. Moreover, DFO reduced hepatic iron in patients with significant iron burden at baseline.
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Efficacy and safety of resveratrol, an oral hemoglobin F-augmenting agent, in patients with beta-thalassemia intermedia
Abstract
Recently, resveratrol showed induction of γ-globin mRNA synthesis in human erythroid precursors and reducing oxidative stress in red cells of thalassemia patients in many in vitro studies. We aimed to investigate the efficacy and safety of resveratrol, for the first time, in non-transfusion-dependent beta-thalassemia intermedia (B-TI) in Southern Iran. In this double-blind randomized clinical trial, 54 patients with B-TI were investigated during 6 months between October 2016 and March 2017. Patients were randomly allocated into three groups by simple randomization method. Group 1 (hydroxyurea (HU) and placebo, 18 patients), group 2 (resveratrol/piperine and placebo, 16 patients), and group 3(HU and resveratrol/piperine, 20 patients). Primary end point was considered as change in hemoglobin (Hb) levels and need for blood transfusion. Drug safety was considered as a secondary end point. Mean age of the patients was 28.2 ± 5.6 (18–42) years. Response rate was not significantly different among the three groups (P > 0.05). Higher percentages of adverse events were detected in groups 2 (31.3%) and 3 (25%) compared to group 1 (5.6%). However, the difference was not statistically significant (P > 0.05). All reported adverse events were gastrointestinal symptoms. Resveratrol showed a similar efficacy with HU in the small population of non-transfusion B-TI patients during a 6-month follow-up. Complications, mostly gastrointestinal, were observed more frequently in resveratrol groups compared to the HU group. Although it was not statistically significant, more attention should be given to safety and efficacy of resveratrol as an oral HbF-augmenting agent.
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Imaging predictors of treatment outcomes in rectal cancer: an overview
Source:Critical Reviews in Oncology/Hematology
Author(s): Lakshmi Shree Mahadevan, James Zhong, BhanuPrasad Venkatesulu, Harmeet Kaur, Shreerang Bhide, Bruce Minsky, William Chu, Martijn Intven, Uulke A. van der Heide, Baukelien van Triest, Sunil Krishnan, William Hall
The treatment protocols for rectal cancer continue to evolve, with increasing acceptance of a watch-and-wait policy for clinical complete responders to neoadjuvant chemoradiation therapy. It still, however, remains unclear who is likely to achieve a pathological complete response, which unequivocally portends a very favorable overall prognosis. Evolution of modern imaging techniques has paved the way for potential prediction of treatment response based on baseline, on-treatment, early post-treatment and subsequent follow-up imaging alone. Independent of tumor grade and stage, tumor marker levels, tumor size, radiation dose and fractionation, chemotherapy regimen, and extent/type of surgery, imaging biomarkers like circumferential resection margin (CRM), extramural venous space invasion (EMVI), imaging-based tumor regression grade, perfusion/diffusion-based functional imaging parameters, and imaging-based metabolic response have the ability to predict the likelihood of local recurrence and/or distant metastases. Textural features of images can add a further dimension to the predictive power of imaging. Finally, integration of genomic data with imaging biomarkers can potentially discern molecular mechanisms associated with distinct radiographic attributes of tumors. In this review, we evaluate and summarize the evidence to date of each imaging modality as a biomarker and its contribution to personalized decision making in rectal cancer.
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A Survey Regarding the Knowledge, Attitudes, and Beliefs of Graduates of Cancer Rehabilitation Fellowship Program
Abstract
Currently there are limited options for physiatrists to further subspecialize in cancer rehabilitation. Since 2007, few cancer rehabilitation fellowship programs have been started. There is currently absolutely no information about such training programs and their graduates. This study is the first to survey a small number of graduates from two cancer rehabilitation fellowship programs. The purpose of this study was to report characteristics, attitudes, and beliefs of cancer rehabilitation fellowship graduates. Graduates of cancer rehabilitation fellowship programs from 2008 through 2015 responded to a 26-question survey. Information collected included exposure to cancer rehabilitation prior to fellowship training, usefulness of fellowship training program, information about current practice, and suggested areas of improvement. The setting of the study is online survey. Participants were graduates of two cancer rehabilitation fellowship programs from 2008 through 2015. Participants were contacted via email about completion of an online survey and information was collected anonymously. Primary outcome measure was satisfaction of respondents with their fellowship training program in meeting the rehabilitation needs of their cancer patients. Sixteen responses, with a response rate of 89%, were recorded. Sixty-three percent of the respondents had exposure to cancer rehabilitation prior to post-graduate year 3 (PGY-3). Majority of graduates had practice involving at least 50% of care to cancer patients. Fifty percent indicated that their position was specifically created after their job interview. Career development was one of the major areas of suggested improvement in training. Graduates of cancer rehabilitation fellowship programs strongly value their training. Majority of the graduates were able to continue their career into jobs that were primarily cancer rehabilitation related. Further work needs to be done to define this subspecialty further and incorporate building practice as part of this training.
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Identification of FDA-approved oncology drugs with selective potency in high-risk childhood ependymoma
Children with ependymoma are cured in less than 50% of cases, with little improvement in outcome over the last several decades. Chemotherapy has not impacted survival in ependymoma, due in part to a lack of preclinical models that has precluded comprehensive drug testing. We recently developed two human ependymoma cell lines harboring high-risk phenotypes which provided us with an opportunity to execute translational studies. ependymoma and other pediatric brain tumor cell lines were subject to a large-scale comparative drug screen of ependymoma -approved oncology drugs for rapid clinical application. The results of this in vitro study were combined with in silico prediction of drug sensitivity to identify ependymoma -selective compounds, which were validated by dose curve and time course modelling. Mechanisms of ependymoma -selective antitumor effect were further investigated using transcriptome and proteome analyses. We identified three classes of oncology drugs that showed ependymoma -selective anti-tumor effect, namely (i) fluorinated pyrimidines (5-fluorouracil, carmofur and floxuridine), (ii) retinoids (bexarotene, tretinoin and isotretinoin), and (iii) a subset of small-molecule multi-receptor tyrosine kinase inhibitors (axitinib, imatinib and pazopanib). Axitinib's anti-tumor mechanism in ependymoma cell lines involved inhibition of PDGFR-alpha and PDGFR-beta and was associated with reduced mitosis-related gene expression and cellular senescence. The clinically available, ependymoma -selective oncology drugs identified by our study have the potential to critically inform design of upcoming clinical studies in ependymoma, in particular for those children with recurrent ependymoma who are in the greatest need of novel therapeutic approaches.
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KDM6B counteracts EZH2-mediated suppression of IGFBP5 to confer resistance to PI3K/AKT inhibitor treatment in breast cancer
Despite showing promise against PIK3CA-mutant breast cancers in preclinical studies, phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors demonstrate limited clinical efficacy as monotherapy. Here, we found that histone H3K27me3 demethylase KDM6B-targeted IGFBP5 expression provides a protective mechanism for PI3K/AKT inhibitor-induced apoptosis in breast cancer cells. We found that overexpression of KDM6B and IGFBP5 in luminal breast cancer are positively associated with poorer disease outcomes. Mechanistically, KDM6B promotes IGFBP5 expression by antagonizing EZH2-mediated repression, and pharmacologic inhibition of KDM6B augments apoptotic response to PI3K/AKT inhibitor treatment. Moreover, the IGFBP5 expression is upregulated upon acquired resistance to the PI3K inhibitor GDC-0941, which is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 gene promoter. Intriguingly, GDC-0941-resistant breast cancer cells remained sensitive to KDM6B or IGFBP5 inhibition, indicating the dependency on KDM6B-IGFBP5 axis to confer the survival advantage in GDC-0941-resistant cells. Our study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer.
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Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial
Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial
Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial, Published online: 21 June 2018; doi:10.1038/s41416-018-0132-8
Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trialhttps://ift.tt/2ytVTGX
Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ
Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ
Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ, Published online: 21 June 2018; doi:10.1038/s41416-018-0120-z
Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situhttps://ift.tt/2lm7cYo
Chilaiditi Syndrome: A Case Report Highlighting the Intermittent Nature of the Disease
Background. Chilaiditi syndrome is a phenomenon where there is an interposition of the colon between the liver and the abdominal wall leading to clinical symptoms. This is distinct from Chilaiditi sign for which there is radiographic evidence of the interposition, but is asymptomatic. Case Presentation. Here, we present the case of a patient who, despite having clinical symptoms for a decade, had a delayed diagnosis presumably due to the interposition being intermittent and episodic. Conclusions. This case highlights the fact that Chilaiditi syndrome may be intermittent and episodic in nature. This raises an interesting question of whether previous case reports, which describe complete resolution of the syndrome after nonsurgical intervention, are perhaps just capturing periods of resolution that may have occurred spontaneously. Because the syndrome may be intermittent with spontaneous resolution and then recurrence, patients should have episodic follow-up after nonsurgical intervention.
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The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients
Objective: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. Materials and Methods: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as ≥80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. Results: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered≥80%). A total of 19% of patients had $20 were 6% to 8% less likely to be adherent compared with patients payinghttps://ift.tt/2tqKW3j
Outcome After Surgery for Extremity Soft Tissue Sarcoma in Patients Presenting With Metastasis at Diagnosis
Objectives: About 10% of patients present with metastasis at diagnosis in extremity soft tissue sarcoma (STS). Although the prognoses of these patients is generally poor, prolonged survival has been demonstrated in some patients. Thus, better prognostication is needed to guide decisions regarding adjuvant therapy and surveillance. This study sought to analyze the survival and to identify clinicopathologic factors associated with survival in extremity STS patients presenting with metastasis at diagnosis. Materials and Methods: Review of 43 patients presenting with metastasis at diagnosis who underwent resection of the primary tumor was performed. Patient, tumor, and treatment-related factors were analyzed for possible prognostic effect on survival. Results: The median survival of all patients was 22±4.1 months. The 2- and 5-year survival rates were 45.6% and 18.0%, respectively. In univariate analysis, tumor location in lower extremity (P=0.041) and the performance of metastasectomy (P=0.001) were significantly associated with better survival. In multivariate analysis, only the performance of metastasectomy remained significant (hazard ratio=3.8, P=0.012). The median survival of patients who underwent metastasectomy was significantly longer than that of patients who did not undergo metastasectomy (41±8.4 vs. 11±3.8 mo, P=0.001). Conclusions: Extremity STS patients who present with metastasis at diagnosis have a poor prognosis. Patients who undergo metastasectomy have a better chance for prolonged survival.https://ift.tt/2lnruAV
Impact of Androgen Deprivation Therapy on Overall Mortality in Prostate Brachytherapy Patients With Low Pretreatment Testosterone Levels
Objectives: To evaluate whether the use of androgen deprivation therapy (ADT) in prostate brachytherapy patients impacts overall mortality (OM) in patients with lower pretreatment serum testosterone levels compared with those with normal or high baseline serum testosterone. Materials and Methods: From October 2001 to May 2014, 1916 patients underwent brachytherapy and had a pretreatment serum testosterone. Baseline serum testosterone values were collected prospectively before initiation of therapy. Median follow-up was 7.2 years. In total, 26% of the patients received ADT, primarily men with higher risk disease. OM and prostate cancer–specific mortality were examined to determine whether men with lower baseline serum testosterone were at increased risk of mortality when ADT was used, compared with men with baseline normal or higher testosterone. Results: Prostate cancer–specific mortality and OM at 10 years was 0.8% and 22.0%. Age, tobacco use, diabetes, cardiovascular disease, and percent positive biopsies were the strongest predictors of OM. ADT use by itself was not associated with an increased risk of OM on multivariate analysis (P=0.695). However, ADT use in men with lower baseline testosterone was associated with a significantly higher risk of OM (Phttps://ift.tt/2lo2QjF
Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection
Objectives: Tumor control (TC), toxicity and survival, following stereotactic body radiation therapy (SBRT) were compared between patients with and without a prior lung resection (PLR). Materials and Methods: The study is comprised of 130 patients with 141 peripheral tumors treated with SBRT at our institution from 2009 to 2013. Primary TC and lobar control (LC) were defined per RTOG 0236. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Survival/TC and toxicity were compared between patients with and without PLR using the Kaplan-Meier method and cumulative incidence, respectively. Fine and Gray regression was used for univariable/multivariable analysis for radiation pneumonitis (RP). Results: Of the 130 patients with median age 70 years (range, 42 to 93 y), 50 had undergone PLR (median time between PLR and SBRT: 33 mo; range, 1 to 206), including pneumonectomy (12%), lobectomy (46%), wedge resection (42%). With a median follow-up of 21 months in survivors, the PLR group had better TC (1-y 100% vs. 93%; Phttps://ift.tt/2lkLFPG
Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer
Objective: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer. Patients and Methods: In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up. Results: Samples from 41 subjects were evaluated for PD-L1 expression; 23 (56%) were positive. Subjects with PD-L1-expressing versus PD-L1-negative tumors respectively had CRRs of 30.8 versus 12.1 recurrences/hPY (P=0.082), CMRs of 16.7 versus 12.0 deaths/hPY (P=0.47), and CERs of 39.2 versus 16.9 events/hPY (P=0.069). Conclusions: PD-L1 positivity was associated with worse CRR and CER, and marginally worse CMR. The effect on progression-free and overall survival needs to be validated in a study with a larger sample size.https://ift.tt/2yuL9bw
Phase II Study of Adjuvant Chemoradiotherapy Using Docetaxel/Cisplatin/5-Fluorouracil Before and After Intensity-modulated Radiotherapy With Concurrent Docetaxel in Patients With Completely (R0) Resected Gastric Carcinoma
Objectives: The Intergroup 0116 study has demonstrated a significant survival benefit for completely resected (R0) gastric cancer patients treated with a fluorouracil/leucovorin chemoradiotherapy regimen. However, this regimen is also toxic and less effective in terms of distant disease control. Therefore, a more efficacious and safer regimen is urgently needed. Methods: Patients with R0 resected gastric carcinoma received up to two 21-day cycles of postoperative adjuvant preradiation and postradiation DCF chemotherapy (docetaxel 37.5 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1 to 3, and a continuous infusion of fluorouracil 750 mg/m2 on days 1 to 5), respectively. Chemoradiotherapy between preradiation and postradiation chemotherapy was initiated on day 43 and consisted of intensity-modulated radiotherapy (45 Gy) plus concurrent docetaxel 20 mg/m2 weekly for 5 weeks. Results: A total of 55 patients were evaluated and 76% (42) of patients completed the prescribed therapy. With a median follow-up of 61 months, the 3- and 5-year progression-free survival rates were 67% (95% confidence interval [CI], 54%-80%) and 59% (95% CI, 46%-72%), respectively; and the 3- and 5-year overall survival rates were 72% (95% CI, 60%-84%) and 61% (95% CI, 48%-74%), respectively. The most common grade 3 or greater toxicity, during the chemotherapy phase, was neutropenia (24%). Common grade 3/4 toxicities during concurrent chemoradiotherapy were nausea (32%), vomiting (26%), fatigue (15%), and anorexia (19%). Conclusions: These results demonstrate that this adjuvant regimen is active with an acceptable toxicity profile. A randomized phase 3 trial comparing the Intergroup 0116 chemoradiotherapy regimen with this regimen is underway.https://ift.tt/2ljEcjY
Benefit of Radiotherapy in Extraskeletal Myxoid Chondrosarcoma: A Propensity Score Weighted Population-based Analysis of the SEER Database
Objectives: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignancy for which the role of radiotherapy is not well-defined. We examine the effect of external beam radiotherapy (EBRT) on cancer-specific survival (CSS) for patients with localized EMC, in a propensity score weighted, population-based analysis. Materials and Methods: The Surveillance, Epidemiology, and End Results database (1973 to 2012) was queried for cases of localized EMC arising from soft connective tissues of the trunk and extremities treated with surgery and/or EBRT. Inverse probability treatment weighting was utilized, with survival analysis by weighted Cox regression and Kaplan-Meier analysis with log-rank testing. The primary endpoint was CSS. Results: One hundred seventy-two patients were identified, diagnosed from 2004 to 2012. Ninety-four percent and 32% of 156 assessable patients underwent surgery and EBRT, respectively. By inverse probability treatment weighting, balancing covariates of age group, sex, race, grade, T stage, N stage, receipt of surgery, and anatomic site, we observed CSS of 97% versus 85% and 94% versus 85% in patients receiving EBRT versus no EBRT, at 3 and 5 years, respectively, at median follow-up of 33 months, P=0.01. A trend toward an overall survival benefit associated with EBRT was noted, P=0.06. Further adjusting for type of resection performed, CSS benefit persisted, 97% versus 85% at 3 years and 94% versus 85% at 5 years, P=0.02, with trend toward an overall survival benefit, P=0.08. Conclusions: The receipt of EBRT is associated with a CSS benefit in localized EMC. Aggressive local therapy, including EBRT, should be considered in these patients.https://ift.tt/2lp3ihA
A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer
Objectives: Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs. Patients and Methods: Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m2 of gemcitabine (on days 1, 8), 650 mg/m2 of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3. Results: In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P=0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P=0.39). Conclusions: Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.https://ift.tt/2yqWvxd
A Review of the Surgical Management of Extrathoracic Solitary Fibrous Tumors
Objectives: Extrathoracic solitary fibrous tumors (ESFTs) are rare low-to-intermediate grade spindle-cell neoplasms of pluripotent fibroblastic or myofibroblastic origin. This review explores prognostic factors in the management of ESFTs and provides guidance on optimal treatment regimens based on the current literature. Patients and Methods: Electronic searches were performed using MEDLINE, Embase, and the Cochrane library to identify studies on prognostic factors in the management of ESFTs published between January 1970 and June 2016. The literature search and review process identified 100 articles that were included in this review article. This included both surgical and nonsurgical studies on the management of ESFTs. Results: Surgical excision with wide resection margins forms the mainstay of treatment and provides optimal long-term oncological outcomes. Large tumor size (>5 to 10 cm diameter), inadequate resection margins, malignant histologic features, dedifferentiation, and tumor location within the abdomen/pelvis are associated with adverse oncological outcomes. Radiotherapy may be used for preoperative tumor shrinkage and/or as adjuvant therapy in patients with malignant disease or incomplete surgical margins. Chemotherapy with molecular-targeted therapies has produced promising results and the results of further phase 2 trials are awaited. Conclusions: Routine long-term follow-up is essential for benign and malignant disease to enable early detection and treatment of recurrent disease.https://ift.tt/2llGEGB
Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer
Purpose: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. Materials and Methods: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. Results: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. Conclusions: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.https://ift.tt/2tqL033
Axillary Ultrasound Fine Needle Aspiration Biopsy: Is There a Role in the Post Z-0011 Era?
Objectives: Axillary ultrasound with fine needle aspiration (AXUSFNA) in early-stage breast cancer has required reappraisal. ACOSOG Z-0011 and after mapping of the axilla: radiotherapy or surgery have shown that women with limited nodal disease at sentinel lymph node biopsy got no survival advantage with completion axillary node dissection. We hypothesize that AXUSFNA may be sufficiently accurate for staging for some patients and sentinel lymph node biopsy need not be performed. We define the false negative rate (FNR) of AXUSFNA in different subsets of patients. Materials and Methods: This retrospective cohort study included node positive patients who also underwent AXUSFNA between 1/2006 and 12/2010 followed by axillary surgery. The FNR was calculated for the entire group and for subgroups determined by tumor, nodal, and ultrasound findings. Results: Out of ∼700 AXUSFNA patients, 128 node positive patients were included in the study. The overall AXUSFNA FNR was 35.9% (95% confidence interval, 28.1%-44.6%). There was a significantly higher FNR with smaller tumors and presence of ductal carcinoma in situ on multivariate analysis. On ultrasound, benign-appearing nodes had a higher FNR than indeterminate nodes (78.9% vs. 60.9%, P=0.2) and significantly higher than suspicious nodes (78.9% vs. 2.9%, Phttps://ift.tt/2lnrfWx
Challenges in Management of Squamous Cell Carcinoma of the Anus in New England and Across the United States: A Review of the National Cancer Data Base
Background: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence continues to increase. The purpose of this study was to evaluate regional and national data to assess trends in epidemiology, access to cancer center care, and overall management strategies in SCCA. Study Design: A review of available data from the American College of Surgeons Committee on Cancer National Cancer Data Base focused on incidence, sex, age, stage at diagnosis, distance traveled for care, and utilization of therapy as first course of treatment (FCT). The analysis included 40,817 patients treated for SCCA at 1513 cancer centers in the United States, of which 2347 patients were treated at 109 cancer centers in New England, between the years 2003 and 2013. Results: Over the 11-year period, incidence of SCCA increased by 76% in the United States and by 83.8% in New England. Stage was unknown in 11.7% of all US cases, significantly higher than more common cancers, for example, breast (4.3%), prostate (6%), or colon (7.8%) (P25 miles less often (14.3% vs. 28.7%) (Phttps://ift.tt/2toDWE8
Safety and Outcome Measures of First-in-Human Intraperitoneal α Radioimmunotherapy With 212Pb-TCMC-Trastuzumab
Purpose: One-year monitoring of patients receiving intraperitoneal (IP) 212Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. Methods: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of 212Pb-TCMC-trastuzumab, deliveredhttps://ift.tt/2lo2NnZ
The Effect of Educational Intervention Based on PRECEDE Model on Promoting Skin Cancer Preventive Behaviors in High School Students
Abstract
School-based education programs can be an effective way of educating adolescents about the dangers of exposure to sunlight and about preventive measures against this exposure and its relation to skin cancer. The aim of this study is to survey the effect of educational intervention based on the PRECEDE model on promoting skin cancer preventive behaviors in high school students of Fasa City, Fars Province, Iran. In this quasi-experimental study, 300 students (150 in experimental group and 150 in control group) in Fasa City, Fars Province, Iran, were selected in 2016–2017. The educational intervention for the experimental group consisted of six training sessions. A questionnaire consisting of demographic information, PRECEDE constructs (knowledge, attitude, self-efficacy, enabling factors, and social support), was used to measure skin cancer preventive behaviors before and 4 months after the intervention. Data were analyzed using SPSS 22 and paired t test, independent t test, and chi-square test at a significance level of p < 0.05. The mean age of the students was 16.05 ± 1.76 years in the experimental group and 16.20 ± 1.71 years in the control group. Four months after the intervention, the experimental group showed a significant increase in the knowledge, attitude, self-efficacy, enabling factors, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the PRECEDE constructs in adoption of skin cancer preventive behaviors in 4 months post-intervention in students. Hence, this model can act as a framework for designing and implementing educational intervention for the prevention of skin cancer.
https://ift.tt/2M9p7gf
Using Film to Disseminate Information on Cervical Cancer Prevention in Lusaka: Results from a Small Intervention Study
Abstract
In order to prevent the spread of cervical cancer, people must be aware and knowledgeable about the available preventive practices such as screening and vaccination. The purpose of this study was to determine the extent that film is effective in disseminating information on cervical cancer and its prevention to women and men in Lusaka. A pilot intervention study was carried out at churches in Lusaka city from August to September 2017. A sample size of 38 women and 43 men filled in both baseline and follow-up questionnaires. A knowledge grade (range, 1–10 points) which linked causes to risk factors for cervical cancer was used to assess the knowledge of a respondent. Significant results (p < 0.01) were obtained at follow-up for watching the film and having awareness and knowledge. The main finding is that a short informational film can be an effective means of disseminating information on cervical cancer and its prevention to women and men.
https://ift.tt/2tdbqpA
LDHA in neuroblastoma is associated with poor outcome and its depletion decreases neuroblastoma growth independent of aerobic glycolysis
Purpose: To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB). Experimental Design: Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated to survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model. Results: Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed. Conclusions: High expression of LDHA is independently associated with poor outcome of NB and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells.
https://ift.tt/2I73jzi
Attendance to Follow-Up Care in Survivors of Adolescent and Young Adult Cancer: Application of the Theory of Planned Behavior
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
https://ift.tt/2JVNIsa
Effect of Fitbit and iPad Wearable Technology in Health-Related Quality of Life in Adolescent and Young Adult Cancer Patients
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
https://ift.tt/2MaDBwx
Identifying and Understanding the Gaps in Care Experienced by Adolescent and Young Adult Cancer Patients at the University of Iowa Hospitals and Clinics
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
https://ift.tt/2MGs4Gp
Emergency Department Visits by Adolescent and Young Adult Cancer Patients Compared with Pediatric Cancer Patients in the United States
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
https://ift.tt/2MbiE4H
Splenogonadal fusion - a rare cause of scrotal swelling: a case report
Splenogonadal fusion is a rare and benign condition. Diagnosis is challenging for clinicians. Despite its indolence, diagnosis is often confirmed after orchidectomy. Surgery is mandatory, particularly to rule ...
https://ift.tt/2yt5n5i
Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15–60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials
Abstract
The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials. Abnormal karyotypes were classified as no subclones present (cytogenetic abnormality in a single clone), defined subclones present (presence of one to three subclones), and composite karyotypes (CP) (clonal heterogeneity not allowing enumeration of individual subclones). The main endpoints were overall survival (OS) and disease-free survival (DFS). Among 1291 patients with an abnormal karyotype, 1026 had no subclones, 226 at least 1 subclone, and 39 a CP. Patients with defined subclones had an OS similar to those with no subclones (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.88–1.26), but CP patients had a shorter OS (HR = 1.58, 95% CI 1.11–2.26). However, in a multivariate Cox model stratified by protocol and adjusted for age, cytogenetic risk group, secondary versus primary AML, and performance status, clonal heterogeneity lost its prognostic importance (HR = 1.10, 95% CI 0.91–1.32 for defined subclones versus no subclones; HR = 0.96, 95% CI 0.67–1.38 for CP versus no subclones). Also, the impact of having a donor on DFS was similar in the three clonal subgroups. In summary, in patients with cytogenetic abnormality, presence of subclones had no impact on OS. The dismal outcome in patients with a CP was explained by the known predictors of poor prognosis. Trial registration: AML-10: ClinicalTrials.gov identifier: NCT00002549, retrospectively registered July 19, 2004; AML12: ClinicalTrials.gov identifier: NCT00004128, registered January 27, 2003.
https://ift.tt/2topcFi
Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma
Cancer Science, EarlyView.
https://ift.tt/2ysH87o
Immunotherapy for osteosarcoma: Where do we go from here?
Pediatric Blood &Cancer, EarlyView.
https://ift.tt/2tl9c6E
Olive ingestion causing a false suspicion of relapsed neuroblastoma: A case of “oliveblastoma?”
Pediatric Blood &Cancer, EarlyView.
https://ift.tt/2lkUMQt
The intersection of financial toxicity and family building in young adult cancer survivors
Cancer, EarlyView.
https://ift.tt/2MHThIw
Cover Image, Volume 117, Number 6, May 1, 2018
Journal of Surgical Oncology, Volume 117, Issue 6, Page i-i, May 1, 2018.
https://ift.tt/2I7KSKZ
Issue Information ‐ Ed Board
Journal of Surgical Oncology, Volume 117, Issue 6, Page 1107-1107, May 1, 2018.
https://ift.tt/2K4rSlB
Issue Information ‐ TOC
Journal of Surgical Oncology, Volume 117, Issue 6, Page 1108-1112, May 1, 2018.
https://ift.tt/2K3nIY6
Do Frequent Follow-Up Tests Benefit Colorectal Cancer Survivors?
Two studies examined the impact of more frequent follow-up testing for cancer recurrence in colorectal cancer survivors. Learn whether the studies showed that frequent testing improved survival.
https://ift.tt/2K20rsT
French Therapeutic Education Programme Aimed at Improving the Quality of Life of Laryngectomised Patients and their Close Relations: the Three Stages (Observational and Interventional Randomised) of the Study “PETAL”
Abstract
The therapeutic education of patients and their close relations is, as yet, poorly developed in France in the field of oncology. Total laryngectomy is a mutilating surgical procedure having a major impact on the patient's life, due to its physical and functional sequelae. Its psychosocial consequences are also important and alter the quality of life of patients and their close relations. Currently, care for laryngectomised patients consists essentially in informing and educating them on some technical procedures during hospital admission. The intervention of a speech therapist, often serves as the link between the patient and the hospital care team. These healthcare modalities often insufficiently account for the social, environmental and personal factors that interact in health-related problems. This report presents the therapeutic education programme protocol "PETAL" for laryngectomised patients and their close relations to improve their quality of life. The trial will be conducted over three phases: (1) the "pilot" phase aims at developing knowledge on the consequences of laryngectomy on the quality of life of patients and their close relations and developed a pluridisciplinary therapeutic education program, (2) the prospective intervention "replication" phase aims at evaluating the programme's transferability in three centres and (3) the cluster-randomised multicentric comparative intervention phase, will assess the benefits of the developed programme. Phase I identified nine themes of workshops related to therapeutic education, training and coordination of care. The developed programme should reinforce town-hospital links to improve help, follow-up and support for patients and their close relations.
https://ift.tt/2tfvUxX
Adjuvant radiation therapy for malignant Abrikossoff’s tumor: a case report about a femoral triangle localisation
Granular cell or Abrikossoff's tumors are usually benign however rare malignant forms concern 1 to 3% of cases reported. Pelvic locations are exceptional.
https://ift.tt/2I6TDoL
Circulating Tumor DNA Assays in Clinical Cancer Research
Abstract
The importance of circulating free DNA (cfDNA) in cancer clinical research was recognized in 1994 when a mutated RAS gene fragment was detected in a patient's blood sample. Up to 1% of the total circulating DNA in patients with cancer is circulating tumor DNA (ctDNA) that originates from tumor cells. As ctDNA is rapidly cleared from the blood stream and can be obtained by minimally invasive methods, it can be used as a dynamic cancer biomarker for cancer early detection, diagnosis, and treatment monitoring. Despite the potential for clinical use, few ctDNA assays have been cleared or approved by the US Food and Drug Administration. As tools for clinical and translational research, current ctDNA assays face some challenges, and more research is needed to advance use of these assays. On September 29–30, 2016, the Division of Cancer Treatment and Diagnosis at the National Cancer Institute convened a workshop entitled "Circulating Tumor DNA Assays in Clinical Cancer Research" to garner input from industry experts, academia, and government research and regulatory agencies to understand and promote the translation of ctDNA assays to clinical research, with potential to advance to use in clinical practice. This Commentary presents the topics of the workshop covered in the presentations and points made in the discussions that followed: 1) background on ctDNA, 2) potential clinical utility of ctDNA assays, 3) assay technology, 4) assay clinical and analytical validation, and 5) industry perspectives. Additional relevant information that has come to light since the workshop has been included.https://ift.tt/2MEscpA
Evaluation of Treatment Patterns and Survival Outcomes in Elderly Pancreatic Cancer Patients: A Surveillance, Epidemiology, and End Results‐Medicare Analysis
AbstractBackground.Management of pancreatic cancer (PC) in elderly patients is unknown; clinical trials exclude patients with comorbidities and those of extreme age. This study evaluated treatment patterns and survival outcomes in elderly PC patients using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data.Materials and Methods.Histology codes 8140, 8500, 8010, 8560, 8490, 8000, 8260, 8255, 8261, 8263, 8020, 8050, 8141, 8144, 8210, 8211, or 8262 in Medicare Parts A and B were identified. Data regarding demographic, characteristics, treatments, and vital status between 1998 and 2009 were collected from the SEER. Determinants of treatment receipt and overall survival were examined using logistic regression and Cox proportional hazards models, respectively.Results.A total of 5,975 patients met inclusion. The majority of patients were non‐Hispanic whites (85%) and female (55%). Most cases presented with locoregional stage disease (74%); 41% received only chemotherapy, 30% chemotherapy and surgery, 10% surgery alone, 3% radiation, and 16% no cancer‐directed therapy. Patients with more advanced cancer, older age, and those residing in areas of poverty were more likely to receive no treatment. Among patients 66–74 years of age with locoregional disease, surgery alone (hazard ratio [HR] = 0.54; 95% confidence interval [CI]: 0.39–0.74) and surgery in combination with chemotherapy (HR = 0.69; 95% CI: 0.53–0.91) showed survival benefit as compared with the no treatment group. Among patients ≥75 years of age with locoregional disease, surgery alone (HR = 2.04; 95% CI: 0.87–4.8) or in combination with chemotherapy (HR = 1.59; 95% CI: 0.87–2.91) was not associated with better survival.Conclusion.Treatment modality and survival differs by age and stage. Low socioeconomic status appears to be a major barrier to the receipt of PC therapy among Medicare patients.Implications for Practice.Elderly patients with cancer are under‐represented on clinical trials and usually have comorbid illnesses. The management of elderly patients with pancreatic cancer is unknown, with many retrospective experiences but low sample sizes. Using Surveillance, Epidemiology, and End Results‐Medicare linked data to analyze treatment patterns and survival of elderly patients with pancreatic cancer on a larger population scale, this study highlights treatment patterns and their effect on survival and proposes possible obstacles to access of care in elderly patients with pancreatic cancer other than Medicare coverage.
https://ift.tt/2MDTix4
Serious Illness Conversations: Paving the Road with Metaphors
AbstractSerious illness conversations can influence the direction of care by supporting decision‐making compatible with the patient's goals. Effective use of core communication techniques, such as active listening and empathic statements, allows for a deeper understanding of the patients' goals, concerns, communication preferences, and questions. Metaphors can be used to augment end‐of‐life care planning. Used inappropriately, metaphors can cause misunderstandings and confusion. Applied skillfully, metaphors can personalize challenging discussions, improving patient comprehension and helping patients and their families to plan ahead. The art of communication is to use the right tool for the right person at the right time.Implications for Practice.Discussions with patients about serious illness concerns are especially challenging for the oncologist. This article provides guidance for preparing for such conversations, including examples of the use of metaphors to personalize and improve communication.
https://ift.tt/2JVhugM
Refugees in Conflict: Creating a Bridge Between Traditional and Conventional Health Belief Models
AbstractThe recent wave of migration from Middle Eastern countries to Europe presents significant challenges to the European health profession. These include the inevitable communication gap created by differences in health care beliefs between European oncologists, health care practitioners, and refugee patients. This article presents the conclusions of a workshop attended by a group of clinicians and researchers affiliated with the Middle East Cancer Consortium, as well as four European‐based health‐related organizations. Workshop participants included leading clinicians and medical educators from the field of integrative medicine and supportive cancer care from Italy, Germany, Turkey, Israel, Palestine, Iran, Lebanon, Jordan, Egypt, and Sudan. The workshop illustrated the need for creating a dialogue between European health care professionals and the refugee population in order to overcome the communication barriers to create healing process. The affinity for complementary and traditional medicine (CTM) among many refugee populations was also addressed, directing participants to the mediating role that integrative medicine serves between CTM and conventional medicine health belief models. This is especially relevant to the use of herbal medicine among oncology patients, for whom an open and nonjudgmental (yet evidence‐based) dialogue is of utmost importance. The workshop concluded with a recommendation for the creation of a comprehensive health care model, to include bio‐psycho‐social and cultural‐spiritual elements, addressing both acute and chronic medical conditions. These models need to be codesigned by European and Middle Eastern clinicians and researchers, internalizing a culturally sensitive approach and ethical commitment to the refugee population, as well as indigenous groups originating from Middle Eastern and north African countries.Implications for Practice.European oncologists face a communication gap with refugee patients who have recently immigrated from Middle Eastern and northern African countries, with their different health belief models and affinity for traditional and herbal medicine. A culturally sensitive approach to care will foster doctor‐refugee communication, through the integration of evidence‐based medicine within a nonjudgmental, bio‐psycho‐social‐cultural‐spiritual agenda, addressing patients' expectation within a supportive and palliative care context. Integrative physicians, who are conventional doctors trained in traditional/complementary medicine, can mediate between conventional and traditional/herbal paradigms of care, facilitating doctor‐patient communication through education and by providing clinical consultations within conventional oncology centers.
https://ift.tt/2JTMPk8
Successful Ovarian Stimulation for Fertility Preservation in a Patient with Chronic Myeloid Leukemia: Switch from Nilotinib to Interferon‐α
AbstractThe development of tyrosine‐kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon‐α before and during ovarian stimulation for fertility preservation. Successful ovarian stimulation was performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell transplantation was performed, and at present, 3 years later, the patient presents a sustained major molecular response.
https://ift.tt/2MBBQtj
Complete Remission Following Pembrolizumab in a Woman with Mismatch Repair‐Deficient Endometrial Cancer and a Germline BRCA1 Mutation
AbstractEndometrial cancer is the most common gynecologic malignancy in the U.S. and, although the majority of cases present at an early stage and can be treated with curative intent, those who present with advanced disease, or develop metastatic or recurrent disease, have a poorer prognosis. A subset of endometrial cancers exhibit mismatch repair (MMR) deficiency. It is now recognized that MMR‐deficient cancers are particularly susceptible to programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitors, and in a landmark judgement in 2017, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab for these tumors, the first tumor‐agnostic approval of a drug. However, less is known about the sensitivity to PD‐1 blockade among patients with known mutations in double‐strand break DNA repair pathways involving homologous recombination, such as those in BRCA1 or BRCA2. Here we report a case of a patient with an aggressive somatic MMR‐deficient endometrial cancer and a germline BRCA1 who experienced a rapid complete remission to pembrolizumab.Key Points. Endometrial cancers, and in particular endometrioid carcinomas, should undergo immunohistochemical testing for mismatch repair proteins.Uterine cancers with documented mismatch repair deficiency are candidates for treatment with programmed cell death protein 1 inhibition.Genomic testing of recurrent, advanced, or metastatic tumors may be useful to determine whether patients are candidates for precision therapies.
https://ift.tt/2M4qrku
FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non‐Small Cell Lung Cancers Harboring BRAF V600E Mutations
AbstractOn June 22, 2017, the Food and Drug Administration expanded indications for dabrafenib and trametinib to include treatment of patients with metastatic non‐small cell lung cancer (NSCLC) harboring BRAF V600E mutations. Approval was based on results from an international, multicenter, multicohort, noncomparative, open‐label trial, study BRF113928, which sequentially enrolled 93 patients who had received previous systemic treatment for advanced NSCLC (Cohort B, n = 57) or were treatment‐naïve (Cohort C, n = 36). All patients received dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily. In Cohort B, overall response rate (ORR) was 63% (95% confidence interval [CI] 49%–76%) with response durations ≥6 months in 64% of responders. In Cohort C, ORR was 61% (95% CI 44%–77%) with response durations ≥6 months in 59% of responders. Results were evaluated in the context of the Intergroupe Francophone de Cancérologie Thoracique registry and a chart review of U.S. electronic health records at two academic sites, characterizing treatment outcomes data for patients with metastatic NSCLC with or without BRAF V600E mutations. The treatment effect of dabrafenib 150 mg twice daily was evaluated in 78 patients with previously treated BRAF mutant NSCLC, yielding an ORR of 27% (95% CI 18%–38%), establishing that dabrafenib alone is active, but that the addition of trametinib is necessary to achieve an ORR of >40%. The most common adverse reactions (≥20%) were pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.Implications for Practice.The approvals of dabrafenib and trametinib, administered concurrently, provide a new regimen for the treatment of a rare subset of non‐small cell lung cancer (NSCLC) and demonstrate how drugs active for treatment of BRAF‐mutant tumors in one setting predict efficacy and can provide supportive evidence for approval in another setting. The FDA also approved the first next‐generation sequencing oncology panel test for simultaneous assessment of multiple actionable mutations, which will facilitate selection of optimal, personalized therapy. The test was shown to accurately and reliably select patients with NSCLC with the BRAF V600E mutation for whom treatment with dabrafenib and trametinib is the optimal treatment.
https://ift.tt/2JVTkmj
Randomized Phase II Trial of Parsatuzumab (Anti‐EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First‐Line Nonsquamous Non‐Small Cell Lung Cancer
AbstractLessons Learned. The lack of efficacy associated with anti‐EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non‐small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti‐EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents.Background.Epidermal growth factor‐like domain 7 (EGFL7) is an extracellular matrix‐associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti‐EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum‐based therapy for advanced or recurrent nonsquamous non‐small cell lung cancer (NS‐NSCLC).Methods.Patients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21‐day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months.Results.The progression‐free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0–2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5–2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab.Conclusion.There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first‐line NS‐NSCLC.
https://ift.tt/2M6uwEM
Effect of Concomitant pH‐Elevating Medications with Pazopanib on Progression‐Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma
AbstractBackground.Pazopanib is an oral tyrosine‐kinase inhibitor that is approved by the U.S. Food and Drug Administration for treatment of metastatic renal cell carcinoma (mRCC). Pharmacokinetic data have shown that concomitant administration of pazopanib and esomeprazole, a proton pump inhibitor (PPI), leads to decreased area under the curve and thus decreased exposure of pazopanib by 40%. Despite the pharmacokinetic data published to date, the clinical significance and impact on patient outcomes resulting from decreased pazopanib exposure remains unknown.Materials and Methods.In this retrospective, observational, cohort study, 90 patients with mRCC who either received pazopanib in combination with a PPI or histamine 2 receptor antagonist (H2RA; concurrent PPI/H2RA group) or who did not take concurrent pH‐elevating medications (no PPI/H2RA group) were compared to determine if there was an impact on progression‐free survival (PFS), the primary endpoint, and secondary endpoints, overall survival (OS) and safety.Results.The differences between the PFS of 9.0 months and OS of 28.0 months for the concomitant PPI/H2RA group versus 11.0 months and 30.1 months, respectively, for the no PPI/H2RA group were not statistically significant. Rates of adverse events were similar between the concomitant PPI/H2RA and no PPI/H2RA groups.Conclusion.Concomitant PPI or H2RA usage was not shown to be associated with a reduction in PFS or OS for patients receiving pazopanib for mRCC, with a similar toxicity profile in each group. Based on the results of this retrospective cohort study and the palliative nature of the treatment of patients with mRCC, clinicians should consider allowing patients to remain on concomitant pazopanib and acid‐reducing therapy.Implications for Practice.Pazopanib is a preferred category‐one first‐line treatment for predominant clear cell metastatic renal cell carcinoma (mRCC). However, because of an aging demographic, coupled with patients with mRCC presenting with multiple comorbidities, including symptomatic dyspepsia or gastroesophageal reflux disease, patients are commonly required to take pazopanib concomitantly with a proton pump inhibitor (PPI) or a histamine 2 receptor antagonist (H2RA). Despite earlier pharmacokinetic reports suggesting that an alkaline pH may result in poorer absorption, this institutional retrospective study found no effect on clinical outcomes. These data suggest that concurrent treatment of mRCC with pazopanib and a PPI or H2RA may be safe in everyday practice.
https://ift.tt/2MGA4aj
A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone‐ and/or Enzalutamide‐Refractory Metastatic Castration‐Resistant Prostate Cancer
AbstractLessons Learned. In abiraterone‐ and/or enzalutamide‐refractory metastatic castration‐resistant prostate cancer (mCRPC) patients, selinexor led to prostate‐specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice‐a‐week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second‐generation anti‐androgen therapies, limiting further clinical development in this patient population.This study highlights the challenge of primary endpoint selection for phase II studies in the post‐abiraterone and/or post‐enzalutamide mCRPC space.Background.Selinexor is a first‐in‐class selective inhibitor of nuclear export compound that specifically inhibits the nuclear export protein Exportin‐1 (XPO‐1), leading to nuclear accumulation of tumor suppressor proteins.Methods.This phase II study evaluated the efficacy and tolerability of selinexor in patients with metastatic castration‐resistant prostate cancer (mCRPC) refractory to abiraterone and/or enzalutamide.Results.Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m2 twice a week (days 1 and 3) and was subsequently reduced to 60 mg flat dose twice a week (days 1 and 3), 3 weeks on, 1 week off, to improve tolerability. The median treatment duration was 13 weeks. At a median follow‐up of 4 months, two patients (14%) had ≥50% prostate‐specific antigen (PSA) decline, and seven patients (50%) had any PSA decline. Of eight patients with measurable disease at baseline, two (25%) had a partial response and four (50%) had stable disease as their best radiographic response. Five patients (36%) experienced serious adverse events (SAEs; all unrelated to selinexor), and five patients (36%) experienced treatment‐related grade 3–4 AEs. The most common drug‐related adverse events (AEs) of any severity were anorexia, nausea, weight loss, fatigue, and thrombocytopenia. Three patients (21%) came off study for unacceptable tolerability.Conclusion.Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second‐line anti‐androgenic agents.
https://ift.tt/2K0m2yn
Administration of the Tablet Formulation of Olaparib in Patients with Ovarian Cancer: Practical Guidance and Expectations
AbstractOlaparib is a poly(ADP‐ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic BRCA1/2 mutations who have received three or more prior lines of chemotherapy for maintenance treatment of recurrent OC that is in response to platinum‐based chemotherapy regardless of BRCA mutation status and for human epidermal growth receptor factor 2‐negative metastatic breast cancer with deleterious or suspected deleterious germline BRCA mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Because olaparib is poorly soluble and requires advanced drug delivery techniques to ensure bioavailability, the originally approved 400 mg dose is taken as eight 50 mg capsules twice daily. An alternative melt‐extrusion tablet formulation was developed to improve the pharmacokinetic and pharmacodynamic profile of olaparib and reduce the pill burden for patients. The recommended tablet dose is 300 mg twice daily (two 150 mg tablets). Phase III studies with the tablet formulation are ongoing for multiple tumor types. Two studies conducted with the olaparib tablet formulation have reported results: one in platinum‐sensitive, BRCA‐mutated recurrent OC (SOLO‐2) and one that included patients with germline BRCA‐mutated metastatic breast cancer (OlympiAD). The tablet is the approved formulation based on the SOLO‐2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC. Prior to implementing any changes in therapy, health care providers should engage their patients in discussion to support an informed transition between the formulations.Implications for Practice.Olaparib has recently been approved for maintenance treatment of recurrent ovarian cancer (OC) that is in response to platinum‐based chemotherapy. The originally approved capsule formulation was dosed as 400 mg twice daily (eight 50 mg capsules). The recommended olaparib tablet dose is 300 mg twice daily (two 150 mg tablets). The tablet is the new approved formulation based on the SOLO‐2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC.
https://ift.tt/2JRs090
A First‐in‐Human Phase I Study of OPB‐111077, a Small‐Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers
AbstractLessons Learned. OPB‐111077 is a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation that exhibited promising anticancer activity in preclinical models.In this first‐in‐human phase I study of OPB‐111077 in unselected advanced cancers, treatment‐emergent adverse events, most frequently nausea, fatigue, and vomiting, were generally mild to moderate in intensity and could be medically managed.Overall, only modest clinical activity was observed after OPB‐111077 given as monotherapy. Notable antitumor activity was seen in a subject with diffuse large B‐cell lymphoma.Background.OPB‐111077 is a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation with promising anticancer activity in preclinical models.Methods.Open‐label, phase I trial of OPB‐111077 in advanced cancers with no available therapy of documented benefit. Initial dose escalation in unselected subjects was followed by dose expansion. Patients received oral OPB‐111077 daily in 28‐day cycles until loss of clinical benefit.Results.Eighteen subjects enrolled in dose escalation, and 127 in dose expansion. Dose‐limiting toxicities were observed at 300 mg and 400 mg QD; maximum tolerated dose was defined as 250 mg QD. Frequently reported treatment‐emergent adverse events (TEAEs) included nausea, fatigue, and vomiting. TEAEs were generally mild to moderate and could be medically managed. OPB‐111077 reached micromolar drug concentrations, had an elimination half‐life of approximately 1 day, and reached steady‐state by day 8. A durable partial response was observed in one subject with diffuse large B‐cell lymphoma. Seven subjects with diverse tumor types had stable disease or minor responses for at least eight treatment cycles (224 days).Conclusion.OPB‐111077 is generally well tolerated, and its pharmacokinetic profile is sufficient for further clinical development. Notable clinical activity was observed in a subject with diffuse large B‐cell lymphoma. Overall, modest efficacy was observed against unselected tumors.
https://ift.tt/2K0Ig3f
Portomesenteric Venous Stenting for Palliation of Ascites and Variceal Bleeding Caused by Prehepatic Portal Hypertension
AbstractBackground.The purpose of this study was to evaluate percutaneous transhepatic portal vein stenting (PVS) for palliation of refractory ascites and/or variceal bleeding caused by extrahepatic portomesenteric venous stenosis in patients with pancreaticobiliary cancer.Materials and Methods.A single‐institution, retrospective review of patients who underwent PVS between January 2007 and July 2015 was performed. A total of 38 patients were identified, of whom 28 met the inclusion criterion of PVS performed primarily for refractory ascites or variceal bleeding. In addition to technical success and overall survival, clinical success was measured by fraction of remaining life palliated. The palliative effect of PVS was also quantified by measuring changes in liver and ascites volumes after the procedure.Results.Technical success was 93% (26/28). Stent deployment involved more than one portomesenteric vessel in most patients (20/26). The cumulative probability of symptom recurrence at 6, 12, 18, and 24 months was 12%, 16%, 26%, and 40%, respectively. There was a significant difference (p < .001) in the probability of symptom recurrence, recurrence of abdominal ascites, and increase in liver volume between patients whose stents remained patent and those whose stents demonstrated partial or complete occlusion. The mean fraction of remaining life palliated was 87%. All but two patients were found to have improvement in clinical symptoms for the majority of their lives after the procedure. There were no major or minor complications.Conclusion.As a low‐risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses.Implications for Practice.Portomesenteric venous stenosis is a challenging complication of pancreaticobiliary malignancy. Portomesenteric stenoses can lead to esophageal, gastric, and mesenteric variceal bleeding, as well as abdominal ascites. The purpose of this study was to evaluate the safety and efficacy of portal vein stenting (PVS) in patients with cancer who have symptomatic portal hypertension caused by portomesenteric venous compression. As a low‐risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses.
https://ift.tt/2JVRj9C
Emerging Perspectives on mTOR Inhibitor‐Associated Pneumonitis in Breast Cancer
AbstractSubstantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor‐associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor‐associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor‐associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor‐associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class‐related complication of mTOR inhibitor therapy.Implications for Practice.This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus‐related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor‐associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.
https://ift.tt/2M8jXkO
Validation and Refinement of the Age, Comorbidities, and Albumin Index in Elderly Patients with Diffuse Large B‐Cell Lymphoma: An Effective Tool for Comprehensive Geriatric Assessment
AbstractBackground.We aimed to validate and refine the Age, Comorbidities, and Albumin (ACA) index in elderly Chinese patients with diffuse large B‐cell lymphoma (DLBCL) and propose a more effective method for comprehensive geriatric assessment (CGA).Materials and Methods.Patients ≥65 years of age who had been diagnosed with de novo DLBCL in the Institute of Hematology, Beijing Hospital, were screened for eligibility (n = 99).Results.Based on the ACA index, 39, 31, 26, and 3 patients were categorized into the "excellent," "good," "moderate," and "poor" groups, respectively. The 2‐year treatment‐related mortality rate was significantly higher and the survival rates poorer in the ACA "moderate to poor" group compared with those of the ACA "good" and "excellent" groups. Multivariable model analysis identified two independent predictors of overall survival: the instrumental activities of daily living (IADL) scale and the ACA index. IADL scores of 6 to 7 and the ACA "good" group were assigned 1 point; IADL scores ≤5 and the ACA "moderate to poor" group were assigned 2 points. Based on these data, we created a three‐category system (IADL ACA index [IACA index]): low risk, score 0; intermediate risk, score 1 to 2; and high risk, score 3 to 4. The IACA index could effectively discriminate the response rates, overall survival, and progression‐free survival rates in elderly patients with DLBCL.Conclusion.We observed that the ACA index could partially predict the clinical outcomes of elderly DLBCL patients in China. Based on this index, we proposed the IACA index as an effective tool for CGA in DLBCL.Implications for Practice.Diffuse large B‐cell lymphoma (DLBCL) is one of the most frequent types of malignant lymphoma in elderly people, and identifying patients suitable for curative therapy is critical in the improvement of clinical outcomes. Recently, some authors proposed the Age, Comorbidities, and Albumin (ACA) index. Combining the use of the instrumental activities of daily living (IADL) scale and the ACA index, this article describes the IADL ACA index (IACA index), which is an effective tool for comprehensive geriatric assessment in DLBCL.
https://ift.tt/2JPqwvI
Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy
AbstractBackground.Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long‐term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant‐chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease‐free survival (DFS) and overall survival (OS) in patients without pCR.Subjects, Materials, and Methods.Four hundred thirty‐five patients with stage IIA–IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67‐positive cells between core biopsy samples and surgical specimens and correlated this value with outcome.Results.Twenty‐five percent of patients presented with luminal A‐like tumors, 45% had luminal B‐like tumors, 14% had triple‐negative BC, 5% had HER2‐positive BC, and 11% had triple‐positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high‐grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty‐seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8–6.37) and 7.03 (95% CI 2.6–18.7), respectively.Conclusion.Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting.Implications for Practice.This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B‐like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B‐like with Ki67 decrease).
https://ift.tt/2M2lE2U
The emerging role of circRNAs and their clinical significance in human cancers
Publication date: Available online 19 June 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Ling Qian, Shulin Yu, Zhen Chen, Zhiqiang Meng, Shenglin Huang, Peng Wang
Circular RNA (circRNA), a recently discovered subclass of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5′ cap structure nor a 3′ polyadenylated tail. Generated from precursor mRNA (pre-mRNA) through "backsplicing" (a type of alternative RNA splicing), the majority of circRNAs are located in the cytoplasm and are widespread among living organisms. They are stable and conserved and exhibit spatiotemporal-specific expression. circRNAs are known to be involved in the development and progression of multiple diseases, including cancer, by acting as microRNA (miRNA) sponges and by regulating processes such as transcription and translation. The extensively aberrant expression profiles of circRNAs in multiple cancerous tissues make these molecules promising diagnostic biomarkers and therapeutic targets for cancer. Here, we briefly review the characteristics, biogenesis, classification, and functions of circRNAs, with a particular focus on the role of circRNAs in various cancers.
https://ift.tt/2I7h0OJ
Characteristics and survival outcomes related to the infra-pyloric lymph node status of gastric cancer patients
Abstract
Background
To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients.
Methods
Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed.
Results
A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p < 0.001).
Conclusions
Patients with no. 6 lymph node metastasis have poor survival outcomes. Complete infra-pyloric lymphadenectomy is necessary and crucial for gastric cancer patients.
https://ift.tt/2K71Nm0
Cancers, Vol. 10, Pages 209: Crosstalk between ERα and Receptor Tyrosine Kinase Signalling and Implications for the Development of Anti-Endocrine Resistance
Cancers, Vol. 10, Pages 209: Crosstalk between ERα and Receptor Tyrosine Kinase Signalling and Implications for the Development of Anti-Endocrine Resistance
Cancers doi: 10.3390/cancers10060209
Authors: Rugaia Z. Montaser Helen M. Coley
Although anti-endocrine therapies have significantly advanced the treatment of breast cancer, they pose the problem of acquired drug resistance. The oestrogen receptor (ER)-expressing breast cancer cell lines MCF-7 and T47D alongside their in vitro derived resistant counterparts MCF-7-TR (tamoxifen-resistant) and T47D-FR (fulvestrant-resistant) showed dual resistance to fulvestrant and tamoxifen in the presence of upregulated HER1 and HER2 growth factor receptors. Our study demonstrated that tamoxifen resistance and fulvestrant resistance are associated with collateral sensitivity to the tyrosine kinase inhibitors (TKIs) lapatinib (p < 0.0001) and afatinib (p < 0.0001). Further, we found that over time, the TKIs reactivated ERα protein and/or mRNA in tamoxifen- and fulvestrant-resistant cells. Combinations of anti-endocrine agents with afatinib gave rise to significantly enhanced levels of apoptosis in both T47D-FR and MCF-7-TR in a synergistic manner versus additive effects of agents used singly. This was associated with p27kip1 induction for anti-endocrine-resistant cells versus parental cells. Our data supports the use of combination treatment utilising dual HER1/2 inhibitors in breast cancer patients showing resistance to multiple anti-endocrine agents.
https://ift.tt/2JQKsOJ
Acute Hospital Encounters in Cancer Patients Treated With Definitive Radiation Therapy
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Mallika Marar, Peter Gabriel, Wei-Ting Hwang, Daniel R. Owen, Melody Ju, Charles B. Simone, John Christodouleas, Neha Vapiwala, Abigail T. Berman
PurposeAcute hospital encounters in patients undergoing curative-intent radiation therapy (RT) have not previously been well characterized. Understanding acute visit patterns among RT patients yields insights for risk assessments and cancer urgent care clinics that could decrease hospitalization rates and reduce health care costs. This study aims to identify patient, disease-site, and treatment characteristics associated with emergency department visits and inpatient admissions in cancer patients treated with definitive RT.Methods and MaterialsA retrospective cohort study was conducted using data from a quaternary-care cancer center. The cohort was defined as all consecutive patients aged ≥ 18 years who began RT between July 1, 2011, and December 31, 2013; were without metastases; and were treated with curative intent. An acute encounter was defined as an emergency department visit or inpatient admission during RT or within 30 days after the conclusion of RT.ResultsAmong 1852 unique RT courses, 666 RT courses (36.0%) involved at least 1 acute encounter, and a total of 1418 acute encounters were identified. RT courses with at least 1 acute encounter corresponded to patients more likely to be on their second (odds ratio [OR], 1.96; P < .001) or third (OR, 3.82; P < .05) RT course and undergoing concurrent chemotherapy (OR, 6.38; P < .001). Among the RT courses with at least 1 acute encounter, the most common disease site was thoracic (22.8%), followed by head and/or neck (22.2%) and gastrointestinal (18.3%). Central nervous system tumors had the greatest proportion of RT courses with acute encounters (77.1%).ConclusionsIn this retrospective analysis, more than one-third of curative-intent RT courses were associated with at least 1 acute hospital encounter during or shortly after irradiation. Given that acute encounters varied by patient, disease-site, and treatment characteristics, these findings can inform targeted preventive measures to reduce cancer-related acute hospital encounters and guide improved management protocols.
https://ift.tt/2ljWZeZ
Do Existing Audiometric Dose-Effect Models and Risk Factors Apply to Children Treated With Proton Therapy?
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Babita Jyoti, Ronny L. Rotondo, Julie A. Bradley, Christopher G. Morris, Daniel J. Indelicato
https://ift.tt/2tmR50d
GI Cancers—Modulating the Modern Management of Gastrointestinal Malignancies: A Look at Liver Metastases, Rectal Cancer, Esophagogastric Cancer, and Anal Cancer
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Salma K. Jabbour, Smith Apisarnthanarax, Christopher L. Hallemeier, Florence Huguet, James D. Murphy, Jeffrey R. Olsen
https://ift.tt/2lnqf4F
In Regard to Palmer et al
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Shearwood McClelland, Jerry J. Jaboin
https://ift.tt/2tnKy5n
In the Eye of the Maximal Storm: Surgery Versus Radiation?
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): James Janopaul-Naylor, Sue S. Yom
https://ift.tt/2llpZ64
Reluctant Induction Followed by Proton Beam Therapy, If Practicable
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Minh Tam Truong, Gregory Grillone
https://ift.tt/2yrmeW3
Organ Preservation in Sinonasal Malignancies Through Particle Therapy
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Alexandra D. Jensen
https://ift.tt/2ln3626
Erratum to: Mohan R, Held KD, Story MD, et al. Proceedings of the National Cancer Institute Workshop on Charged Particle Radiobiology. Int J Radiat Oncol Biol Phys 2018;100:816-831.
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
https://ift.tt/2yqVsx3
Time to Rethink Our Strategy With a Preoperative Intensification Approach
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Nabil F. Saba
https://ift.tt/2lk5XZN
Issue Highlights
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
https://ift.tt/2ytYtNe
Intra-arterial Chemoradiation Therapy as an Option for Maxillary Sinus Cancers
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Akihiro Homma, Rikiya Onimaru
https://ift.tt/2llpHMw
Preoperative Radiation Therapy for Locally Advanced Sinus Malignancies
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Brian O'Sullivan, John Waldron
https://ift.tt/2yoAlvy
Carl Mansfield, MD, ScD, FACR, FASTRO (1928-2018)
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Dwight E. Heron, Nagalingam Suntharalingam, Karen M. Winkfield, William F. Regine
https://ift.tt/2llpyss
In Regard to Chen et al
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Melek Tugce Yilmaz, Pervin Hurmuz, Mustafa Cengiz
https://ift.tt/2yqVh4R
Radiation Therapy Research: A Global Analysis 2001-2015
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 101, Issue 4
Author(s): Ajay Aggarwal, Grant Lewison, Danielle Rodin, Anthony Zietman, Richard Sullivan, Yolande Lievens
Radiation therapy is a core modality of cancer treatment; however, concerns have been expressed regarding its underutilization and its lack of prioritization as a research domain relative to other cancer treatment modalities, despite its rapid technical evolution. It is therefore important to understand, from a public policy perspective, the evolution of global radiation therapy research, to identify strengths, weaknesses, and opportunities. This study used a bibliometric approach to undertake a quantitative analysis of global radiation therapy research published between 2001 and 2015 and available in the Web of Science (Wos) database, with particular focus on the 25 leading research-active countries. A total of 62,550 radiation therapy research articles from 127 countries, published in 2531 international journals, were analyzed. The United States was responsible for 32.3% of these outputs, followed by Japan (8.0%) and Germany (7.7%). Nearly half of all publications related to preparation and delivery of radiation therapy, combined-modality regimens, and dose fractionation studies. Health services research, palliative care, and quality of life studies represented only 2%, 5%, and 4% of all research outputs, respectively. Countries varied significantly in their commitment to different research domains, and trial-related publications represented only 5.1% of total output. Research impact was analyzed according to 3 different citation scores, with research outputs from Denmark, The Netherlands, and the United States consistently the highest ranked. Globally, radiation therapy publication outputs continue to increase but lag behind other spheres of cancer management. The types of radiation therapy research undertaken appear to be regionally patterned, and there is a clear disconcordance between the volume of research output from individual countries and its citation impact. Greater support for radiation therapy research in low- and middle-income countries is required, including international collaboration. The study findings are expected to provide the requisite knowledge to guide future radiation therapy research programs.
https://ift.tt/2ln3RZi
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