The derived neutrophil–lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial.
http://ift.tt/2eTEG0v
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 8 Σεπτεμβρίου 2017
The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy
Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma
We recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects.
http://ift.tt/2wQOqgT
A systematic review of synthetic CT generation methodologies for use in MRI-only radiotherapy
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Emily Johnstone, Jonathan J. Wyatt, Ann M. Henry, Susan C. Short, David Sebag-Montefiore, Louise Murray, Charles G. Kelly, Hazel M. McCallum, Richard Speight
MRI offers superior soft tissue contrast as compared to CT, which is conventionally used for radiotherapy treatment planning (RTP) and patient positioning verification, resulting in improved target definition. The two modalities are co-registered for RTP, however this introduces a systematic error. Implementing an MRI-only radiotherapy workflow would be advantageous as this error would be eliminated, the patient pathway simplified and patient dose reduced. Unlike CT, in MRI there is no direct relationship between signal intensity and electron density, however various methodologies for MRI-only RTP have been reported. A systematic review of these methods was undertaken.The PRISMA guidelines(1) were followed. Embase and Medline databases were searched (1996-03/2017) for studies which generated synthetic CTs (sCT)s for MRI-only radiotherapy. 61 articles met the inclusion criteria.This review showed that MRI-only RTP techniques could be grouped into three categories: i]bulk density override ii]atlas-based and iii]voxel-based techniques, which all produce an sCT scan from MR image(s).Bulk density override techniques either used a single homogeneous or multiple tissue override. The former produced large dosimetric errors (>2%) in some cases and the latter frequently required manual bone contouring. Atlas-based techniques used both single and multiple atlases and included methods incorporating pattern recognition techniques. Clinically acceptable sCTs were reported, but atypical anatomy led to erroneous results in some cases. Voxel-based techniques included methods using routine and specialised MRI sequences, namely ultra-short echo time imaging. High quality sCTs were produced, however use of multiple sequences led to long scanning times increasing the chances of patient movement. Using non-routine sequences would currently be problematic in most radiotherapy centres.Atlas-based and voxel-based techniques were found to be the most clinically useful methods, with some studies reporting dosimetric differences of <1% between planning on the sCT and CT and <1mm deviations when using sCTs for positional verification.
http://ift.tt/2xkGkAb
IGRT strategies for pelvic lymph node irradiation in high-risk prostate cancer: motion and margins
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Lucy Kershaw, Laila van Zadelhoff, Wilma Heemsbergen, Floris Pos, Marcel van Herk
PurposeFor optimal irradiation of pelvic lymph nodes (LN) in high-risk prostate cancer, definition of margins to determine the planning target volume(s) is essential. Detailed quantification of the relative motion of the LN, seminal vesicles (SV) and prostate is currently lacking. This work aimed to quantify these motions and define margins for image-guided radiotherapy based on bony anatomy or prostate correction strategies for a 3 or 6 degrees-of-freedom couch.Material and MethodsNineteen patients had a planning CT followed by a mean of 11 repeated CTs during radiotherapy. The prostate, SV, external and internal iliac LN regions on the left and right were outlined on each CT. Systematic and random uncertainties were determined along with correlations between the motion of these regions. CTV-PTV margins required to take only motion into account were calculated for each guidance method.ResultsFor bone guidance, motion of prostate and LNs was largely uncorrelated. Margins to compensate for motion ((LR, SI, AP) in cm) based on a 3 degrees-of-freedom couch were; prostate: (0.2, 0.6, 0.8), SV: (0.4, 0.9, 1.0) and LN: (0.3, 0.4, 0.6). For prostate guidance, margins were calculated for correlated motion; prostate: (0, 0, 0), SV: (0.3, 0.5, 0.4) and LN: (0.3, 0.5, 0.9). For a 6 degrees-of-freedom couch, these margins were; prostate: (0.2, 0.6, 0.8), SV: (0.3, 0.9, 1.0) and LN: (0.3, 0.4, 0.3) for bone guidance. For prostate guidance, margins were; prostate: (0, 0, 0), SV: (0.2, 0.5, 0.4) and LN: (0.3, 0.6, 0.6)ConclusionsImage-guided radiotherapy based on bony anatomy requires larger prostate and SV margins, and guidance on prostate requires larger LN margins. Neither guidance strategy is optimal, and a combination of the two, or treatment adaption after a number of fractions might be preferable. Calculation of the total margin should also include delineation uncertainties.
Teaser
Definition of margins to determine the optimal image-guided radiotherapy (IGRT) strategy for pelvic lymph node irradiation is essential in high-risk prostate cancer. In this work, these margins were derived from systematic and random motions measured using repeated CT scans in 19 patients, based on matching to either bony anatomy or prostate for a 3 or 6 degrees-of-freedom (DOF) couch. When matching to bony anatomy, margins were smaller for lymph nodes than when matching to prostate, but larger for prostate and seminal vesicles. The prostate and seminal vesicle margins were unchanged when using a 3 vs 6 DOF couch, but lymph node margins were smaller in the anterior-posterior direction.http://ift.tt/2gQCvI7
Subcutaneous implant-based breast reconstruction, a modern challenge in post mastectomy radiation planning
Source:Practical Radiation Oncology
Author(s): Melissa P. Mitchell, Jamie Wagner, James Butterworth
As survival rates for breast cancer continue to improve, there has been increasing interest in reducing toxicity of therapy. In the field of breast surgery, we have seen advancements in the surgical approach from total mastectomy to skin and nipple sparing mastectomy. Nodal surgery has also been significantly impacted by a "less is more" approach, sparing patients with healthy lymph nodes the side effect of axillary lymph node dissection by performing sentinel lymph node dissection to accurately assess the draining nodal basin. More recently, there have been increasing reports of techniques to improve options for reconstruction. A growing trend has been use of acellular dermal matrix (ADM). This has been reported to improve cosmesis and reduce the number of surgical procedures required to obtain desired aesthetic results. Additionally, there have been increasing reports of use of prepectoral ADM covered implants. As compared to traditional methods of using submuscular tissue expanders, devices placed in the prepectoral plane have been reported to reduce animation deformities and postoperative pain. There is also the benefit that muscular function will be preserved with a subcutaneous expander. Furthermore, there is a growing push for single stage procedures made possible through the use of ADM. This benefits the patient by subjecting them to less operations and benefits the health care system by decreasing health care costs, as compared to multiple stage surgeries.
http://ift.tt/2gRQVvs
Factors Associated with Fatigue in Prostate Cancer (PC) Patients Undergoing External Beam Radiation Therapy (EBRT)
Source:Practical Radiation Oncology
Author(s): Hann-Hsiang Chao, Abigail Doucette, David M. Raizen, Neha Vapiwala
PurposeFatigue is a common adverse effect among cancer patients undergoing external beam radiation therapy (EBRT), yet the underlying disease- and treatment-related factors influencing its development are poorly understood. We hypothesized that clinical, demographic, and treatment-related factors differentially affect fatigue and aimed to better characterize variables related to fatigue development in prostate cancer (PC) patients during EBRT.MethodsWe identified a 681 patient cohort with non-metastatic PC undergoing a 6–9week EBRT course. Patient fatigue scores (range 0–3) were prospectively recorded by providers during treatment visits using standardized criteria. Clinical and demographic factors including age, race, EBRT details, disease staging, smoking status, comorbidities, urinary symptoms, employment status, weight, and concurrent medication use were assessed for their relationship to fatigue levels. Significant differences in fatigue severity by each variable at the beginning and end of EBRT were assessed by non-parametric-means testing, and differences in the level of fatigue increase over the treatment course were assessed using an ordered logistic regression model.ResultsSignificant increases in reported fatigue severity were seen in patients with: age<60years (p=0.006), depressive symptoms (p<0.001) and use of androgen deprivation therapy prior to radiation start (p=0.04). In addition, the prescription of antiemetics prior to radiation start was associated with reduced fatigue severity (p=0.03).ConclusionsWe identify factors associated with increased (young age, depressive symptoms, androgen deprivation therapy) and decreased (antiemetic prescription) fatigue in a large cohort of PC patients receiving EBRT. Continued investigation is needed to further elucidate clinical drivers and biological underpinnings of increased fatigue to guide potential interventions.
http://ift.tt/2vMBUxe
HPV related Nasopharyngeal and Cervical Cancer in a Married Couple in North America
Source:Practical Radiation Oncology
Author(s): Daniel B. Vanderbilt, Quoc-Anh Ho, Uma Goyal, Robert C. Bell, Robert R. Klein, Sun K. Yi
http://ift.tt/2vMgBw4
Pancreatic injury in children: a case report and review of the literature
Trauma is the main cause of morbidity and mortality in the pediatric population. Blunt trauma to the abdomen accounts for the majority of abdominal injuries in children. Pancreatic injury, although uncommon (2...
http://ift.tt/2wR46k3
Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
Abstract
Background
Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC).
Methods
Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed.
Results
Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65–85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0–10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1–4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items.
Conclusions
The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified.
http://ift.tt/2jcvG8p
IGF system targeted therapy: therapeutic opportunities for ovarian cancer
Source:Cancer Treatment Reviews
Author(s): J.A.L. Liefers-Visser, R.A.M. Meijering, A.K.L. Reyners, A.G.J. van der Zee, S. de Jong
The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential.
http://ift.tt/2jcLlV8
Skin Cancer-Sun Knowledge and Sun Protection Behaviors of Liver Transplant Recipients in Turkey
Abstract
The aim of this study was to compare liver transplant recipients (LTRs) with the general population regarding their knowledge of skin cancer, sun health, sun protection behaviors, and affecting factors. This cross-sectional study was conducted in Turkey between March 2016 and September 2016 with 104 LTRs and 100 participants from the general population group (GPG). The mean age of the LTRs was 53.2 ± 11.8 and that of the GPG was 42.7 ± 14.5. The LTRs' skin cancer and sun knowledge were significantly lower than in the GPG, but there was no difference between the two groups in terms of their sun protection behavior scores. The most commonly used sun protection behaviors of LTRs were not being outside and not sunbathing between 10 a.m. and 4 p.m., wearing clothing that covers the skin, and avoiding the solarium. Behaviors commonly practiced by the GPG were wearing sunglasses, wearing sunscreen with a sun protection factor of 15 or higher before going outside, wearing sunscreen at the beach, while swimming or doing physical activity outside, and reapplying it every 2 h. Results of our study will contribute to the development of education and training programs for LTRs on skin cancer. The results also demonstrated the importance of practicing adequate sun protection behaviors which will certainly impact their future health.
http://ift.tt/2gQ95tz
Skin Cancer-Sun Knowledge and Sun Protection Behaviors of Liver Transplant Recipients in Turkey
Abstract
The aim of this study was to compare liver transplant recipients (LTRs) with the general population regarding their knowledge of skin cancer, sun health, sun protection behaviors, and affecting factors. This cross-sectional study was conducted in Turkey between March 2016 and September 2016 with 104 LTRs and 100 participants from the general population group (GPG). The mean age of the LTRs was 53.2 ± 11.8 and that of the GPG was 42.7 ± 14.5. The LTRs' skin cancer and sun knowledge were significantly lower than in the GPG, but there was no difference between the two groups in terms of their sun protection behavior scores. The most commonly used sun protection behaviors of LTRs were not being outside and not sunbathing between 10 a.m. and 4 p.m., wearing clothing that covers the skin, and avoiding the solarium. Behaviors commonly practiced by the GPG were wearing sunglasses, wearing sunscreen with a sun protection factor of 15 or higher before going outside, wearing sunscreen at the beach, while swimming or doing physical activity outside, and reapplying it every 2 h. Results of our study will contribute to the development of education and training programs for LTRs on skin cancer. The results also demonstrated the importance of practicing adequate sun protection behaviors which will certainly impact their future health.
http://ift.tt/2gQ95tz
Biomarker-Stratified Phase III Clinical Trials: Enhancement with a Subgroup-Focused Sequential Design
Among various design approaches to phase III clinical trials with a predictive biomarker, the marker-stratified all-comers design is advantageous because it allows for establishing the utility of both treatment and biomarker, but it is often criticized for requiring large sample sizes, since the design includes both marker-positive and marker-negative patients. In this paper, we propose a simple but flexible subgroup-focused design for marker-stratified trials that allows both sequential assessment across marker-defined subgroups and adaptive subgroup selection, while retaining an assessment using the entire patient cohort at the final analysis stage, possibly using established marker-based multiple testing procedures. Numerical evaluations indicate that the proposed marker-stratified design has a robustness property in preserving statistical power for detecting various profiles of treatment effects across the subgroups, while effectively reducing the number of randomized patients in the marker-negative subgroup with presumably limited treatment efficacy. In contrast, the traditional all-comers and sequential enrichment designs could suffer from low statistical power for some possible profiles of treatment effects. The latter also need long study durations and a large number of marker screened patients. We also provide an application to SWOG S0819, a trial to assess the role of cetuximab in treating non-small cell lung cancers. These evaluations indicate that the proposed subgroup-focused approach can enhance the efficiency of the marker-stratified design for definitive evaluation of treatment and biomarker in phase III clinical trials.
http://ift.tt/2xjzXNc
A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Abstract
Background
B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Patients and methods
Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. Results
A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72–1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53–1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38–1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). Conclusion
The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. Clinical trial number
EudraCT# 2011-002564-24.http://ift.tt/2vU5t4g
Increased incidence of bowel cancer after non-surgical treatment of appendicitis
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Malin Enblad, Helgi Birgisson, Anders Ekbom, Fredrik Sandin, Wilhelm Graf
BackgroundThere is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis.Patients and methodsPatients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987 − 2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated.ResultsOf 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7–4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26–46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6–8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1–5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0–5.2), and without abscess (SIR 3.5, 95% CI 2.9–4.1).ConclusionPatients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis.
http://ift.tt/2wPcgcx
Oncologic significance of para-aortic lymph node and inferior mesenteric lymph node metastasis in sigmoid and rectal adenocarcinoma
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Seung Hyung Lee, Jong Lyul Lee, Chan Wook Kim, Han IL. Lee, Chang Sik Yu, Jin Cheon Kim
BackgroundRecurrence patterns or survival in colorectal cancer patients might differ according to inferior mesenteric lymph node (IMLN) metastasis. However, few studies have compared para-aortic lymph node (PALN) metastasis and IMLN metastasis. The aim of the current study is to identify survival and recurrence patterns in patients with sigmoid colon and rectal adenocarcinoma with either PALN or IMLN metastasis and to evaluate the prognostic significance of PALN and IMLN metastasis.MethodsA retrospective study involving 3,076 patients with stage III and IV sigmoid and rectal cancer, who underwent curative surgery between January 2000 and December 2009, was performed. Clinicopathologic features, recurrence patterns, and survival outcomes of 27 patients with PALN metastasis were compared with those of 47 patients with IMLN metastasis. Patients with both IMLN and PALN metastasis were included in the PALN+ group.ResultsAfter curative resection, there was no significant difference in the 5-year disease-free and overall survival rates between the PALN+ and IMLN+ groups (27.5% vs. 29.8%, p = 0.24, and 37% vs. 39.2%, p = 0.19, respectively). Furthermore, there were no significant differences in recurrence rate (PALN+ group, 70.4%; and IMLN+ group, 63.8%; p = 0.69) or recurrence patterns.ConclusionsThe results suggest that IMLN metastasis, similar to PALN metastasis, is associated with adverse oncologic outcomes and has prognostic significance. Therefore, it is preferable that IMLN metastasis should be considered under the category of systemic metastasis (M1).
http://ift.tt/2wObv67
The prognostic relevance of parapyloric lymph node metastasis in Siewert type II/III adenocarcinoma of the esophagogastric junction
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Jia-Bin Wang, Man-Qiang Lin, Ping Li, Jian-Wei Xie, Jian-Xian Lin, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Chao-Hui Zheng, Chang-Ming Huang
BackgroundThe purpose of this study was to evaluate the prognosis of patients with Siewert type II /III adenocarcinoma of the esophagogastric junction (AEG) with parapyloric lymph node (No. 5 and 6 lymph nodes, PLN) metastasis and to determine the need for PLN dissection for patients with type II/III AEG.MethodsA total of 1008 patients with type II/III AEG who underwent a transabdominal total gastrectomy were enrolled. The long-term surgical outcome of PLN-positive patients and the therapeutic value of PLN dissection were analyzed.ResultsThere was no significant difference in the incidence of PLN metastasis between type II and III cancers (5.7% vs. 8.5%, P>0.05). PLN metastasis was a significant prognostic factor for type II/III cancers (HR 1.63; P=0.001). Among type II/III cancers, the 5-year survival of patients with PLN-positive cancers was much lower than that of patients with PLN-negative cancers (21.3% vs. 60.8%, P<0.001). Even after radical resection, the 5-year survival of patients with stage I-III PLN-positive cancers was similar to that of patients with stage IV cancers without PLN metastasis (23.5% vs. 23.1%, P>0.05). In the analysis of the therapeutic value of lymph node dissection in each station for type II and III cancers after radical resection, lymph nodes with the lowest therapeutic value index after No. 12a were No. 5 and 6 lymph nodes.ConclusionsPatients with type II/III AEG with PLN metastasis have a poor prognosis, similar to patients with stage IV disease. PLN dissection offers marginal therapeutic value for patients with type II/III AEG.
http://ift.tt/2wQSMVe
Multi-institutional study of peritoneal sarcomatosis from uterine sarcoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Publication date: Available online 7 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Armando Sardi, Arkadii Sipok, Dario Baratti, Marcello Deraco, Paul Sugarbaker, George Salti, Yutaka Yonemura, Paolo Sammartino, Olivier Glehen, Naoual Bakrin, Teresa P. Díaz-Montes, Vadim Gushchin
ObjectiveUterine sarcoma (US) is a rare tumor representing 1% of female genital tract malignancies. Peritoneal sarcomatosis (PS) after US, diminishes median overall survival (OS) and progression-free survival (PFS) with cytoreductive surgery (CRS) alone, with or without systemic chemotherapy is <1 year and 6 months, respectively. A multi-institutional review of PS from US was conducted to evaluate CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) and effects on survival outcomes.MethodsA retrospective review of 36 patients from 7 specialized international centers was performed. Selection criteria included PS of uterine origin with CRS/HIPEC treatment. Clinical data were analyzed. OS and PFS were estimated with Kaplan-Meier method.ResultsThirty-six patients underwent a total 38 HIPEC procedures performed from 2005-2014; 35 previous treatment and 1 primary treatment. Twenty-nine (81%) LMS patients, 3 (8%) endometrial stromal sarcoma (ESS), 3 (8%) adeneosarcoma (AS), and 1 (3%) categorized as other. Median PCI was 16 (range: 2-39), 10 patients had PCI ≥20. Thirty-four patients (94%) had complete cytoreduction (CC 0-1), 19 patients recurred. CRS/HIPEC OS at 1, 3, and 5-years was 75%, 53%, and 32% respectively, with median OS of 37 months (CI 95%: 20-54). PFS in 32 patients with CC at 1, 3, and 5-years was 67%, 32% and 32%, respectively with median PFS of 18.9 months (CI 95%: 6.7-31).ConclusionsCRS/HIPEC is a promising treatment modality for patients with PS. Histological subtype may influence survival. A global prospective registry of patients to further assess the efficacy of CRS/HIPEC is needed.
http://ift.tt/2wOMkR0
The association between performance parameters of physical fitness and postoperative outcomes in patients undergoing colorectal surgery: an evaluation of care data
Publication date: Available online 7 September 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): A.F.J.M. Heldens, B.C. Bongers, A.F. Lenssen, L.P.S. Stassen, W.F. Buhre, N.L.U. van Meeteren
BackgroundPreoperative cardiorespiratory fitness, as measured by cardiopulmonary testing or estimated using the less sophisticated incremental shuttle walk test, timed up-and-go test or stair climb test is known to be associated with postoperative outcome. This study aimed to evaluate whether parameters of physical fitness are associated with postoperative outcome in patients with colorectal cancer scheduled for elective resection.Patients and MethodsPerioperative data of patients who underwent colorectal resection at Maastricht University Medical Center were retrospectively analyzed. Preoperative variables (e.g., age, body mass index, comorbidities, physical fitness, tumour characteristics, neoadjuvant treatment, American Society of Anesthesiologists score, level of perceived fatigue and nutritional status) were compared with postoperative outcomes.ResultsOut of 80 consecutive cases, 75 (93.8%) were available for analysis (57.3% male, median ± interquartile range age 69.2 ± 11.7 years). A higher Charlson comorbidity index (odds ratio (OR) of 1.604, 95% confidence interval (CI) 1.120-2.296), worse functional exercise capacity (in meters, OR of 0.995, 95% CI 0.991-1.000), a lower physical activity level (in min/day, OR of 0.994, 95% CI 0.988-1.000), and a higher level of perceived fatigue (OR of 1.047, 95% CI 1.016-1.078), were associated with a slower time to recovery of physical functioning. A better functional exercise capacity was associated with a lower OR (OR of 0.995, 95% CI 0.991-1.000) for non-surgical complications.ConclusionThere is an association between preoperative parameters and postoperative outcomes in patients with colorectal cancer scheduled for resection. Patients benefit from an optimal preoperative physical fitness level. Specific interventions can target this physical fitness level.
http://ift.tt/2wPbKv7
Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development
Strong epidemiologic evidence documents the protective effect of physical activity on breast cancer risk, recurrence, and mortality, but the underlying mechanisms remain to be identified. Using human exercise–conditioned serum for breast cancer cell incubation studies and murine exercise interventions, we aimed to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer. Exercise-conditioned serum from both women with breast cancer (n = 20) and healthy women (n = 7) decreased MCF-7 (hormone-sensitive) and MDA-MB-231 (hormone-insensitive) breast cancer cell viability in vitro by 11% to 19% and reduced tumorigenesis by 50% when preincubated MCF-7 breast cancer cells were inoculated into NMRI-Foxn1nu mice. This exercise-mediated suppression of cell viability and tumor formation was completely blunted by blockade of β-adrenergic signaling in MCF-7 cells, indicating that catecholamines were the responsible exercise factors. Both epinephrine (EPI) and norepinephrine (NE) could directly inhibit breast cancer cell viability, as well as tumor growth in vivo. EPI and NE activate the tumor suppressor Hippo signaling pathway, and the suppressive effect of exercise-conditioned serum was found to be mediated through phosphorylation and cytoplasmic retention of YAP and reduced expression of downstream target genes, for example, ANKRD1 and CTGF. In parallel, tumor-bearing mice with access to running wheels showed reduced growth of MCF-7 (–36%, P < 0.05) and MDA-MB-231 (–66%, P < 0.01) tumors and, for the MCF-7 tumor, increased regulation of the Hippo signaling pathway. Taken together, our findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth. Cancer Res; 77(18); 1–11. ©2017 AACR.
http://ift.tt/2gRM2Cz
ATG5 mediates a positive feedback loop between Wnt signaling and autophagy in melanoma
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin. To define the physiological relevance of this loop, melanoma cells with different Wnt status were treated in vitro and in vivo with the potent lysosomotropic compound Lys05. Wnt5Ahigh cells were less sensitive to Lys05 and could be reverted by inducing β -catenin activity. Our results suggest the efficacy of autophagy inhibitors might be improved by taking the Wnt signature of melanoma cells into account.
http://ift.tt/2eTO7gB
Post-Traumatic Growth and Resilience in Adolescent and Young Adult Cancer Patients: An Overview
Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.
http://ift.tt/2gQr4E3
Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women
Abstract
Purpose
Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women.
Methods
Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features.
Results
Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women.
Conclusions
High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.
http://ift.tt/2wPjzBf
Theoretical method for evaluation of therapeutic effects and adverse effects of epidermal growth factor receptor tyrosine kinase inhibitors in clinical treatment
Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for non-small cell lung cancer patients with an EGFR gene mutation. However, skin disorders are known as adverse events. In the present study, we investigated whether EGFR-TK occupancy is useful as an index for assessing clinical efficacy and adverse events for the proper use and development of EGFR-TKIs. Average binding occupancies (Φ ss) of EGFR-TKIs, gefitinib and erlotinib, for the EGFR-TK of cancer or skin cells were calculated. The relationships of Φ ss with response rate (RR) or frequency of rash were analyzed using the ternary complex model. Then, the relationships between the dose of EGFR-TKIs and RR or frequency of rash were examined. Gefitinib showed a greater difference for Φ ss value for both wild-type and mutant EGFR as compared to erlotinib at usual dose. The RR increased in a nonlinear manner rapidly rising when Φ ss exceeded 95%. It was thought that a very high Φ ss value might be needed to obtain the therapeutic effect of EGFR-TKIs. Meanwhile, the frequency of rash increased in a linear manner along with elevation of Φ ss. It was shown that the K d ratio (K d for mutant/K d for wild type) was less than 0.001, when the high RR and low frequency of rash were obtained simultaneously. The results showed that the therapeutic effects and skin disorder can be assessed by using Φ ss. Furthermore, it is likely that a proper choice of drug and dose can be made by using Φ ss in EGFR-TKI therapy.
http://ift.tt/2xj5Ndf
Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors
Abstract
Background
Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70–80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair.
Methods
Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay. The 50% Inhibitory concentration (IC50) of PI3K and PARP inhibitors in these cells was assessed, and western blotting was performed to determine the expression of proteins involved in the PI3K/mTOR pathway. Moreover, we explored the interaction between RAD51 and PI3K/mTOR by immunofluorescence. Next, the combination effect of PI3K and PARP inhibitors on cell proliferation was evaluated by a clonogenic assay.
Results
Cells with mutated PTEN showed over-activation of the PI3K/mTOR pathway. These cells were more sensitive to PARP inhibition compared to PTEN wild-type cells. In addition, PI3K inhibitor treatment reduced RAD51 foci formation in PTEN mutated cells, and sensitized these cells to PARP inhibitor.
Conclusion
Targeting both PARP and PI3K might lead to improved personalized therapeutic approaches in endometrial cancer patients with PTEN mutations. Understanding the complex interaction of PTEN mutations with DNA repair in endometrial cancer will help to better select patients that are likely to respond to some of the new and costly targeted therapies.
http://ift.tt/2vKIDrM
Refining the predictors of outcome in patients with resectable esophageal cancer
Better integration of clinical features with molecular and genomic data may help to establish a more reliable regression grading system that could serve as a future predictor of outcomes for patients with resectable esophageal cancer. See also pages 000-000.
http://ift.tt/2webvrR
Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival—The University of Texas MD Anderson Cancer Center experience
BACKGROUND
Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution.
METHODS
The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS).
RESULTS
Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051).
CONCLUSIONS
In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2wNwYva
Survivorship care planning in skin cancer: An unbiased statistical approach to identifying patterns of care-plan use
BACKGROUND
Nearly 1 in 5 Americans will develop skin cancer, and as a result, survivors of skin cancer compose one of the largest groups of cancer survivors. Survivorship care plans (SCPs) are an important tool for improving patient outcomes and provide critical information to both survivors and health care professionals. Recent efforts have been made to expand SCP utilization; however, which patients currently receive SCPs is poorly understood.
METHODS
This study used 596 individuals with a diagnosis of melanoma (n = 391) or nonmelanoma skin cancer (n = 205) who had used an Internet-based SCP tool from May 2010 to December 2016 to model the patient and provider characteristics that determine SCP utilization.
RESULTS
Survivors were predominantly white (95.3%) and female (56.5%). Survivors who received a treatment summary were more likely to also receive an SCP. University and nonuniversity cancer centers used SCPs at a higher rate than other care settings. Survivors whose care was managed by a team rather than just an individual physician were also more likely to receive an SCP. Survivors older than 70 years at diagnosis were almost twice as likely to receive a plan as survivors who were diagnosed at a younger age.
CONCLUSIONS
With a convenience sample of skin cancer survivors, it is possible to model factors that predict the receipt of SCPs. Important variables include the diagnosis age, treatment setting, physician type, and treatment-summary utilization. A closer examination of these variables identified several disparities in care-plan use and, therefore, opportunities to improve the distribution of SCPs. Further validation in additional cohorts of survivors is necessary to confirm these conclusions. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2weNctJ
Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials
BACKGROUND
Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies.
METHODS
The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab.
RESULTS
From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial enrollment.
CONCLUSIONS
This recent COG cohort of patients with recurrent/refractory neuroblastoma is inclusive and representative. To the authors' knowledge, the current study is the first meta-analysis of PFS, TTP, and OS within the context of modern therapy. These results will inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2wO6SIF
Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT)
BACKGROUND
Measuring patient-reported outcomes (PROs) is becoming an integral component of quality improvement initiatives, clinical care, and research studies in cancer, including comparative effectiveness research. However, the number of PROs limits comparability across studies. Herein, the authors attempted to link the Functional Assessment of Cancer Therapy-General Physical Well-Being (FACT-G PWB) subscale with the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) calibrated item bank. The also sought to augment a subset of the conceptually most similar FACT-G PWB items with PROMIS PF items to improve the linking.
METHODS
Baseline data from 5506 participants in the Measuring Your Health (MY-Health) study were used to identify the optimal items for linking FACT-G PWB with PROMIS PF. A mixed methods approach identified the optimal items for creating the 5-item FACT/PROMIS-PF5 scale. Both the linked and augmented relationships were cross-validated using the follow-up MY-Health data.
RESULTS
A 5-item FACT-G PWB item subset was found to be optimal for linking with PROMIS PF. In addition, a 2-item subset, including only items that were conceptually very similar to the PROMIS item bank content, were augmented with 3 PROMIS PF items. This new FACT/PROMIS-PF5 provided superior score recovery.
CONCLUSIONS
The PROMIS PF metric allows for the evaluation of the extent to which similar questionnaires can be linked and therefore expressed on the same metric. These results allow for the aggregation of existing data and provide an optimal measure for future studies wishing to use the FACT yet also report on the PROMIS PF metric. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2xUojpr
Computer-assisted cytologic diagnosis in pancreatic FNA: An application of neural networks to image analysis
BACKGROUND
Fine-needle aspiration (FNA) biopsy is an accurate method for the diagnosis of solid pancreatic masses. However, a significant number of cases still pose a diagnostic challenge. The authors have attempted to design a computer model to aid in the diagnosis of these biopsies.
METHODS
Images were captured of cell clusters on ThinPrep slides from 75 pancreatic FNA cases (20 malignant, 24 benign, and 31 atypical). A K-means clustering algorithm was used to segment the cell clusters into separable regions of interest before extracting features similar to those used for cytomorphologic assessment. A multilayer perceptron neural network (MNN) was trained and then tested for its ability to distinguish benign from malignant cases.
RESULTS
A total of 277 images of cell clusters were obtained. K-means clustering identified 68,301 possible regions of interest overall. Features such as contour, perimeter, and area were found to be significantly different between malignant and benign images (P <.05). The MNN was 100% accurate for benign and malignant categories. The model's predictions from the atypical data set were 77% accurate.
CONCLUSIONS
The results of the current study demonstrate that computer models can be used successfully to distinguish benign from malignant pancreatic cytology. The fact that the model can categorize atypical cases into benign or malignant with 77% accuracy highlights the great potential of this technology. Although further study is warranted to validate its clinical applications in pancreatic and perhaps other areas of cytology as well, the potential for improved patient outcomes using MNN for image analysis in pathology is significant. Cancer Cytopathol 2017. © 2017 American Cancer Society.
http://ift.tt/2gQPi0Y
Histopathologic follow-up and HPV test results with HSIL Papanicolaou test results in China's largest academic women's hospital
BACKGROUND
Cervical cancer screening in China is largely limited to occasional opportunistic screening in urban centers. The current study reports histopathologic follow-up and human papillomavirus (HPV) results in women with high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) tests reported at the largest academic women's hospital in China and compares these findings with those of published Western studies among frequently screened women.
METHODS
A retrospective cohort study documented HSIL Pap tests, patient age, HPV results, and histopathologic follow-up from 2011 through 2015 in the Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai, China. Of 886,122 Pap test results, 4269 (0.48%) reported HSIL. Histopathologic follow-up was available for 2351 cases and HPV results were available for 2092 cases.
RESULTS
HSIL reporting rates increased with patient age from 0.16% at age <30 years to 0.58% at ages 30 to 49 years and 0.75% at age ≥50 years. HSIL rates were found to be significantly higher for women tested using liquid-based cytology (0.52%-0.55%) compared with conventional Pap tests (0.19%). Among 2351 cases with histopathologic follow-up, cervical intraepithelial neoplasia of type 2/3 was diagnosed in 74.1% of cases and squamous cell carcinoma in 14.2% of cases. Squamous cell carcinoma was diagnosed in 22.8% of patients aged ≥50 years who underwent biopsy. HPV-positive HSIL rates using 3 different HPV tests ranged from 88.1% to 93.9%.
CONCLUSIONS
At OGHFU, the finding of an increase in HSIL cytology rates with increasing patient age contrasted with a finding of decreasing HSIL rates with increasing age previously reported in regularly screened cotested patients in the United States. The increasing HSIL rates with older age and high rates of cervical cancer diagnoses noted at OGHFU appear to be best explained by the absence of consistent intraepithelial lesion ablation achievable with frequent screening and treatment. Cancer Cytopathol 2017. © 2017 American Cancer Society.
http://ift.tt/2eRXvS6
Cancer in First Nations people living in British Columbia, Canada: an analysis of incidence and survival from 1993 to 2010
Abstract
Background
For First Nations (FN) peoples living in British Columbia (BC), little is known regarding cancer in the population. The aim of this study was to explore cancer incidence and survival in the FN population of BC and compare it to the non-FN population.
Methods
All new cancers diagnosed from 1993 to 2010 were linked to the First Nations Client File (FNCF). Age-standardized incidence rates (ASIR) and rate ratios, and 1- and 5-year cause-specific survival estimates and hazard ratios were calculated. Follow-up end date for survival was December 31, 2011 and follow-up time was censored at a maximum of 15 years.
Results
ASIR of colorectal cancer (male SRR = 1.42, 95% CI 1.25–1.61; female SRR = 1.21, 95% CI 1.06–1.38) and cervical cancer (SRR = 1.84, 95% CI 1.45–2.33) were higher overall in FN residents in BC, compared to non-FN residents. Incidence rates of almost all other cancers were generally similar or lower in FN populations overall and by sex, age, and period categories, compared to non-FN residents. Trends in ASIR over time were similar except for lung (increasing for FN, decreasing for non-FN) and colorectal cancers (increasing for FN, decreasing for non-FN). Conversely, survival rates were generally lower for FN, with differences evident for some cancer sites at 1 year following diagnosis.
Conclusion
FN people living in BC face unique cancer issues compared to non-FN people. Higher incidence and lower survival associated with certain cancer types require further research to look into the likely multifaceted basis for these findings.
http://ift.tt/2wOFF6W
Protective effects of carbenoxolone, an 11β-HSD1 inhibitor, against chemical induced dry eye syndrome
Abstract
Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11β-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11β-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11β-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11β-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11β-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11β-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.
Graphical Abstract
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Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor
Abstract
Background
Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in β-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014.
Methods
PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. After cycle 9, patients were evaluated as clinically indicated.
Results
Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0–96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5–21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily.
Conclusions
PF-03084014 was effective in treating desmoid tumors, with an objective response rate of 71.4% (95% CI 29.0–96.3%) in this small cohort of patients. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation.
http://ift.tt/2vKz6Rn
The association between dietary protein intake and colorectal cancer risk: a meta-analysis
Abstract
Background
Association between dietary protein intake and colorectal cancer risk has not been fully quantified, while the results were controversial. This study aimed to evaluate the role of protein intake in the development of colorectal cancer.
Methods
PUBMED and EMBASE were searched up to December 2016. Two independent reviewers independently extracted data from eligible studies. Relative risk (RR) with 95% confidence intervals (CI) was pooled using random-effects model to estimate the result. Besides, publication bias and sensitivity analysis were conducted.
Results
Thirteen articles involving 21 studies comprising 8187 cases were included in this report. The pooled RR of colorectal cancer was 1.006 (95% CI = 0.857–1.179) indicating that there is no significant association between dietary protein intake and colorectal cancer risk. Furthermore, the pooled RRs for colon cancer and rectum cancer were 1.135(95% CI = 0.871–1.480) and 0.773(95% CI = 0.538–1.111), respectively, with the highest category of dietary protein intake. The association was not significant either in subgroup analysis of study design, protein type (animal protein or vegetable protein), sex, and or geographic locations.
Conclusions
The present study indicated that the highest category compared to the lowest category of protein intake had no significant association on colorectal cancer risk. Dose-response analysis was not conducted due to limited information provided. Therefore, more studies with large cases and participants as well as detailed amounts of dietary protein intake are wanted to confirm this result.
http://ift.tt/2xiM3WU
Annexin A2 contributes to cisplatin resistance by activation of JNK-p53 pathway in non-small cell lung cancer cells
Abstract
Background
Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. We previously identified that Annexin A2 is significantly up-regulated in cisplatin-resistant non-small cell lung cancer (NSCLC) A549/DDP cells. However, the exact function and molecular mechanism of Annexin A2 in cisplatin resistance of NSCLCs has not been determined.
Methods
Western blot and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively. Immunohistochemistry was performed to analyze the expression of Annexin A2 in NSCLC tissue samples. MTS assay, Colony formation assays, AnnexinV/PI apoptosis assay, Luciferase Reporter Assay, Chromatin-immunoprecipitation, and nude mice xenograft assay were used to visualize the function of Annexin A2 on cisplatin resistance.
Results
Our results demonstrated that knockdown of Annexin A2 increased cisplatin sensitivity of cisplatin-resistant A549/DDP cells both in vitro and in vivo, whereas overexpression of Annexin A2 increased cisplatin resistance of A549, H460 and H1650 cells. Moreover, we found that Annexin A2 enhanced cisplatin resistance via inhibition of cisplatin-induced cell apoptosis. Our studies showed that Annexin A2 suppressed the expression of p53 through activation of JNK/c-Jun signaling, which in turn resulted in a decrease in the expression of p53-regulated apoptotic genes p21, GADD45 and BAX, as well as p53-dependent cell apoptosis. Furthermore, we found that in NSCLC cases that Annexin A2 is highly expressed; it is positively correlated with a poor prognosis, as well as correlated with short disease-free survival for patients who received chemotherapy after surgery.
Conclusions
These data suggested that Annexin A2 induces cisplatin resistance of NSCLCs via regulation of JNK/c-Jun/p53 signaling, and provided an evidence that blockade of Annexin A2 could serve as a novel therapeutic approach for overcoming drug resistance in NSCLCs.
http://ift.tt/2jai25q
Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing
Abstract
Purpose
To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (Dmean), and total cisplatin dose.
Material and methods
In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared.
Results
Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though Dmean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m2, with the highest abnormal level found 8–12 months after RT regardless of radiation technique or fraction dose.
Conclusion
The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when Dmean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies.
http://ift.tt/2wNMqHK
Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing
Abstract
Purpose
To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (Dmean), and total cisplatin dose.
Material and methods
In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared.
Results
Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though Dmean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m2, with the highest abnormal level found 8–12 months after RT regardless of radiation technique or fraction dose.
Conclusion
The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when Dmean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies.
http://ift.tt/2wNMqHK
Internet-based computer technology on radiotherapy
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): James C.L. Chow
Recent rapid development of Internet-based computer technologies has made possible many novel applications in radiation dose delivery. However, translational speed of applying these new technologies in radiotherapy could hardly catch up due to the complex commissioning process and quality assurance protocol. Implementing novel Internet-based technology in radiotherapy requires corresponding design of algorithm and infrastructure of the application, set up of related clinical policies, purchase and development of software and hardware, computer programming and debugging, and national to international collaboration. Although such implementation processes are time consuming, some recent computer advancements in the radiation dose delivery are still noticeable. In this review, we will present the background and concept of some recent Internet-based computer technologies such as cloud computing, big data processing and machine learning, followed by their potential applications in radiotherapy, such as treatment planning and dose delivery. We will also discuss the current progress of these applications and their impacts on radiotherapy. We will explore and evaluate the expected benefits and challenges in implementation as well.
http://ift.tt/2eLL2vo
Radiotherapy for a breast cancer patient with Schnitzler syndrome: Report of acute toxicity and early follow-up
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): Samir Abdallah Hanna, Ana Luisa Garcia Calich, Artur Katz, Isidio Calich, Gustavo Gibin Duarte, José Luiz Barbosa Bevilacqua
This article provides description about acute toxicity and early follow-up of one patient treated for breast cancer and Schnitzler syndrome. There are no previously reported cases exploring this interaction on medical literature.The expected radiodermitis to occur in the region treated with radiotherapy along with urticarial-like lesions might be challenging in view of the interaction between symptoms and therapeutic measures.
http://ift.tt/2xaUWRB
Pancreatic neuroendocrine tumor in a patient with a TSC1 variant: case report and review of the literature
Abstract
The majority of pancreatic neuroendocrine tumors (PNETs) are sporadic while 10–15% are attributable to one of several familial cancer syndromes. Hereditary forms are more commonly associated with Multiple Endocrine Neoplasia Type I and von Hippel Lindau Syndrome. However, patients with Tuberous sclerosis complex also have an increased incidence of PNETs. More often this has been reported in patients with TSC2 variants. In this case report, we summarize the literature regarding PNETs associated with Tuberous sclerosis complex, as well as present a case of a patient with a TSC1 variant and a PNET. This case highlights the association of TSC1 gene variants with these tumors and emphasizes the importance of considering such diagnoses in this patient population.
http://ift.tt/2gNYbVl
Dental anomalies in pediatric patients with familial adenomatous polyposis
Abstract
Familial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anomalies in these patients. Twenty-two pediatric familial adenomatous polyposis patients and 46 controls, who were age and gender matched participated. Familial adenomatous polyposis patient's had a dental examination with panoramic radiograph and medical record review for age at diagnosis, the presence of the adenomatous polyposis coli gene mutation, and determination of other extra-intestinal manifestations on the body. The control group was identified from a retrospective chart review and selected if there was a current panoramic radiograph. The only significant difference between familial adenomatous polyposis patients and controls were the presence of jaw osteomas and sclerosis (p = .0001). Patients with a mutation in, or upstream of codon 1309 had a higher frequency of osteomas (77.8%) and jaw-bone sclerosis (44.4%), and 77% of these had at least one dental anomaly. This preliminary study showed an association between a genetic variant at, or upstream of codon 1309, and radiographic dental anomalies.
http://ift.tt/2xhItfJ
Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity
Abstract
Background
In general, late side effects after salvage radiotherapy (RT) for prostate cancer are below 10%. Patients with impaired DNA repair ability and genetic instability can have significantly increased reactions after RT.
Case, clinical follow-up, and examination
We present a patient who experienced severe side effects after additive RT for prostate cancer and died from the complications 25 months after RT. Imaging (MR) is shown as well as three-color fluorescence in situ hybridization. The blood sample testing revealed that radiosensitivity was increased by 35–55%. We undertook a review of the literature to give an overview over the tests established that are currently considered useful.
Conclusion
This case highlights that the identification of patients with increased radiosensitivity is an important task in radiation protection. Groups of patients who should be screened have to be found and corresponding research facilities have to be set up.
http://ift.tt/2xicoV4
Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity
Abstract
Background
In general, late side effects after salvage radiotherapy (RT) for prostate cancer are below 10%. Patients with impaired DNA repair ability and genetic instability can have significantly increased reactions after RT.
Case, clinical follow-up, and examination
We present a patient who experienced severe side effects after additive RT for prostate cancer and died from the complications 25 months after RT. Imaging (MR) is shown as well as three-color fluorescence in situ hybridization. The blood sample testing revealed that radiosensitivity was increased by 35–55%. We undertook a review of the literature to give an overview over the tests established that are currently considered useful.
Conclusion
This case highlights that the identification of patients with increased radiosensitivity is an important task in radiation protection. Groups of patients who should be screened have to be found and corresponding research facilities have to be set up.
http://ift.tt/2xicoV4
Development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI)
Abstract
Measures of treatment intensity for childhood cancer are needed in research in order to control for variability in treatments. Existing measures of treatment intensity for childhood cancers do not reflect the complexities of treatment protocols for central nervous system (CNS) tumors. This paper describes the development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI). PNORTI development occurred in three phases. Phase 1: five experts in pediatric neuro-oncology created a 5-point scale of treatment intensity and 42 pediatric neuro-oncology providers completed a three-part online questionnaire to evaluate the classification system and apply the rating system to 16 sample patients. Validity was determined by respondents classifying therapy modalities into intensity levels. Inter-rater reliability was calculated from ratings of the 16 sample patients. Phase 2: three experts revised the PNORTI based on survey results and 18 pediatric neuro-oncology providers evaluated the classification system. Phase 3: ten experts in pediatric neuro-oncology refined and finalized the PNORTI and rated 10 sample patients using the PNORTI. Agreement between median ratings of the survey respondents and criterion raters for chemotherapy intensity (r's = .82 and 1.0) and overall treatment intensity level (r's = .91 and .94) were high in Phases 1 and 2. Inter-rater reliability also was very high when using the PNORTI to classify the 16 sample patients in Phase 1 (median agreement of r = .93 and rICC = .99) and the 10 sample patients in Phase 3 (median agreement of r = .92 and rICC = .98). The PNORTI is a valid and reliable method for classifying the intensity of different treatment modalities used in pediatric neuro-oncology.
http://ift.tt/2wNerz7
SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway
Abstract
Spalt-like transcription factor 4 (SALL4), a oncogene, is known to participate in multiple carcinomas, and is up-regulated in glioma. However, its actual role and underlying mechanisms in the development of glioma remain unclear. The present study explored the molecular functions of SALL4 in promoting cell proliferation in glioma. The expression level of SALL4 in 69 human glioma samples and six non-tumor brain tissues was determined using real-time polymerase chain reaction (PCR). Then, we transfected U87 and U251 cell lines with siRNA, and assessed cellular proliferation and cell cycle to understand the function of SALL4, and the relationship between SALL4, PTEN and PI3K/AKT pathway. PCR confirmed that the expression of SALL4 was higher in the glioma samples than non-tumor brain tissues. Cellular growth and proliferation were dramatically reduced following inhibition of SALL4 expression. Western blot showed increase in PTEN expression when SALL4 was silenced, which in turn depressed the activation of PI3K/AKT pathway, suggesting that PTEN was a downstream target of SALL4 in glioma development. Therefore, SALL4 could act as a proto-oncogene by regulating the PTEN/PI3K/AKT signaling pathway, thereby facilitating proliferation of glioma cells.
http://ift.tt/2vSshl2
Pediatric spine imaging post scoliosis surgery
Abstract
Many orthopedic articles describe advances in surgical techniques and implants used in pediatric scoliosis surgery. However, even though postoperative spine imaging constitutes a large portion of outpatient musculoskeletal pediatric radiology, few, if any, radiology articles discuss this topic. There has been interval advancement over the last decades of the orthopedic procedures used in the treatment of spinal scoliosis in adolescents with idiopathic scoliosis. The goal of treatment in these patients is to stop the progression of the curve by blocking the spinal growth and correcting the deformity as much as possible. To that end, the authors in this paper discuss postoperative imaging findings of Harrington rods, Luque rods, Luque–Galveston implants and segmental spinal fusion systems. Regarding early onset scoliosis, the guiding principles used for adolescent idiopathic scoliosis do not apply to a growing spine because they would impede lung development. As a result, other devices have been developed to correct the curve and to allow spinal growth. These include spine-based growing rods, vertically expandable prosthetic titanium rods (requiring repetitive surgeries) and magnetically controlled growing rods (with a magnetic locking/unlocking system). Other more recent systems are Shilla and thoracoscopic anterior vertebral body tethering, which allow guided growth of the spine without repetitive interventions. In this paper, we review the radiologic appearances of different orthopedic implants and techniques used to treat adolescent idiopathic scoliosis and early onset scoliosis. Moreover, we present the imaging findings of the most frequent postoperative complications.
http://ift.tt/2vKCoUF
Unusual case of splenic sarcoidosis without morphological lesions detected by PET-CT in a patient with breast cancer: functional imaging between pitfalls and therapeutic guide
http://ift.tt/2xhZN4c
The potential of multi-compound nanoparticles to bypass drug resistance in cancer
Abstract
Purpose
The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer.
Methods
The PubMed literature was consulted and reviewed.
Results
Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.
http://ift.tt/2xRnSLs
Treatment withdrawal and end-of-life care in the intensive care unit
1F052C063A07
http://ift.tt/2wNkEec
http://ift.tt/2wNkEec
De la démarche qualité vers la gestion dynamique par la qualité : déploiement au sein d’un groupe de radiothérapie
Source:Cancer/Radiothérapie
Author(s): B. Guerrier, É. Halm, M. Craman, J.-P. Dujols, J.-L. Norkowski, K. Meynard
Dans l'optique d'une optimisation continue, la cellule qualité du Groupement de radiothérapie et d'oncologie des Pyrénées (GROP) a décidé en 2015, de faire évoluer le déploiement de sa démarche qualité. Pour ce faire, deux axes d'amélioration ont été proposés : l'implication de pilotes de processus et l'investissement matériel et financier dans un logiciel de gestion documentaire. La mise en place de ces dispositions organisationnelle et managériale a permis de mieux satisfaire aux exigences de la norme International Organization for Standardization (ISO) 9001, référence internationale en management de la qualité.In 2015, the quality group of the radiotherapy clinic Groupement de Radiothérapie et d'Oncologie des Pyrénées (GROP, Pau, France) decided to review the deployment of its quality approach in order to optimize it continuously. For this, two improvements were proposed: an involvement of process drivers and a material and financial investment in document management software. The implementation of these organizational and managerial provisions enabled us to better cover the requirements of the ISO 9001 standard, the international reference in quality management.
http://ift.tt/2xTjMn3
Innovations thérapeutiques en radiothérapie du cancer de la prostate localisé
Source:Cancer/Radiothérapie
Author(s): G. Créhange, L. Cormier
La radiothérapie avec modulation d'intensité, puis le guidage par l'image avec marqueurs fiduciels intraprostatiques et la curiethérapie prostatique en monothérapie sont des traitements qui permettent de délivrer une escalade de dose pour des cancers de prostate localisés avec des taux faibles de toxicité aiguë et encore plus faibles de séquelles à long terme. Cette diminution de l'irradiation des tissus sains ainsi que les évolutions technologiques permettent aujourd'hui de proposer des traitements plus courts avec des doses par fraction élevées, de mieux préserver le rectum, d'escalader la dose sur prostate par curiethérapie ou focalement par radiothérapie externe, de mieux cibler les aires ganglionnaires à risque d'être envahies pour des cancers à plus haut risque, de délivrer des irradiations focalisées partielles ou combinées grâce à l'IRM fonctionnelle et la tomographie par émission de positons (TEP) – scanographie. L'innovation en radiothérapie reste étroitement liée à l'innovation imagerie grâce à l'IRM et la TEP-scanographie.Intensity-modulated radiation therapy, image-guided radiation therapy with fiducial markers and prostate brachytherapy allow the delivery of dose escalation for localized prostate cancer with very low rates of long-term toxicity and sequelae. Nowadays, modern radiotherapy techniques make it possible to shorten treatment time with hypofractionation, to better protect surrounding healthy tissues and to escalate the dose even further. Advances in radiotherapy are closely linked to advances in magnetic resonance imaging (MRI) and/or PET imaging. Functional imaging makes it possible to deliver personalised pelvic nodal radiotherapy, targeting the nodal areas at higher risk of microscopic involvement. In patients with an index lesion at baseline or at failure, MR-based focal therapy or focal dose escalation with brachytherapy or stereotactic body radiation therapy is also currently investigated. MR-based adaptive radiotherapy, which makes it possible to track prostate shifts during radiation delivery, is another step forward in the integration of MR imaging in radiation delivery.
http://ift.tt/2xTjqwJ
Management of local relapse after prostate cancer radiotherapy: Surgery or radiotherapy?
Source:Cancer/Radiothérapie
Author(s): C. Hennequin, J.-M. Hannoun-Lévi, F. Rozet
Isolated local relapse after prostate cancer radiotherapy corresponds to 40% of biochemical failure. The management of these relapses is not well defined. Several strategies are available including surgery, high-intensity focused ultrasounds (HIFU), cryotherapy and reirradiation. Radical prostatectomy is the historical approach; biochemical control is obtained in 50 to 80% at 5 year. However, morbidity is higher after irradiation than as a first line treatment. Some limited series of HIFU and cryotherapy have been published with interesting results, but again the risk of urinary and rectal toxicity is high. However, new generation technologies could decrease the complication rate. Reirradiation could be performed with brachytherapy and more recently with stereotactic radiation therapy. The results of salvage low-dose-rate brachytherapy have been reported in some series with a 5-year biochemical control rate of 34 to 88%. High-dose rate brachytherapy seems to be better tolerated, but the number of patients treated and reported is too low to draw firm conclusions. This is the same for stereotactic radiation therapy salvage treatment. A prospective trial of salvage brachytherapy (CAPRICUR) is now open in France and inclusion in this trial is recommended.
http://ift.tt/2xhEOyK
Séquençage des tumeurs : évolutions et révolutions
Source:Cancer/Radiothérapie
Author(s): N. Piton, A. Lamy, J.-C. Sabourin
Nous sommes depuis quelques années entrés pleinement dans l'ère génomique de l'analyse génétique des cancers à visée médicale. Les bouleversements technologiques en biologie associés à ceux des sciences de l'information permettent maintenant une analyse du génome des cancers en pratique courante, avec dans certains cas un impact majeur sur la prise en charge des patients, sur le plan thérapeutique bien sûr (exemple des mutations du gène EGFR, codant pour l'epidermal growth factor receptor, dans l'adénocarcinome pulmonaire), mais aussi dans le diagnostic et le suivi de la maladie. Le génotypage des tumeurs s'effectue le plus souvent à partir du tissu fixé au formol et inclus en paraffine à partir duquel un diagnostic de malignité a été posé. Cependant, de nouvelles approches voient le jour, comme la pratique maintenant de plus en plus répandue des « biopsies liquides ». La diffusion sur tout le territoire français de séquenceurs « à haut débit » rend possible en routine l'analyse de plusieurs dizaines de gènes d'intérêt dans la prise en charge de certains types de cancer, et il est à parier que le perfectionnement de ces automates rendra encore plus facile et accessible le génotypage des tumeurs dans un avenir proche. Le défi actuel n'est cependant principalement plus la détection des anomalies moléculaires, mais leur traitement, leur analyse et leur interprétation pertinente, de manière à être le plus utile possible au patient dans le traitement de sa maladie.For some years now, we have entered the genomic age of tumour genotyping from a medical point of view. Technological breakthroughs in both biology and information science now allow a genomic analysis of cancers in everyday medical practice with, in some case, a major impact on patient care not only for the choice of therapy (i.e. EGFR mutations in lung adenocarcinoma), but also for diagnosis and monitoring of the disease. Tumour genotyping is performed from formalin-fixed paraffin-embedded tissues used for diagnosis of cancer. However, new approaches have emerged, with for example the more and more spread use of "liquid biopsies". Genotyping of a gene panel implicated in carcinogenesis is now routinely performed in some cancer types, with the help of high-throughput sequencers, and it is likely that improvement of these machines will make tumour genotyping easier and more accessible in the near future. Nevertheless, the current challenge is not anymore detection of molecular alterations, but their relevant interpretation, so as to be the most useful in patient care.
http://ift.tt/2xUCta6
Acquis et objectifs de la recherche clinique sur le cancer du rectum
Source:Cancer/Radiothérapie
Author(s): P. Maingon, J.-M. Simon, C.-H. Canova, I. Troussier, N. Besson, É. Caillot, F. Huguet
Le traitement des cancers du rectum repose sur une prise en charge pluridisciplinaire et le plus souvent sur une approche multimodale comprenant la gastro-entérologie, l'oncologie médicale, l'oncologie–radiothérapie et la chirurgie. Les différents objectifs qui doivent être discriminés dépendent des caractéristiques de la tumeur. Le défi de la prise en charge des petites tumeurs repose sur la conservation d'un sphincter fonctionnel sans risque de récidive locale. Le traitement standard des maladies localement évoluées vise, par ordre de priorité, à guérir le malade en minimisant les séquelles tardives de la prise en charge. Chacune de ces situations cliniques se trouve désormais démembrée grâce aux progrès de la chirurgie et d'une approche personnalisée au patient à la caractéristique clinique de la maladie. Elles sont désormais l'objet d'études thérapeutiques spécifiques.The treatment of rectal carcinoma is based on multidisciplinary strategy and multimodal approaches including gastrointestinal tract specialists, medical oncologists, radiation oncologists and surgery. The different objectives should be declined according to the characteristics of the tumours. The aim of the therapist would be to select the best strategy offering to the patient to be cured with as less as possible late adverse toxicity. The challenge of the treatment of small tumours is to maintain a functional anal sphincter while minimizing the risk of local recurrence. The standard treatment of locally advanced disease is aiming firstly to cure the patient and secondly to prevent late complications. Each of these clinical presentations of the disease has to be considered as a whole taking into account the new surgical techniques and a personalized approach adapted to the tumour. Nowadays they should be studied with dedicated clinical trials.
http://ift.tt/2xhEFLI
Renaud Mazeron (1977–2016)
Source:Cancer/Radiothérapie
Author(s): Olivier Pradier
http://ift.tt/2xU1EcE
Qu’attend le physicien médical de l’oncologue radiothérapeute et inversement ?
Source:Cancer/Radiothérapie
Author(s): A. Lisbona
La coopération entre oncologue radiothérapeute et physicien médical est indispensable pour garantir la qualité et la sécurité des irradiations de nos patients. On aurait tort de considérer que l'intervention des physiciens médicaux dans le processus de prise en charge des patients se borne à la mise à disposition d'équipements étalonnés, réglés et contrôlés et à garantir la validité de la distribution de dose et du temps de traitement, alors que l'oncologue radiothérapeute a la maîtrise complète de toutes les activités cliniques liées à l'irradiation. L'intervention des physiciens médicaux à l'étape d'acquisition des données anatomiques et dans toute la phase d'optimisation du traitement est une réalité. La reconnaissance de la profession de physicien médical comme une profession de santé vient légitimer cette intervention. Faut-il limiter la coopération médecin–physicien à ces tâches communes et à la participation à la permanence des soins ? Peut-on envisager une véritable synergie d'action qui dépasse le domaine du soin ? La réponse à la question : « qu'attend le physicien de l'oncologue radiothérapeute et inversement ? » peut apporter des éléments pour renforcer la coopération de demain. Cet article est la deuxième partie de la question.The cooperation between radiation oncologist and medical physicist is essential to guarantee the quality and safety of the irradiation of our patients. It would be wrong to consider that the intervention of medical physicists in the patient management process is limited to the provision of calibrated and controlled equipment and to guarantee the validity of the dose distribution and the treatment time, while the radiation oncologist has the complete control of all clinical activities related to irradiation. The intervention of physicists at the stage of acquisition of anatomical data and throughout the phase of optimization of the treatment is already a reality. The recognition of the profession of medical physicist as a health profession comes to legitimize this intervention. Should physician–physicist cooperation be limited to these common tasks and participation in continuing care? Can we envisage a true synergy of action that goes beyond the field of care? The answer to the question: what does the physicist expect from the radiation oncologist and vice versa may bring elements to reinforce tomorrow's cooperation. This article is the second part of the question.
http://ift.tt/2xh8Tyt
Exploiting poly(I:C) to induce cancer cell apoptosis.
Exploiting poly(I:C) to induce cancer cell apoptosis.
Cancer Biol Ther. 2017 Sep 07;:0
Authors: Bianchi F, Pretto S, Tagliabue E, Balsari A, Sfondrini L
Abstract
TLR3 belong to the Toll-like receptors family, it is mainly expressed on immune cells where it senses pathogen-associated molecular patterns and initiates innate immune response. TLR3 agonist poly(I:C) was developed to mimic pathogens infection and boost immune system activation to promote anti-cancer therapy. Accordingly, TLR agonists were included in the National Cancer Institute list of immunotherapeutic agents with the highest potential to cure cancer. Besides well known effects on immune cells, poly(I:C) was also shown, in experimental models, to directly induce apoptosis in cancer cells expressing TLR3. This review presents the current knowledge on the mechanism of poly(I:C)-induced apoptosis in cancer cells. Experimental evidences on positive or negative regulators of TLR3-mediated apoptosis induced by poly(I:C) are reported and strategies are proposed to successfully promote this event in cancer cells. Cancer cells apoptosis is an additional arm offered by poly(I:C), besides activation of immune system, for the treatment of various type of cancer. A further dissection of TLR3 signaling would contribute to greater resolution of the critical steps that impede full exploitation of the poly(I:C)-induced apoptosis. Experimental evidences about negative regulator of poly(I:C)-induced apoptotic program should be considered in combinations with TLR3 agonists in clinical trials.
PMID: 28881163 [PubMed - as supplied by publisher]
http://ift.tt/2xhtQcn
Leptomeningeal Carcinomatosis from Gastric Cancer Successfully Treated by the Intrathecal Methotrexate plus Temozolomide and Simultaneous Radiotherapy: Case Report and Literatures Review.
Leptomeningeal Carcinomatosis from Gastric Cancer Successfully Treated by the Intrathecal Methotrexate plus Temozolomide and Simultaneous Radiotherapy: Case Report and Literatures Review.
Cancer Biol Ther. 2017 Sep 07;:0
Authors: Liu Y
Abstract
Leptomeningeal carcinomatosis (LMC) from gastrointestinal cancer is rare. A 56-year-old man with complaint of upper abdominal pain exhibited adenocarcinoma upon histopathologic examination of biopsy specimens. At the end of adjuvant chemotherapy, the patient was affected by hearing loss. Malignant cells were observed by cerebrospinal fluid (CSF) cytology. Therefore, the patient received intrathecal methotrexate and oral temozolomide chemotherapy and radiotherapy. The progress-free survival was approximately 11 months. To our knowledge, such cases of LMC from gastric cancer are very rare. Here, we describe the case of a patient with LMC from gastric cancer and review the literature associated with treatment. We hope that the present report may be helpful when considering how to improve treatment of LMC in gastric cancer patients and offer some tips for the adjuvant treatment modality.
PMID: 28881161 [PubMed - as supplied by publisher]
http://ift.tt/2gOl9Mc
Effective Treatment of Aggressive Fibromatosis with Celecoxib Guided by Genetic testing.
Effective Treatment of Aggressive Fibromatosis with Celecoxib Guided by Genetic testing.
Cancer Biol Ther. 2017 Sep 07;:0
Authors: Yang S, Wang X, Jiang H, Wang Y, Li Z, Lu H
Abstract
Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see policy. The use of non-steroidal anti-inflammatory drugs (NSAIDs) and targeted therapies has demonstrated good results. In the case report, a 39-year-old man presented with progressive chest wall pain. Computed tomography (CT) showed an approximately 46 × 13mm soft-tissue mass between the inside of the fifth and sixth rib on the right side. The entire mass was excised and an AF was confirmed based on histopathology. Four months after surgery, magnetic resonance imaging (MRI) showed a soft-tissue mass in surgical areas and biopsy confirmed local recurrence. Therefore, Tomotherapy was administered. However, two months later, an (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography combined with CT (PET-CT) revealed the presence of an FDG-avid mass in the area of local recurrence. Genetic testing reported the presence of a p.T41A mutations on the CTNNB1 gene, which predicted that he is sensitive to the COX-2 inhibitor celecoxib. The tumor regressed rapidly after the application of celecoxib. Within the 20-month follow-up period, the patient showed remarkable regression without any signs and symptoms. Our case report provides further evidence for the efficacy of celecoxib in AF with CTNNB1 gene mutations. To our knowledge, this is the first report of AF treated with celecoxib under the guidance of the genetic testing. However, further studies are required.
PMID: 28881160 [PubMed - as supplied by publisher]
http://ift.tt/2xhPCg0
Respiratory distress syndrome in preterm infants and risk of epilepsy in a Danish cohort
Abstract
Infant respiratory distress syndrome (IRDS) may be complicated by intracerebral hemorrhage, a known trigger of epilepsy. However, few data exist on long term epilepsy risk following IRDS. We therefore examined the association between IRDS in preterm infants and childhood epilepsy. We conducted a population-based cohort study using individual-level data linkage among nationwide registries. All infants born at 32–36 weeks of gestation in 1978–2009 were identified in the Medical Birth Registry. We identified children with IRDS and those with epilepsy using the Danish National Patient Registry. We computed the cumulative incidence of epilepsy with follow-up from birth until epilepsy, emigration, death, age 15, or December 31, 2014. We used Cox's regression analysis to compute hazard ratios comparing children with and without IRDS, adjusting for sex, birth year, gestational age, multiplicity, major malformations, and maternal age. We identified 95,026 infants, of whom 6426 (6.8%) had IRDS. The cumulative incidence of epilepsy was 3.4% by age 15 in children with IRDS and 2.1% in children without IRDS. The adjusted hazard ratio of epilepsy among children with IRDS compared to those without was 1.4 (95% CI 1.2–1.6). When we restricted the IRDS cohort to children with no simultaneous morbidities that had clinical symptoms overlapping with IRDS, the overall adjusted HR was 1.1 (95% CI 0.9–1.4). In children born preterm at 32–36 weeks' gestation, IRDS was associated with increased risk of childhood epilepsy.
http://ift.tt/2weh6yi
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