Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Hexokinase 2 is a determinant of neuroblastoma metastasis
British Journal of Cancer 114, 759 (29 March 2016). doi:10.1038/bjc.2016.26
Authors: Liat Edry Botzer, Shelly Maman, Orit Sagi-Assif, Tsipi Meshel, Ido Nevo, Ilana Yron & Isaac P Witz
Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer
British Journal of Cancer 114, 809 (29 March 2016). doi:10.1038/bjc.2016.45
Authors: Stacey M Stein, Edward S James, Yanhong Deng, Xiangyu Cong, Jeremy S Kortmansky, Jia Li, Carol Staugaard, Doddamane Indukala, Ann Marie Boustani, Vatsal Patel, Charles H Cha, Ronald R Salem, Bryan Chang, Howard S Hochster & Jill Lacy
Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection
British Journal of Cancer 114, 767 (29 March 2016). doi:10.1038/bjc.2016.47
Authors: Yi-Peng Fu, Yong Yi, Xiao-Yan Cai, Jian Sun, Xiao-Chun Ni, Hong-Wei He, Jia-Xing Wang, Zhu-Feng Lu, Jin-Long Huang, Ya Cao, Jian Zhou, Jia Fan & Shuang-Jian Qiu
Long working hours and cancer risk: a multi-cohort study
British Journal of Cancer 114, 813 (29 March 2016). doi:10.1038/bjc.2016.9
Authors: Katriina Heikkila, Solja T Nyberg, Ida E H Madsen, Ernest de Vroome, Lars Alfredsson, Jacob J Bjorner, Marianne Borritz, Hermann Burr, Raimund Erbel, Jane E Ferrie, Eleonor I Fransson, Goedele A Geuskens, Wendela E Hooftman, Irene L Houtman, Karl-Heinz Jöckel, Anders Knutsson, Markku Koskenvuo, Thorsten Lunau, Martin L Nielsen, Maria Nordin, Tuula Oksanen, Jan H Pejtersen, Jaana Pentti, Martin J Shipley, Andrew Steptoe, Sakari B Suominen, Töres Theorell, Jussi Vahtera, Peter J M Westerholm, Hugo Westerlund, Nico Dragano, Reiner Rugulies, Ichiro Kawachi, G David Batty, Archana Singh-Manoux, Marianna Virtanen & Mika Kivimäki
Triapine potentiates platinum-based combination therapy by disruption of homologous recombination repair
British Journal of Cancer 114, 777 (29 March 2016). doi:10.1038/bjc.2016.54
Authors: Elena S Ratner, Yong-Lian Zhu, Philip G Penketh, Julie Berenblum, Margaret E Whicker, Pamela H Huang, Yashang Lee, Kimiko Ishiguro, Rui Zhu, Alan C Sartorelli & Z Ping Lin
Relationship between ambient ultraviolet radiation and Hodgkin lymphoma subtypes in the United States
British Journal of Cancer 114, 826 (29 March 2016). doi:10.1038/bjc.2015.383
Authors: Emily M Bowen, Ruth M Pfeiffer, Martha S Linet, Wayne T Liu, Dennis D Weisenburger, D Michal Freedman & Elizabeth K Cahoon
A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer
British Journal of Cancer 114, 787 (29 March 2016). doi:10.1038/bjc.2016.31
Authors: Anita Annaházi, Szabolcs Ábrahám, Klaudia Farkas, András Rosztóczy, Orsolya Inczefi, Imre Földesi, Mónika Szűcs, Mariann Rutka, Vassilia Theodorou, Helene Eutamene, Lionel Bueno, György Lázár, Tibor Wittmann, Tamás Molnár & Richárd Róka
Is birthweight associated with total and aggressive/lethal prostate cancer risks? A systematic review and meta-analysis
British Journal of Cancer 114, 839 (29 March 2016). doi:10.1038/bjc.2016.38
Authors: Cindy Ke Zhou, Siobhan Sutcliffe, Judith Welsh, Karen Mackinnon, Diana Kuh, Rebecca Hardy & Michael B Cook
In ovarian cancer patients and mouse models, psychosocial stress is associated with higher circulating markers of angiogenesis and cell migration, impaired immune response, and increasing tumor burden and aggressiveness. In the Nurses' Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker of chronic distress, was associated with risk of incident ovarian cancer as well as survival among ovarian cancer patients.
We used Cox proportional hazards regression to model the relative risks (RRs) and 95 % confidence intervals (CI) of ovarian cancer incidence and survival by categories of the Crown–Crisp phobic anxiety index (CCI).
We identified 779 cases of ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS: 1988; NHSII: 1993), we observed a statistically nonsignificant increased risk of epithelial ovarian cancer (RR for CCI ≥ 4 vs. 0 or 1: 1.14; 95 % CI 0.96–1.36). However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR for ≥4 vs. 0 or 1: 1.00; 95 % CI 0.77–1.31); results were similar for post-diagnosis CCI.
Distress, as measured by phobic anxiety symptoms, was not associated with ovarian cancer risk, although we cannot rule out a modest association. Future research should explore the role of phobic anxiety and other forms of psychological distress and ovarian cancer risk and survival.
Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer.
We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score).
We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85–102 nmol/L) compared to the first (<68 nmol/L), HR 0.54 (0.34–0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22–0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35–2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32–0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer mortality.
This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may improve survival in men with prostate cancer.
A new generation of prostate cancer (PCa) biomarkers has emerged, including diagnostic serum and urine markers aimed at refining the identification high-grade tumors and tissue-based gene expression assays offering prognostic and predictive clinical information. Such tests seek to improve treatment-related decisions at multiple decision points, including initial diagnosis and following initial primary therapy. In this review, we aim to contextualize the body of evidence surrounding these emerging tests, with attention on studies addressing clinical utility.
Accurately diagnosing pancreatic ductal adenocarcinomas (PDACs) is challenging because of the loss of vascularity and poor imaging. The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict poor prognosis in several types of malignancy including PDAC; however, the diagnostic role of NLR in PDAC has never been addressed.
This study retrospectively assessed 297 patients who underwent curative pancreatic resection for pancreatic tumors from 1995−2015, including 140 with PDACs, 58 with pancreatic neuroendocrine tumors (PNETs), 76 with intraductal papillary mucinous neoplasms (IPMNs), 13 with mucinous/serous cyst neoplasms, 7 with solid pseudopapillary neoplasms, and 3 with tumor-forming pancreatitis. The role of preoperative NLR in predicting PDACs was investigated.
Preoperative NLR was significantly higher in patients with PDACs (2.52 ± 1.34) than in patients with PNETs (1.93 ± 0.68, P = 0.0004) and IPMNs (2.17 ± 0.79, P = 0.0253). Only eight patients with PDACs (5.7 %) had NLR >5; of these, three had normal carcinoembyronic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. Multivariate analysis revealed that abnormal CA19-9 levels, abnormal CEA levels, age >67 years, and NLR >5 were independent predictors of PDACs. Both the specificity and the positive predictive value of NLR >5 for predicting PDACs were 100 %; however, the sensitivity was 4.6 % and the negative predictive value was 43.8 %.
NLR >5 could independently predict the occurrence of PDACs in pancreatic neoplastic disease irrespective of other tumor markers, CEA and CA19-9, in pancreatic disease.
The number of operations for laparoscopic antireflux surgery in Japan is much less than that in Western countries. This study's aim was to evaluate outcome measures for redo antireflux surgery (redo-ARS) in Japanese patients.
Subjects consisted of 11 patients (2.3 %) who required redo-ARS, from an original group of 474 patients who had a primary ARS between December 1994 and January 2015. The mean age of the subjects was 57.7 years, and six of 11 patients were women (55 %). Clinical data were collected in a prospective manner, and were then reviewed retrospectively.
The most common cause of failed primary ARS was dislocation of the wrap (6/11 or 54 %). Of the 11 patients, 10 (91 %) were approached laparoscopically, with one requiring conversion to open surgery. Eight (73 %) underwent redo fundoplication, and the others had hiatal hernia repair alone. Mean operation time and blood loss were 202 min and 56 mL, respectively. A perioperative gastric wall injury occurred in three patients. The postoperative course was uneventful in majority patients. Three (27 %) were required to take proton pump inhibitor (PPI), and two (18 %) had a recurrence of hiatal hernia. A postoperative questionnaire was answered by seven of 11 (63 %), and these all reported a high level of satisfaction with their surgery.
Redo-ARS can be performed safely under laparoscopy. There was no recurrence rate in almost 80 %, and more than 70 % of patients were withdrawn from PPI treatment postoperatively.
Lymphangiomas are benign hamartomatous malformations which can arise either from congenitally sequestered lymphatic channels or due to acquired obstruction caused by fibrosis of lymph channels. They are common in the pediatric age group in the soft tissue of neck and the axilla. Abdominal lymphangiomas are rare; even rarer is the primary involvement of pancreas. It occurs more frequently in females and is often located in the distal pancreas. The authors report the case of cystic lymphangioma of pancreas in a 26-year old female presenting with recurrent episodes of upper abdominal pain that was treated with laparoscopic cyst excision. Although exceptionally rare, lymphangioma of the pancreas should be considered in the differential diagnosis of pancreatic cystic lesions, especially in young women.
The months immediately after the completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after the completion of treatment were examined.
Participants included 160 children aged 2 to 9 years with standard-risk ALL who were enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of their children's emotional-behavioral functioning and measures of coping and family functioning at approximately 1 month, 6 months, and 12 months after diagnosis and again 3 months after the completion of chemotherapy.
At 3 months off therapy, approximately 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, which are significantly higher than the expected 15% in the general population (P = .028 and .001, respectively). Patients with elevated anxiety 1 month after diagnosis were at greater risk of off-therapy anxiety (odds ratio, 4.1; 95% confidence interval, 1.31-12.73 [P = .022]) and those with elevated depressive symptoms 6 months after diagnosis were at greater risk of off-therapy depression (odds ratio, 7.88; 95% confidence interval, 2.61-23.81 [P = .0002]). In adjusted longitudinal analyses, unhealthy family functioning (P = .008) and less reliance on social support coping (P = .009) were found to be associated with risk of emotional distress. Children from Spanish-speaking families (P = .05) also were found to be at a greater risk of distress.
A significant percentage of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening and psychosocial interventions to support family functioning and coping skills. Cancer 2015. © 2015 American Cancer Society.
The objective of this study was to examine the source of advanced cancer patients' information about their prognosis and determine whether this source of information could explain racial disparities in the accuracy of patients' life expectancy estimates (LEEs).
Coping With Cancer was a prospective, longitudinal, multisite study of terminally ill cancer patients followed until death. In structured interviews, patients reported their LEEs and the sources of these estimates (ie, medical providers, personal beliefs, religious beliefs, and other). The accuracy of LEEs was calculated through a comparison of patients' self-reported LEEs with their actual survival.
The sample for this analysis included 229 patients: 31 black patients and 198 white patients. Only 39.30% of the patients estimated their life expectancy within 12 months of their actual survival. Black patients were more likely to have an inaccurate LEE than white patients. A minority of the sample (18.3%) reported that a medical provider was the source of their LEEs; none of the black patients (0%) based their LEEs on a medical provider. Black race remained a significant predictor of an inaccurate LEE, even after the analysis had been controlled for sociodemographic characteristics and the source of LEEs.
The majority of advanced cancer patients have an inaccurate understanding of their life expectancy. Black patients with advanced cancer are more likely to have an inaccurate LEE than white patients. Medical providers are not the source of information for LEEs for most advanced cancer patients and especially for black patients. The source of LEEs does not explain racial differences in LEE accuracy. Additional research into the mechanisms underlying racial differences in prognostic understanding is needed. Cancer 2016;000:000–000. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
The objective of this article was to report the results from a randomized clinical trial comparing intensity-modulated radiotherapy (IMRT) with 3-dimensonal conformal radiotherapy (3DCRT) for the treatment of prostate cancer on a hypofractionated schedule.
The authors randomly assigned 215 men who had localized prostate cancer to receive hypofractionated radiotherapy to a total dose of 70 grays (Gy) in 25 fractions (at 2.8 Gy per fraction) using either IMRT or 3DCRT. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified Radiation Therapy Oncology Group criteria. Biochemical control was defined according to the Phoenix criteria (prostate-specific antigen nadir + 2 ng/mL).
In total, 215 patients were enrolled in the IMRT group (n = 109) or the 3DCRT group (n = 106). The 3DCRT arm had a 27% rate of grade ≥ 2 acute GU toxicity compared with a 9% rate in the IMRT arm (P = .001) and a 24% rate of grade ≥ 2 acute GI toxicity compared with a 7% rate in the IMRT arm (P = .001). The maximal rate of grade ≥2 late GU toxicity during the entire period of follow-up was 3.7% in the IMRT group versus 12.3% in the 3DCRT group (P = .02). The maximal rate of grade ≥2 late GI toxicity during the entire follow-up was 6.4% in the IMRT group versus 21.7% in the 3DCRT group (P = .001). The 5-year rate of freedom from biochemical failure was 95.4% in the IMRT arm and 94.3% in the 3DCRT arm (P = .678).
IMRT reduced the delivery of significant radiation doses to the bladder and rectum using a similar target volume. This dosimetric advantage resulted in a lower rate of acute/late grade ≥ 2 GI and GU toxicity for IMRT compared with 3DCRT. Cancer 2016. © 2016 American Cancer Society.
Publication date: Available online 29 March 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Niloy R. Datta, Michael Heuser, Stephan Bodis
PurposeTo propose a roadmap and explore the cost implications of establishing a teleradiotherapy network to provide comprehensive cancer care and capacity building in countries without access to radiation therapy.Methods and MaterialsTen low-income sub-Saharan countries with no current radiotherapy facilities were evaluated. A basic/secondary radiotherapy center (SRTC) with two teletherapy, one brachytherapy, one simulator and a treatment planning facility was envisaged at a cost of USD 5M. This could be networked with one to four primary radiotherapy centers (PRTC) with one teletherapy unit, each costing USD 2M. The numbers of PRTCs and SRTCs for each country were computed based on cancer incidence, assuming that a PRTC and SRTC could respectively treat 450 and 900 patients annually.ResultsAn estimated 71215 patients in these countries will need radiotherapy in 2020. Step-wise establishment of a network with 99 PRTCs and 28 SRTCs would result in 155 teletherapy units and 96% access to radiotherapy. 310 radiation oncologists, 155 medical physicists and 465 radiotherapy technologists would be needed. Capacity building could be undertaken through telementoring by networking to various international institutions and professional societies. Total infrastructure costs would be around USD 860.88M, only 0.94% of the average annual GDP of these 10 countries. 1.04 million patients could receive RT during the 15 year lifespan of a teletherapy unit for an investment of USD 826.69/patient. For the entire population of 218.32 million, this equates to USD 4.11 per inhabitant.ConclusionA teleradiotherapy network could be a cost-contained innovative healthcare strategy to provide effective comprehensive cancer care through resource sharing and capacity building. The network could also be expanded to include other allied specialties. The proposal calls for active coordination between all national and international organizations backed up by strong geopolitical commitment and action from all stakeholders.
Publication date: Available online 29 March 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Paulien G. Westhoff, Mathilde G.E. Verdam, Frans J. Oort, Jan J. Jobsen, Marco van Vulpen, Jan Willem H. Leer, Corrie A.M. Marijnen, Alexander de Graeff, Yvette M. van der Linden
BackgroundIn palliative care, quality of life (QoL) is an important endpoint. We studied the course of QoL after radiotherapy for painful bone metastases.MethodsThe Dutch Bone Metastasis Study randomized 1,157 patients with painful bone metastases between a single fraction of 8 Gray and six fractions of 4 Gray between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for two years. In these analyses, physical, psychosocial and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics.ResultsIn general, QoL stabilized after a month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (-0.11 to -0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gray and six fractions of 4 Gray, except for a temporary worsening of physical QoL after six fractions.ConclusionAlthough radiotherapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterwards a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gray lead to a temporary worse physical QoL compared to a single fraction of 8 Gray.
Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.
A Phase II selection design trial was conducted to identify the most promising regimen for comparison with standard therapy in chemo-naive patients with unresectable or recurrent biliary tract cancer (JCOG0805). Gemcitabine plus S-1 therapy showed better efficacy than S-1 monotherapy with acceptable safety in JCOG0805 study. Based on this result, a randomized Phase III trial was started in May 2013 to confirm the non-inferiority of gemcitabine plus S-1 therapy relative to gemcitabine plus cisplatin therapy, which is the current standard treatment for chemo-naive patients with unresectable or recurrent biliary tract cancer. A total of 350 patients will be accrued from 32 Japanese institutions within 4 years. The primary endpoint is overall survival, while the secondary endpoints are progression-free survival, adverse events, serious adverse events, clinically significant adverse events, response rate and %planned dose. This trial has been registered with the UMIN Clinical Trials Registry (http://ift.tt/1lXJedE) and the registration number is UMIN000010667.
Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities.
Objective
To compare the efficacies of conventional three-dimensional conformal radiotherapy and image-guided hypofractionated intensity-modulated radiotherapy treatments in advanced hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi.
MethodsA total of 118 hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi who received external beam radiation therapy focused on tumor thrombi and intrahepatic tumors were retrospectively reviewed. During the three-dimensional conformal radiotherapy treatments, a median total dose of 54 Gy with a conventional fraction (1.8–2.0 Gy/fx) was delivered. During the image-guided hypofractionated intensity-modulated radiotherapy treatments, a median total dose of 60 Gy with fractions of 2.5–4.0 Gy/fx was delivered.
ResultsThe median follow-up time was 11.8 months (range, 1.7–43.7 months). Higher radiation doses were delivered by image-guided hypofractionated intensity-modulated radiotherapy than by three-dimensional conformal radiotherapy (average dose 57.86 ± 7.03 versus 50.88 ± 6.60 Gy, P ≤ 0.001; average biological effective dose 72.35 ± 9.62 versus 61.45 ± 6.64 Gy, P < 0.001). A longer median survival was found with image-guided hypofractionated intensity-modulated radiotherapy than with three-dimensional conformal radiotherapy (15.47 versus 10.46 months, P = 0.005). Multivariate analysis showed that image-guided hypofractionated intensity-modulated radiotherapy is a significant prognostic factor for overall survival. Toxicity was mild for both image-guided hypofractionated intensity-modulated radiotherapy and three-dimensional conformal radiotherapy.
ConclusionsHigh dose radiotherapy delivered by image-guided hypofractionated intensity-modulated radiotherapy appears to be an effective treatment that provides a survival benefit without increasing severe toxicity in hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi.
Cancer treatment guidelines are compiled on the basis of established evidence. Such evidence is obtained from epidemiological, pathological and pharmacological study and, most importantly of all, the information gained from clinical trials. However, very little of the kind of evidence that is required for the compilation of treatment guidelines is actually obtained from Asian countries. When one considers the ethnic differences and disparities in medical care, coupled with the tremendous cultural diversity that characterize the Asian region, it would be difficult to conclude that there is currently sufficient evidence that could form the basis for the formulation of guidelines that would be relevant and applicable to all Asian countries. An urgent issue that needs to be addressed in order to achieve a breakthrough in this difficult situation is to build up a body of evidence at an advanced level that is specific to the Asian region and Asian ethnicities. For the interim, however, it is also necessary to efficiently incorporate evidence that has been obtained in Western countries. Furthermore, an effective method of utilizing guidelines that have already been compiled in Western countries is considered to be not by simply translating them into local languages, but rather to engage in a process of adaptation, whereby the guidelines are adjusted or modified to match the circumstances of a particular country or region. The NCCN Clinical Practice Guidelines-Asian Consensus Statement (NCCN-ACS) documents have been compiled with this intention in mind, utilizing the NCCN guidelines that are widely used internationally.
Objective
We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer.
MethodsThe clinical responses of 63 consecutive patients with breast cancer (T1–4, N0–1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time–intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens.
ResultsTwenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5–99.2%), 77.5% (69.9–79.5%) and 84.1% (74.5–86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057).
ConclusionsContrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy.
Objective
Cisplatin is administered in combination with massive hydration to avoid renal toxicity, making its administration difficult in an outpatient setting. Although a short hydration protocol for cisplatin has been recently developed, its safety is not fully understood.
MethodsConsecutive patients with lung or other cancer and an Eastern Cooperative Oncology Group performance status of 0–2 who were receiving chemotherapy containing cisplatin at a dose of ≥60 mg/m2 in a single administration were evaluated. Seventy-four patients were treated with a short hydration protocol consisting of 1750–2250 ml of hydration with mannitol and magnesium supplementation over a period of 3.75–4.75 h on Day 1. Sixty-nine patients were treated with a conventional hydration protocol consisting of 2100–2600 ml of hydration over 6.5–7.5 h on Day 1 with pre- and post-hydration on Days 0, 2 and 3. Toxicity was then compared between the two groups.
ResultsAn elevated serum creatinine level ≥grade 1 was significantly less frequent in the group receiving the short hydration protocol than in the group receiving conventional hydration. Other toxicities were similar between the two groups. Consequently, the completion rate for the planned treatment in the short hydration group (73.0%, 54/74) was significantly higher than that in the conventional hydration group (53.6%, 37/69).
ConclusionsShort hydration is safe, making cisplatin-containing chemotherapy easier to perform.
Objective
The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients.
MethodsThis study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study.
ResultsIn total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively.
ConclusionsUpper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population.
Objective
To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging.
MethodsBetween October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis.
ResultsPathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement.
ConclusionsPatients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although the predictability is moderate.
Objective
Abnormal expression of microRNA-215 has been identified in a variety of solid cancers. However, little is known about the expression pattern of microRNA-215 in acute myeloid leukemia. This study was to investigate the status of microRNA-215 expression and further analyze its clinical significance in acute myeloid leukemia.
MethodsReal-time quantitative polymerase chain reaction assay was performed to evaluate the expression level of microRNA-215 in 113 patients with acute myeloid leukemia. Besides, the relationship between microRNA-215 levels and clinical and pathological factors was explored.
ResultsCompared with the healthy individuals, microRNA-215 expression in acute myeloid leukemia patients was significantly down-regulated (P= 0.001). MicroRNA-215 low-expressed patients had higher white blood cells than microRNA-215 high-expressed patients (P= 0.014). The incidence of FLT3/ITD mutation in the patients with low microRNA-215 expression was significantly higher than those with high microRNA-215 expression (P= 0.025). MicroRNA-215 low-expressed patients had significantly shorter overall survival than microRNA-215 high-expressed patients in both non-M3 acute myeloid leukemia patients and cytogenetically normal patients (P= 0.017 and P= 0.044, respectively). Meanwhile, multivariate analysis confirmed the adverse prognostic value of microRNA-215 expression in acute myeloid leukemia patients with non-M3 subtypes.
ConclusionsOur study demonstrates that reduced microRNA-215 expression is a common event and is associated with poor clinical outcome in acute myeloid leukemia.
Objective
Laparoscopy-assisted gastrectomy for advanced gastric cancer still remains controversial. The aim of this study is to compare oncologic feasibility and technical safety of laparoscopic versus open gastrectomy for advanced gastric cancer with D2 lymphadenectomy by comparing patients' short-term postoperative outcomes.
MethodsOne hundred and one patients with laparoscopy-assisted gastrectomy and 101 patients with open gastrectomy were one-to-one matched and then compared in terms of operative outcomes and hospital courses.
ResultsThe laparoscopic group showed significantly longer operating time (297.4 vs. 198.1 min, P < 0.001), earlier first flatus time (2.8 vs. 3.6 days, P < 0.001), earlier diet start time (3.8 vs. 4.6 days, P < 0.001), shorter hospital stay (10.5 vs. 11.9 days, P < 0.001) and less morbidity (21.8 vs. 37.6%, P = 0.019). However, retrieval lymph nodes, intraoperative blood loss, transfused patients, postoperative fever and mortality were similar in the two groups. As for complications, incision infection (1.0 vs. 8.9%, P = 0.021) was significantly more common in the open group than in the laparoscopic group. In the subgroup comparisons of outcomes of laparoscopy-assisted gastrectomy, the tumor, node, metastasis III group showed significantly increased retrieval lymph nodes (37.2 vs. 31.0, P < 0.001), increased intraoperative blood loss (147.2 vs. 120.5 ml, P = 0.010), increased length of hospital stay (11.1 vs. 9.9 days, P < 0.001) and increased morbidity (32.6 vs. 13.8%, P = 0.024) when compared with the tumor, node, metastasis II group.
ConclusionsLaparoscopy-assisted gastrectomy is feasible and safe for the treatment of advanced gastric cancer with D2 lymphadenectomy compared with open gastrectomy. Higher-level tumor stage (tumor, node, metastasis III) may increase the operative risk and should be performed with caution by surgeons with considerable experience of laparoscopic gastrectomy.
Objective
To investigate practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea.
MethodsIn June 2013, the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology conducted a national patterns-of-care survey about stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma, consisting of 19 questions and 2 clinical scenarios.
ResultsAll 208 radiation oncologists (100%), who are regular members of Korean Society for Radiation Oncology, responded to this survey. Among these, 95 radiation oncologists were specialists for hepatology; 64 physicians did not use stereotactic body radiotherapy for hepatocellular carcinoma, and 31 physicians used stereotactic body radiotherapy. Most physicians (52%) performed stereotactic body radiotherapy to hepatocellular carcinoma in ≤5 cases per year. Physicians applied stereotactic body radiotherapy according to tumour size and baseline Child–Pugh class. All physicians agreed the use of stereotactic body radiotherapy to 2.8-cm hepatocellular carcinoma with Child–Pugh class of A, while 23 physicians (74%) selected stereotactic body radiotherapy for Child–Pugh class of B. Nineteen physicians (61%) selected stereotactic body radiotherapy to 5-cm hepatocellular carcinoma with Child–Pugh class of A, and only 14 physicians (45%) selected stereotactic body radiotherapy for Child–Pugh class of B. On the other hand, the preferred dose scheme was same as 60 Gy in three fractions.
ConclusionsAmong radiation oncologists in Korea, there was diversity in the practice for stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma. Additional prospective studies are necessary to standardize the practice and establish Korea-specific practice guidelines for hepatocellular carcinoma stereotactic body radiotherapy.
Objective
Intracorporeal reconstruction of the digestive tract is technically challenging. The V-Loc 180 wound closure device (Covidien) is a self-anchoring unidirectional barbed suture that obviates the need for knot tying. The aim of this prospective cohort study was to investigate the use of the novel suture in gastrointestinal enterotomy closure.
MethodsThe subjects comprised patients with malignant disease who were scheduled to undergo laparoscopic gastrectomy with curative intent. The barbed suture was used to close the entry hole for the linear stapler during intracorporeal reconstruction following laparoscopic gastric resection. The primary endpoint was the proportion of patients who developed anastomotic leakage at the site where the barbed suture was applied.
ResultsBetween July 2012 and March 2015, 242 patients were enrolled. Of 362 anastomoses, the enterotomy hole at 256 sites was closed using the barbed suture. These 256 sites consisted of 95 gastroduodenostomies, 25 gastrogastrostomies, 13 gastrojejunostomies, 90 jejunojejunostomies, 17 esophagojejunostomies and 16 primary closures of the stomach following local gastric resection. There were no anastomosis-related complications, conversion to usual sutures, mechanical closure of the entry hole and reoperation due to adhesive obstructions or mortality over a median follow-up period of 17.8 months.
ConclusionsThe use of the unidirectional barbed absorbable suture for gastrointestinal closure is safe and effective in laparoscopic gastrectomy.
Objective
To investigate the expression pattern of a novel long non-coding ribonucleic acid activated by transforming growth factor β, long non-coding ribonucleic acid activated by transforming growth factor β, in renal cell carcinoma tissues among the patients with various clinicopathologic features and to detect the possible role of dysregulated long non-coding RNA-ATB in renal cell carcinoma.
MethodsThe expression of long non-coding ribonucleic acid activated by transforming growth factor β in the renal cell carcinoma tissues and renal cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association with clinicopathologic features was analyzed. The effects of long non-coding ribonucleic acid activated by transforming growth factor β on the renal cell carcinoma cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition were investigated by the loss-of-function approach.
ResultsThe expression of long non-coding ribonucleic acid activated by transforming growth factor β was higher in the renal cell carcinoma tissues and renal cancer cells than in the adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. In addition, the long non-coding ribonucleic acid activated by transforming growth factor β expression was significantly higher in the renal cell carcinoma patients with metastasis. The elevated expression of long non-coding ribonucleic acid activated by transforming growth factor β was associated with tumor stages, histological grade, vascular invasion, lymph node metastasis and distant metastasis. Notably, we found that long non-coding ribonucleic acid activated by transforming growth factor β knockdown could (i) inhibit cell proliferation; (ii) trigger apoptosis; (iii) reduce epithelial-to-mesenchymal transition program; (iv) suppress cell migration and invasion.
ConclusionsOur data have shown that long non-coding ribonucleic acid activated by transforming growth factor β actively functions as a regulator of epithelial-to-mesenchymal transition during renal cell carcinoma metastasis, which suggests that long non-coding ribonucleic acid activated by transforming growth factor β may be a potential prognostic biomarker and therapeutic target for renal cell carcinoma.
Objective
The aim of the study was to establish an effective prognostic nomogram for esophageal squamous cell carcinoma after radical esophagectomy followed by adjuvant chemotherapy in those previously untreated patients.
MethodsThe clinicopathological data from 328 patients who underwent radical esophagectomy followed by adjuvant chemotherapy or not at the Tianjin Medical University Cancer Institute and Hospital between 2006 and 2010 were retrospectively studied. Nomograms which predicted survival of esophageal squamous cell carcinoma were established based on the Cox proportional hazards regression model. To determine its predictive accuracy and discriminatory capacity, the concordance index and calibration curve were calculated after bootstrapping in the internal validation. An external validation of 76 patients in 2011 was prospectively studied at the same institution. To verify the performance of the nomogram, the comparison between the nomogram and Tumor-Node-Metastasis staging system was conducted.
ResultsThe 5-year overall survival was 43.1% in the primary cohort. Based on multivariate analyses, five independent prognostic variables including gender, tumor length, T stage, N stage and chemotherapy cycles were selected to build the nomograms to predict disease-free survival and overall survival. The concordance index of the nomogram to predict overall survival was 0.71 (95% confidence interval, 0.63–0.79), which was superior to the predictive power of Tumor-Node-Metastasis staging system (0.64) in the primary cohort. Meanwhile, the calibration curve showed good accuracy between predictive and actual overall survival. In the validation cohort, the concordance index (0.77) and calibration plot displayed favorable performances. The other nomogram to predict disease-free survival also performed well.
ConclusionsThe prognostic nomogram provided individualized risk estimate of survival in patients after esophagectomy followed by adjuvant chemotherapy.
It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1-year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9–60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
Objective
A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer.
MethodsPreviously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66–70 Gy was delivered to the primary and involved nodes and 36–54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006.
ResultsThe median follow-up time of this cohort was 43.4 months (range; 6.9–151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0–85.0), 58.4% (95% confidence interval; 51.8–65.9) and 67.5% (95% confidence interval; 61.0–74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively.
ConclusionsThe efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation.
Publication date: Available online 28 March 2016
Source:Cancer Epidemiology
Author(s): Esther de Vries, Mónica Sierra, Marion Piñeros, Dora Loria, David Forman
Rationale and objectiveVery little is known about the burden of cutaneous melanoma in Central and South America, despite the existence of a reasonable amount of population-based data. We present data on melanoma incidence calculated in a standardized way for Central and South America, as well as an overview of primary and secondary prevention issues in the region.MethodsCancer registry data on all incident cases reported in the different registries present in Central and South America were combined to provide registry-based country estimates of age-standardized, sex-specific cutaneous melanoma incidence overall, and by histological subtype and anatomical site. A literature search provided additional information.ResultsAge-standardized incidence rates were between 1 and 5 per 100,000 and tended to be higher further away from the equator. Cutaneous melanomas of the acral type, mostly occurring on the lower limbs, are a distinguishing feature of melanoma in Central and South America in comparison with high-incidence areas. Several preventive measures, both primary and secondary, are in place, albeit largely without evaluation.ConclusionDue to incomplete registration and different registration practices, reliable and comparable data on melanoma were difficult to obtain; thus it is likely that the true burden of melanoma in Central and South America has been underestimated. The different characteristics of the cutaneous melanoma patient population in terms of anatomical site and histological type distribution imply a need for adapted primary and secondary prevention measures. The generally high ambient ultraviolet radiation levels require sufficient sun protection measures.
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Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Michael Gnant
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Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Gabriela G.F. van der Schoot, Nico-Derk L. Westerink, Sjoukje Lubberts, Janine Nuver, Nynke Zwart, Annemiek M.E. Walenkamp, Johan B. Wempe, Coby Meijer, Jourik A. Gietema
BackgroundBleomycin and cisplatin are of key importance in testicular cancer treatment. Known potential serious adverse effects are bleomycin-induced pulmonary toxicity (BIP) and cisplatin-induced renal toxicity. Iron handling may play a role in development of this toxicity. Carriage of allelic variants of the HFE gene induces altered iron metabolism and may contribute to toxicity. We investigated the association between two common allelic variants of the HFE gene, H63D and C282Y, with development of pulmonary and renal toxicity during and after treatment with bleomycin- and cisplatin-containing chemotherapy.MethodsIn 369 testicular cancer patients treated with bleomycin and cisplatin at the University Medical Center Groningen between 1978 and 2006, H63D and/or C282Y genotypes were determined with an allelic discrimination assay. Data were collected on development of BIP, pulmonary function parameters, renal function, and survival.ResultsBIP developed more frequently in patients who were heterozygote (16 in 75, 21%) and homozygote (2 in 4, 50%) for the H63D variant, compared with those who had the HFE wild-type gene (31 in 278, 11%) (p = 0.012). Overall survival, testicular cancer-related survival, and change in renal function were not associated with the H63D variant.ConclusionWe observed an association between presence of one or both H63D alleles and development of BIP in testicular cancer patients treated with bleomycin combination chemotherapy. In patients heterozygote and homozygote for the H63D variant, BIP occurred more frequently compared with wild-type patients. When validated and confirmed, HFE H63D genotyping may be used to identify patients with increased risk for pulmonary bleomycin toxicity.
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Publication date: May 2016
Source:European Journal of Cancer, Volume 59
Author(s): Mikael Eriksson, Peter Reichardt, Kirsten Sundby Hall, Jochen Schütte, Silke Cameron, Peter Hohenberger, Sebastian Bauer, Mika Leinonen, Annette Reichardt, Maria Rejmyr Davis, Thor Alvegård, Heikki Joensuu
PurposePreoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes.MethodsWe collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS).ResultsA total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour ≥10 cm in diameter.ConclusionA preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy.
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Publication date: Available online 28 March 2016
Source:Cancer/Radiothérapie
Author(s): A. El Bousaadani, L. Eljahd, R. Abada, S. Rouadi, M. Roubal, M. Mahtar
La mucite orale est une inflammation de la muqueuse de la cavité orale d'étiologies diverses. C'est une complication fréquente et invalidante de la chimioradiothérapie chez les enfants. Sa prise en charge reste une préoccupation majeure aussi bien pour le médecin que le patient. Elle altère la qualité de vie des malades et des familles. Elle peut engager le pronostic fonctionnel, et même vital, à cause de l'arrêt du traitement anticancéreux. Plusieurs possibilités thérapeutiques sont disponibles, mais il n'y a pas de consensus thérapeutique clair, surtout pour la population pédiatrique. Nous avons recensé, à travers une recherche bibliographique exhaustive, les publications indexées sur ce sujet afin de mettre le point sur les approches pharmacologiques et non pharmacologiques qui ont été utilisées pour prévenir et traiter la mucite orale. Ainsi, les recommandations actuelles sur la gestion des mucites orales sont très limitées et, par conséquent, la norme de soins pour cette complication a été palliative. Depuis quelques années, plusieurs études ont révélé que l'utilisation du laser basse énergie était particulièrement intéressante dans la prévention et le traitement des mucites radio-induites ou chimio-induites. Elle diminue significativement la douleur, la sévérité et la durée de l'ulcération en favorisant la cicatrisation des lésions. Des essais contrôlés randomisés avec un effectif important de patients sont attendus pour établir des protocoles préventifs et curatifs. Le traitement par laser de faible puissance, connu, dénué d'effet indésirable, est un soin de support oncologique très prometteur pour les mucites radio- et chimio-induites.Oral mucositis is an inflammation of the mucosa of the oral cavity of various etiologies. This is a common and debilitating complication in children treated with chemoradiotherapy for cancer. Its management remains a major concern both for the doctor than the patient. It affects the quality of life of patients and families. It may initiate the functional and vital prognosis because of the judgment of cancer treatment. Several treatment options are available, but there is no clear consensus therapeutic especially for the pediatric population. We have identified, through a comprehensive literature search indexed publications on this subject in order to review the pharmacological and non-pharmacological approaches that have been used to prevent and treat oral mucositis. Thus, current recommendations for the management of oral mucositis are very limited, and therefore the standard of care for this complication was palliative. In recent years several studies have revealed that the use of low-energy laser was particularly interesting in the prevention and treatment of radiation-induced or chemically induced mucositis. It significantly reduces the pain, the severity and duration of the ulcer by promoting wound healing. Randomized controlled trials with a large number of patients are expected to establish preventive and therapeutic protocols. Treatment with low power laser, known devoid of side effects, is a very promising oncology care to support radio-induced mucositis and chemotherapy.
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Publication date: Available online 28 March 2016
Source:Cancer/Radiothérapie
Author(s): M. Viau, A.-F. Perez, L. Bodgi, C. Devic, A. Granzotto, M.-L. Ferlazzo, M. Bourguignon, A. Puisieux, T. Lacornerie, É. Lartigau, J.-L. Lagrange, N. Foray
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Ran GTPase regulates nuclear import, nuclear export, and mitotic spindle assembly. The multifunctional involvement of seventeen Ran GTPase components in these processes has complicated research into how each contributes to cancer development.
To assess whether individual and process-specific misexpression of Ran GTPase components contribute to chromosome instability (CIN) and worsen breast cancer patient prognosis.
Using publicly available datasets, we studied the degree of misexpression of all Ran GTPase signaling components in breast cancer, assessed their involvement in CIN and used four clinical tests to evaluate whether their misregulation may constitute independent prognostic predictors.
A significant majority of Ran GTPase signaling components is overexpressed in breast cancer. Strikingly, spindle assembly components are overexpressed and associated with CIN with only marginal significance and four independent tests indicate that this does not worsen patient outcome. Overexpression of nuclear import components is neither CIN-associated nor clinically significant. In sharp contrast, overexpression of nuclear export components constitutes a strong independent marker for both CIN and poor patient prognosis. We identify Exportin 2/CSE1L, Exportin 3/XPOT, Exportin 5/XPO5, and RANBP1 as novel potential targets.
We find that overexpression of Ran GTPase components involved in nuclear export, but not nuclear import or mitotic spindle assembly, is a strong CIN-associated marker for poor breast cancer prognosis. This could mean that increased nuclear export (of, for instance, pRb, p53, p73, BRCA1, p21, p27, E2F4, IκB, survivin), rather than spindle defects, mainly drives CIN and tumorigenesis. Hence, selective inhibitors of nuclear export may be effective for treating the most aggressive and chromosomally unstable breast cancers.
Cancer cachexia is associated with patient outcomes.
The objective was to evaluate the effect of cachexia on survival among patients with metastatic renal cell carcinoma (mRCC) who had received first-line sunitinib treatment.
Seventy-one patients were retrospectively evaluated. Sarcopenia was diagnosed using sex-specific cut-offs for skeletal muscle index (measured using pre-treatment computed tomography) that were adjusted for body mass index. The modified Glasgow prognostic score (mGPS) was measured using C-reactive protein (CRP) and albumin levels (mGPS 2: CRP >1.0 mg/dL and albumin <3.5 g/dL; mGPS 1: CRP >1.0 mg/dL; mGPS 0: CRP ≤1.0 mg/dL). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Forty-five patients (63.4 %) had sarcopenia, with 53 (74.6 %), ten (14.1 %), and eight (11.3 %) patients having an mGPS of 0, 1, and 2, respectively. Sarcopenia was associated with significantly inferior PFS and OS, compared to non-sarcopenic patients (PFS: 7.6 vs. 18.2 months, p = 0.0004; OS: 22.3 months vs. not reached, p = 0.0019). Higher mGPS was associated with inferior PFS and OS (mGPS 0, 1, and 2: PFS = 11.5, 10.9, and 4.12 months, p < 0.0001; OS = 47.2, not reached, and 5.28 months, p < 0.0001; respectively). Sarcopenia was an independent predictor of shorter PFS (p = 0.0163), and mGPS was an independent predictor of shorter OS (p = 0.0012).
Sarcopenia and mGPS can predict outcomes among patients with mRCC who are receiving first-line sunitinib treatment.
