tbuckley/cabot-search huggingface dataset:
Treatment trends in gastroesophageal and gastric cancers in the United States.
Authors: Ali Mokdad, Amna Ali, Ibrahim Nassour, John C. Mansour, Sam C. Wang, Matthew R. Porembka
Journal: Journal of Clinical Oncology (2017)

136 Background: Randomized clinical trials reported in the last decade have helped define gastroesophageal junction (GEJ) and gastric cancer (GC) treatment. It is unclear, however, how practice patterns have evolved following these trials. This study explores the trends in treatment of GEJ and GC over the past decade in the United States. Methods: Patients with adenocarcinoma of the stomach and distal esophagus were identified in the National Cancer Database between 2006 and 2013. Tumor located in the distal esophagus and gastric cardia was denoted GEJ. Tumors distal to the cardia constituted GC. Tumors were categorized as early (Stage IA), locally advanced (IB-IIIC), and metastatic (IV). Detailed treatment was compared according to tumor stage and location. A time trend analysis was conducted. Results: A total of 120,729 patients (GEJ: 79,654 [66%], GC: 41,075 [34%]) were identified. Stage was similar in both groups (early: 12%, locally advanced: 55%, and metastatic: 33%). Overall, 73% of early GEJ and 74% of early GC underwent resection; of those, 43% and 12% were local excisions, respectively. Local excisions increased over time in both groups (annual odds ratio [OR] = 1.2; P &lt; 0.01). In locally advanced GEJ, neoadjuvant chemoradiotherapy (CRT) increased among patients that received multimodality treatment (53% in 2006 to 73% in 2013; OR = 1.1, P &lt; 0.01). In locally advanced GC, the use of neoadjuvant chemotherapy (CT) increased (5% to 20%; OR = 1.2, P &lt; 0.01) as did perioperative CT (1% to 9%; OR = 1.3, P &lt; 0.01) in lieu of adjuvant CRT (68% to 43%; OR = 0.9, P &lt; 0.01). Multimodality treatment use remained stable over the study period in both groups (GEJ: 42%, GC: 47%). Among patients with metastatic disease, only 61% of GEJ and 40% of GC patients received CT, with 32% and 40%, respectively, not receiving any therapy at all. Conclusions: Practice patterns for GEJ and GC changed in the last decade with increasing adoption of neoadjuvant therapy in locally advanced disease and local excision of early stage cancers. Treatment for metastatic disease remains markedly underutilized, particularly GC.
The relationship between serum vitamin D levels and breast cancer prognosis: A meta-analysis.
Authors: April Ann Nicole Rose, Christine Elser, Pamela Jean Goodwin
Journal: Journal of Clinical Oncology (2013)

1521 Background: Vitamin D (VitD) is a circulating hormone known to regulate gene transcription in breast cancer (BC) cells. The association between VitD and BC risk has been extensively studied. Until recently, however, the role of VitD in BC progression and its association with clinical outcomes among BC patients was poorly understood. To assess these new developments, a systematic review and meta-analysis was performed. Methods: A systematic review and meta-analysis by searching MEDLINE (1982 – 2012), ASCO, and SABCS for abstracts (2009 – 2012), with the following keywords: “breast cancer” and “prognosis” or “survival”, and “vitamin D” or ”calcitriol.” Abstracts were scrutinized for reports correlating serum VitD levels with breast cancer clinical outcomes, including: disease-free survival (DFS) and overall survival (OS). Studies were included if serum VitD samples were taken shortly after diagnosis and survival data were reported. Meta-analyses were performed using an inverse-variance weighted fixed-effects model. Results: We identified 7 studies reporting correlative data between serum VitD levels and BC survival. These data included 4,885 patients evaluated for DFS and 3858 patients evaluated for OS. VitD-deficiency was defined as &lt;30ng/mL, &lt;20ng/mL, and &lt;14ng/mL in 3, 3, and 1 studies, respectively, and was identified in an average of 48.1% of patients (range: 17.9-87.8%). VitD deficiency was associated with a pooled hazard ratio (HR) of 2.13 (CI: 1.64 - 2.78) and 1.76 (CI: 1.35 - 2.30) for DFS and OS, respectively. Conclusions: To our knowledge, this is the first report of a meta-analysis of the relationship between serum VitD and BC prognosis. The prevalence of VitD-deficiency varied widely across studies and may reflect differences in geographic location, race, and rates of supplementation across patient populations. These findings support the hypothesis that VitD-deficient breast cancer patients have poorer clinical outcomes than VitD sufficient patients; but do not establish whether this relationship is causative. Further studies are warranted to investigate the possible protective effects of VitD supplementation on survival among VitD-deficient BC patients.
The national biomarker development alliance: An end-to-end systems approach for biomarker development for precision medicine.
Authors: Carolyn C. Compton
Journal: Journal of Clinical Oncology (2014)

e22129 Background: The development of new robust biomarkers is essential to the realization of the vision of precision medicine. At present, the high costs and failure rates in biomarker development represent a significant roadblock to medical progress. The biomarker development process itself requires re-engineering to reduce the massive inefficiencies, fragmentation, and failure rates that now characterize the system. Methods: The National Biomarker Development Alliance (NBDA) is a new nonprofit organization of academic, industry and government partners that aims to create a standards-based, end-to-end approach to the development of biomarkers of different categories within a given context of use, guided throughout the development pipeline by regulatory and clinical implementation requirements. Results: The NBDA will work with multi-sector stakeholders across the biomarker development continuum to identify where in the process standards matter, determine the status of existing standards, identify gaps, aggregate information on specific biomarkers and biomarker classes, and reproduce the work. NBDA will publish the recommendations it develops by consensus and science, building on the best of current practices. It will act in consultation with the FDA and professional organizations such as ASCO in order to meet the levels of evidence for biomarker qualification by regulators and validation in clinical use. It will link and integrate discovery, pre-clinical development, assay development and performance, clinical testing, regulatory approval, and post-market applications. Conclusions: The ever more rapid development of assay technologies dictates that standards that allow them to be applied successfully to biomarker development keep pace. This can only be accomplished through broad coordination of effort and consensus, which is the goal of the NBDA.
Statins decrease the risk of decompensation in hepatitis B virus– and hepatitis C virus–related cirrhosis: A population‐based study
Authors: Fu‐Ming Chang, Yen‐Po Wang, Hui‐Chu Lang, Chia‐Fen Tsai, Ming‐Chih Hou, Fa‐Yauh Lee, Ching‐Liang Lu
Journal: Hepatology (2017)

Statin use decreases the risk of decompensation and mortality in patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in the general population or cirrhosis due to other causes, such as hepatitis B virus (HBV) infection or alcohol, remains unknown. Statin use also decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients with pre-existing cirrhosis. The goal of this study was to determine the effect of statin use on rates of decompensation, mortality, and HCC in HBV-, HCV-, and alcohol-related cirrhosis. Patients with cirrhosis were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000 to 2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥28, were selected and served as the case cohort. Statin nonusers (<28 cDDD) were matched through propensity scores. The association between statin use and risk of decompensation, mortality, and HCC were estimated. A total of 1350 patients with cirrhosis were enrolled. Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner (P for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.25-0.62) or HCV infection (HR, 0.51; 95% CI, 0.29-0.93). The lowered risk of decompensation was of borderline significance among statin users with alcohol-related cirrhosis (HR, 0.69; 95% CI, 0.45-1.07).Statin use decreases the decompensation rate in both HBV- and HCV-related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol-related cirrhosis. (Hepatology 2017;66:896-907).
Patterns of care of elderly patients with metastatic colorectal cancer.
Authors: Sagun Parakh, Sayed Sahanawaz Ali, Hui-li Wong, Kathryn M Field, Jeremy David Shapiro, Louise M. Nott, Joseph James McKendrick, Peter Gibbs, Desmond Yip
Journal: Journal of Clinical Oncology (2013)

e14640 Background: Elderly patients (pts) account for a large proportion of pts with metastatic colorectal cancer (mCRC). Despite this they are underrepresented in clinical trials and often undertreated. The purpose of this study is to review the patterns of care of elderly pts with mCRC in the community setting. Methods: Retrospective analysis of 507 elderly (age ≥ 65 years (yrs)) pts with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database enrolled between July 2009 and November 2012. Comprehensive clinical data was collected prospectively on pts with mCRC from 14 sites across Australia. In this analysis pts were grouped according to age: 65-75, 75-85 and ≥85 yrs. Treatment patterns and intent, performance status (PS), and overall survival (OS) were analysed by age cohorts. Kaplan-Meier method was used for survival analysis. Results: In this cohort, 213 (42.0%), 216 (42.6%) and 78 (15.4%) pts were aged 65-75, 75-85 and &gt;85 yrs respectively. Older patients were more likely to be female (30.5% vs 42.1% vs 52.6%, p=0.0012) and have worse PS (PS≥2: 18.3% vs 25.9% vs 48.7%, p&lt;0.0001). There were no differences in comorbidity score, primary tumour site or resection rates between age groups. In total, 358 (70.6%) elderly pts received chemotherapy. However, chemotherapy use declined significantly with increasing age (83.1% vs 70.8% vs 35.9%, p&lt;0.0001). Among the very elderly (≥85 yrs) pts who received chemotherapy (n=28), 12 (42.9%) received combination chemotherapy and 6 (21.4%) were given bevacizumab. Median OS was 24.3, 17.7 and 11.3 months in the 65-75, 75-85 and &gt;85 yrs age groups respectively (p&lt;0.0001). Pts receiving chemotherapy had significantly longer OS than those who did not (median OS 22.7 vs 6.4 months, HR 0.28 (95% CI 0.21-0.38, p&lt;0.0001)). Conclusions: This is the largest series of elderly pts with mCRC in Australia. Multiple studies have confirmed the safety and efficacy of fluorouracil and bevacizumab but in our cohort, chemotherapy and bevacizumab appear to be underutilised in the elderly. Chart review is planned to explore reasons for not administering chemotherapy.
Post-neoadjuvant chemotherapy sentinel node biopsy and axillary sampling for node negative (N0) axilla.
Authors: Vani Parmar, Nita S. Nair, Rohini W Hawaldar, Vaibhav Vanmali, Aruna Laxman Prabhu, Rucha Vishal Kaushik, Tanuja Shet, Sangeeta Desai, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2012)

1108 Background: Post neoadjuvant chemotherapy (NACT) sentinel node biopsy (SNB) is not a standard of care due to the wide variability in false negative rate (FNR), varying from 5.7% to 33%. In operable breast cancer (OBC), FNR of less than 10% is acceptable. We attempted to find out the reliability of low axillary sampling(LAS), with dissection limited below the first intercostobrachial nerve, to correctly identify the node negative axilla in the post NACT clinically node negative (N0) patients. Methods: Women with large operable (LOBC) and locally advanced breast cancer (LABC), post-NACT clinically N0, underwent concomitant blue dye-colloid guided SNB and LAS. The identification rate, FNR, and negative predictive value (NPV) of both procedures were compared. Results: Post-NACT 209 eligible women underwent combined LAS and SNB procedure. At presentation, the tumors were large (median 5.0 cm) with 70% clinically palpable nodes. All patients received 4 cycles of neo-adjuvant anthracycline-based chemotherapy and were clinically node negative after chemotherapy. SNB was defined as blue and/or hot node plus palpable node(s). A blue or hot node (median 2 nodes) was identified in 93.8%, and median of 5 sentinel nodes were removed. The false negative rate of SNB was 15.3% (95% CI 8.7%-25.3%). The LAS technique comparatively had nodal yield in 98.5% with median 8 nodes removed; and FNR 8.5% (95% CI, 4.2%-16.6%, p=0.19). Comparative NPV for LAS and SNB were 94.6% and 91.8% respectively. Conclusions: Axillary sampling results for FNR and NPV are similar if not superior to SNB and could be a reliable method of axillary nodal evaluation in advanced breast cancers following neo-adjuvant chemotherapy.
TACE 2: A randomized placebo-controlled, double-blinded, phase III trial evaluating sorafenib in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma (HCC).
Authors: Tim Meyer, Richard Fox, Deborah Bird, Anthony Watkinson, Nigel Hacking, Deborah Stocken, Philip James Johnson, Daniel H. Palmer
Journal: Journal of Clinical Oncology (2012)

TPS4150 Background: TACE is regarded as the standard of care for patients with intermediate stage HCC (BCLC B), while sorafenib (S) is the current standard for advanced disease (BCLC C). The combination of S with TACE for intermediate disease is rational since sorafenib inhibits the action of VEGF which may be induced by tumour hypoxia following TACE, and S also has direct anti-tumour effect. The combination has been shown to be safe in and active in phase I and II studies. Phase III trials are now required to determine whether TACE + S is superior to TACE alone in terms of survival. Methods: We are conducting a double blind multicentre trial to determine if the addition of S to TACE is superior to TACE alone. This is a UK NCRI trial sponsored by University College London (UCL) (EudraCT 2008-005073-36). Patients with intermediate stage HCC are randomised 1:1 to continuous S (400mg BD) or placebo (P). Key inclusion criteria include unresectable HCC confined to the liver, patent main portal vein, ECOG PS ≤1 and Child Pugh A liver score. After randomisation patients commence study drug and TACE is performed at 2-5 weeks using drug eluting beads loaded with 150mg doxorubicin (Biocompatibles UK Ltd) according to a standard protocol. Further TACE is performed at the discretion of the investigator based on radiological response and patient tolerance. The primary outcome measure is progression free survival and central, external, real time radiology review is required to confirm progression. Secondary outcome measures are overall survival, time to progression, toxicity, disease control, quality of life and number of TACE procedures performed in 12 months. The target recruitment is 412 in order to detect a hazard ratio of 0.72 using a 2-sided level of significance of α=0.05 with 85% power. The trial was reviewed by the IDMC after the presentation of the SPACE trial (Lencioni et al J Clin Oncol 30, 2012). The IDMC concurred with the conclusion of the SPACE investigators that the combination is tolerated and results required confirmation in a phase III trial. Thus recruitment into the TACE2 trial will continue as planned.
Comparison of genomic alterations in bladder urothelial tumors with and without telomerase reverse transcriptase promoter mutation using a next-generation sequencing assay.
Authors: Sumit Isharwal, Francois Audenet, Eugene J. Pietzak, Eugene K. Cha, Gopa Iyer, Ahmet Zehir, Barry S. Taylor, Michael F. Berger, Satish Tickoo, Victor E. Reuter, Jonathan E. Rosenberg, Dean F. Bajorin, Guido Dalbagni, Bernard H. Bochner, David B. Solit, Hikmat Al-Ahmadie
Journal: Journal of Clinical Oncology (2017)

310 Background: Telomerase reverse transcriptase (TERT) is the most frequently altered gene in urothelial cancer (UC), detected across all grades and stages of disease. We sought to characterize TERT alterations within a prospective cohort of UC treated at our institute and compare the frequency of genomic alterations in TERT promoter mutant vs wild-type UC specimens. Methods: Patients diagnosed with bladder urothelial tumors were enrolled onto an institutional review board approved prospective sequencing protocol. Tumor and matched germline DNA were analyzed for somatic point mutations, truncations, copy number alterations, and insertions/deletions using the MSK-IMPACT NGS assay that detects alterations in all exons and select introns of 410 oncogenes and tumor suppressor genes as well as the entire TERT promoter region. Results: 329 UC were sequenced of which 236 (71.7%) harbored TERT mutations, the majority being promoter region hotspots (chr5: 1295228 G &gt; A [81%] and chr5:1295250 G &gt; A [16%]). Patients with TERT promoter mutations were significantly older than those without (69.01±10.70 years vs. 65.44±11.78 years, p = 0.0317). UC with TERT promoter mutations had significantly higher mutation count [median 10 (range: 2-76) vs median 5 (range: 0-119)] as well as copy number alterations [median 0.11 (range: 0-0.68) vs median 0.047 (range: 0-0.65)]. Between UC with and without TERT promoter mutations, there was a very significant difference in mutation frequencies of ARID1A(33% vs 11%), PIK3CA(28% vs 13%), FGFR3(32% vs 16%), CREBBP(19% vs 4%), CDKN1A(17% vs 2%), ERBB2(26% vs 9%), ERCC2(15% vs 3%), TSC1(11% vs 0%), MT2C(17% vs 9%) (all with p &lt; 0.005). Conclusions: TERT is the most frequently altered gene in bladder cancer with the majority of TERT alterations comprised of two hotspot mutations. UC with TERT promoter mutations tends to occur in older patients and is associated with overall higher mutation count and copy number alterations. A number of genes are differentially mutated in UC with and without TERT promoter mutations and may suggest a link between TERT promoter mutations and distinct mutations profiles in UC.
Phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for refractory relapsed small cell lung cancer (SCLC): North Japan Lung Cancer Group 0802.
Authors: Ryota Saito, Akira Inoue, Shunichi Sugawara, Satoshi Oizumi, Makoto Maemondo, Koichi Okudera, Toshiro Suzuki, Kazuhiro Usui, Masao Harada, Naoto Morikawa, YUkihiro Hasegawa, Osamu Ishimoto, Tomohiro Sakakibara, Hajime Asahina, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2012)

7086 Background: AMR, a new anthracycline agent, has achieved some promising results for advanced SCLC both in the first-line and the second-line setting. However the efficacy of AMR alone against refractory relapsed SCLC was relatively low in previous studies. This study was conducted to evaluate the safety and efficacy of the combination of AMR plus CBDCA in patients with refractory relapsed SCLC. Methods: Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30 mg/m 2 , day1-3) and CBDCA (AUC 4.0, day 1) every 3 weeks. The primary endpoint of this study was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 45% in eligible patients would indicate potential usefulness while ORR of 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.10, at least 24 patients were required. Results: From September 2008 to May 2011, 30 patients were enrolled from 10 institutions. One patient was excluded because of ineligible histology. Patient characteristics were: Male/Female 26/3; median age 67 (range 50-81); Performance status 0/1/2 9/16/4. The median number of treatment cycles were 4 (range 1-7). The objective responses evaluated by RECIST were: CR 0, PR 10, SD 14, PD 5. The ORR was 34% and the disease control rate was 83%. Median PFS was 3.5 months and median survival time was 7.3 months. Grade 3-4 neutropenia was observed in 23 patients (79%) and grade 3-4 thrombocytopenia was observed in 7 patients (24%). One patient (3%) suffered from grade 3-4 febrile neutropenia. Other grade 3 non-hematological toxicities such as infection, interstitial lung disease, hyponatremia, hypoglycemia, were observed in 7 patients (24%). No treatment related death was observed. Conclusions: This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. Further investigation of this treatment is warranted.
Higher prevalence of BRCA2 mutations among Chinese breast cancer patients in a community oncology clinic.
Authors: Yi-Kong Keung, Adriana Hu, Annie Yeung, Amy Chan, Eddie Hu
Journal: Journal of Clinical Oncology (2012)

e12017 Background: According to a large US population-based study, BRCA1 and 2 mutations occur in about 6 and 4% breast cancer cases age &lt;45. Asians have the lowest prevalence of BRCA1 mutation among five US racial groups. The prevalence of BRCA1 and BRCA2 mutations was reported as 8.1% and 2.7% among pts with family history in Shanghai, compared to 4.9% and 7.5% respectively in Hong Kong. We would like to explore the BRCA mutations in a clinic located in an Asian-majority community in California. Methods: Consecutive female breast cancer pts selected for BRCA testing according to NCCN guidelines are retrospectively studied from 10/2009 to 10/2011. Sequencing of all translated exons and immediately adjacent intronic regions of the BRCA1 and BRCA2 was performed on the peripheral blood (Myriad, Utah). Results: Twenty-six pts were included in this study. Six pts have bilateral breast cancers; 2 synchronous and 4 metachronous with intervals of 11-13 years. Nine pts (34.6%) had BRCA2 germline mutations, of which 5 were considered deleterious and 4 of uncertain significance. Eleven pts (42.3%) had no BRCA mutation. BRCA results were unavailable in six pts because they were either not yet done or denied by health insurance. Conclusions: 1. High prevalence of BRCA2 mutation is seen in our pts selected according to NCCN guidelines. The presence of BRCA2 but not BRCA1 mutation in our study is intriguing. 2. Triple negative breast cancer is not more prevalent in BRCA2 mutation carriers. 3. Similar frequency of family history of breast/ovarian cancer is noted among pts with or without BRCA2 mutation, deleterious or of uncertain significance. The role of the BRCA2 mutation of uncertain significance needs to be further elucidated. 4. Due to the small sample size, further study is required to confirm our findings. [Table: see text]