tbuckley/cabot-search huggingface dataset:
Targeted prostate cancer screening in <i>BRCA1</i> and <i>BRCA2</i> mutation carriers to detect clinically significant disease: Results from the initial screening round of the IMPACT study.
Authors: Christos Mikropoulos, Elena Castro, Elizabeth Bancroft, Elizabeth Page, Natalie Taylor, Mahbubl Ahmed, Chee Leng Goh, Ros A. Eeles
Journal: Journal of Clinical Oncology (2014)

8 Background: Men with germline BRCA1/2 mutations have a higher risk of developing prostate cancer (PrCa) than non-carriers. IMPACT is an international consortium of 62 centers in 20 countries evaluating the use of targeted PrCa screening in men with BRCA1/2 mutations. This analysis reports the first year’s screening results for all men at enrolment in the study. Methods: We recruited men aged between age 40 and 69 with germline BRCA1/2 mutations and a control group that tested negative for a BRCA1/2 mutation. All men underwent prostate-specific antigen (PSA) testing at enrollment and those with a PSA of greater than 3ng/ml threshold were offered prostate biopsy. All men are offered a biopsy irrespective of PSA level after five years of screening. Results: We recruited 2,481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls) of whom 199 (8%) presented with a PSA greater than 3ng/ml. We performed a total of 162 biopsies and diagnosed 59 PrCas (18 BRCA1 carriers, ten BRCA1 controls; 24 BRCA2 carriers, seven BRCA2 controls); 66% of the tumors were classified as intermediate or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3·0ng/ml in BRCA2 mutation carriers was 48%, double that reported in population screening studies. A significant difference in detecting intermediate or high-risk disease was observed in BRCA2 carriers using this threshold. Conclusions: The IMPACT screening network will be useful for targeted PrCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this yields a high proportion of aggressive disease. Early data indicate that the majority of BRCA1/2 mutation carriers diagnosed with prostate cancer at biopsy had developed clinically significant disease (requiring radical treatment). Clinical trial information: NCT00261456.
Assessing patients’ values when standard-of-care options are exhausted.
Authors: R. D. Pentz, Z. L. Farmer, M. J. Green, C. Daugherty, F. J. Hlubocky, S. K. Peterson, C. C. Sun, C. M. Lewis, T. K. Owonikoko, F. R. Khuri, R. D. Harvey
Journal: Journal of Clinical Oncology (2011)

9108 Background: ASCO recently published guidelines recommending that physicians assess the treatment goals and preferences of patients with advanced cancer. Formal assessment is important before an early phase trial is recommended. No standard assessment tool currently exists. Methods: We surveyed a convenience sample of oncologists and palliative care physicians (MDs) and interviewed patients (pts) at an academic medical center (AH) in an active early phase clinical trial program and at a public hospital (PH) with no such program. MDs were asked about interest in and barriers to values assessment. Pts were asked to rank values important to advanced cancer treatment decisions. Results: 36/64 (56%) MDs and 29/31 (93.5%) pts participated. All MDs reported trying to incorporate pts’ values into their recommendations, but identified the following barriers: a) lack of time to discuss values, b) pt reluctance to share values, c) lack of a simple tool to assess values, and d) family members monopolizing the conversation. Most (69%) were strongly or moderately interested in methods to facilitate values discussions, including a) a paper and pencil tool that the pt completes (64%), b) a list of questions for the MD to ask (55%), and c) a report by a nurse or social worker on the pt’s values (47%). MDs rated the following patient values as important to assess: a) wants access to experimental agents, b) chooses quantity over quality of life, c) wants to help others, and d) is concerned about side effects. Pts’ self-reported values varied by hospital type. More AH than PH pts reported getting the best information (p=0.01) and having access to investigational drugs (p=0.00007) as important. More PH pts reported being healthy/finding a cure (p=0.03), spending time with family (p=0.07) and avoiding treatment side effects (p=0.09) as important. Conclusions: Barriers to assessing patient values in advanced cancer care exist. A simple tool to facilitate discussion of values may be feasible, useful, and may help overcome these barriers. A diverse sample of patients can help identify the values to assess as well as identify a subset of values that could help physicians distinguish patients who value early trial participation from those who do not. Support: 5P01 CA116676-04 NCI PO1.
Whole exome sequencing and gene expression profiling of neuroendocrine carcinoma in the stomach.
Authors: Rie Makuuchi, Masanori Terashima, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Keiichi Hatakeyama, Masatoshi Kusuhara, Ken Yamaguchi, Keiichi Oshima, Kennichi Urakami, Makoto Hikage
Journal: Journal of Clinical Oncology (2016)

57 Background: Neuroendocrine carcinoma (NEC) in the stomach is a rare disease with the incidence of about 0.6 % of all gastric cancer and is well known as a highly malignant tumor with poor survival. Despite the malignant phenotype of this disease, the global gene expression profiling of gastric NEC has not yet been elucidated. We have started a comprehensive molecular profiling project that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from January 2014, setting a goal to get 3,000 samples in 3 years. We had already evaluated more than 1,500 samples from various types of malignancies, including 111 samples from gastric cancer. Here, we performed deep sequencing of 409 cancer-related genes for gastric NEC patients, adding whole-exome sequencing and gene expression profiling, to identify a gene variant of gastric NEC. Methods: Surgically-resected fresh tumor samples and peripheral blood were analyzed by whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies). A total of 111 patients with gastric cancer were evaluated until August 2015, including 6 gastric NEC (5.4 %). We compared single nucleotide variants (SNVs) and gene expression profiles between gastric NEC and gastric adenocarcinoma. Results: All the gastric NEC patients were male with median age of 69 years (59–79 years). According to classification of TNM 7th, there were two patients with stage IA, one with IIA, one with IIIB and two with IIIC. Three of them had adenocarcinoma components constituted &gt; 30% of the respective tumors, fulfilling the criteria for mixed adenoneuroendocrine carcinoma (MANEC), as defined by the WHO classification. There was no specific SNV for NEC. However, gene expression profiling identified several specific genes expressing in NEC; most of the highly expressed genes were also known to be expressed in neuroendocrine cells. Furthermore, CPLX2 and SCG3, which had been reported to be expressed in various neuroendocrine tumors, were included. Conclusions: Gastric NEC could be characterized by specific gene expression including those expressed in neuroendocrine cells and neuroendocrine tumors.
Adjuvant paclitaxel followed by oral fluoropyrimidines for gastric cancer: Safety data of the factorial phase III SAMIT trial.
Authors: Michiya Kobayashi, Akira Tsuburaya, Kazuhiro Yoshida, Shigefumi Yoshino, Yumi Miyashita, Satoshi Morita, Koji Oba, Marc E. Buyse, John S. Macdonald, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2012)

72 Background: Adjuvant chemotherapy with fluoropyrimidine (FP) with or without platinum for gastric cancer (GC) has become standard almost worldwide; however, there has been no comparison among concurrent, sequential, and monotherapy. Paclitaxel (PTX) is one of key drugs in GC widely used as 2 nd -line chemotherapy in Japan. Methods: SAMIT is a randomized, multicenter phase III study of FP (S1 or UFT) vs. PTX followed by FP in patients (pts) with gastric adenocarcinoma. Eligibility includes T3/T4, N0-2, M0 except for positive lavage cytology, chemotherapy- and radiotherapy- naive, being able to start chemotherapy 14 and 56 days after D2 gastrectomy. Pts received either UFT 267 mg/m 2 /day for 4w, q4w x 6 cycles (arm A); S1 80 mg/m 2 /day for 2w, q3w x 8 cycles (arm B); PTX 80 mg/m 2 Day 1, 8 for the first 3w x 1 cycle, Day 1, 8, 15 q4w x 2 cycles, followed by UFT 267 mg/m 2 /day for 4w, q4w x 3 cycles (arm C); or PTX as in C, followed by S1 80 mg/m 2 /day for 2w, q3w x 4 cycles (arm D). The FP cycles was prolonged by 24w after ACTS-GC publication in 2007. Primary endpoint is disease-free survival and total number of patients was calculated to be1480 where 90% power for superiority of C+D group vs. A+B. The Independent Data Monitoring Committee undertook a review of the 1417 pts at the 2nd interim analysis in 2011. Results: Arm A (n=353), arm B (n=359), arm C (n=352), arm D (n=353) were well balanced for baseline factors. The compliance with UFT in arm A and S1 in B was 74% and 76% in the first 12 weeks, and 89% and 90% between week 37 and 48; that in arm C and D was 83% and 80% in the second 12 weeks, and 94% and 84% between week 37 and 48. Numbers of grade 3/4 hematological and non-hematological adverse events (AEs) were 3 and 46, 0 and 64, 5 and 35, and 16 and 67 for arm A, B, C, and D, respectively. Anorexia was the most common AE observed in 5.8%, 6.8%, 1.7%, and 5.1% for arm A, B, C, and D, respectively. There were 363/1323 (27%) deaths and 762/1323 (58%) of pts survived disease free. Conclusions: Adjuvant chemotherapy with sequential PTX and FP for GC was safe and the compliance of the FP part could be better than that of FP monotherapy. The final efficacy results will be formally assessed in 2012.
The impact of neoadjuvant therapy for gastroesophageal adenocarcinoma on postoperative morbidity and mortality.
Authors: Eva Fuentes, Rima Ahmad, Theodore S. Hong, Jeffrey W. Clark, Eunice Lee Kwak, David W Rattner, John Thomas Mullen
Journal: Journal of Clinical Oncology (2015)

156 Background: The effects of neoadjuvant chemotherapy (CTX) or chemoradiotherapy (CTX-RT) on postoperative complications following surgical resection of adenocarcinomas of the stomach and gastroesophageal junction (GEJ) have not been well studied. Methods: We identified 308 patients undergoing a surgery-first approach and 145 patients undergoing neoadjuvant therapy (CTX, n = 73 and CTX-RT, n = 72) followed by curative-intent surgeryfor adenocarcinomas of the stomach and GEJ from 1995-2014. We compared the baseline characteristics and the postoperative outcomes between the two groups using univariate and multivariate analyses. Results: Patients receiving neoadjuvant therapy were significantly more likely to be of younger median age (63 y vs. 71 y), have tumors of the GEJ (37% vs. 17%), to undergo esophagogastrectomy (51% vs. 26%) and D2 lymphadenectomy (39% vs. 27%), and to have more advanced stage disease than patients undergoing surgery first. There were no differences in overall 30-day morbidity or mortality rates between the neoadjuvant therapy and surgery-first groups, respectively (Table). However, patients undergoing surgery first were significantly more likely to have higher-grade complications than those undergoing neoadjuvant therapy. Conclusions: Despite having more advanced disease and undergoing higher-risk surgical procedures, patients with adenocarcinomas of the stomach or GEJ who receive neoadjuvant therapy prior to surgery are less likely to have major post-operative complications than patients treated with a surgery-first approach. Concerns about higher rates of post-operative complications should not deter the use of neoadjuvant therapy for gastroesophageal cancer. [Table: see text]
Quality measures that focus on patient and family engagement in oncology.
Authors: Kyung Min Song, Kristi Mitchell
Journal: Journal of Clinical Oncology (2014)

270 Background: National Quality Strategy set forth by the Department of Health and Human Services emphasizes that each person and family is engaged as partners in their care. Appropriate use of quality measures can serve as a means of achieving this. Studies have shown that patient engagement can lead to improved healthcare outcomes, lower resource utilization, and reduced costs. As such, Avalere sought to identify oncology-related quality measures that address patient and family engagement, and determine ways to advance engagement in oncology through the use of quality measures. Methods: Avalere assessed publicly available sources to identify person and family engagement measures related to oncology, including measures related to patient education, care preferences, and care planning. Avalere also assessed the current use of these measures in CMS’ quality programs. Results: Avalere identified six oncology-specific measures related to person and family engagement. One of the measures is included in CMS’ Physician Quality Reporting System and the Electronic Health Record Incentive Programs. Three measures identified are related to documenting patients’ preferences during end of life care, two are related to care planning for pain and depression, respectively, and one is related to patient education on treatment. None of the measures are related to specific cancers. Conclusions: Avalere found lack of measures related to patient and family engagement in oncology. Given the importance of patient and family engagement during the course of disease management, opportunity exists to improve oncology care quality through measurement and evaluation of engagement. Oncology patients’ quality of care can be improved through data support, stakeholder buy-in, standardized methodology for measuring engagement, evidence linking engagement and outcomes, and implementation measures in incentive programs.
Evaluating malignant intraductal papillary mucinous neoplasm: A population-based study.
Authors: Carrie Luu, Rebecca A. Nelson, Byrne Lee, Gagandeep Singh, Joseph Kim
Journal: Journal of Clinical Oncology (2013)

324 Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been increasingly recognized. Due to a paucity of evidence, the management and treatment of IPMN is still under debate. We hypothesize that with increased awareness, the incidence and resection rates for IPMN would increase. Using a population-based cancer registry, we examined incidence, prognostic factors, and survival for IPMN. Methods: Patients diagnosed with invasive IPMN from 1988 to 2009 were identified by the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographics, clinical and pathologic factors, and therapies received (surgery and/or radiation) were analyzed. Survival was assessed by Kaplan-Meier method; Cox proportional hazard modeling was used for multivariate analysis. Results: 2,987 patients were identified. Over the study period, there was a decrease in age-adjusted incidence. The overall resection rate was 20.6% with an increase in annual rates of resection. On univariate analysis, age greater than 65 years, tumor location, poorly differentiated tumor grade, higher T stage, and positive lymph nodes predicted worse survival; more recent diagnosis, higher number of lymph nodes examined, and surgery were indicators of improved survival. On multivariate analysis, curative surgery remained predictive of survival. Patients who underwent surgery had median survival rates of 87, 18, and 14 months compared to 6, 7, and 5 months in the no surgery group for stages I, II, and III, respectively. Conclusions: Although recent reports show increasing incidence of IPMN, our study involving a population-based cohort demonstrates decreasing incidence of malignant IPMN. This may be accounted for by increased detection of non-malignant disease. It is imperative that we identify patients with invasive IPMN early so that they may benefit from the survival advantage conferred by curative resection.
Biochemical response to ketoconazole therapy in post-chemotherapy mCRPC patients.
Authors: M. Andreas Roeder, Kasper Drimer Berg, Daniel Hunde, Camilla Nerstroem, Frederik Birkebæk Thomsen, Klaus Brasso, Peter Iversen
Journal: Journal of Clinical Oncology (2014)

174 Background: Ketoconazole for the treatment of metastatic castration resistant prostate cancer (mCRPC) has never been investigated in randomized trials. In fact, although ketoconazole is a less potent inhibitor of the CYP-17 enzyme systems compared to abiraterone, there is no head-to-head evidence demonstrating that this translates into improved survival. We analyzed biochemical response rates in post-chemotherapy mCRPC patients who were treated with ketoconazole 200 mg TID plus prednisone 5 mg BID at a single center in Denmark. Methods: Between 2008 and 2012, where neither abiraterone nor enzalutamide was available in Denmark, a total of 30 post-chemotherapy mCRPC patients were managed with ketoconazole. Percent change in prostate-specific antigen (PSA) and alkaline phosphatase (ALP) from baseline were registered. Overall survival was calculated from the initiation of ketoconazole. Results: At initiation of ketoconazole, median age was 66 (range: 58 to 76). Median PSA was 547 ng/ml (65 to 4,241). Median ALP was 159 U/L (51 to 750). The median number of prior cancer therapies was five (three to nine). The median time on ketoconazole treatment was 150 days (14 to 648). A total of 44% patients had any decline in PSA, whereof 31% experienced a decline of &gt;=50%. At three months, a total of 19 patients still received ketoconazole, whereof 26% sustained a PSA decline of &gt;=50% from baseline. A total of 71% experienced any decline in ALP, whereof 36% experienced a maximum decline of &gt;=50%. At three months, 7 of 19 patients (36%) sustained an ALP decline of &gt;=50% from baseline. At follow-up, 28 of 30 patients had died. The median overall survival was 10.5 months (95%CI: 8.3-12.6). Conclusions: Compared to the post-chemotherapy phase II study of abiraterone (58 patients) our cohort most likely had a larger tumor burden (e.g. higher PSA, more therapies prior to start of ketoconazole). Nonetheless, we demonstrated a reasonably comparable maximum &gt;=50% PSA response-rate (43% in phase II) and three-months response-rate &gt;=50% (36% in phase II). Also a significant decline in ALP was demonstrated here which has not been reported in abiraterone trials. Given the large difference in expenditure, a head-to-head comparison of abiraterone and ketoconazole in mCRPC patients still seem justified.
Temozolomide and radiotherapy in malignant glioma: Final update of a phase II monoinstitutional study.
Authors: R. Ratti, Z. Coccorullo, D. Guarneri, E. Campora, M. Orsatti, G. Addamo, G. Colloca, A. Venturino, M. Boccardo
Journal: Journal of Clinical Oncology (2011)

e12521 Background: Temozolomide (TMZ), an oral imidazotetrazine second-generation alkylating agent that enters the cerebrospinal fluid, has demonstrated antitumor activity in high-grade glioma when given as adjuvant therapy concomitant with RT, and then alone (Stupp R., NEJM,2005). Methods: The aim was to evaluate disease free (DFS) overall survival (OS) and safety TMZ in combination with RT in high-grade cerebral glioma, after surgery. RT to limited fields was administered once a day at 2 Gy/fraction, 5 days a week for 6 weeks, for a total of 60 Gy, with concomitant TMZ 75 mg/sqm daily, followed by 6 cycles of TMZ 150-200 mg/sqm daily on days 1->5 q 28 days. Results: From 11/2004 to 9/2007, we accrued 23 consecutive pts, median age 63 years (range 34-72), 18 M, 5 F; ECOG PS was 0 in 21 pts and 3 in remaining 2. 10 pts. (43,5%) had R0 resection; 7.(30,4%) underwent not-radical resection, and 6 (26,1%) were considered inoperable. Pathology was as follows: glioblastoma 14 (60,9%), anaplastic astrocytoma 4 (17,4%), astrocytoma GII 4 (17,4%), anaplastic oligodendroglyoma 1 (4,3%). 19 pts (82,6%) completed concomitant RT/CT treatment and 8 (34,7%) also completed the subsequent 6 cycles of TMZ as planned. 2 pts. (8,7%), R2 resected and inoperable respectively, suspended TMZ/RT program due to early progression and the other 2 (8,7%) PS 3 pts., received no treatment. 10/19 (52,6%) pts., who completed the first part of the planned treatment, delayed TMZ cause of PD after a median of 3 cycles (range 1-5); 1/19 (5,3%) did not receive TMZ due to PD after TMZ/RT. No G3/4 toxicity occurred DFS was 5,5 + months (range 1-47+). Second line CT with PCV was given to 5/23 pts (21,7%), TMZ dose dense in 2/23 (8,7%) and 1/23 (4,3%) underwent third line CT with fotemustine.1/23 (4,3%)was treated with rescue surgeryand 2/23 (8,7%) with stereotassic radiotherapy. Median OS was 10,1+ months (range 1,1-72+). Conclusions: Even if debulking surgery occurred in only 74% pts, this schedule is safe, feasible and active in malignant glioma. During following years, due to improvement of OS, more pts underwent further lines of CT or stereotassic radiotherapy or novel surgery, unthinkable since few years ago.
Optimising magnetic resonance imaging for preoperative staging and surgical planning in colon cancer at 1.5 tesla and 3.0 tesla.
Authors: C. J. Hunter, E. Scurr, N. Jeyadevan, D. J. Collins, M. Abulafi, P. P. Tekkis, P. A. Georgiou, M. O. Leach, G. Brown
Journal: Journal of Clinical Oncology (2011)

395 Background: The aim of this study was to determine best technique for future preoperative staging and operative planning in colon cancer using MRI at 1.5T, and feasibility at 3.0T. Methods: 39 scans were performed in 4 healthy volunteers comparing bowel distension using different oral contrast techniques; no oral preparation, 1L of water, 1L of poly ethylene glycol (Klean-Prep), and 1L of 2.1% barium sulphate and 3.2% sorbitol solution (E-Z-Cat) at 1.5T. Bowel distension was scored blindly by 2 experienced radiologists. A further 35 scans compared image quality of T2-weighted pulse sequences; 2D-TrueFISP, 3D-TrueFISP, HASTE, 2D-TSE and 3D-TSE. Scans were scored for movement artefact, colon wall and colon mesentery visualisation. Signal to noise ratio (SNR) was calculated. Inter-observer agreement was assessed using Cohen's Kappa. Equivalent optimised protocols were derived at 3.0T and tested for feasibility. Results: Inter-observer agreement for scoring was good (kappa = 0.61-0.67). Sorbitol-barium sulphate gave significantly better small bowel distension than no oral preparation, water and Klean-Prep (mean score 3.8 vs 1.6, 2.2 and 1.9, p≤0.007). 2D TrueFISP sequences gave the highest mean score for scan quality, significantly better than 3D-TSE, 2D-TSE, 3D-TrueFISP and HASTE (mean 10.6 vs 3.2, 7.8, 7.7 and 7.4, p≤0.012). 2D-TSE sequences obtained best SNR, significantly greater than obtained using 3D-TSE (p=0.045). 3.0T sequences were comparable or superior. Conclusions: Colon imaging using MRI requires fast sequences and adequate bowel distension. Our observations indicate that 2D-TrueFISP and 2D-TSE sequences with 1L Sorbitol-Barium sulphate orally give the best T2-weighted images of the colon wall and adjacent structures for cancer staging at 1.5T; equivalent 3.0T protocols are possible. No significant financial relationships to disclose.