tbuckley/cabot-search huggingface dataset:
Delivering more, earlier, and better goals-of-care conversations to seriously ill oncology patients.
Authors: Rachelle Bernacki, Joanna Paladino, Daniela Lamas, Mathilde Hutchings, Josh Lakin, Bridget A. Neville, Stuart R. Lipsitz, Atul Gawande, Susan Block
Journal: Journal of Clinical Oncology (2015)

39 Background: Patients with serious illness routinely receive treatments that are not aligned with their goals. Earlier clinical conversations about patients’ values and priorities lead to more goal-concordant care and improved quality of life, but these conversations often happen too late or not at all. The Serious Illness Care Program has designed a systematic approach to train and support clinicians in conducting more, earlier, and better conversations about goals of care with their patients. Objectives: Evaluate clinician adoption and acceptability of the training program and the Serious Illness Conversation Guide; determine the frequency, timing, and quality of goals of care documentation before death. Methods: Cluster-randomized trial including oncology clinicians and their patients. Intervention: clinician identification of high risk patients; 2½ hour clinician training on the Serious Illness Conversation Guide; email trigger/reminder; EMR documentation. Preliminary chart review to extract goals-of-care conversations for deceased patients in intervention and control. Results: 90 oncology clinicians: 47 intervention; 43 control. Of 47 intervention clinicians, 46 are trained and rate the training as effective (4.3/5). 97% of trained clinicians who have been triggered have adopted the Conversation Guide and find it acceptable (4.2/5). 342 patients enrolled: 176 intervention; 166 control; 38% have died (n = 131). A preliminary chart review revealed more goals-of-care conversations occurred before death in intervention compared to control (92% versus 70%, p = 0.0037); intervention conversations took place four months earlier than control (median 143 days versus 63 days, p = 0.0008). In addition, conversations were more patient centered (95% versus 45%, p &lt; 0.001) and more readily retrievable in the EMR (68% versus 28%, p &lt; 0.001). Conclusions: Preliminary data about the Serious Illness Care systematic approach demonstrate strong clinician adoption and acceptability. The intervention results in more, earlier, and better conversations about patient values and priorities, in addition to more patient-centered and retrievable documentation of goals of care in the medical record. Clinical trial information: NCT01786811.
Use of genetic variants in c-MET to predict clinical outcome in localized gastric cancer (GC) patients (pts) treated with surgery.
Authors: Yu Sunakawa, Takeru Wakatsuki, Wu Zhang, Dongyun Yang, Mizutomo Azuma, Yan Ning, Sebastian Stintzing, Stefan Stremitzer, Shinichi Yamauchi, Ana Sebio, Nico Benjamin Volz, Rita El-khoueiry, Wasaburo Koizumi, Masahiko Watanabe, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

50 Background: Dysregulation of the c-MET signaling pathway occurs in a wide range of human cancers including GC. Such derangements result from various molecular mechanisms, including mutations, amplification and overexpression of c-MET. Overexpression and amplification of c-MET have been correlated with poor clinical outcomes in pts with GC. However, the association between c-MET polymorphisms and prognosis in GC is not well defined. We examined the prognostic impact of c-MET polymorphisms on clinical outcomes in pts with localized GC treated with surgery. Methods: One-hundred and sixty-one Japanese pts were included, with localized GC (stage Ib-IV) treated with surgery alone (n=58), or surgery plus adjuvant therapy (n=103) between 2002 and 2010. Median follow up was 4 years. Genomic DNA was extracted from the pts’ blood or tissue. Six functionally significant c-MET SNPs (rs1621, rs40239, rs41736, rs41739, rs184953, rs10234854) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with disease free survival (DFS) and overall survival (OS) by uni- and multivariate analyses, adjusting for age, sex, stage and type of adjuvant therapy. Results: The MET rs40239 variant was associated with favorable clinical outcomes. Univariate analysis showed pts with any G (AG/GG) allele had significantly longer DFS and OS compared to those with the AA genotype (HR: 0.43; 95% CI: 0.25-0.74; P=0.001, HR: 0.47; 95% CI: 0.27-0.81; P=0.006, log-rank test, respectively); this remained significant upon multivariate analysis (HR: 0.48; 95% CI: 0.27-0.83; P=0.009, HR: 0.50; 95% CI: 0.28-0.88; P=0.017, respectively). In the subgroup analysis by gender, men, but not women, with the AG/GG genotypes maintained a DFS and OS benefit. Conclusions: Our results show for the first time that the c-MET polymorphism, rs40239, may serve as a prognostic marker in pts with localized GC treated with surgery. There also appears to be a gender-related difference in the impact on clinical outcome by genetic variants of c-MET. Prospective validation of this study is warranted.
Clinical outcomes of patients of different races in a phase IV community-based trial of first-line trastuzumab plus a taxane in HER2+ metastatic breast cancer (MBC)
Authors: J. C. Reddy, C. R. Barker, D. Lim, P. M. Klein
Journal: Journal of Clinical Oncology (2005)

751 Background: Trastuzumab (Herceptin, H) is a humanized monoclonal antibody which showed a significant survival benefit in a randomized trial comparing chemotherapy plus H vs. chemotherapy alone in first-line treatment of HER2+ MBC. Race has been associated with differences in clinical outcome in breast cancer in numerous studies, and non-White patients (pts) are typically underrepresented in clinical trial populations. To investigate differences in outcomes for patients with HER2+ MBC, we performed an exploratory analysis to determine whether baseline characteristics or clinical outcomes differed by race in this large non-randomized, community-based, phase IV trial of first-line taxane/H therapy. Methods: Pts had previously untreated HER2+ MBC (prior hormonal therapy allowed), normal left ventricular ejection fraction (LVEF), and measurable or evaluable disease. All pts received H weekly with either paclitaxel or docetaxel at standard doses. Results: 466 pts have been enrolled: 364 White (78%), 61 African-American (13%), 41 Other (9%) (Hispanic, Asian/Pacific Islander, Native American). The distributions of selected baseline characteristics (age, median time since primary diagnosis, stage at initial diagnosis) were similar between the groups. See table for clinical outcomes. Non-White patients had a lower response rate to taxane/H therapy than did White patients. Conclusions: These exploratory analyses suggest that in this large, non-randomized phase IV community-based study of HER2+ MBC, patients obtained clinical benefit from taxane/H therapy regardless of race. Median survival has not yet been reached for African-American subjects. Cardiac evaluations (serial LVEF measurements) were similar for all groups. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
First Analysis of an International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the Remarc Study from Lysa
Authors: Catherine Thieblemont, Hervé Tilly, Maria Gomez da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Sebastian Grosicki, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen Van Eygen, Josette Briere, Jose Cabecadas, Gilles Andre Salles, Philippe Gaulard, Andre Bosly, Bertrand Coiffier
Journal: Blood (2016)
Single Agent Arsenic Trioxide Regimen for the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Initial Results of a Multicenter Randomized Controlled Study From India to Study the Optimal Duration of Arsenic Trioxide Maintenance Therapy (IAPLSG04).
Authors: Vikram Mathews, Biju George, Farah Jijina, Cecil Ross, Reena Nair, Shashikant Apte, Geetha Narayanan, Atul Sharma, Kavitha M Lakshmi, Auro Viswabandya, Ezhilarasi Chendamarai, Poonkuzhali Balasubramanian, Vivi Srivastava, Alok Srivastava, Mammen Chandy
Journal: Blood (2009)
Pancreatic cancer and BRCA mutation in familial breast cancer families
Authors: M. Hall, O. Olopade
Journal: Journal of Clinical Oncology (2005)

9550 Background: The majority of individuals presenting to a high-risk cancer clinic have a personal/family history (FHx) of breast cancer. For those individuals who wish to have genetic testing, germ-line sequencing for the familial breast cancer genes BRCA1/2 may help to quantify risk of breast and/or ovarian cancer and may provide guidance regarding screening or prophylaxis. Pancreatic adenocarcinoma (PC) is one of a spectrum of cancers related to BRCA mutation. Recently, BRCA2 has been identified as a major familial PC susceptibility gene. Approximately 5–15% of unselected PC’s have germ-line mutations of the BRCA2 gene. While few practitioners currently offer BRCA testing to individuals with a personal/FHx of PC, individuals from hereditary breast/ovarian cancer (HBOC) kindreds who undergo genetic testing may also have a FHx of PC. Methods: From a database of 1411 probands presenting to the University of Chicago Cancer Risk Clinic over the past 10 years, 66 families meeting criteria for HBOC with >1 close (1st or 2nd degree) PC were identified. FHx was obtained by proband proxy and verified by medical records when available. Malignancy history, familial mutation status, and cancers in close relatives were assessed. Results: Among 66 HBOC kindreds, germ-line testing for BRCA1 and BRCA2 mutations was performed in 31(47%) probands or close relatives. 8BRCA1 and 9BRCA2 mutations were found, as well as 2 families with BRCA2 variants. In total 17/31(55%) families with mutations had a solitary PC in a close relative. One family each with BRCA1 and BRCA2 mutations had two close relatives with PC, and one BRCA2 family contained 4 PC’s. Age of PC diagnosis did not correlate with mutation status; however, PC in BRCA2 families had a mean younger age of onset [57.1 yrs, 49.1–64.3] than in BRCA1 [66 yrs, 57.1–74.7].[p=0.12] or families with a negative test [70.0 yrs, 61.2–84.2][p=0.03]. Conclusions: In a high-risk population, BRCA1 and BRCA2 mutations are common among HBOC families with PC in a close relative. FHx of PC, particularly early-onset, may have predictive power in identifying individuals with germ-line BRCA mutations, including BRCA+ familial PC kindreds. No significant financial relationships to disclose.
Interim results of a phase 1b/2a study evaluating the nano pharmaceutical CRLX101 with bevacizumab (bev) in the treatment of patients (pts) with refractory metastatic renal cell carcinoma (mRCC).
Authors: Stephen Michael Keefe, Daniel Heitjan, Meliessa Hennessey, Janelle Robinson, Kristine Mykulowicz, Amy Marshall, Orvar Gunnarsson, Ronac Mamtani, David J. Vaughn, Jean H. Hoffman-Censits, Katherine L. Nathanson, Priti Lal, Daniel A. Pryma, Scott Eliasof, Edward Graeme Garmey, Roger B. Cohen, Naomi B. Haas
Journal: Journal of Clinical Oncology (2014)

412 Background: VHL is inactivated in most clear cell RCC (ccRCC) tumors giving rise to the HIF hypoxia response program and tumor angiogenesis. Antiangiogenic therapies are active in ccRCC, but resistance develops in all pts. Dual inhibition strategies may be needed to overcome resistance. CRLX101, a novel nano pharmaceutical formulation of camptothecin, has been shown in pre-clinical models to target HIF. We combined CRLX101 with bev in the treatment of pts with refractory mRCC in order to determine the safety and the recommended phase 2 dose (RP2D) of the combination, and to determine the therapeutic activity of treatment. Methods: Pts with mRCC refractory to conventional antiangiogenic therapies (all subtypes) were treated every 2 weeks with bev 10 mg/kg and escalating doses of CRLX101 (12 mg/m 2 , 15 mg/m 2 ) in a standard 3+3 design with an expansion at the RP2D. Pts were treated until progression, death, or prohibitive toxicity. Adverse events were classified using CTCAE v 4.0. Radiographic results were assessed by RECIST v1.1. Results: 10 pts were enrolled on study – 6 clear cell, 2 papillary, 2 chromophobe. Median prior number of therapies was 2. No dose limiting toxicities were observed. CRLX101 at its single-agent RP2D (15 mg/m 2 ) was safely combined with standard bev. 2 episodes of grade 3 non-infectious cystitis and 1 episode of grade 3 hypertension were observed. All other toxicities were grade 1 or 2. The median progression free survival (PFS) was 7.6 months which exceeded our pre-specified threshold of 16 weeks and has triggered 2 nd stage accrual. 3 of 9 evaluable pts (33%) achieved a confirmed partial response (PR) including 1 patient with papillary mRCC; 4 pts (44%) displayed stable disease, and 2 had progressive disease as their best overall response. Conclusions: Our results demonstrate that CRLX101 can be safely combined with bev in pts with refractory mRCC. The RP2D is 15 mg/m 2 q2w of CRLX101 with standard bev. Preliminary outcomes to date suggest that clinical benefit, manifest as prolonged PFS, is conferred to pts with all histologic subtypes of mRCC. Clinical trial information: NCT01625936.
Patient-specific quality assurance measurements for VMAT treatments: Do we really catch errors?
Authors: Wolfram Laub, Charles R. Thomas
Journal: Journal of Clinical Oncology (2013)

81 Background: Patient-specific quality assurance measurements are time consuming and Gamma pass/fail criteria are often picked based on typical criteria used for IMRT QA measurements in the past. The questions needs to be asked if with these criteria QA plans could still show clinically significant deviations from the treatment plan calculated and how we should be doing QA for treatment delivery of complex treatment plans. In our study DICOM files of clinical Rapidarc plans were modified with in-house developed software to mimic leaf alignment errors and gravitation shifts. The Octavius 2D-ARRAY (PTW-Freiburg) and the Delta4 device (Scandidos) were used to investigate the effect of the simulated errors on the passing rate of quality assurance results. The manipulated Rapidarc plans were recalculated on patient CT scans in Eclipse. Methods: Three different types of errors were simulated and applied to five prostate (two arcs), three 2-arc head and neck cases and three 3-arc head and neck cases. The MLC modifications were: (1) both MLC banks are opened by 0.25mm, 0.50mm and 1.00mm in opposing directions resulting in larger fields, (2) both MLC banks are closed by 0.10mm, 0.25mm and 0.50mm, (3) both MLC banks are shifted in the same direction for lateral gantry angles to simulate effects of gravitational forces onto the leaves by 1mm, 2mm and 3mm, (4) 25%, 50% 70% and 100% of all active leaves are shifted by 3mm as in (3). QA evaluations were performed according to a gamma-index criterion of 3mm and 3% as well as 2mm and 2%. Results: All unmodified plans and the majority of the plans with the smallest modification pass the gamma-index criterion of 2%/2mm with &gt;90%. After that the passing rate drops below 90%. For the largest modifications passing rates were typically below 85%. The Delta4 is generally more sensitive and the passing rate for modified plans drops below 90% earlier and more drastically. With the standard criteria (3mm, 3%) even the largest modifications would satisfy a &gt;90% passing rate. Conclusions: A stricter gamma-index (2mm, 2%) is necessary in order to detect MLC positional errors and a passing rate of &gt;90% should be expected. Clinical pass/fail criteria need to be developed.
Differential overall survival (OS) results in RECORD-3 study based on three distinct mRCC molecular subgroups classified by BAP1 and/or PBRM1 mutations.
Authors: James Hsieh, David Chen, Patricia Wang, Yingbei Chen, Mahtab Marker, Parul Patel, Michael Chevinsky, Umesh Bhanot, Patrizia Pinciroli, Michael F. Berger, Emily Cheng, William Lee, Jennifer J. Knox, Martin Henner Voss, Maurizio Voi, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

561 Background: PBRM1 and BAP1, both of which encode chromatin modulating proteins, have recently been identified as frequently mutated tumor suppressor genes in RCC. However, their correlation with outcomes of targeted therapies is unknown. We explored correlations between overall survival (OS) and mutations in archival tumor samples from RECORD-3, a randomized phase 2 trial comparing first-line everolimus (EVE) then sunitinib (SUN) to first-line SUN then EVE at progression in 471 treatment-naïve mRCC patients (J Clin Oncol 2014; 32:2764). Methods: Somatic mutations in exons of 341 cancer related genes were identified by a next generation sequencing (NGS) assay (MSK IMPACT). Association between genotypes and OS was assessed by Cox PH models and log-rank tests. Results: DNA of 258 archival tumor and 181 matched germline samples was successfully analyzed (median coverage 530X). Three molecular subgroups Gr1 (BAP1 MT [mutant], PBRM1 WT [wild-type]/MT; 17.4%), Gr2 (PBRM1 MT, BAP1 WT; 38.4%), and Gr3 (PBRM1 WT, BAP1 WT; 44.2%) with different OS outcomes after sequential EVE-SUN or SUN-EVE were identified (Table). In the sequential EVE-SUN arm, median OS (months) was shortest with Gr1 (9.8; 95% CI, 7.8–20.0), longest with Gr2 (39.6; 95% CI, 31.7–not estimable), and intermediate with Gr3 (18.1; 13.7–30.0), whereas in the SUN-EVE arm there was no significant difference among groups. When comparing OS between treatment sequences within molecular groups, a trend suggested differences for EVE-SUN vs SUN-EVE in Gr1 (HR 1.5), Gr2 (0.8), and Gr3 (1.2), although comparisons were not statistically significant. Conclusions: Our results suggest that these genotypes may represent distinct RCC molecular subtypes with potentially different predictive/prognostic values on targeted therapies. Different treatment sequences may be considered depending on the genotypes. Clinical trial information: NCT00903175. [Table: see text]
Review of utilization of trastuzumab in the adjuvant treatment of breast cancer in four university-teaching hospitals in Quebec, Canada
Authors: N. Letarte, D. Froment, B. Cossette, D. Pilon, M. Michel, L. Deschenes, H. Roy, B. Bailey, C. Dupont, R. Rajan
Journal: Journal of Clinical Oncology (2008)

6615 Background: The use of trastuzumab in the early treatment of breast cancer is now a standard of care. In the province of Quebec, the Programme de Gestion Thérapeutique des Médicaments (PGTM) (www.pgtm.qc.ca) in collaboration with the Comité d'Évolution des Pratiques en Oncologie (CEPO), wrote practice guidelines to promote the optimal use of trastuzumab in adjuvant treatment of breast cancer. Objectives: To measure the conformity of trastuzumab utilization in the adjuvant setting based on predefined criteria: adjuvant treatment with or following chemo, Her-2 positive tumor, tumor > 1 cm or < 1 cm with positive lymph nodes, LVEF > 55% measured before therapy and to evaluate toxicity. Methods: A review of pharmacy databases was performed to identify patients receiving trastuzumab between June 1st 2005 and May 31st 2006. Patients' medical records were also reviewed for pathology and side effects. Results: 211 patients received trastuzumab in that time period with 108 (51%) of patients receiving it in the metastatic, 91 (44%) in the adjuvant and 11 (5%) in the neoadjuvant settings. For the adjuvant setting, the mean age was 46 and 51% were hormone receptor positive. Most of the patients received an anthracycline or a taxane containing regimen, prior to (55%) or concomitant (37%) with trastuzumab. Three (3,3%) patients had to stop treatment because of cardiotoxicity. Surgery was complete in 95% of the cases. Tumor size was between 1–5 cm in 75% of patients. 60% of patients had involved nodes. Her-2 testing was done by IHC and/or FISH. 96% of patients had a positive FISH test or an IHC 3+. All the IHC 2+ tests were confirmed by FISH. The overall conformity analysis showed that 59% of the patients receiving trastuzumab met all criteria. When patients with a baseline LVEF > 50% were considered eligible, the conformity rose to 83%. Missing data prevented conformity for 13% of the cases. Only 4 cases did not meet the criteria of tumor < 1 cm with node involvement. Conclusions: The review shows a good conformity to practice guidelines. Only 4% clearly did not conform. Recommendations to better document patient charts for LVEF and side effects were made to clinicians and tools were developed in the different centers to facilitate follow-up. No significant financial relationships to disclose.
Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with nonmetastatic squamous cell carcinoma of the anus.
Authors: Doug Baughman, Krishna Bilas Ghimire, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2015)

721 Background: Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population-based study evaluated disparities in receipt of radiotherapy (RT) and its effect on survival in patients with localized and regional SCCA in the United States. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with localized and regional SCCA diagnosed between 1998 and 2008. We used univariate and multivariate logistic regression to model the relationships between receipt of RT and age, sex, marital status, stage, and race. Relative survival rates were calculated and compared using two sample z-tests. A Cox proportional hazards model was used to find adjusted hazard ratios (HR). Results: A total of 3,971 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which 3,278 (82.6%) received RT. After adjusting for covariates, those 65 years and older (adjusted OR 0.82, p=0.029) were less likely to receive RT. Females were more likely to receive RT compared to males (adjusted OR 1.54, p&lt;0.001). We found no difference in receipt of RT by race. Comparisons of 1- and 5-year relative survival rates showed lower survival for blacks (p-value &lt;0.01 at 1-year and &lt;0.0001 at 5-years), those 65 years and older, and males. A 1-year survival disparity was found for those not receiving RT (p-value &lt;0.0001 at 1-year), but no difference was observed at 5-years. A Cox proportional hazards model adjusting for all covariates showed greater hazard for blacks (adjusted HR 1.36, p=0.001), those not receiving RT (adjusted HR 1.23, p=0.03), patients 65 years or older, and males. Conclusions: This population based study identified older patients as less likely to receive RT and females as more likely to receive RT. Survival analysis identified blacks, males, older patients, and those not receiving RT as having lower rates of survival.