tbuckley/cabot-search huggingface dataset:
Prognostic impact of <i>KRAS</i> and <i>BRAF<sup>V600E</sup></i> mutations stratified by tumor site in resected stage III colon cancer patients treated with adjuvant mFOLFOX6 with or without cetuximab: NCCTG N0147 (Alliance).
Authors: Frank A. Sinicrope, Michelle R. Mahoney, Thomas C. Smyrk, Stephen N. Thibodeau, Richard M. Goldberg, Garth D. Nelson, Daniel J. Sargent, Steven R. Alberts
Journal: Journal of Clinical Oncology (2013)

3523 Background: The association of KRAS or BRAF V600E mutations with prognosis in colon cancers has been inconsistent. Since primary tumor site may influence outcome, we analyzed KRAS and BRAF V600E stratified by tumor site in resected stage III colon cancers from a randomized adjuvant trial of mFOLFOX6 + cetuximab chemotherapy (N= 2,686) where no survival difference by treatment was found. Methods: 2,580 tumors were analyzed for mutations in BRAF V600E (exon 15) or KRAS (codons 12, 13), and for deficient DNA mismatch repair (dMMR). Cox models were used, adjusting for mutation status, age, sex, treatment, T-stage, histologic grade, nodal status, tumor site, and MMR. After study initiation, eligibility was restricted to patients (pts) with KRAS wild-type (WT) tumors. At a median follow-up 4.1 yrs, 83% of pts are alive. Results: KRAS and BRAF V600E mutations were detected in 716 (28%) and 346 (14%) tumors, respectively; dMMR was found in 314 (12%). Proximal (to splenic flexure) tumors (50%) were associated with older age and were more likely to be high grade (33 vs 18%), T-stage 3,4 (88 vs 82%), mutated for KRAS (33 vs 23%) or BRAF V600E (23 vs 4%), and dMMR (21 vs 3%)[all p &lt;0.02]. Pts with distal vs proximal tumors showed improved disease-free survival (DFS)[ HR 0.7, 95% CI (0.6-0.9); p&lt;0.01 unadjusted for KRAS or BRAF;]. Mutant KRAS [HR=1.5 (1.2-1.7); p&lt;.0001] or mutant BRAF [HR=1.4 (1.1-1.7); p=0.02] were each independently associated with worse DFS. The KRAS and tumor site interaction was significant (unadjusted p interaction =0.02; adjusted p interaction =0.07), with poorer DFS among distal tumors having mutant KRAS [HR 1.7 (1.3-2.2); p&lt;.0001]. No interaction was observed for BRAF V600E and tumor site, despite worse DFS for mutant BRAF V600E among proximal tumors [HR 1.3 (1-1.8); p=0.04]. Conclusions: The adverse prognostic impact of KRAS, but not BRAF V600E , mutations was confined to the distal colon. This finding underscores the importance of tumor site in the interpretation of the prognostic impact of KRAS status, and motivates similar analyses in pts with advanced disease.
Epidermal growth factor receptor mutation in small cell lung cancer patients detected by mutant-enriched liquidchip technology from plasma in China.
Authors: Hongyang Lu, Zhen-Yi Lu, Qiao-Yuan Cheng, Ju-Fen Cai, Yiping Zhang, Wang Xiao Jia, CaiJin Lou, Xinmin Yu, Jing Qin, Wei-Wu Ye, Lei Lei, Zeng Wang, Yong-Qing Zheng, Weimin Mao
Journal: Journal of Clinical Oncology (2012)

e17512 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been widely used in non-small cell lung cancer (NSCLC), and the incidence of EGFR mutation in NSCLC is higher in China than in the United States and European countries. EGFR exons 19 and 21 mutation in NSCLC is related to response of tumors to EGFR TKIs, suggesting its usefulness as a biomarker. Some case studies reported that gefitinib-responsive small cell lung cancer (SCLC) with EGFR mutation. However, there are few large studies which reported the mutation status of SCLC patients. It is difficult to obtain tumor tissues to detect EGFR mutation in SCLC patients especially from surgery. This aim of the study is to know the EGFR mutation status in SCLC patients in China, and evaluate the feasibility of EGFR mutation detection from plasma by mutant-enriched liquidchip (MEL) technology. Methods: From September 2011 to January 2012, 27 cases of SCLC plasmas were collected at our Hospital, China. There are 6 female, 21 male. Age from 46 to 74 years old and median age is 60 years old. The stage (Veterans Administration Lung Study Group, VALSG): limited disease (LD) 6 cases, extensive disease (ED) 21 cases. Smoking history: non-smoker 8 cases, light smoker 0 cases, moderate smoker 3 cases and heavy smoker 16 cases. MEL technology was used to detect EGFR exon 19 and exon 21 mutations from plasma of 27 SCLC patients. Results: One of 27 cases was found with mutation in exon 19 of the EGFR gene. The patient with EGFR exon 19 mutation is a female and non-smoker. Conclusions: EGFR mutation is rare in SCLC patients, and may be more easily occurred in female and non-smokers. It is feasible to detect EGFR mutation for SCLC from plasma by MEL technology.
Assessment of <i>HER2</i> gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial.
Authors: Michael Alexander Gordon, Holly Gundacker, Jacqueline Benedetti, John S. Macdonald, Joaquina Celebre Baranda, Wendy J. Levin, C. D. Blanke, Wafaa Elatre, Peggy Weng, Heinz-Josef Lenz, Michael F. Press
Journal: Journal of Clinical Oncology (2012)

4010 Background: Trastuzumab has been approved for treatment of patients with HER2-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. Methods: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial (n=559) were retrospectively evaluated for HER2 gene amplification by fluorescence in situ hybridization (FISH)(n=258), overexpression by immunohistochemistry (IHC)(n=148) and HER2 amplification by silver-enhanced in situ hybridization (n=77) based on availability of tissue specimens. The purpose of the original clinical trial was to evaluate the benefit of post-operative 5-fluorouracil/leucovorin plus radiation therapy compared to surgery alone. Results: HER2 gene amplification rate by FISH was 10.9% in tumor tissue from 258 patients evaluated. HER2 status determined by FISH was 92% concordant with SISH. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 status by FISH and treatment with respect to both OS (p=0.034) and DFS (p=0.020). Among patients with HER2 non-amplified cancers, treated patients had a median OS of 44 months compared to 24 months for patients in the surgery only arm (34 and 17 months respectively for DFS, p=0.003). Among 28 patients with HER2 amplified cancers, the medians for OS were 16 months in the treated arm, and 22 months in the surgery arm (p=0.55) (13 and 11 months respectively for DFS, p=0.87). We were unable to detect a statistically significant treatment benefit in this small subset of patients with HER2 amplification. HER2 amplification status was not an independent prognostic marker of OS among patients who received no postoperative chemotherapy or radiation therapy (p=0.76). Conclusions: Patients lacking HER2 amplification responded significantly to treatment as indicated by both OS and DFS.
Phase 2, multicenter, safety and efficacy study of pidilizumab in patients with metastatic melanoma.
Authors: Michael B. Atkins, Ragini Reiney Kudchadkar, Mario Sznol, David F. McDermott, Michal Lotem, Jacob Schachter, Jedd D. Wolchok, Walter John Urba, Timothy Kuzel, Lynn Mara Schuchter, Craig L. Slingluff, Marc S. Ernstoff, Joseph W. Fay, Philip Adam Friedlander, Thomas Gajewski, Hassane M. Zarour, Rinat Rotem-Yehudar, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2014)

9001 Background: Pidilizumab (CT-011), a humanized anti PD-1 IgG1k, was studied in two Phase 2 studies in aggressive and indolent lymphomas showing clinical activity correlated with PD-1/PD-L1+ lymphocytes. Thus, we initiated a Phase 2 multicenter, randomized, open-label, study to evaluate the safety and efficacy of pidilizumab in patients (pts) with metastatic melanoma (MM). Methods: Eligibility criteria: measurable disease; Stage IV clearly progressive; ECOG 0-1; ≤ 3 prior systemic therapies for MM; stabilized brain mets allowed; 6 weeks from prior ipilimumab (Ipi), no prior PD-1/PD-L1/PD-L2 blockade. Pts were randomized to 2 dose levels (1.5 or 6 mg/kg IV q2 wk X 27), each with 50 pts and each balance stratified by prior Ipi (yes/no). Results: 103 pts were randomized; 75% M1c, 15.5% brain mets, 30% elevated LDH, 33% disease spread to ≥ 3 organs. 77% received prior systemic therapy for MM; 51% prior Ipi, 7.8% prior Braf inhibitor, 44% prior biologics (cytokines). 45% did not respond to most recent therapy. 45% received pidilizumab less than 4 months after prior therapy. ORR using irRC for all pts was 5.9% [90% CI: 2.3, 12.0] and 10.0% [90% CI: 1.8, 28.3] for 1.5mg/kg & prior Ipi. Pts with prior Ipi had higher irSD (53.7% vs 20.5%) and slightly longer median PFS (2.8 vs 1.9 months). Overall Survival at 12 months (12mo survival) was 64.5% (90% CI: 55.6, 72.0), with insignificant differences between strata or doses and irrespective of therapies given before study entry or after study withdrawal; 12mo survival for pts without prior or post-study Ipi (n=26) was 55.7% [90% CI: 35.6, 71.8], 12mo survival for pts with B-RAF V600 WT tumors (n=63) was 69.3% [90% CI: 58.2, 78.1]. 12mo survival for M1c pts (n=77) was 67.2%; [90% CI: 57.0, 75.5]. The most frequent AEs were fatigue (43%), diarrhea (22.5%), arthralgia (21%) and SAEs of pneumonia (5%) and dyspnea (3%). Conclusions: Despite low response rates, pidilizumab therapy results in substantial 12mo survival in heavily pretreated pts. The 12mo survival appears comparable to that of other anti- PD-1 MAbs. Treatment is very well tolerated. Further studies of pidilizumab in pts with MM are warranted, preferably in combination with other therapeutics. Clinical trial information: NCT01435369.
Molecular characterization of urothelial carcinoma of bladder and upper urinary tract.
Authors: In Gyu Hwang, Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Jinhyun Cho, Youjin Kim, Sang-Cheol Lee, Jung Hun Kang, Se Hoon Park
Journal: Journal of Clinical Oncology (2017)

361 Background: It is a considerable unmet need to increase understanding of the molecular basis of urothelial carcinoma (UC) to refine the clinical decision-making process. We also aim to assess that whether we can apply similar principles in the management of upper tract UC (UTUC) based on the behavior of urinary bladder UC (UBUC). Methods: To study the molecular nature of UC, we performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes using the Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between UTUC and UBUC were compared. Results: Tumor samples from 34 UTUC and 63 UBUC patients were eligible for analyses. Two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was, although statistically insignificant, longer in UTUC than UBUC patients (59 vs. 41 months, P = 0.63). In total, we found 920 genetic alterations from 97 samples: most common type of somatic mutation was single nucleotide variants (SNVs; 494/525, 94.1%). After analyzing total genomic alteration frequency, we found that the frequency of CNVs was not significantly different between UTUC and UBUC group: most commonly observed mutation in the UBUC patients was TP53 (18.9%), followed by KDR (7.2%), FGFR3 (4.1%) and PIK3CA (4.1%). In the UTUC patients, TP53 (22.9%), KDR (6.5%), NOTCH1 (5.3%) and FGFR3 (4.1%) are most frequentl somatic mutations. We also identified five translocations in total UC cohort including one case with FGFR3–TACC3 (Chr4) fusion. Conclusions: Within the limitation of small sample size, we found no relevant differences in somatic mutation frequencies between UTUC and UBUC, indicating a basis for similar management strategies.
A multinational, randomized, phase III trial of XELIRI with or without bevacizumab versus FOLFIRI with or without bevacizumab as second-line therapy for metastatic colorectal cancer: Safety analysis of Asian XELIRI project (AXEPT).
Authors: Masato Nakamura, Tae Won Kim, Rui-hua Xu, Young Suk Park, Yong Sang Hong, Tao Zhang, Takeshi Kato, Sang Hee Cho, Wei Wang, Hiroshi Matsuoka, Sae-Won Han, Yanhong Deng, Akitaka Makiyama, Keun-Wook Lee, Yi Ba, Mitsuyoshi Ota, Satoru Iwasa, Satoshi Morita, Yasuhide Yamada, Kei Muro
Journal: Journal of Clinical Oncology (2017)

681 Background: Several studies have shown that capecitabine plus irinotecan (XELIRI) has promising efficacy and safety in patients with metastatic colorectal cancer. AXEPT is a non-inferiority, phase III comparison of XELIRI with or without bevacizumab vs 5-fluorouracil/folinic acid plus irinotecan (FOLFIRI) with or without bevacizumab as second-line therapy in patients with metastatic colorectal cancer. Methods: We undertook an open-label, non-inferiority, randomized phase III trial in South Korea, China and Japan. Patients were randomized 1:1 to XELIRI (irinotecan 200 mg/m 2 on day 1 plus capecitabine 800 mg/m 2 twice daily for 2 weeks in a 3-week cycle) with or without bevacizumab 7.5 mg/kg or FOLFIRI with or without bevacizumab. The primary endpoint was overall survival. Results: From December 2013 to August 2015, 650 patients were enrolled and 625 (311 in FOLFIRI and 314 in XELIRI) were included to safety analysis at the cutoff dates on August 31, 2016. Patient baseline characteristics including KRAS status and UGT1A1 gene polymorphism were similar between the two treatment arms. Prior chemotherapy with oxaliplatin was given to 97.4% in both arms. The overall incidence of grade 3-4 toxicity was 73% in FOLFIRI arm and 53.2% in XELIRI arm. Whereas FOLFIRI was associated with more grade 3-4 neutropenia (43.7% vs 16.2%), leucopenia (13.5% vs 7.3%) and all grades anemia (80.4% vs 69.4%) than XELIRI, XELIRI was associated with more all grades hand-foot syndrome (34.1% vs 14.8%) and grade 3-4 diarrhea (7.0% vs 3.2%). There was no significant difference in febrile neutropenia (4.2% in FOLFIRI and 2.9% in XELIRI). The addition of bevacizumab did not alter safety profiles between XELIRI and FOLFIRI. There was a treatment-related death in FOLFIRI arm (0.3%). Conclusions: Both FOLFIRI and XELIRI were safe and well tolerated, though there were differences in the rates and toxicity profiles at which adverse events occur. Clinical trial information: NCT01996306. UMIN000012263.
Burnout among palliative care clinicians in the United States: Results of a national survey.
Authors: Arif Kamal, Janet Bull, Steven Wolf, Gregory Samsa, Katherine Ast, Keith Mark Swetz, Tait D. Shanafelt, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2014)

e20530 Background: The increasing demand for specialist palliative care (PC) in cancer care requires an available and responsive clinical workforce. But as the volume of work expands, PC providers face an increased risk of burnout, characterized by depersonalization and work-related emotional exhaustion. The prevalence and predictors of burnout among PC providers is poorly understood. Methods: Members of the American Academy of Hospice and Palliative Medicine and other palliative care clinicians (e.g. advanced practice provider, nurses, chaplains) completed the Human Services Survey of the Maslach Burnout Inventory (MBI) via electronic survey in the second half of 2013; respondents were recruited via e-mail, blog and Facebook posts, and Twitter tweets. The MBI determine burnout severity across two domains, Emotional Exhaustion (EE) and Depersonalization (DP). Severity is reported as “low”, “moderate”, or “high”; “high” is consistent with burnout. Demographic and work-related variables associated with burnout in other studies were determined via logistic regression. Results: We received surveys from 1241 clinicians. While it was difficult to calculate a response rate, we estimated it at 30%. 68% of respondents were physicians. Most respondents were over age 50 (57%), female (65%), and had worked in the field for less than 10 years (67%). 42% took overnight call regularly and 30% reported working 50 hours per week or more. Regarding burnout, 24% reported high DP, 59% reported high EE, and 61% of reported high burnout symptoms on either EE or DP scales. In multivariate analysis, high levels of DP or EE was associated with age <50, working >50 hours per week, low number of PC clinician colleagues, and reported likelihood to leave PC within 10 years (p<0.02). Conclusions: PC clinicians report a burnout rate of 61%. Even with the limitations of our methods and potentially biased sampling, this prevalence is remarkable and higher than data reported in medical oncology (45%). Burnout severity is associated with working in isolation, working longer hours, and a high intent to leave the field. Further studies on burnout in PC are needed, especially since this workforce is so critical to the provision of high quality cancer care.
Primary care providers' awareness and utilization of survivorship care plans.
Authors: Alicia R. Rosales, Tina Schaal, Shelby Darland, Dan Sayam Zuckerman
Journal: Journal of Clinical Oncology (2017)

94 Background: The Commission on Cancer (CoC) standard 3.3 requires that all patients who complete cancer treatment receive a survivorship care plan (SCP). To aid in care coordination, the standard also requires that the SCP be provided to the patient’s primary care provider (PCP). St. Luke’s Mountain States Institute (MSTI) has been providing patients and PCPs with SCPs for more than 5 years. Other local accredited cancer centers also provide SCPs for their patients. Methods: In partnership with the local chapter of the American Cancer Society, MSTI created an online survey aimed at assessing the utilization of the SCP in primary care clinics and the PCP’s comfort level carrying out the recommended surveillance. The survey link was distributed through email to approximately 300 PCPs across a large geographical area in varying sized practices. Results: Sixty three responses were received in 3 weeks with 46 responses from physicians and 17 responses from advanced practice providers. All of the respondents said they care for cancer survivors in their practice but 54% have never received a SCP. Twenty nine reported having received a SCP and answered 8 questions related to how they use the SCP in practice. The majority refer to the SCP to monitor for recurrence and 52% use it as a tool for coordination of care. Forty eight percent use the SCP to manage co-morbid conditions. Ninety-five percent of all respondents indicated they feel comfortable carrying out a surveillance plan provided by the oncologist for patients 2 years out from treatment. Sixty-four percent indicated they would like additional education about caring for cancer survivors. A common theme in comments included the desire for improved communication between the oncologists and PCPs. Conclusions: This standard was created in part to improve care coordination between oncologists and PCPs. More than have of the PCPs in the MSTI service area have not seen a SCP for their patients. Most indicated they are comfortable providing surveillance if they have a clear follow-up care plan from the oncologist. More than half want additional information about caring for cancer survivors. Future exploration could include assessment of barriers to communication and utilizing the SCP in practice.
Long-term survival and prognostic factors in neuroendocrine tumors: Results from a large multicenter study.
Authors: Antongiulio Faggiano, Franco Grimaldi, Marco Manzoni, Maria Vittoria Davi, Diego Ferone, Dario Giuffrida, Ignazio Roiter, Giuseppe Fanciulli, Enrico Papini, Chiara Martini, Giulia Maria Franchi, Giampiero Fasola, Manuela Albertelli, Lucio Crinò, Annamaria Colao, Piero Ferolla
Journal: Journal of Clinical Oncology (2012)

1604 Background: The clinical behavior of neuroendocrine tumors (NET) is highly variable, but the only data available in literature on large series are mainly based on retrospective register data collected in 3-5 decades, focusing on short-term follow-up. These are clearly insufficient due to the frequent evolution in classification criteria, diagnostic techniques and the scarcity of clinical data. Methods: Data from a total of 1659 NET patient were collected from 12 Italian referral centers. A specific software was developed for the study. Only patients with histological diagnosis revised according to the WHO Classification in active long term follow-up in the period 1990-2010 were included in the study. Patients with incomplete diagnostic work-up, without clinical data or lost at follow-up were excluded. Cumulative survival were analyzed according to site of origin, histotype, grading, ki67 score, secreting pattern (functioning or not functioning) and staging. Results: At 2 yr cumulative survival do not differ between pancreatic (pNET 94.9%), gastrointestinal (GINET 94.4%) and lung NET (TNET 94.6%), functioning (93.5 %) and non functioning (93.9%), while was significantly different between T1N0M0 (98%), T1N1M0 (92.9%), T1N1M1 (90.2%) and grading (G1 98%, G2 96.8%, G3 84.1%). At 5, 10 and 15 yr, cumulative survival were respectively 90.9, 77.1, 62.7% for pNET, 88.7, 83.5, 62.7% for GINET 90.3, 80.2, 67.9% for TNET. 88.4, 77.0, 59.0% in functioning and 89.8, 79.1, 64.6% in not functioning. 96.1, 89.5 and 77.0% for T1N0M0, 88.2, 83.5, 70.4 for T1N1M0 and 82.0, 55.8 and 43.9 for T1N1M1, 93.1, 82.3, 75.4% for G1, 87.8, 64.8, 48.6% for G2, 81.4, 75.2, 40.1% for G3. Conclusions: Brief (2y) and very long term (15y) survival do not significantly differ between different site of NET origin. Functioning tumors have the same survival rate at 2 y but lower at 15 y. Staging and grading appear as the most significant prognostic factors particularly at 10 and 15 y. Long-term cumulative survival in NET results significantly higher than in historical series, probably due to the anticipation of the diagnosis and the availability of new therapeutic strategies.
A phase II salvage trial of transdermal estradiol in the treatment of hormone and chemotherapy refractory prostate cancer: A Cancer Institute of New Jersey Oncology Group Study NJ1803
Authors: N. Morganstein, S. Doyle-Lindrud, S. Goodin, J. Shih, A. Altscher, E. Teller, R. Zager, M. Todd, H. Durivage, R. S. Dipaola
Journal: Journal of Clinical Oncology (2004)

4695 Background: Options for patients with progression of prostate cancer following androgen ablation and chemotherapy are limited. Prior studies have demonstrated the efficacy of estrogen in this group of patients, but safe and effective agents are limited. Given prior data demonstrating the safety and ease of using an estradiol patch, we tested the hypothesis that the patch would be a safe and effective option for patients with hormone and chemotherapy refractory prostate cancer. Methods: In this ongoing study, ten patients with hormone refractory prostate cancer who had progressed after at least one chemotherapy regimen were enrolled. Patients were treated with two transdermal patches (total daily dose: 0.2 mg of estradiol) changed weekly. Results: 7/10 patients received one prior and 3/10 two or more prior chemotherapy regimens. Median age was 64 years (range 57 to 76). Prostate specific antigen (PSA) decreased in 5/10 patients (mean decrease 27%). 2/3 patients that were treated for at least 3 months had stable disease, as defined as < 25% increase over the first 3 months of therapy. 7/10 patients remain on study. Therapy was well tolerated. There were no grade 2 or 3 adverse events. Conclusion: In patients with hormone and chemotherapy refractory prostate cancer, transdermal estradiol patches may offer a safe and active option of therapy, but further study is warranted and ongoing. No significant financial relationships to disclose.