tbuckley/cabot-search huggingface dataset:
CheckMate 577: A randomized, double-blind, phase 3 study of nivolumab (Nivo) or placebo in patients (Pts) with resected lower esophageal (E) or gastroesophageal junction (GEJ) cancer.
Authors: Ronan Joseph Kelly, Albert C. Lockhart, Derek J. Jonker, Bohuslav Melichar, Thierry Andre, Ian Chau, Stephen John Clarke, James M. Cleary, Yuichiro Doki, Fabio Andre Franke, Yuko Kitagawa, Christophe Mariette, Paola Catherine Montenegro, Enrique Luis Roca, Marika Ciprotti, Markus Moehler
Journal: Journal of Clinical Oncology (2017)

TPS212 Background: Chemoradiotherapy (CRT) followed by surgical resection is a current standard of care (SOC) for pts with E/GEJ cancer, with 3- and 5-year survival rates ranging from 30% to 40%. Currently, no effective adjuvant SOC is available following resection. Expression of programmed death-1 (PD-1) ligands 1/2 (PD-L1/L2) has been associated with a poor prognosis in E/GEJ cancer, suggesting that PD-1 inhibition may improve outcomes. Nivo is a fully human IgG4 monoclonal antibody that targets PD-1, with demonstrated survival benefit in multiple tumor types and long-term responses in some patients. A phase 1/2 study of nivo monotherapy in chemotherapy-refractory pts with gastric/E/GEJ cancer demonstrated tumor regression, a median overall survival (OS) of 5 months, and a 12-month OS rate of 36% in pts with PD-L1+ and PD-L1- tumors (Janjigian Y, et al. J Clin Oncol. 2016;34:suppl; abstract 4010). This multinational, double-blind, phase 3 trial will evaluate nivo as an adjuvant therapy for pts with resected E/GEJ cancer (CheckMate 577; NCT02743494). Methods: In this study, an estimated 760 pts aged ≥ 18 years with stage II/III E/GEJ cancer are randomized to receive nivo or placebo. Prior to randomization, pts must have completed preoperative CRT followed by surgery and been diagnosed with residual pathological disease after being surgically rendered free of disease with negative margins following complete resection. Pts with stage 4 resectable disease, cervical esophageal cancer, or those who have not received concurrent CRT prior to surgery are not eligible for study enrollment. Primary endpoints are OS and disease-free survival. The secondary endpoint is OS rate at 1, 2, and 3 years. Clinical trial information: NCT02743494.
A phase II trial of escalated dose proton radiotherapy with elective nodal irradiation and concomitant chemotherapy for patients with unresectable, borderline resectable, or medically inoperable pancreatic adenocarcinoma.
Authors: Romaine Charles Nichols, Christopher G. Morris, Bradford S. Hoppe, Michael Scott Rutenberg
Journal: Journal of Clinical Oncology (2017)

TPS513 Background: The prognosis for patients with localized pancreatic adenocarcinoma who are not surgical candidates is poor. Median survival for patients with unresectable disease on the LAP-07 trial was between 15.2 and 16.4 months (Hammel P, et al. J Clin Oncol 31, 2013 [suppl; abstr LBA4003]). The absence of a survival advantage for x-ray based radiotherapy may be due to toxicity. Patients characterized as having “borderline resectable” disease fair somewhat better - although many are not converted to resectability with standard regimens. Intensified local/regional therapy for "initially unresectable" patients might 1.) Increase the share of patients undergoing curative surgery and 2.) Improve local disease control for patients who remain unresectable. A phase II study for patients with unresectable disease treated with proton therapy to a dose of 59.4 Gy (RBE) demonstrated an 18.4 month median survival without grade 2 or higher GI toxicity – suggesting the feasibility of dose intensification (Sachsman S, et al. Int J Particle Ther. 2014;1[3]:692–701.). The current protocol offers a 6% increase in radiotherapy dose with a 25% increase in dose per fraction with the goal of improving local control and extending survival. Methods: Eligibility: Biopsy proven adenocarcinoma of the pancreas that is unresectable, borderline resectable, or medically inoperable. No evidence of metastatic disease. Prior chemotherapy allowed. Treatment: 40.50 Gy (RBE) in 18 fractions to gross disease and an elective nodal volume followed by a 22.50 Gy (RBE) in 10 fraction boost to gross disease (total dose 63 Gy [RBE] in 28 fractions) with concomitant capecitabine (1,000 mg PO BID) on radiation treatment days. Surgery between 8 and 16 weeks of radiotherapy completion if radiographic studies suggest operability. Primary Objective: Improve 12 month survival from 50% to 75%. Secondary Objectives: Improve local and regional disease control Increase share of patients being converted to resectable. Compare GI toxicity with historical benchmarks. Assess quality of life. Sample Size:60 patients Clinical trial information: 02598349.
Effects of metformin on pancreatic cancer survival among Medicare beneficiaries.
Authors: Elan R. Witkowski, Elizaveta Ragulin-Coyne, Zeling Chau, Theodore P. McDade, Sing Chau Ng, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2012)

e14691 Background: Evidence from preclinical models suggests that metformin may have antitumor activity against pancreatic adenocarcinoma. The effect in humans has not been well-described. A recent single-institution retrospective analysis suggested improved survival in diabetic patients who had been exposed to metformin. The current study was designed to determine whether metformin was independently associated with improved pancreatic cancer (PC) survival when compared to non-metformin controls using newly available national pharmacy data from Medicare Part D. Methods: Patients with diagnosed with AJCC Stage II-IV PC during 2007 were identified in the SEER-Medicare linked database. Part D events for oral diabetic medications were identified from the date of diagnosis until death or 12/31/2008, and divided into metformin-containing or non-metformin. Patients who did not receive an oral medication for diabetes, lacked continuous Part D prescription drug coverage, underwent surgical resection, or survived less than 30 days were excluded. Patient characteristics were compared by chi-square and Wilcoxon. Overall survival was compared by Kaplan-Meier log rank. Results: From an initial cohort of 899 patients, 100 met inclusion criteria and received oral diabetic medication. Of these, 31 received metformin and 69 non-metformin. Patient characteristics were similar among the groups, including median age (76.6 vs. 76.2, p=0.75), race distribution, Charlson comorbidity score and disease stage (p&gt;0.05 for each). There was no statistically significant difference in median survival between the two groups: 5.6 months for metformin vs. 6.1 for non-metformin, p=0.93. Conclusions: This study using national Medicare Part D prescription drug claims revealed no detectable survival benefit for unresectable pancreatic cancer patients who received metformin when compared to non-metformin oral hypoglycemics. Sufficient power to detect modest benefits, however, will require additional subjects, which we anticipate in the near future. Additional studies are warranted and ongoing to determine the effect of metformin on pancreatic cancer survival.
A phase IB study of the combination of selumetinib (AZD6244; ARRY-142886) and cyclosporin A (CsA) in patients with advanced solid tumors with an expansion cohort in metastatic colorectal cancer (mCRC).
Authors: Anuradha Krishnamurthy, A. Dasari, Albert C. Lockhart, Mark N. Stein, Hanna Kelly Sanoff, James J. Lee, Aaron Richard Hansen, Tanios S. Bekaii-Saab, Usha Malhotra, Sarah Rippke, Sarah Lindsey Davis, Wells A. Messersmith, James C. Yao, Funda Meric-Bernstam, S. Gail Eckhardt, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2017)

609 Background: Targeting MEK is of interest in the development of novel agents for treatment of many malignancies. However, better strategies are needed to overcome acquired resistance to MEK inhibitors. Preclinical studies have shown Wnt pathway overexpression in KRAS mutant cell lines resistant to the MEK inhibitor, Selumetinib. The combination of selumetinib and cyclosporin A (CsA), a non-canonical WnT pathway modulator, demonstrated antitumor activity in patient-derived xenograft (PDX) models. We are conducting an NCI CTEP-approved Phase I/IB trial (NCI # 9571/COMIRB # 13-2628) of selumetinib and CsA combination. Biomarkers of response to therapy are being co-developed. We hypothesize that this combination will be safe and potentially effective in patients with mCRC and that upregulation of FZD2 may predict for sensitivity. Methods: Phase I trial with initial dose escalation investigating the combination of selumetinib and CsA in patients with advanced solid tumors (n = 18) followed by an expansion cohort in patients with irinotecan and oxaliplatin-refractory mCRC (n = 20). The expansion cohort utilizes a selumetinib “run-in” to evaluate efficacy in RAS-WT and RAS-MT mCRC to identify those patients most likely to respond to the combination. Results: 18 patients were enrolled in the dose escalation phase and 10 patients have been enrolled in the dose expansion phase as of September 2016. Grade 1 or 2 nausea and rash were reported as the most common AEs. Most commonly reported Grade 3 or 4 toxicities were hypertension, elevated liver enzymes and rash. Three DLTs were reported with Grade 3 hypertension noted at dose level 1 and 2 and grade 3 rash reported at dose level 2. The maximum tolerated dose was defined as Selumetinib 75 mg BID and CsA 2 mg/kg BID on a 28-day cycle. Two partial responses and sixteen stable disease responses have been observed. Six patients have exhibited progressive disease. Conclusions: Selumetinib in combination with cyclosporin A appears to be well-tolerated with evidence of activity in solid tumors. Expansion cohort will complete enrollment this month. Clinical trial information: NCT02188264.
Staging CT Scans in Early-Stage Chronic Lymphocytic Leukemia
Authors: Arjun Gupta, David H. Johnson, Sung-hee Choi
Journal: JAMA Internal Medicine (2017)

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Phenotypic expression of Bax is a predictive marker of 5-fluorouracil treatment in colorectal cancer
Authors: U. Manne, C. Suarez-Cuervo, N. C. Jhala, J. Posey, C. B. Herring, S. Meleth, W. E. Grizzle
Journal: Journal of Clinical Oncology (2006)

3605 Background: The anti-tumor activity of 5-fluorouracil (5-FU) has been related to its ability to induce apoptosis. Therefore, we assessed the predictive value of phenotypic expression of key apoptotic molecules in colorectal adenocarcinomas (CRC) of patients treated with 5-FU-based adjuvant therapies. Methods: Archival tissues of CRCs from 56 patients who received a complete regimen of 5-FU-based chemotherapy after surgery, and 56 age, gender, ethnicity, tumor stage, tumor location, and tumor differentiation matched patients who had undergone only surgery (without any pre- or post-surgery chemo- or radiation therapy), were evaluated for immunophenotypic expression of Bax, Bcl-2 and nuclear accumulation of p53 (p53 nac ). Immunophenotypic expression of these markers was categorized into low and high expressors and cut-point values were determined based on their expression in benign epithelium. These tumors Ability of these markers in predicting the efficacy of 5-FU-based treatment was assessed by estimating overall survival utilizing the Kaplan-Meier and Cox proportional hazards methods. Results: There was no significant difference in overall survival rates between the two patient categories (logrank P=0.487). However, a better survival was observed for patients who received chemotherapy when their CRCs lacked Bax expression; in contrast, patients with high Bax expression CRCs had worse survival when they received chemotherapy (logrank P=0.016). Surgically treated patients with CRCs lacked Bax expression had 5.33 times higher mortality than those with high Bax expression (HR, 5.33; CI: 1.78–15.94), when controlled for tumor stage and other confounding variables. Bcl-2 or p53 nac had no predictive value in either patient group. Conclusions: These preliminary findings are the first to provide good evidence to suggest that patients with CRCs lacking Bax phenotypic expression benefit from 5-FU-based adjuvant therapies but not those with high Bax expression (Supported by NIH/NCI R01-CA98932–01). No significant financial relationships to disclose.
Gemcitabine/taxane adjuvant therapy in resected pancreatic cancer: A signal of improved survival?
Authors: Zaheer S Kanji, Alicia M Edwards, Margaret T Mandelson, Bruce Lin, Kasra Badiozamani, Goubin Song, Adnan Alseidi, Thomas Biehl, Richard A. Kozarek, William Scott Helton, Vincent J. Picozzi, Flavio G. Rocha
Journal: Journal of Clinical Oncology (2017)

392 Background: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit in metastatic pancreatic cancer (PC). We present our experience with gemcitabine/docetaxel (gem/tax) based adjuvant treatment (Rx) following curative intent surgery. Methods: Patients with upfront resectable PC from January 1, 2010 to December 31, 2015 were identified from our institutional database and tumor registry. We included resected patients who received gem/tax as initial Rx administered exclusively at our institution with or without chemoradiation (CRTx). Patients were excluded if they died or recurred prior to Rx or received neoadjuvant Rx. Survival was estimated by Kaplan-Meier methods and prognostic factors identified by Cox regression. Results: Of 185 eligible patients, 58 met study criteria. Characteristics included: median age of diagnosis 64.9 years, female gender 56.9%, Whipple procedure 69% and R1 resection in 55.2%%. Tumour characteristics included: median size 28.0mm, poor differentiation 53.5% and AJCC stage 2A/2B 27.6%/67.2%. Patients completing ≥ 80% of 24 week Rx was 89.7% (n = 52). Of those patients, 71.2% received post gem/tax CRTx. With a 51.2 month median follow-up (95%CI: 37.1-55.7), median disease-free survival (DFS) and overall survival (OS) were 35 months (95%CI: 20.7-NR) and 52.3 months (95%CI: 27.4-NR), respectively. Five year OS was 49.5% (95%CI: 33.7-63.4). Patients receiving CRTx (n = 37) had a superior OS compared to patients who only completed gem/tax Rx (n = 15)(61.5 vs. 26.7 months, p = 0.04). Prognostic variables impacting OS on multivariate analysis (HR, 95%CI) included: margin status (4.55, 1.46-14.2, p = 0.01), AJCC stage (10.9, 2.46-47.9, p = 0.002) and administration of CRTx (0.08, 0.03-0.24, p &lt; 0.000). Variables impacting DFS included: AJCC stage (3.29, 1.15-9.41, p = 0.03), tumour size (2.59, 1.11-6.04, p = 0.03) and administration of CRTx (0.23, 0.09-0.56, p = 0.001). Conclusions: In this select cohort of resected PC patients with adverse pathologic features, adjuvant gem/tax with or without CRTx is feasible with favorable DFS and OS. These findings support further prospective studies of gem/taxane-based adjuvant Rx in PC.
Weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC): Preliminary results of a phase study.
Authors: Youhua Jiang, Fan Yun, Qixun Chen, Xinming Zhou, Zhiyu Huang, Lei Gong, Haiyan Yang, Haifeng Yu, Jinshi Liu, Pengcheng Chen, Qiang Zhao, Weimin Mao
Journal: Journal of Clinical Oncology (2013)

e15062 Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m 2 , d1, d8, d22 and d29) and cisplatin (75 mg/m 2 , d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and progression-free survival (PFS). Results: From 01/2011 to 10/2012, 31 pts were enrolled . 28 male:3 females; II A/II B/III A/III B/III C in 2 (6.5%), 4 (12.9%), 9 ,(29.0%), 8 (25.8), and 8 (25.8%) pts. 26/31 pts went to surgery (83.9%). 26 had R0 resection (100%).Pathological complete response (pCR) was achieved in 3 pts (11.5%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 1 pt (3.8 %). Down-staging was observed in 15 of 26 patiens (57.7%). 5 pts did not going to surgery: 2 for progressive disease (6.5%), 3 for refused. 20/26 pts (76.9%) received adjuvant chemotherapy,3 pts (11.5%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 31 evaluable pts during chemotherapy were as follow: neutropenia (12.9%), anemia (6.5%), thrombocytopenia (3.2%), nausea/vomiting (12.9%), neutropenia fever (6.5%), asthenia (12.9%). Surgical complications: 1anastomotic leaks (3.8%). No treatment-related death. At a median follow up of 9 months, 26 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate .The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.
Clinicopathologic features predicting HER2 overexpression in gastric cancer.
Authors: Ji Soo Park, Minkyu Jung, Hye Ryun Kim, Sun Young Rha, Hyun Cheol Chung, Hyo Song Kim
Journal: Journal of Clinical Oncology (2013)

e15098 Background: HER2-based therapy was found to improve survival outcome of patients with HER2-positive advanced gastric cancer. In gastric cancer, HER2 overexpression is commonly defined as IHC 3+ or IHC 2+/FISH amplification. Because positivity of HER2 overexpression is reported in below 20%, identifying the predictive clinical factors for the HER2 overexpression before the pathologic analysis may be helpful and cost-effective. Methods: From JAN 2005 to DEC 2010, 517 gastric cancer patients performed with HER2 IHC and/or FISH tests at Yonsei University College of Medicine were enrolled. Results: Among the 517 patients, 61 patients (11.8%) were confirmed as HER2 overexpression. Forty three out of stage IV, 258 patients (16.7%) and 18 out of 259 (6.9%) localized gastric cancer patients had HER2 overexpression (p &lt;0.001). HER2 overexpression was more common in male (14.2% vs. 7.5% in female, p-value 0.024), moderately differentiated (26.4% vs. 11.1%, 8.9%, 4.9% and 5.9% in well differentiated, poorly differentiated, signet ring cell, and mucinous, retrospectively, p &lt;0.001). Patients with elevated CEA (&gt; 5.0 ng/mL vs. ≤ 5.0 ng/mL: 24.3% vs. 8.4%, p &lt;0.001), metastasis to distant lymph node (with vs. without: 28.6% vs. 14.8%, p-value 0.042), without carcinomatosis (without vs. with: 21.2% vs. 11.6%, p-value 0.039) and pulmonary metastasis (with vs. without: 47.4% vs. 14.2%, p &lt;0.001) also frequently had HER2-positive disease. In addition, high risk patients with 4 or more of the 7 features (metastatic disease, male, moderate differentiated adenocarcinoma, elevated CEA level, metastasis to distant lymph node, pulmonary metastasis, and without carcinomatosis) had 32.9% of HER2 positivity. (p &lt;0.001). Conclusions: Those clinicopathologic factors may be helpful to predict the high likelihood of HER2 positive cases prior to pathologic confirmation in gastric cancer. Further molecular study for the HER2 overexpression is needed to clarify and explain this clinical phenomenon.
Developing oncology goals and objectives for medical students: A national Delphi process.
Authors: Vincent Channing Tam, Paris Ann Gfeller-Ingledew, Scott R. Berry, Sunil Verma, Meredith Elana Giuliani
Journal: Journal of Clinical Oncology (2015)

6567 Background: Our previous study showed that oncology education in medical schools is currently inadequate. The purpose of this process was to develop oncology goals and objectives for medical students based on a national consensus by oncology educators. Methods: A comprehensive list of oncology objectives was created using existing resources. Experts in oncology education and undergraduate medical education (UME) from all 17 medical schools in Canada were asked to participate in a 3-round Delphi consensus process. For round 1, experts scored objectives on a 9-point scale according to the degree with which they agreed an objective should be taught in UME. Objectives with a mean score of ≥ 7.0 were included. Round 2 was a web meeting where objectives with a mean score of 4.0 to 6.9 were discussed. In round 3, experts voted on inclusion and exclusion of round 2 objectives. Results: 34 of 37 (92%) invited experts from 14 medical schools participated. Experts consisted of oncologists (medical, radiation, pediatric, surgical, gynecologic), family physicians, UME curriculum committee members, and oncology residency program directors. The comprehensive list reviewed in round 1 contained 214 objectives. 146 received a mean score ≥ 7.0 and 68 scored 4.0 to 6.9. Nine new objectives were suggested. Main themes of expert comments were to reduce the number of objectives and to aim objectives at the general knowledge level of a family physician. In round 2, 77 objectives were discussed. In round 3, > 75% of experts agreed to include 7 (9%) objectives. The final 153 objectives were divided into the following categories: Basic Science of Oncology, Public Health, Diagnosis, Treatment, Prognosis, Knowledge of Common Cancers, Psychosocial Issues, Ethics and Professionalism, Communication, and Essential Oncology Experiences. Conclusions: Through a systematic process we have created a comprehensive and consensus-based set of oncology goals and objectives which may be used in UME curriculum design and also by educators and medical students. The objectives will be made available online to be shared with educators and learners globally, which will hopefully facilitate improvements in oncology education and patient care.