tbuckley/cabot-search huggingface dataset:
Outcome of chemotherapy with or without targeted therapy in metastatic colorectal cancer with deficient mismatch repair phenotype: A cohort study in a single center.
Authors: Yue Yu, Yi-Xin Zeng, Jianming Ying, Wen Zhang, Ai-Ping Zhou
Journal: Journal of Clinical Oncology (2018)

e15669 Background: Deficient mismatch repair (dMMR) phenotype, is presented in 4-5% of metastatic colorectal cancer (mCRC). Little is known about the efficacy of targeted therapy and prognostic factors in this rare subset. In this study, we evaluate clinical features and survival outcome of bevacizumab-contained therapy, cetuximab-comtained therapy and chemotherapy alone in first-line therapy of dMMR mCRC. Methods: A retrospective review of 43 dMMR mCRC patients in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, was conducted. Kaplan–Meier method, Log-rank test and Fisher exact test were utilized for statistical analyses. Results: Median age of entire cohort was 54 years (range: 18–76 years), among which 67.4% were male, 65.1% had simultaneous metastases, and 58.1% were left-sided. The median overall survival (OS) of entire group was 21.7 months. Eleven patients (25.6%) received bevacizumab-based treatment, seven patients (16.3%) received cetuximab-based treatment and twenty-five patients (58.1%) received chemotherapy alone treatment as first-line therapy respectively. Patients in bevacizumab arm presented substantially higher overall response rate (ORR) comparing with patients in chemotherapy arm (63.6 vs. 21.1%, P = 0.046) and numerically higher ORR comparing with cetuximab arm (63.6 vs. 14.3%, P = 0.065). The median progression-free survival (PFS) of patients in bevacizumab arm was also significantly longer than chemotherapy arm (10.0 vs. 4.8 months P = 0.034) and numerically longer than cetuximab arm(10.0 vs. 6.8 months P = 0.534). The median OS also favored bevacizumab group though significant difference was not achieved (33.7 vs. 21.7 vs.15.3 months P = 0.345). In univariate analysis, Primary tumor resection is the only factor associated with improved OS (HR 2.28 95%CI 1.04-5.02, P = 0.004). Conclusions: dMMR mCRC appears to be resistant to chemotherapy, but responds well to bevacizumab-contained therapy. The rational combination of efficient bevacizumab targeted therapy and palliative primary tumor resection may provide with more benefit for specific dMMR patients.
The benefit of integrating safety data from the FDA mandated registry with medwatch reports: A Southern Network on Adverse Reactions (SONAR) analysis based on the Tysabri Outreach Commitment to Health Registry (TOUCH).
Authors: Charles L. Bennett, Virginia Noxon, Paul R Yarnold, A. Oliver Sartor, Brian Chen
Journal: Journal of Clinical Oncology (2016)

e18237 Background: Natalizumab is an effective therapy for multiple sclerosis. Its most notable toxicity is PML. The FDA mandated registry, TOUCH, focuses on PML cases. We identified an unusual case of natalizumab associated urethral melanoma and queried FDA databases for 2 purposes. First, to determine if the TOUCH registry included information on natalizumabassociated melanoma cases. Second if individual reports of natalizumab-associated melanoma were more complete when the report was reported via: 1) the TOUCH registry (heavy TOUCH) versus 2) those where data from TOUCH was added to a previously submitted FDA adverse event report (light TOUCH), or 3) if no data from TOUCH were included in the FDA report (no TOUCH). Methods: Case details of all natalizumab-associated melanoma cases in the MedWatch database were reviewed (2005-2014). A completeness score for individual reports was developed consisting of clinical, demographic, and pharmacy items. Optimal discriminant analysis was used to compare completeness across TOUCH groups. As the TOUCH Registry is for the United States, cases from outside the United States were evaluated separately. Results: Overall, 137 natalizumab-associated melanoma cases were identified. Of US cases, 73% were categorized as light, 15% as heavy, and 13% as no TOUCH. Median clinical completeness scores were 2.0, 4.0, 3.5, and 4.0 for heavy, light, no TOUCH, and non-US cases. Clinical completeness scores were significantly poorer for heavy versus light TOUCH cases (p<.01). Conclusions: FDA reports of natalizumab associated melanoma cases from the United States contain only 50% of relevant clinical information. Heavy TOUCH reports had the lowest completeness scores. TOUCH should be extended to include reporting melanoma cases based on the potential that it is a malignancy that develops in immune compromised individuals. Median completeness scores across TOUCH categories. Completeness Scores
Neoadjuvant chemotherapy with gemcitabine and cisplatin followed by chemoradiation in locally aadvanced cervical cancer.
Authors: Abdul Mateen, Allah Rakha Adil, Muhammad Saqib Khan, Rab Nawaz Maken, Quratul Ain Hashmi, Arif Moin Duraishi, Famya Abdullah
Journal: Journal of Clinical Oncology (2018)

e17501 Background: Cervical cancer is one of the common gynecological cancer which usually presents in advanced stage. The aim of this study to find out the best possible treatment in patients having limited financial resources. Methods: A total of 55 patients were enrolled for the study. All patients had biopsy proven cervical carcinoma. Patients had FIGO stage range from IB to IVA were selected. The patients were planned for three cycles of gemcitabine and cisplatin (GC) every three weeks in a dose of 1000 mg/m² and 40 mg/m² on D1 and D8 of each cycle respectively. After three cycles of chemotherapy, patients were planned for external radiotherapy (ERT) along with weekly gemcitabine 100 mg/m². A total of 50 Gray (Gy) was planned with 2.0 Gy per fraction and five fractions a week. Gemcitabine was given on 1st day of every week during ERT. ERT was followed by high dose rate (HDR) brachytherapy (BT) on Ir-192. A total of 21 Gy was delivered with weekly 7 Gy fraction. Primary end point was to assess disease free survival (DFS) and overall survival (OS) was also assessed as a secondary end point. Results: 51 patients (93%) completed treatment as per scheduled and 47 patients (85%) of them completed with eight weeks from start. Three patients (6%) showed disease progression during treatment and were switched to other treatment. 15 patients (30%) showed bowel, 12 patients (24%) showed bladder and 5 patients (10%) showed hematological related grade 1-2 toxicity. By using Kaplan-Meier analysis three year DFS and OS were 62% and 71% respectively. Most of the patients recovered from acute bladder and bowel related toxicity. 5 patients (10%) developed bleeding per rectum confirmed as chronic radiation induced proctitis. Conclusions: Neoadjuvant chemotherapy with GC followed by concomitant CRT using gemcitabine is a reasonable choice for locally advanced cervical cancer but a larger phase III trial is mandatory to confirm these findings.
Combination of pembrolizumab and metronomic cyclophosphamide in patients with advanced sarcomas and GIST: A French Sarcoma Group phase II trial.
Authors: Maud Toulmonde, Nicolas Penel, Julien Adam, Christine Chevreau, Jean-Yves Blay, Axel Le Cesne, Emmanuelle Bompas, Sophie Piperno-Neumann, Sophie Cousin, Thomas Ryckewaert, Alban Bessede, Francois Ghiringhelli, Thomas Grellety, Marina Pulido, Antoine Italiano
Journal: Journal of Clinical Oncology (2017)

11053 Background: There is a good rationale for immunotherapy in sarcoma. We report results of the first open-label multicentre phase 2 study assessing the anti-PD-1 antibody pembrolizumab in combination with metronomic cyclophosphamide (CP) in patients (pts) with advanced soft tissue sarcomas (STS) and gastro-intestinal stromal tumor (GIST). Methods: This trial included 4 cohorts of pts with advanced STS: leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), other sarcomas (Others), and GIST. All pts received CP 50 mg BID one week on, one week off, and pembrolizumab 200mg IV q21 days. The primary endpoint encompassed non-progression and objective response at 6 months per RECIST evaluation criteria v1.1 for LMS, UPS, and Others, and 6-month non-progression for GIST. Correlative studies of immune biomarkers were planned on pt’s tumor and plasma samples. Results: Between June 2015 and July 2016, 57 pts were included, and 50 were assessable for efficacy. Three pts experienced tumor shrinkage resulting in a partial response (PR) in one of them. The 6-month non-progression rate was 0%, 0%, 14.3% (95%CI 1.8-42.8), and 11.1% (95%CI 2.8-48.3) in LMS, UPS, Others, and GIST respectively. The most frequent adverse events were grade 1 or 2 fatigue, diarrhea, anemia. The only pt who experienced PR was the only one with a PD-L1-positive staining in more than 10% of immune cells on archived tumor sample. A strong macrophage infiltration was observed in tumor samples, and these macrophages largely expressed the inhibitory enzyme Indoleamine-2,3-dioxygenase-1 (IDO1). Moreover, a significant increase of the kynurenine/tryptophane ratio was observed in pts plasma samples during study treatment (p =0.0007). Conclusions: PD-1 inhibition has limited activity in advanced STS and GIST. This primary resistance may be explained by the low percent of PD-L1 positivity in these tumors, and an immune-suppressive tumor microenvironment resulting from macrophage infiltration and IDO1 pathway activation. Further strategies assessing drugs such as CSF1-R inhibitors and/or IDO inhibitors combined with anti-PD-1/PD-L1 in selected sarcoma subtypes are warranted. Clinical trial information: NCT02406781.
Hepatosplenic T-cell lymphoma (HSTL): A SEER data analysis.
Authors: Samip R. Master, Nebu V. Koshy, Glenn Morris Mills, Richard P. Mansour, Runhua Shi
Journal: Journal of Clinical Oncology (2017)

e19035 Background: HSTL is a very rare neoplasm accounting for less than one percent of non- Hodgkin lymphomas. The most common presentation of the patient with HSTL is marked hepatosplenomegaly and thrombocytopenia without lymphadenopathy. We performed SEER data analysis for the patients with HSTL to investigate the socio-economic factors and survival outcomes for this rare disease. Methods: Data from 92 adult patients registered in the SEER data with diagnosis of HSTL, between year 1998-2012 and follow up through 2013 were analyzed. Impact of patient demographics (sex, age, and race, year of diagnosis, family income, education, unemployment) and treatment characteristics (delivery of radiotherapy and tumor directed surgery) on survival were evaluated via univariate analysis. Results: The mean age of diagnosis 40.4 ± 18 years (see table). The education, income and employment are zip code level based on 2000 census data. The annual income is cost of living adjusted median family income. The education is the percentage of people in patient’s zip code with college education. The median survival was 13 months. Out of the factors analyzed only surgery and radiation affected survival. The median survival for the patient who got tumor specific surgery was 20 months , compared to 8 months for those who did not get tumor specific surgery(p = 0.04). Conclusions: HSTL is more common in younger population with majority of patient less than 64 years of age. Also, it is more common in males. Age, sex, race, income, employment, education and year of diagnosis do not affect survival. Unfortunately, SEER database does not have details about chemotherapy or bone marrow transplant. Previous literature in form of case reports and case series has suggested splenectomy for management of HSTL. Our data suggest that pts who underwent tumor specific surgery had improved outcomes. [Table: see text]
Safety of use of granulocyte colony stimulating factor during concurrent chemotherapy and thoracic radiotherapy in limited-stage small-cell lung cancer.
Authors: Roma Srivastava, Aman Naim Ajmeri, Leesah Al-Qawasmi, Charles Murphy, Yehuda Z. Lebowicz, Sutoidem M Akpanudo, Muhammad Omer Jamil
Journal: Journal of Clinical Oncology (2018)

e20570Background: Small cell lung cancer (SCLC) comprises approximately 15% of all lung cancers with 5 year mortality > 90%. Early initiation of chemotherapy with radiotherapy is the current standa...
Phase two clinical trial of combination oxaliplatin, irinotecan, and cetuximab for patients with locally advanced or metastatic pancreatic cancer.
Authors: Yara Abdou, Sarah Cooke Friend, Yehuda Z. Patt, Christine Gan, Fa-Chyi Lee
Journal: Journal of Clinical Oncology (2017)

e15781 Background: Pancreatic cancer remains a leading cause of cancer death with limited treatment options. After promising results from a retrospective chart review of the combination of irinotecan, oxaliplatin, and cetuximab (OIC), a prospective phase II trial was conducted to determine the efficacy and safety of this novel combination regimen in patients with advanced pancreatic cancer. Methods: Patients aged 18 and older, with a performance status of 0-2, and a life expectancy of minimum 12 weeks were eligible if they had confirmed locally advanced or metastatic pancreatic cancer. Patients were treated with intravenous irinotecan at 90 mg/m 2 , oxaliplatin at 60 mg/m 2 , and cetuximab at 250 mg/m 2 on day 1 of a 14-day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary efficacy endpoint was objective response rate (ORR) and disease control rate (DCR) per RECIST 1.1 criteria. The secondary endpoints included progression free survival (PFS), overall survival (OS), and tolerability of the regimen. Results: 60 patients were enrolled and 58 were evaluable; of these, 78% had metastatic disease and 22% had locally advanced cancer at time of enrollment. 41.4% of patients had received at least one prior line of cytotoxic chemotherapy. The ORR and DCR were 6.9% and 58.6%, respectively (complete response n = 1; partial response, n = 3; stable disease, n = 30). The median PFS was 3.6 months [95 % confidence interval (CI): 2.24-4.31], and median OS was 4.8 months [95 % CI: 3.68-6.25]. The most common grade 3 or 4 toxicities were hypokalemia (20.7%), fatigue (17.2%), abdominal pain (15.5%), hyperglycemia (13.8%) and dehydration (13.8%). Conclusions: OIC on a two-week regimen was well tolerated and demonstrated a high disease control rate, encouraging further investigation of this regimen in advanced pancreatic cancer. Clinical trial information: NCT00871169.
Demographic, clinicopathologic and survival differences among left sided versus right sided metastatic colorectal adenocarcinoma.
Authors: Smith Giri, Kathan Mehta, Shreesh Shrestha, Santosh Sharma, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2017)

e15068 Background: Clinical outcomes may differ between left versus right sided (CA) independent of stage. We utilized a large database to identify real world differences in characteristics and overall survival (OS) of left versus right sided CA. Methods:We used the National Cancer Database (NCDB) to identify 36,271 patients with metastatic (stage IV) CA diagnosed between the years 2010 to 2012. Right-sided CA was defined as CA of the cecum, ascending colon or hepatic flexure, and left-sided CA was defined as CA of splenic flexure, descending colon, sigmoid colon and rectum. We compared demographic and pathologic features (tumor size, grade, lymphovascular invasion, metastatic site) as well as OS of CA based on laterality. Results:36% of metastatic CAs were right sided. Left versus right sided CAs were more likely to be diagnosed in older patients (median age 68 vs. 62 yr; p&lt;0.01), females (52% vs. 43%; p&lt;0.01), and African Americans (17% vs. 13%; p &lt;0.01). Left-sided CAs were more likely to be &gt;5 cm (58% vs. 54%, p&lt;0.01), grade 3 or 4 (35% vs. 22%; p&lt;0.01), have lymphovascular invasion (62% vs. 50%; p &lt;0.01) and liver metastasis (72% vs 67%; p&lt;0.01) and less likely to have lung (20% vs. 27%;p &lt;0.01) or bone metastasis (5% vs. 6%; p value &lt;0.01). The median OS was lower in right versus left-sided CAs(12 vs. 20 months; p &lt;0.01) Conclusions:Our study suggests important differences in metastatic CAs based on laterality. Patients with right-sided CAs are more likely to be older, females and African Americans, present with larger tumor, lymphovascular invasion and differ in sites of metastases. Future studies should assess any difference in molecular characteristics and tumor biology based on laterality. [Table: see text]
Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line (1L) treatment of <i>RAS</i> wild-type (wt) metastatic colorectal cancer (mCRC) in Germany: Data from the FIRE-3 (AIO KRK-0306) study.
Authors: Sebastian Stintzing, Ilse van Oostrum, Chris Pescott, Alma Katharina Steinbach-Buechert, Bart Heeg, Volker Heinemann
Journal: Journal of Clinical Oncology (2018)

800 Background: The randomized, phase 3 FIRE-3 trial evaluated 1L FOLFIRI + cetuximab or bevacizumab in patients with RAS wt mCRC; overall survival favored FOLFIRI + cetuximab by &gt; 8 months. The purpose of this analysis was to evaluate the cost-effectiveness of FOLFIRI + cetuximab vs that of FOLFIRI + bevacizumab as 1L treatment for patients in Germany with RAS wt mCRC (including the patient subgroup with RAS wt, left-sided [LS] primary tumors, as LS is a predictive factor). Methods: A standard oncology 3–health-state partitioned survival cost-utility model was developed to analyze the costs and health benefits of FOLFIRI + cetuximab vs those of FOLFIRI + bevacizumab from a German payer perspective based on data from FIRE-3 and the literature. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs) gained. A 3.5% discounting rate was applied to the modeled costs and outcomes. Results: Discounted costs, health gains, and incremental cost-effectiveness ratios (ICERs) for patients with RAS wt (base case) and patients with RAS wt, LS (subgroup) mCRC are summarized in the Table. Probabilistic sensitivity analyses showed that at relevant European willingness-to-pay (WTP) thresholds of €55,000 and €80,000, FOLFIRI + cetuximab had a 64.0% and 81.6% (base case) and 80.5% and 92.4% (subgroup) probability of being cost-effective vs FOLFIRI + bevacizumab, respectively. Clinical trial information: NCT00433927. Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients in Germany with RAS wt mCRC at official WTP thresholds applied by relevant European health technology assessment agencies. The cost-effectiveness of FOLFIRI + cetuximab is more pronounced in the subgroup of patients with RAS wt, LS tumors.[Table: see text]
A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor (TKI) naïve patients with advanced NSCLC.
Authors: Aaron Elliott Lisberg, Amy Lauren Cummings, Jonathan Wade Goldman, Krikor Bornazyan, Nicholas Dean Reese, Tina Wang, Paul Coluzzi, Blanca A. Ledezma, Melody A. Mendenhall, Benjamin Jones, John Madrigal, James M. Carroll, Jaklin Gukasyan, Tawny Williams, Lauren Sauer, Courtney L Wells, Ariana R Hardy, Paulina J Linares, Carlos R. Adame, Edward B. Garon
Journal: Journal of Clinical Oncology (2018)

9014 Background: Despite the significant antitumor activity of pembrolizumab in non-small cell lung cancer (NSCLC), clinical benefit has been less frequently observed in patients whose tumors harbor epidermal growth factor receptor (EGFR) mutations compared to EGFR wild-type patients. Our single center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with PD-L1 expression ≥50%. Methods: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation positive, advanced NSCLC and PD-L1 positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200mg q3wks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. Results: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. 82% of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (ORR: 9%), but repeat analysis of this patient’s tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. Conclusions: Pembrolizumab’s lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting. Clinical trial information: NCT02879994.
Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals
Authors: Fateh Bazerbachi, Samir Haffar, Zhen Wang, Joaquín Cabezas, Maria Teresa Arias-Loste, Javier Crespo, Sarwa Darwish-Murad, M. Arfan Ikram, John K. Olynyk, Eng Gan, Salvatore Petta, Alessandra Berzuini, Daniele Prati, Victor de Lédinghen, Vincent W. Wong, Paolo Del Poggio, Norberto C. Chávez-Tapia, Yong-Peng Chen, Pin-Nan Cheng, Man-Fung Yuen, Kausik Das, Abhijit Chowdhury, Llorenç Caballeria, Núria Fabrellas, Pere Ginès, Manoj Kumar, Shiv Kumar Sarin, Fabio Conti, Pietro Andreone, Roxana Sirli, Helena Cortez-Pinto, Sofia Carvalhana, Takaaki Sugihara, Seung Up Kim, Pathik Parikh, Kazuaki Chayama, Christophe Corpechot, Kang Mo Kim, George Papatheodoridis, Ayman Alsebaey, Patrick S. Kamath, M. Hassan Murad, Kymberly D. Watt
Journal: Clinical Gastroenterology and Hepatology (2018)