tbuckley/cabot-search huggingface dataset:
A dose finding study with erlotinib in combination to irinotecan and capecitabine in metastatic colorectal cancer (mCRC) patients
Authors: M. Di Bartolomeo, E. Bajetta, R. Buzzoni, E. Ferrario, L. Mariani, A. Gevorgyan, K. Dotti, R. Longarini, M. Platania, S. Canova
Journal: Journal of Clinical Oncology (2006)

13075 Background: Erlotinib is an oral selective and reversible small molecule inhibitor with specificy for the EGFR/HER1. This study evaluated the maximum tolerated dose and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine. Secondary objectives included the safety profile and the response rate of the combination. Methods: Twenty-two pts (median age 57 yrs, range: 39–69; M/F:12/10) with mCRC refractory to first-line therapy (oxaliplatin-combinations) were accrued. Five dose level combinations with irinotecan (from 180 to 240 mg/m 2 , day 1, q21), capecitabine (1500 to 2400 mg/m 2 /d, days 2–15 q21) and erlotinib (50 to 150 mg/d., continuously until progression) were planned. Cycles were repeated every 3 weeks, maximum of 6–8 cycles. Tumor assessments (RECIST criteria) performed every 3 cycles. Maximum tolerated dose was defined as the highest dose where the toxicity rate does not exceed the 30% target level. Patients were enrolled in cohorts of three, and evaluated for first cycle acute toxicity. Results: Three pts entered the first dose group (no DLT), six the second (1 DLT; G4 neutropenic fever), six the third dose group (2 DLT; G3 diarrhea, G4 neutropenic fever), and one (protocol deviation in the dose escalation scheme) the fourth dose group (1 DLT; G3 diarrhea and vomiting). Cutaneous rash and mucositis G3 (no DLT), were documented in one pt (dose group 2). To confirm these results, six pts were additionally accrued in dose groups 2 and 3 showing no DLT. Among twenty evaluable pts, two had an objective response, 15 showed disease stabilization and completed the 6-cycle treatment, 3 had disease progression. Conclusions: Erlotinib at a dose of 100 mg/d, combined with irinotecan 240 mg/m 2 and capecitabine 1500 mg/m 2 /d, (as correspond to dose group 3) has an acceptable safety profile and appears suitable for further investigation. Editorial Assistance by the Scientific Service of the I.T.M.O. group. No significant financial relationships to disclose.
Adequacy of breast cancer screening in women previously treated with chest wall radiation for lymphoma at the Cancer Therapy and Research Center in San Antonio.
Authors: Jessica Trevino Jones, Kate Ida Lathrop, Michelle Janania Martinez, Uzair Mushtaq, Faraz Fiazuddin
Journal: Journal of Clinical Oncology (2017)

232 Background: Research has established that woman with a history of lymphoma who receive chest wall radiation are at a greater risk to develop breast cancer. As such, recommendations for breast cancer screening for woman who received prior RT &lt; 30yr of age have been a topic of discussions for the better part of 20 ears. Survivorship screening programs for our successfully treated hematologic malignancies should include referring survivors for breast cancer screening given their substantially increased risk of treatment related breast cancer. Methods: We investigated 88 patients who had lymphoma treated by radiation for lymphoma from 2016 to present time. We excluded 49 patients due to age, or not receiving chest wall radiation. For the 39 patients identified, further data included was the average amount of total grays received, if they were counselled about possibility of treatment related breast cancer, if they were Hispanic, and if they were referred for breast cancer screening/referred to specialty breast clinics. Results: We identified that all 39 patients in our study have not had any breast cancer screening despite being qualified to get breast MRI or mammogram. Less than 10% were advised of the possibility of treatment related breast cancer by radiation oncology per documentation. We have found that 48% of our patients are Hispanic, 7 patients’ records did not show total amount of grays received but 61% received greater than or equal to 30 grays. Conclusions: As our results showed that all 39 subjects were not properly screened to the best of our knowledge, we intervened because of our results. As a result, we plan on doing further quality care measures in our clinics to increase breast clinic referrals. Additionally, we are working on IRB approval to contact patients we have found needing screening to get screened appropriately. We are optimistic that our study will ensure future protocols for patients who received radiation to the chest, and look forward to presenting data as it becomes available.
A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis
Authors: Haiyang Yu, Mykyta Artomov, Sebastian Brähler, M. Christine Stander, Ghaidan Shamsan, Matthew G. Sampson, J. Michael White, Matthias Kretzler, Jeffrey H. Miner, Sanjay Jain, Cheryl A. Winkler, Robi D. Mitra, Jeffrey B. Kopp, Mark J. Daly, Andrey S. Shaw
Journal: Journal of Clinical Investigation (2016)

In Table 4, the units for ApoC-III conc.
A pooled analysis of 1,144 patients with HIV-associated lymphoma: Assessment of lymphoma-, HIV-, and treatment-specific factors on clinical outcomes.
Authors: Stefan K. Barta, Xiaonan Xue, Roni Tamari, Jeanette Y Lee, Nicolas Mounier, Lawrence D. Kaplan, Josep-Maria Ribera, Michele Spina, Rudolf Weiss, Lionel Galicier, Francois Boue, Wyndham Hopkins Wilson, Christoph Wyen, Jose-Tomas Navarro, Kieron Dunleavy, Richard F. Little, Lee Ratner, Mireia Morgades, Olga Garcia, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2012)

8005 Background: Non-Hodgkin Lymphoma (NHL) remains the most common malignancy in patients with HIV. Outcomes have significantly improved over the last decade, but there is no accepted consensus regarding the optimal initial therapeutic approach. Our objective was to assess the effects of clinical factors on response and survival. Methods: We performed a systematic review to search for prospective clinical phase II or III trials that assessed therapeutic interventions for HIV-associated NHL and assembled individual patient data from 16 trials published between 2000 and 2011 including 1144 patients (median N=62/trial, range 17-195). Treatment factors included type of chemotherapy (CHOP, N=642; EPOCH, N=178; CDE, N=191; intensive regimens, N=155) and rituximab use (N=542). Endpoints included complete response (CR), progression-free survival (PFS), and overall survival (OS). We used logistic regression and Cox proportional hazard models adjusted for age, sex, age-adjusted International Prognostic Index (IPI), baseline CD4 count, baseline HIV viral load, use of concurrent antiretroviral therapy, and histology. Odds ratios (OR) &gt; 1 for CR denote improved CR, and hazard ratios (HR) &lt; 1 indicate reduced risk of progression or death. Results: Among the lymphoma- and HIV-specific covariates evaluated, only a higher IPI score was associated with inferior CR rate, PFS and OS (p&lt;0.001). Rituximab was associated with a higher CR rate (OR 1.75; p=0.017), better PFS (HR 0.39, p&lt;0.001) and OS (HR 0.39, p&lt;0.001); patients with a higher baseline CD4 count benefited more from rituximab (HR for OS 0.57 if baseline CD4 count ≥100/ul vs. &lt;100/ul; p&lt;0.001). For all histologies, initial therapy with the EPOCH regimen resulted in a better CR rate (OR 1.78, p=0.039), PFS (HR 0.61, p=0.032) and OS (HR 0.47, p&lt;0.001) when compared to CHOP. Conclusions: In this pooled analysis including 1144 patients with HIV-associated NHL, the addition of rituximab to chemotherapy was associated with significantly improved CR rate, PFS, and OS, specifically for patients with a baseline CD4 count ≥100/uL. Treatment with infusional EPOCH was also more effective than CHOP.
A phase I/II trial of MEK162 in combination with gemcitabine (G) and cisplatin (C) for patients (pts) with untreated advanced biliary cancer (ABC).
Authors: Maeve Aine Lowery, Eileen Mary O'Reilly, James J. Harding, Kenneth H. Yu, Andrea Cercek, Ellen Hollywood, Erica Salehi, Ezra Margona, Mikaela Bradley, Trevor Witter, Scott R. Gerst, Marinela Capanu, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2017)

290 Background: Activating mutations in the RAS/RAF/MEK/ERK signaling pathway are commonly found in ABC. MEK162 is an oral, selective small molecule inhibitor of MEK1/2; single agent activity of MEK162 in ABC has previously been observed. Preclinical data support anti-tumor synergy for MEK inhibition (MEKi) when combined with G &amp; C, only when MEKi is held for 2 days prior to and on day of each G and C infusion. Methods: A Single arm, non-randomized, open-label, phase I/II,evaluated oral MEK162 twice daily with G and C IV infusions day 8 and 15 of a 21 day cycle. MEK162 was. Eligibility criteria were: untreated ABC, with advanced measurable disease, ECOG 0-1, adequate hematologic, renal, hepatic and cardiac function. The primary endpoints were to determine the MTD (phase 1); and 6 month PFS and response rate (RR) (phase II). Tumor tissue for targeted somatic mutational sequencing was evaluated. Results: Between 09/13 and 09/15, 12 pts were enrolled on phase 1, the MTDs were MEK162 45mg PO BID, in combination with G 800 mg/m 2 and C 20mg/m 2. 35 pts evaluable for primary endpoint of phase II (29 treated on phase II &amp; 6 pts treated at MTD in phase 1): Male = 19, median age 63 years (range 48- 77). Cholangiocarcinoma (CC) = 24, and gallbladder adenocarcinoma (GB) = 11. Median overall survival was 21 months (95% CI 11- NA), median PFS 6 months (95% CI 4-14). Molecular profiling using MSK-IMPACT 410 gene panel was feasible in 29 pts; aberrations in the RAS-RAF-MEK-ERK pathway were notable in responding pts including mutations in PIK3CA, AKT2, PIK3CG, KRAS, BRAF and MAP3K1. Overall RR was 36%, GB 45%, CC 32%. Two pts had CR, two pts remain on study &gt; 24 months, currently on MEK162 alone. Conclusions: The MTDs were MEK162 45mg PO BID, in combination with G 800 mg/m 2 and C 20mg/m 2. . Significant activity of the combination was noted in select pts with prolonged and complete response to treatment. Molecular profiling of BTC may facilitate selection of pts for further development of the combination. Clinical trial information: NCT01828034.
Phase III trial evaluating the addition of bevacizumab to letrozole as first-line endocrine therapy for treatment of hormone-receptor positive advanced breast cancer: CALGB 40503 (Alliance).
Authors: Maura N. Dickler, William Thomas Barry, Constance T. Cirrincione, Matthew James Ellis, Mary Ellen Moynahan, Federico Innocenti, Arti Hurria, Hope S. Rugo, Diana Lake, Olwen Mary Hahn, Bryan P. Schneider, Debu Tripathy, Eric P. Winer, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2015)

501 Background: Preclinical data suggest estradiol modulates angiogenesis under both physiologic and pathologic conditions. High vascular endothelial growth factor (VEGF) levels in breast tumors have been associated with decreased response to endocrine therapy (ET). We performed a multicenter, open label phase III trial of the addition of bevacizumab (B) to first-line letrozole (L) in patients (pts) with hormone-receptor positive (HR+) advanced breast cancer to test the hypothesis that anti-VEGF therapy may delay progression on ET. Methods: Pts were randomized 1:1 to L (2.5 mg orally daily) or L+B (15 mg/kg intravenously every 3 weeks) within strata defined by measurable disease (Yes/No) and disease-free interval (≤ / > 24 months (mo)). Pts electing to receive tamoxifen by physician choice were enrolled in a parallel, randomized phase II trial. The primary endpoint was progression-free survival (PFS), defined as time from randomization to progression (RECIST v1.0) or all-cause death. Secondary endpoints were response rate, clinical benefit rate, overall survival (OS) and adverse events (CTCAE v3.0). Three hundred and fifty-two pts and 274 events were needed for 90% power to detect a hazard ratio (HR) of 0.67 (corresponding to an increase in median PFS from 6 to 9 mo). Results: From May 2008 to November 2011, 350 pts were randomized to the phase III trial. 343 pts received treatment and are included in the efficacy analysis. Median age was 58 (25-87). After 36 mo of additional follow-up, 258 PFS events were observed. Median PFS for L+B was 20 mo vs. 16 mo for L (HR = 0.74, 95% CI: 0.58 - 0.95; p = 0.016). There was no significant difference in OS (L+B, 47 mo vs. L, 41 mo; HR = 0.84; 95% CI, 0.61 - 1.15; p = 0.27). The most frequently reported grade 3/4 toxicities on L+B and L, respectively, were hypertension (23 vs 2%) and proteinuria (11 vs 0%). Conclusions: Adding B to first-line L improves PFS in HR+ advanced breast cancer with increased B-related toxicity. Updated data will be presented. Correlative studies are underway to identify potential biomarkers of response or resistance to therapy. Supported by U10CA180821, U10CA180882, CA31946, CA180888, CA180858, CA180820, CA180785. Clinical trial information: NCT00601900.
Prospective evaluation of the clinical implications of the tumor metabolism and chemotherapy-related changes in advanced biliary tract cancer.
Authors: Jaemin Jo, Do-Youn Oh, Seongyeol Park, Hyun Woo Kwon, Gi Jeong Cheon, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2017)

261 Background: Tumor metabolism measured by [18F] fluorodeoxy-D-glucose ( 18 F-FDG) positron emission tomography (PET) has a diagnostic and prognostic role in several cancers. The clinical implication of tumor metabolism in biliary tract cancer (BTC) has not been studied well. Therefore, we prospectively evaluated the prognostic value of tumor metabolism and chemotherapy-related changes in advanced BTC patients. Methods: We prospectively enrolled advanced BTC patients before the initiation of palliative chemotherapy. Using 18 F-FDG PET, we assessed the baseline maximum standardized uptake value (SUVmax) and monitored the changes of SUVmax during chemotherapy. We analyzed the associations between SUVmax, and clinicopathologic factors and clinical outcomes. Results: A total of 75 patients were enrolled. All patients received gemcitabine/cisplatin as first-line chemotherapy. Primary tumor site, histologic differentiation, molecular characteristics, laboratory findings, and disease extent were associated with the metabolic characteristics. The high metabolism group showed worse survival outcome [Hazard ratio (HR)=4.09, p=0.001 for progression-free survival (PFS); HR=2.61, p=0.019 for overall survival (OS)] than the low metabolism group. The lesser reduction of SUVmax during chemotherapy was also associated with worse outcome (HR=3.35, p=0.002 for PFS; HR=1.96, p=0.082 for OS). Considering both baseline tumor metabolic activity and chemotherapy-related changes in the tumor metabolism, patients with a low metabolism and a more reduction in metabolism obtained the best OS (20.7 months, p=0.013). Conclusions: Tumor metabolic activity and the chemotherapy-related changes in the metabolism were associated with prognosis in advanced BTC patients.
Incidence of brain metastasis from esophageal cancer.
Authors: Jonathan Ben Ashman, Gabrielle Welch, Naresh P. Patel, Dawn E. Jaroszewski, David Fleischer, William G. Rule, Harshita Paripati, Francisco Ramirez, Helen J. Ross
Journal: Journal of Clinical Oncology (2017)

165 Background: Distant metastases are common in primary esophageal cancer, but data conflict regarding the rates of brain metastases (BM) ranging from 0% to 13%. We sought to investigate whether the incidence of BM from esophageal malignancies is increasing in the modern era. Methods: After IRB approval, a single institution retrospective review identified 583 patients (pts) treated between 1/1997 and 1/2016 for stage I-IV cancer of the esophagus/esophagogastric junction with at least 3 months follow-up. Data collected included demographic information, primary diagnosis date and staging, histologic subtype, treatment regimens for primary and BM, date of BM diagnosis, status of neurologic symptoms and extracranial disease at BM diagnosis, and date of death. Data were analyzed by Fischer’s exact test and Kaplan-Meier analysis. Results: The overall cohort was comprised of 495 pts (85%) with adenocarcinoma and 82 pts (14%) with squamous cell carcinoma. 492 pts (84%) were male; the median age was 68 years (range 26-90). BM were identified in 22 pts (3.8%) with a median latency of 11 months from the primary diagnosis. Of the pts with BM, the primary histology was adenocarcinoma in 21 pts and squamous cell carcinoma in 1 pt ( P = 0.3). BM developed in 12 pts who were initially treated for locally advanced disease and in 10 pts who presented with distant metastases. Diagnosis of BM was at the time of initial presentation in 4 of these 10 stage IV pts. A solitary BM was identified in 9 pts. Initial treatments of BM were surgical resection followed by stereotactic radiosurgery (SRS; n = 5); surgical resection followed by whole brain radiotherapy (WBRT; n = 1); WBRT alone (n = 13); SRS alone (n = 3). Overall survival (OS) following diagnosis of BM was 18% at 1 year with a median of 4 months. OS was superior for pts who had surgical resection as initial treatment of BM compared to pts treated with WBRT or SRS alone (1-year OS 67 vs. 0%; median OS 13.5 vs. 3 months; P = 0.003). Conclusions: The incidence of BM is low in esophageal cancer with no statistically significant increased rate of BM developing in patients with adenocarcinoma compared with squamous cell carcinoma. Outcomes were poor overall for pts who developed BM, but pts who were appropriate for neurosurgical resection had improved survival.
Potential driver mutations in ovarian Brenner tumors.
Authors: Sara E. Patterson, Christopher S. Potter, Vanessa Spotlow, Talia Mitchell, Roger Liu, Guruprasad Ananda, Gregory J. Tsongalis, Laura J. Tafe, Susan M. Mockus
Journal: Journal of Clinical Oncology (2015)

e22087 Background: Brenner tumors are characteristically benign ovarian neoplasms, often found in association with mucinous tumors. The pathogenesis of Brenner tumors is still unknown but it has been suggested that associated mucinous neoplasms may arise from mucinous metaplasia in the Brenner tumors, however, this has not been well characterized. To address the relationship between these coexisting neoplasms, we have run pairwise comparisons of genetic variants associated with benign Brenner tumors and ipsilateral mucinous tumors, and performed genetic profiling to identify potential driver mutations. Methods: DNA from FFPE sections of 14 ovarian tumor samples (7 benign Brenner tumors, 2 proliferating Brenner tumors, 3 mucinous cystadenoma (MCA), and 2 mucinous borderline tumors (MBT) was sequenced using the JAX Cancer Treatment Profile consisting of a 358-gene targeted panel, and submitted to the Clinical Genomics Analytical (CGA) bioinformatics pipeline. SnpEff/SnpSift variant call files were sorted based on high/medium impact and calls not passing established quality control metrics were removed from analysis. High/medium impact variant calls were compared within tumor pairs to assess variant overlap. Results: Pairwise comparisons of genetic variants within 4 sets of paired samples demonstrated high concordance (84.5%-93.8%, p = 0.175). Hotspot oncogenic mutations in RAS were identified in all (2/2) proliferating Brenner tumors, and in 80% (4/5) of mucinous (MCA or MBT) tumors (KRAS G12X = 3; KRAS Q61H = 2; HRAS G12S = 1), and 0% of benign Brenner tumors (0/7). 75% (3/4) of tumor pairs demonstrated KRAS hotspot mutations specifically in the mucinous tumor, and KRAS hotspot variant allele frequencies for 2/3 of these pairs fell below 10%, indicating a potential early driver event. Conclusions: The high concordance between benign ovarian Brenner tumors and coexisting mucinous tumors suggests a genetic relationship between these tumor types, with ipsilateral mucinous tumors potentially arising from benign Brenner tumors. Our finding that RAS hotspot mutations occur frequently in proliferating Brenner tumors and mucinous tumors, but not benign Brenner tumors, implicates these as potential driver mutations.
EXIBIT: An international multicenter phase II trial of gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer
Authors: T. André, J. M. Reyes-Vidal, L. Fartoux, P. Ross, M. Leslie, O. Rosmorduc, M. R. Clemens, C. Louvet, N. Perez, W. Scheithauer
Journal: Journal of Clinical Oncology (2006)

4135 Background: Biliary tract carcinomas (BTC) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) showed promising activity in a French Phase II study (4 centers) in advanced BTC (André. Ann Oncol 2004;15:1339–1343). The objective of this study is to further evaluate the efficacy and safety of GEMOX as first-line therapy in patients (pts) with advanced BTC. Methods: Eligible pts were &gt;18 years of age with histologically proven and measurable, locally advanced or metastatic BTC, had an ECOG PS ≤ 2, adequate renal and hematologic functions, bilirubin &lt; 2.5 × upper limit of normal, and no prior malignancy or brain metastases. Gemcitabine 1000 mg/m 2 (Day 1) and oxaliplatin 100 mg/m 2 (Day 2) were administered every 2 weeks. The primary objective was response rate (RR) by RECIST (one dimension); secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Here we report an interim analysis of OS and safety. Results: A total of 70 pts were enrolled between April 2003 and April 2005. The median age was 62 years (range 30–83), 40.0% of pts were male, 94.3% had ECOG PS 0–1. Tumor sites were intrahepatic bile ducts (37.1%), gallbladder (31.4%), extrahepatic bile ducts (12.9%), ampulla of Vater (1.4%), intra/extrahepatic bile ducts (1.4%), missing data (15.7%); 98.6% of pts had no prior radiotherapy and 50% had no prior surgery for BTC. Median OS is 8.25 months (68% of pts are dead and 32% have censored data). Sixty-seven pts were evaluable for safety. Grade 3/4 (NCI-CTC v. 2) hematologic toxicities (% of pts) included thrombocytopenia 10.4%, anemia 9.0%, and neutropenia 9.0%. One pt had febrile neutropenia. Grade 3/4 nonhematologic toxicities included pain 10.4%, ALT elevation 9.0%, fatigue 9.0%, infection 10.4%, vomiting 9.0%, sensory neuropathy 4.5%, nausea 4.5%, and diarrhea 3.0%. One patient died during treatment (cause unknown). Conclusions: GEMOX has acceptable toxicity in pts with BTC. Updated efficacy data (RR, PFS, and OS for the entire population and also by tumor sites) will be presented at the meeting. [Table: see text]