tbuckley/cabot-search huggingface dataset:
Implementing genetic risk assessment in a community free clinic.
Authors: Leah Marsh, Daniella Kamara, BJ Rimel
Journal: Journal of Clinical Oncology (2018)

1585 Background: Assessment of hereditary cancer risk plays an integral role in reproductive healthcare. ACOG and NCCN recommend that OB/GYNs assess hereditary cancer risk annually. The Saban Community Clinic is a Resident-run clinic in Los Angeles, California, serving a predominantly non-white, uninsured patient population of low socioeconomic status (SES) with no access to genetic counseling. Prior to this study, no formal cancer family history was elicited. Methods: We adapted a bilingual screening tool developed at the UCSF Cancer Risk Program that is compliant with NCCN and ACOG guidelines. It relies on fact recall that patients can complete independently assuming low health literacy. Clinic providers were briefed on the project and distribution commenced in April of 2017. The questionnaires were scored and entered into a secured database. Results: Between April 2017-January 2018, a total of 98 questionnaires were collected. Ages ranged from 19-67. Thirty-two percent (32%) of the patients identified as Hispanic. Of those who identified as non-Hispanic, only 3 of these identified as White, the others identified as Asian or Black. Twenty-one percent (21%) of the forms were completed in Spanish. First degree relative with ovarian cancer and/or multigeneration presence of breast cancer accounted for 11% of the patients who screened “positive” for referral to further genetic counseling. Conclusions: This study sought to 1) determine the feasibility of implementing a brief genetic risk screening tool and 2) assess the unmet need for referral to genetic counseling/testing in a community clinic serving predominantly non-white, low SES patients without health insurance. The preliminary data is promising that a patient administered survey can aid clinicians in identifying patients for referral. It also demonstrates the unmet need in this population, with 32% of these patients meeting criteria for referral. This tool identified an important area of health inequity in cancer prevention in this population.
Mismatch Repair Genes and EPCAM germline mutations in patients with gastric or colorectal cancer with suspected of Lynch syndrome.
Authors: Nora Manoukian Forones, Fernanda Tereza Lima, Renan Paulo Martin, Leonardo Martins, Patricia Valera Lima Teixeira, Joao Bosco Pesquero, Celina Tisuko Fujiyam Oshima, Celia Aparecida Marques Pimenta
Journal: Journal of Clinical Oncology (2018)

e13623 Background: Lynch syndrome (LS) is the most common inherited colorectal cancer syndrome (CRC), comprising 2-4% of CRC, that may cause others cancers. Individuals with LS have at least one MMR (mismatch repair) germline gene mutation of MLH1, MSH2, MSH6 or PMS2. EPCAM mutation can influence MSH2 immunoexpression. Aim: to evaluate the immunoexpression of the genes repair proteins and the mutation of MMR genes and EPCAM in patients with CRC or gastric cancer with suspicion of LS. Methods: Patients with CRC or gastric cancer with at least one positive Bethesda criteria was included after an interview and medical appointment with the geneticist. The immunohistochemical test was performed to investigate the repair proteins MLH1, MSH2, MSH6 and PMS2 immunoexpression. The MMR genes and EPCAM were sequenced by New Generation Sequencing (NGS). Results: 95 patients were included, 85 with CRC and 52% were females. The mean age at diagnosis in women was 50.7 years and in men 54.03 (p = 0.01). Among CRC, 34% presented tumor in right colon and 53% had moderately differentiated histological grade. 75.6% of the tumors showed absence of expression in at least 1 protein, being the lack of expression of MLH1 the most common (40.4%). NGS was performed on 95 blood samples. Pathogenic mutations was found in 26 (27.30%) and VUS in 22 (23%) patients. MLH1 gene had 13 pathogenic mutations, MSH2 7, MSH6 5, and EPCAM 1. The variant c.215_2155 del CA was the most frequent on MLH1 and the c.338 A > G on MSH2. In patients with pathogenic mutations, the CRC was sited mainly on right colon (69%). No pathogenic mutation in PMS2 and in BRAF V600E was found. Conclusions: MLH1 gene pathogenic mutation was the most common and was not associated to BRAF V600E mutation. Pathogenic mutation of EPCAM was rare. Forty percent of the patients with lack of expression of repair genes had pathogenic gene mutation by sequencing. The difference between immunohistochemical and NGS reinforces the importance of the study of germline mutation cancer population with suspicion of Lynch Syndrome.
Impact of neoadiuvant treatment (NAT) in pancreatic adenocarcinoma (PDAC): Retrospective observational study in Pancreatic Cancer Registry of Reggio Emilia Province (REPCR).
Authors: Licia Baldi, Michele Panebianco, Tiziana Cassetti, Annalisa Berselli, Romano Sassatelli, Carmine Pinto
Journal: Journal of Clinical Oncology (2018)

e16213 Background: Optimal treatment strategies of locally advanced PADC and clinical impact on Overall Survival (OS) demand greater knowledge of factors influencing their outcomes. Neoadjuvant chemotherapy (NAC) may increase the proportion of patients undergoing surgical resection but there are no univocal data on predictive response factors. Methods: Patients diagnosed with locally advanced PDAC from 2008 to 2016 were retrieved by REPCR. The patients’ variables (sex, age), clinical tumour characteristics (stage, grade, subsite, CA 19.9), treatment (palliation of jaundice, chemotherapy, radiotherapy, surgery) were collected from clinical files and REPCR data. Descriptive statistics were used for all qualitative data. Time to Progression (TTP) and OS were analysed via Kaplan-Meyer curves and median with corresponding 95% CI. Results: A total of 47 patients were treated with NAC, 26 (55%) females and 21 (45%) males, median age 66.2 years (39-84). Stage at diagnosis was II in 26 (55%) and III in 21 (45%). 29 (62%) PDACs occur in the pancreatic head and 25 (53%) patients underwent endoscopic palliation of obstructive jaundice. The chemotherapy regimen was 18 (38%) FOLFIRINOX and 29 (62%) Gemcitabine-based (in 7 cases Nab-paclitaxel/Gemcitabine). The median number of chemotherapy cycles for different regimens was 5.59 (2-14). At the end of chemotherapy, 26 (55%) patients were in progression disease or inoperable, 21 (45%) reached a clinical partial response and underwent surgical treatment, with resection R0-R1 in 12 patients (57%). The median OS of all patients was 37.8 months [CI 29.8-45.7], with 97.6 months [CI 65.0-128.7] for patients resected, 31 months [CI 22.4-39.5] in non-resected. TTP was 7.4 months [CI 6.1-8.8], 15.3 months [CI 11.1-19.6] and 6.2 months [CI 4.1-8.3] respectively in two groups. Conclusions: The outcomes in patients undergoing NAC and surgery were improved, and only the clinical selection criteria data is unsatisfactory. It is necessary to further analyse biological and molecular characteristics to identify patients susceptible to NAC and surgery or candidates for different treatment strategies.
FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology)-gastric cancer (GC): A randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC.
Authors: Praveen Aanur, Martin Gutierrez, Ronan Joseph Kelly, Jaffer A. Ajani, Geoffrey Yuyat Ku, Crystal Shereen Denlinger, Thomas J. George, Megan Wind-Rotolo, Xiaowei Guan, Manish Gupta, Timothy P. Reilly, Paula M. Fracasso
Journal: Journal of Clinical Oncology (2017)

TPS4137 Background: Nivolumab, a fully human IgG4 mAb that targets programmed death-1, alone and in combination with ipilimumab, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte antigen 4, has demonstrated encouraging clinical activity in patients with advanced GC. These data support the rationale that nivolumab in combination with other IO agents or targeted therapies may improve treatment outcomes in patients with advanced GC. Given the rapid development of novel IO agents, traditional studies cannot efficiently evaluate all possible IO-IO and IO-targeted therapy combinations. FRACTION is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new combination regimens, as well as withdrawal of ineffective regimens. Here we describe the study concept, key design components, and the first IO treatment combinations of FRACTION-GC, a phase 2, randomized, open-label, adaptive study in advanced GC (NCT02935634). Methods: Patients with advanced GC or gastroesophageal junction (GEJ) cancer will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 (fully human IgG4 mAb that targets lymphocyte activation gene 3) or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on their treatment exposure and response. The primary endpoints are objective response rate, duration of response, and progression-free survival rate at 24 weeks. The secondary endpoint is safety. Comprehensive biomarker analyses will also be performed. New treatment combinations will be added over time to explore their potential benefits and to provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments. In this way, FRACTION-GC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic GC and GEJ cancer. Clinical trial information: NCT02935634.
Effect of bilateral supraclavicular lymph nodes irradiation in stage III lower thoracic esophageal squamous cell carcinoma after radical surgery.
Authors: Min Deng, Youling Gong
Journal: Journal of Clinical Oncology (2017)

e15555 Background: Surgery is the most important treatment for patients with lower thoracic esophageal squamous cell carcinoma (LT-ESCC) at stage III, but the locoregional failure is common, especially mediastinal and supraclavicular lymph nodes metastases. Postopearative radiotherapy (PORT) is benefit for those patients. However, the clinic target volume (CTV) remains controversial, especially whether or not including bilateral supraclavicular lymph nodes radiotherapy. Methods:79 patients of lower LT-ESCC at stage III who had undergone radical surgery and PORT were enrolled. 51 patients received the PORT CTV without bilateral suparclavicular lymph nodes region (group A), while 28 patients received the CTV with suparclavicular region (group B). Results: Totally, 26 patients had the tumor recurrences of supraclavicular lymph nodes. Among them, 23(45.1%) patients had the metastasis in group A, 3(10.7%) patients had the metastasis in group B. Univariate analysis showed the bilateral supraclavicular region RT can decrease of supraclavicular lymph nodes recurrence (p = 0.007). However, it could not prolong the overall survival (p = 0.273) or control the distant metastasis (p = 0.760).The Cox analysis revealed it was independent factor to control supraclavicular lymph node recurrence (HR = 0.027; 95 % CI 0.068-0.757; p = 0.016). PORT includingsupraclavicular region didn’t increase the radiotherapy complications, such as radiation pneumonia (p = 0.354), radiation esophagitis (p = 0.456), gastrointestinal reaction (p = 0.809), neutropenia (p = 0.470), thrombocytopenia (p = 0.137) and anemia (p = 0.642). Conclusions:PORT including bilateral supraclavicular region can reduce the metastasis of supraclavicular lymph nodes in LT-ESCC at stage III, and it does not increase radiotherapy complications. However, it can’t prolong OS or control the distant metastasis. Chemotherapy is essential to control distant metastasis and prolong OS.
Abstract 12453: Over-expression of NDNF Rejuvenates Aged Human Mesenchymal Stem Cells and Improves Mouse Heart Function After Myocardial Infarction
Authors: Hui-Fang Song, Shu-Hong Li, Jun Wu, Jian Guo, Zheng-Bo Shao, Sheng He, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2015)

Introduction: The benefits of cell transplantation for cardiac repair are diminished in aged individuals and effective methods to rejuvenate aged stem cells are required to treat the increasing number of elderly patients with heart failure. Neuron-derived neurotrophic factor (NDNF) has biological effects which could restore stem cell activity. This study determined whether NDNF could regenerate aged human bone marrow mesenchymal stem cells (hMSCs) and improve their regenerative capacity after a myocardial infarction (MI). Methods and Results: hMSCs were harvested from young (24±7 years, n=9) and aged (72±8 years, n=13) patients after informed consent, evaluated and then transfected with a lentiviral expression vector carrying the NDNF gene. NDNF overexpression was confirmed by RT-PCR and Western blot. Aged hMSCs had 54% lower NDNF mRNA levels and 66% lower NDNF protein levels (relative NDNF protein expression: 0.26±0.06 in young and 0.09±0.05 in old patients, p&lt;0.001). Proliferation (assayed by BrdU staining) was 54% lower and migration (by a scratch-wound assay) was 58% lower in aged compared with young hMSCs. Overexpression of NDNF in aged hMSCs increased cell proliferation and decreased apoptosis. The rejuvenation of the aged hMSCs was associated with a 45% decreased in p16 (a cyclin-dependent kinase inhibitor, relative protein expression: 0.55±0.34 in NDNF-transduced hMSCs and 1.00±0.30 in non-transduced hMSCs, p=0.04). Regucalcin (a senescence marker protein) was increased 2-fold in the NDNF-transduced aged hMSCs compared with empty vector-transduced aged hMSCs. In vivo implantation of NDNF-overexpressing aged hMSCs into a mouse cardiac infarct decreased scar size and preserved function at 28 days after MI compared with mice that received aged empty vector-transduced hMSCs (fractional shortening was 26±3% in the NDNF group and 20±3% in the empty vector group, p=0.04). Exploration of potential mechanisms revealed that phospho-Akt (Ser473), a key cell survival factor, was increased in mouse heart tissue after NDNF hMSC transplantation compared to the empty vector group. Conclusions: NDNF could be an important new target to rejuvenate aged stem cells that could then become potent vehicles for cardiac repair of the aged heart after injury.
A retrospective natural history study of patients (pts) with PDGFRα D842V mutant advanced gastrointestinal stromal tumor (GIST) previously treated with a tyrosine kinase inhibitor (TKI).
Authors: Margaret von Mehren, Michael C. Heinrich, Hongliang Shi, Patrick McNamara, Khalid Kevin Mamlouk, Anthony Boral, Suzanne George
Journal: Journal of Clinical Oncology (2018)

11533 Background: Activating mutations in KIT or PDGFRA kinases drive the vast majority of GIST in adult pts, making the disease highly amenable to targeted therapy. KIT-driven disease is more common (~80% of cases of advanced GIST), while PDGFRA-driven GIST is rare (~5-10% of cases of advanced GIST). TKIs have transformed therapy of advanced GIST; however, evidence suggests the benefit of currently approved TKIs has been predominantly in patients with KIT-driven GIST. We initiated this study to characterize response and survival of pts with PDGFRα D842 mutant GIST treated with currently approved TKIs. Methods: This was a multicenter, retrospective study of adult pts with locally advanced, metastatic, or recurrent PDGFRα D842 mutant GIST diagnosed between Jan 2000 and Jul 2016 who were treated with at least one TKI. Demographic and clinical data were collected through chart review and analyzed to determine overall survival (OS) and best overall response, duration of response, and progression-free survival (PFS) for each line of TKI therapy. Results: Twenty-two pts, all with PDGFRα D842V GIST, were identified at 3 US academic institutions: men, n = 15; median age, 57 y [range: 31-72]; median TKI lines of therapy, 4 [range: 1–8]. Ten pts had primary tumor size ≥ 15 cm, and 8 pts had mitotic index > 10/50 HPF at the time of diagnosis. Imatinib was the most common TKI used (n = 21); followed by sunitinib (n = 15), dasatinib (n = 8), sorafenib (n = 6), regorafenib (n = 4), nilotinib (n = 2) and pazopanib (n = 1). Imatinib was the first line TKI in 20 pts (91%). Only 1 (5%) pt responded to first-line TKI therapy (complete response to imatinib in a pt with residual disease following primary resection). Median PFS on first line TKI was 6.4 months. Median OS from initial diagnosis of GIST was 4.2 years. Conclusions: These results confirm and extend previous data suggesting that pts with advanced PDGFRα D842V GIST have a low response rate, and poor overall survival with currently available TKIs. To transform therapy for PDGFRa D842V GIST, novel TKIs that potently and selectively inhibit D842V mutant PDGFRα are needed.
Outpatient intra-arterial chemotherapy without radiotherapy for oral cancer to reduce irradiation-related complications: A new treatment that improves the quality of life.
Authors: Masatoshi Ohmae, Itsuro Kato, Yusei Fujita, Hiroo Takaoka, Takatoshi Meshii, Mitsuhiro Nakazawa
Journal: Journal of Clinical Oncology (2016)

e17543 Background: We developed a superselective intra-arterial chemotherapy (iaCT) approach with concurrent radiotherapy (RT) for treating oral cancer. This approach results in remarkable improvement in the curative efficiency but leads to a decrease in the quality of life (QOL), because of prolonged hospitalization, severe stomatitis, and lifelong dry mouth, dysgeusia, and radiation osteonecrosis of the maxillo-mandibular bone. Methods: We assessed a newly developed outpatient iaCT approach that involves complete implantation of an intra-arterial catheter connected to a subcutaneous infusion reservoir, without concurrent RT. In this approach, the chemotherapeutic agents (Cisplanin and Dosetaxel) were intra-arterially administered at the outpatient chemotherapy center twice a week. Intra-arterial infusion was repeated 6 times per course. We included 22 patients with oral cancer (9 with stage II, 9 with stage III, and 4 with stage IV cancer) who were treated with the outpatient iaCT approach. Results: The response rate was 100%, with 19 patients (86%) showing a complete response and 3 patients (14%) showing a partial response (PR). Five patients with regional lymph node metastasis or a PR underwent salvage surgery. In all, 18 patients (82%) experienced disease-free survival without irradiation-related complications, while 4 patients (18%) died of distant metastasis (n = 2) or local recurrence (n = 2). With the exception of the ambulatory visits twice a week for 3 weeks, the patients’ activities of daily living (ADLs) were mostly undisturbed. Moreover, they scarcely complained of dry mouth or dysgeusia and were free from radiation osteonecrosis after therapy. Conclusions: In this approach, the catheter is completely implanted subcutaneously; therefore, the common catheter-related complications rarely occur, resulting in good maintenance of ADLs. Moreover, patients can avoid the adverse effects of RT, such as dry mouth, dysgeusia, and radiation osteonecrosis of the maxillo-mandibular bone. Thus, our new outpatient iaCT approach without RT improves the QOL and has curative effects for patients with oral cancer.
Does addition of neck ultrasonography to physical examination, in follow-up of patients with early stage, clinically node negative oral cancers, influence outcome? A randomized control trial (RCT).
Authors: Anil D'Cruz, Richa Vaish, Sudeep Gupta, Supreeta Arya, Rohini W Hawaldar, Snehal Shah, Mitali Dandekar, Devendra Chaukar, Gouri Pantvaidya, Pankaj Chaturvedi, P. S. Pai, Anuja Deshmukh, Shubhada Kane, Deepa Nair, Sudhir Vasudevan Nair, Sarbani Laskar Ghosh, Jaiprakash Agarwal
Journal: Journal of Clinical Oncology (2016)

6020 Background: We previously reported results of a RCT demonstrating superiority of elective neck dissection (END) over therapeutic neck dissection (TND) in early oral cancer patients with clinically node negative neck1. We now report the results of the second question in this trial –elucidating the role of ultrasonography (USG) during follow-up, based on the hypothesis that addition of imaging would detect neck nodes earlier and improve salvage and survival (NCT00193765). Methods: Patients with lateralized T1 or T2 squamous carcinoma of oral cavity after initial surgery (excision of primary with/without neck dissection) were randomized to follow up with physical examination plus neck ultrasound (PE+USG) performed in a standardized manner versus physical examination (PE). The primary end point was overall survival (OS)1. Results: This report includes results of 500 patients in the same cohort reported earlier1with a median follow up of 39 months; 252 patients were randomized to PE+USG and 244 to PE. Both arms were balanced for stratification factors and surgical procedure (END vs. TND). There were 118 recurrences with 67 deaths in PE+USG and 109 recurrences with 62 deaths in PE, respectively. There was no OS difference between PE+USG and PE in unadjusted analysis (3-year OS 73.3% and 73.8%, respectively, HR = 1.02, 95%CI 0.73-1.45, p = 0.89) and after adjustment (HR = 0.81, 95%CI 0.51-1.29, p = 0.37) for stratification factors, prognostic factors, surgical treatment (END vs. TND) and an interaction term between two study questions, in a Cox model. END vs. TND continued to be highly significant for OS in this model (HR = 0.54, 95%CI 0.32 - 0.92, p = 0.02). Within TND (wait and watch) arm there was no significant difference between PE+USG and PE (3-year OS 67.3% and 67.6% respectively, HR = 0.96, 95%CI 0.62–1.5, p = 0.86). Conclusions: Neck ultrasound confers no survival advantage over physical examination in postoperative follow-up of clinically node negative early stage oral cancer patients. 1. N Engl J Med 2015;373:521-9 Clinical trial information: NCT00193765.
Attributable failure and costs associated with continued smoking by cancer patients.
Authors: Graham W. Warren, Elizabeth Garrett-Mayer, Kenneth Michael Cummings
Journal: Journal of Clinical Oncology (2018)

1559 Background: Smoking by cancer patients causes adverse outcomes including increased cancer specific mortality, but there are no estimates of the effects of continued smoking in cancer patients on costs of continued medical care for cancer. Methods: Attributable failure (AF) was modeled across expected first-line cancer treatment failure in non-smoking patients (ns-FLF), prevalence of current smoking, risk for escalated first-line cancer treatment failure caused by smoking, and cost of subsequent treatment after failure of first-line cancer treatment. Results: As smoking prevalence increases, AF increases with peak AF in cancer treatment conditions where ns-FLF ranged from 30-50%. In disease sites with 90% ns-FLF, the AF caused by smoking was lower than in patients with 10% ns-FLF, supporting a more significant effect of continued smoking in patients with higher expected cure rates. Using a conservative 60% increased risk of treatment failure caused by smoking across all cancer patients and cancer treatments published from median cancer related mortality estimates of risk from the 2014 Surgeon General’s Report, the conditions of 20% smoking prevalence and 30% ns-FLF resulted in 10.7 AF per 100 smoking patients. Cost per smoking patient per $100,000 incremental cost of ns-FLF cancer treatment was $10,675, Extending results to 1.6 million cancer patients, treatment of AF due to continued smoking by cancer patients cost $3.4 billion for every $100,000 increment of cost of cancer treatment per AF. Conclusions: Treatment of AF caused by continued smoking in cancer patients results in significant costs. Because estimates did not include costs associated with medical care not related to cancer progression, results are expected to underestimate the true costs of medical care caused by smoking in cancer patients.