tbuckley/cabot-search huggingface dataset:
The utility of chemotherapy after immunotherapy failure in metastatic melanoma: A multicenter case series.
Authors: Simone M. Goldinger, Serigne Lo, Jessica Cecile Hassel, Andrea Forschner, Meredith Ann McKean, Lisa Zimmer, Chloe Chia Hoey Khoo, Reinhard Dummer, Zeynep Eroglu, Elizabeth Iannotti Buchbinder, Paolo Antonio Ascierto, Ralf Gutzmer, Elisa A. Rozeman, Christoph Hoeller, Douglas Buckner Johnson, Anja Gesierich, Peter Kolblinger, Naima Benannoune, Justine Vanessa Cohen, Alexander M. Menzies
Journal: Journal of Clinical Oncology (2018)

e21588 Background: Immune checkpoint inhibitors are standard of care for most patients (pts) with MM, yet only a minority has durable disease control. CTX has limited activity when used first-line, but can alter the tumor microenvironment and has improved efficacy when used in combination with IT in lung cancer. Whether CTX given after IT failure has clinically significant activity in MM pts is unknown. Methods: Consecutive MM pts treated with CTX after failing IT were retrospectively identified from 24 melanoma centers. Primary endpoints were RECIST objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 463 pts were treated with CTX between 2007 and 2017. Prior IT included ipilimumab (44%), PD1 antibodies (44%), and combination immunotherapies (12%). 37% had 2+ lines of IT, and 42% had received PD1 antibodies just prior to CTX. The median interval between IT and CTX was 1.9 months (0 - 40.8). At start of CTX, median age was 58y, 86% were stage M1c, 57% had elevated LDH, and 58% had ECOG > 1. CTX included carboplatin + paclitaxel (C+P, 32%), dacarbazine (DTIC, 25%), temozolomide (TMZ, 15%), taxanes (9%), fotemustine (FOT, 6%), and others (13%). Median (med) duration of therapy was 7.9 weeks (0 - 108). No unexpected toxicities were observed. In the whole cohort, 0.4% had CR, 12% PR, 21% SD and 65% PD. Med PFS was 2.7 months (2.4, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3). In pts who had received anti-PD1 prior to CTX, the ORR was 11%, and med PFS 2.5 months (2.1, 2.8). Best activity was achieved with taxanes (N = 41), with ORR 27% and med PFS 3.9 months (2.1, 6.2). ORR for other regimens included C+P (14%), FOT (11%), DTIC (10%), TMZ (3%). 48% of patients had further therapy after CTX, including PD1 in 59%. Med OS from CTX start was 7.1 months (6.5, 8.0); 16.8 months (13.0, 40.6) in CTX responders and 6.5 months (5.9, 7.5) in non-responders (p < 0.0001). Conclusions: Overall, CTX had low response rate and short PFS in MM pts who have failed IT, although activity varied between regimens. Additional analyses are ongoing to identify predictors of clinical benefit with CTX in this setting.
Understanding real-world outcomes in patients with NSCLC who progress on 1st-/2nd-generation EGFR TKIs.
Authors: Ancilla Fernandes, Karen E Skinner, Mark Stephen Walker, Melissa Pavilack, Ari M. Vanderwalde
Journal: Journal of Clinical Oncology (2017)

e20589 Background: Epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (TKIs) are recommended for patients (pts) with EGFR mutation ( EGFRm) positive non-small cell lung cancer (NSCLC). Limited data are available for real-world outcomes in pts who experience progression on 1st-/2nd-generation EGFR TKIs, which was the focus of this study. Methods: A retrospective chart review of pts with advanced NSCLC (stage IIIb/IV) from 10 US community oncology practices was conducted. Patients were included if they were diagnosed 1/1/2008—1/1/2015, were treated with erlotinib or afatinib (TKIs) either first line (1L) or second line (2L), and had disease progression (per clinician’s assessment) prior to 10/31/2015. Pts were classified into cohorts based on TKI initiation (1L or 2L) and EGFRm status. Progression-free survival (PFS) and overall survival (OS) were evaluated for the TKI treatment period and the post-progression period. Results: The study included 364 pts: 77.7% white, 17.3% African American; mean (SD) age 66.3 (11.3) years. PFS and OS were longer for 1L and EGFRm+ pt cohorts during the TKI treatment period. After progression, 25.3% (80/316) pts continued TKI, while around half received chemotherapy (56.3%; 178/316). The effects of other variables evaluated as predictors of PFS and OS were largely nonsignificant. Conclusions: Outcomes were worse after progression irrespective of EGFRm status and whether TKI was initiated 1L or 2L. This finding highlights the need for therapeutic options that improve outcomes in pts after progression on a 1st-/2nd-generation EGFR TKI. [Table: see text]
Paired somatic and germline genetic testing for ovarian cancer patients: Observations, benefits and implications for treatment.
Authors: Daniel Chen, Patrick Reineke, Negar Ghahramani, Ashley Deckman, Erica Wellington, Monalyn Umali Salvador, Lucia Guidugli, Melissa Pronold, Holly LaDuca, Michelle Jackson
Journal: Journal of Clinical Oncology (2018)

5579 Background: Germline and somatic genetic testing have traditionally been offered separately; however, the clinical applications of these tests are now converging with continued FDA approval of targeted therapies for both germline and somatic mutation carriers. This study aims to describe the findings of a paired testing (germline and somatic) approach among ovarian cancer (OC) patients. Methods: Study participants consisted of 95 consecutive OC patients undergoing paired testing at a clinical diagnostic laboratory. Eleven OC predisposition genes in the homologous recombination (HR) repair pathway were targeted by capture-based NGS: ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Paired analysis of sequence data from both tumor (minimum of 20% neoplastic cellularity) and blood specimens was performed to differentiate variants of somatic vs. germline origin. Customized NGS pipelines and/or microarray were used to detect gene copy number variants. Additional test results included hypermethylation analysis of BRCA1 and RAD51C promoter regions by methylation-specific PCR, when available. Results: In total, 41 patients (43.2%) were eligible for PARP-inhibitor therapy based on the presence of a germline (n = 3, 7.3%), somatic (n = 34, 82.9%) or germline and somatic (n = 4, 9.8%) BRCA1 or BRCA2 pathogenic mutation. Of 38 (40.0%) patients with somatic alterations, 3 (7.9%) had sequencing mutations, 32 (84.2%) had whole gene deletions of BRCA1 and/or BRCA2, and 3 (7.9%) had both alteration types. Somatic whole gene deletions of BRCA1 or BRCA2 were often accompanied by gains or losses of other genes in the tumor. Twenty-nine patients (30.5%) were germline and tumor BRCA1/2-negative, but tested positive for germline or somatic pathogenic mutations in other HR genes or tumor promoter methylation in BRCA1 or RAD51C. Conclusions: Our findings highlight the benefits of paired testing over germline and/or somatic testing alone, such as concurrent confirmation of germline mutations and maximizing detection of patients who would benefit from therapy. Further research is needed to determine the impact of paired testing on healthcare costs and patient outcomes.
A phase 2, multicenter study to evaluate the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-145) for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (HNSCC).
Authors: Rom S. Leidner, Ammar Sukari, Christine H. Chung, James Ohr, Missak Haigentz, Ezra E.W. Cohen, Robert James Brown, Samuel Suzuki, Igor Gorbatchevsky, Maria Fardis, Robert L. Ferris
Journal: Journal of Clinical Oncology (2018)

TPS6096 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has demonstrated efficacy in the treatment of immunogenic tumors with high mutation loads, such as melanoma. Despite the heterogeneity of HNSCC tumors, most tumors are either virally-associated or carry high mutation loads that increase the potential antigens targeted by TIL ACT. Since outcomes for patients with recurrent and/or metastatic HNSCC remain poor despite existing approved therapies, a clear rationale exists for the potential application of ACT with TIL in patients with HNSCC. Methods: Clinical trial C-145-03 (NCT03083873) is a prospective phase 2 multicenter, open-label study evaluating the efficacy of a single autologous TIL infusion (LN-145) followed by IL-2 after a non-myeloablative lymphodepletion (NMA-LD) regimen in patients with recurrent and/or metastatic HNSCC. Patients undergo a surgical resection of a tumor lesion from which TIL are extracted and expanded at a central GMP manufacturing facility that prepares a cryo-preserved TIL (LN-145) product ready for shipment and infusion. One week prior to LN-145 infusion, patients undergo NMA-LD consisting of cyclophosphamide (60 mg/kg) daily x 2 days followed by fludarabine (25 mg/m2) daily x 5 days. LN-145 is infused 24 hours after NMA-LD followed by up to 6 doses of IL-2 (600,000 IU/kg) every 8-12 hours. The primary efficacy endpoint is the objective response rate per RECIST v1.1. Secondary endpoints include an assessment of safety & other efficacy parameters such as progression free and overall survival. Patients must have been treated with at least one systemic therapy for recurrent and/or metastatic HNSCC and, in addition to the tumor resected for TIL manufacture, must have an additional measurable lesion for assessment of response. Additional eligibility criteria include amongst others: adequate bone marrow, liver, pulmonary, cardiac, and renal function; and ECOG performance status of 0 or 1. Clinical trial information: NCT03083873.
Comprehensive analysis of mutation and expression based pathways in head and neck squamous cell carcinoma.
Authors: Bhumsuk Keam, In Sook Woo, Heui-june Ahn, Yun-Gyoo Lee, Seong-Hoon Shin, Sang-Cheol Lee, Hyeok Shim, Kyoung Eun Lee, Moon Young Choi, Joo Han Lim, Hyo Jung Kim, Jun-Eul Hwang, So Yeon Oh, Sanggon Park, HyeRyun Kim, Byoung Chul Cho, Hwan Jung Yun, Jin Young Park, Gun Do Kim, Yunsuk Yu
Journal: Journal of Clinical Oncology (2018)

e18015 Background: Over- or under expression of mRNA result from genetic alteration. mRNA expression based pathway are as important as single gene level mutations analyzed by next generation sequencing (NGS). We have compared the mutation and expression based signal transduction pathway in head and neck squamous cell carcinoma (HNSCC). Methods: A total of 96 recurred/ metastatic HNSCC patients from 19 institutions were enrolled. We performed targeted gene sequencing using Agilent 244 customized gene panel for NGS, and nanostring nCounterR for mRNA expression. mRNA expression classified as over- or under expression groups based on the expression levels that are 2 fold change in tumor compared with non-tumor tissues. We investigate mutation and nanostring data into the CBSJukeboxR system which is a big-data driven platform to analyze druggable pathways, genes, and protein-protein interaction. Analysis were based on 14 databases related to protein, interaction, signaling pathways and drugs such as NCBI, Uniprot, KEGG, Biogrid, DIP, HPRD and Drugbank. High interaction genes were mapped to investigate druggable pathways. We calculated TBPS (Treatment Benefit Prediction Score). Results: Mutation profile consistent with the previously known HNSCC genes (TP53, CDKN2A, CCND1 and PIK3CA etc.). By mapping the high interaction genes to investigate druggable pathways, we found that highly related signaling pathways with mutation mapping were Influenza A, pathways in cancer, EBV, HPV, HTLV-1 pathways. Based on mRNA expression and interaction gene scoring model, several pathways were found to be associated with over- and under-expression. Comparison between NGS based pathway and mRNA based pathway, we observed that 19.8% of NGS based pathways matched with mRNA over-expression based pathways, and 43.2% of NGS based pathways consist with mRNA under-expression based pathways. TBPS found several matching drugs such as cetuximab, paclitaxel and erlotinib. Conclusions: NGS based pathways were associated with mRNA under-expression based pathways. The results suggest that HNSCC are mainly related to loss-of-function mutations, but big data based platform for druggable pathway can find potential matching drugs. Clinical trial information: NCT03292250.
Comparative performance of surveillance mammography and breast MRI in women with a history of breast cancer.
Authors: Karen Wernli, Laura E Ichikawa, Karla Kerlikowske, Mary Bush, Dianne Johnson, Diana SM Buist, Susan Brandzel, Wendy DeMartini, Louise Henderson, Lariss Nekhlyudov, Tracy Onega, Brian Sprague, Diana Miglioretti
Journal: Journal of Clinical Oncology (2016)

e18051 Background: National guidelines recommend women with a history of breast cancer and no clinical concerns undergo annual mammography for surveillance to detect second breast cancers. Increasingly women are also receiving breast magnetic resonance imaging (MRI), despite limited evidence regarding its comparative effectiveness. Methods: We evaluated the performance of surveillance mammography and breast MRI from 2005-2012 in 13,038 women aged ≥ 18 with history of stage 0-III breast cancer. Data from the Breast Cancer Surveillance Consortium on 33,601 mammograms and 2,397 breast MRI examinations were included. Exams were linked to pathology and cancer registry data to assess second cancers. Logistic regression was used to compare sensitivity and specificity of MRI to mammography using inverse probability weighting for adjustment. Results: During the study period, 11% of women received a breast MRI. Patient characteristics associated with receipt of MRI included: younger age at diagnosis, recent breast cancer diagnosis, higher AJCC stage, primary diagnosis of invasive lobular carcinoma, mammographically occult breast cancer, treatment with radiation or chemotherapy, and having heterogeneously or extremely dense breasts. There were 427 breast cancers within 1 year of a surveillance exam (301 invasive, 126 DCIS; cancer rate 17.9 for breast MRI vs 11.1 mammography). Comparative performances for breast MRI and mammography were: overall sensitivity60.5% vs. 64.2% (OR = 0.94, 95% CI 0.15-5.9); invasive cancer sensitivity 62.1% vs. 59.3% (OR = 5.08, 95% CI 1.08-23.8); and specificity 87.8% vs. 93.2% (OR = 0.71, 95% CI = 0.44-1.15). Conclusions: In women with a history of breast cancer, surveillance MRI was most frequent in women with a younger age at diagnosis, higher breast density, and more advanced cancers. Breast MRI was more likely to detect invasive cancers at a lower specificity than mammography. Additional research should evaluate the relative performance and benefits of MRI for patient subgroups.
Survivor feedback on a late effects-oriented survivorship care plan for head and neck cancer.
Authors: Talya Salz, Mary S. McCabe, Kevin C. Oeffinger, Rebecca B Schnall, Stacie Corcoran, Andrew J. Vickers, Andrew L. Salner, Ellen A Dornelas, Nirupa Jaya Raghunathan, Elizabeth Fortier, David Finitsis, Shrujal S. Baxi
Journal: Journal of Clinical Oncology (2017)

e21596 Background: Survivorship care plans (SCPs) typically include generic advice for the management of late effects (LEs) that can occur, rather than addressing LEs that the survivor actually has. We developed a platform called HN-STAR that uses electronic patient-reported outcomes (ePROs) and evidence-based LE management to generate a personalized SCP for survivors of head and neck cancer (HNC), a population vulnerable to various LEs. We assessed HNC survivors’ experiences with HN-STAR to ensure its acceptability and usefulness. Methods: Disease-free HNC survivors at two cancer hospitals used HN-STAR in conjunction with a routine survivorship visit. Prior to the visit, survivors used a validated ePRO measure (PRO-CTCAE) to report up to 22 physical LEs. Based on clinic visit discussions, HN-STAR generated an SCP that included a treatment summary and LE management plans. Survivors indicated their level of agreement to statements regarding the ease of use of the ePROs, content of the SCP, and intentions to adhere to LE management recommendations. Results: 47 survivors completed surveys (mean 5.4 years from treatment completion). Most were white (89%), male (85%), had an oropharynx tumor (58%), and received multimodality therapy (81%). More than half (51%) experienced at least 9 of the 22 LEs in the last 30 days (mean 8.2 per person). Most survivors reported that completing ePROs improved the discussions with their provider (98%), the quality of their care (96%), and their communication with their provider (98%). 91% agreed the SCP was the right length, and 98% agreed it was easy to follow. 98% intended to follow at least some of the recommendations for LEs management, and 98% reported feeling confident that they could follow the recommendations. The majority agreed that the SCP accurately summarized the clinic visit (98%), they would refer back to the SCP (98%), they trust the SCP (100%), and they plan to share the SCP with a primary care provider (87%). Conclusions: Among HNC survivors, an automatically generated SCP that was tailored to their LEs was acceptable, was trusted, and provided recommendations they intended to follow. Patient-centered SCPs that focus on existing LEs hold promise as a means to help survivors manage LEs.
The impact of Massachusetts health reform on breast cancer surgery.
Authors: Lindsay M Sabik, Kirsten Y. Eom, Bassam Dahman, Jie Li, G J. Van Londen, Cathy J Bradley
Journal: Journal of Clinical Oncology (2018)

e18629 Background: There are substantial disparities in breast cancer treatment by insurance and socioeconomic status. Women with private insurance are more likely to undergo reconstruction post-mastectomy than Medicaid-insured or the uninsured. Private insurance is also associated with higher rates of breast-conserving therapy. Insurance coverage expansions provide a natural experiment for studying the relationship between insurance availability and patterns of care. Methods: We employ a quasi-experimental framework to assess the effects of Massachusetts Health Reform on whether women undergoing surgery for breast cancer receive breast conserving surgery (BCS) and whether those receiving mastectomy undergo reconstruction. Data come from the Massachusetts Cancer Registry and the Surveillance Epidemiology and End Results (SEER) cancer registries for 2001-2013. We exploit variation across states and age groups to estimate the relationship between health reform and type of BCA surgery within a difference-in-difference-in-differences (DDD) framework. Regression models control for age; race/ethnicity; stage; area-level demographics and provider supply; and state and year fixed effects. Results: We observe statistically significant increases in rates of BCS and reconstruction post-mastectomy among non-elderly women in Massachusetts (n = 38,593) relative to comparison groups in other SEER states and elderly patients, who were not directly impacted by the reform. Estimates suggest a 2.8 to 4.2 percentage point increase in the likelihood of receiving BCS (relative 73% at baseline in Massachusetts). Similarly, we estimate a 5.3 to 7.5 percentage point increase in reconstruction after mastectomy (relative to 33% at baseline). Conclusions: Massachusetts Health Reform was associated with increased rates of BCS and reconstruction. Increased availability of health insurance coverage and generosity of covered benefits under reform may have impacted access to and out-of-pocket cost of surgery. Given differences in treatment by income and insurance, these findings suggest that insurance expansions may reduce disparities in the types of surgical therapies received for breast cancer.
Pathological central review of 290 thymic epithelial tumors (TET): The national network RYTHMIC experience.
Authors: Thierry Molina, Maria Virginia Bluthgen, Lara Chalabreysse, Vincent Thomas De Montpreville, Anne De Muret, Veronique Hofman, Sylvie Lantuejoul, Marie Parrens, Isabelle Rouquette, Veronique Secq, Nicolas Girard, Alexander Marx, Benjamin Besse
Journal: Journal of Clinical Oncology (2016)

8568 Background: RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a nationwide network for TET appointed in 2012 by the French National Cancer Institute. The objectives of the network are management of clinical tumor board and central pathologic review of all cases.RYTHMIC Tumor Board is based on initial histopathological diagnosis. Methods: Pathological central review of patients diagnosed with TET from January 2009 to December 2015 was made by a panel of 10 expert pathologists from the working group. Assessment of agreement or disagreement between the initial institution and the panel review was made according the WHO 2004/2015 and new ITMIG proposals for histologic typing and staging. Discordances were classified as “major” when they would have changed the therapy or management of patients according to the RYTHMIC guidelines. Results: A total of 290 specimens were reviewed. Considering either histological subtype and/or staging, a total of 117 discordances in 109 patients (38%) were identified as follow: 73 concerning histological diagnosis and 44 regarding stage. A total of 20 major discordances in 19 patients (6.6%) were identified: 12 patients for whom post-surgical treatment recommendation concerning adjuvant radiotherapy would have been changed and 7 patients for whom management of disease should have been modified. The most frequent disagreement was the sub-diagnosis of stage III reflecting the underlying difficulty in pericardial and/or mediastinal pleura histological invasion. Additionally, major disagreement between the initial and panel pathology’s stage and subsequent interpretation by the working group at national tumor board was found in 3 patients, enhancing the importance of an expert pathologist at the RYTHMIC network committee. Conclusions: The RYTHMIC experience confirms the relevance of an expert histopathological panel diagnosis of thymic malignancies and for better decision-making in particular concerning post-operative radiotherapy to avoid over- or under-treatment of the patients.