tbuckley/cabot-search huggingface dataset:
Clinical performance pilot using cognitive computing for clinical trial matching at Mayo Clinic.
Authors: Jane Helgeson, Melissa Rammage, Alexandra Urman, M Christopher Roebuck, Sadie Coverdill, Katharine Pomerleau, Irene Dankwa-Mullan, Li-Ing Liu, Robert William Sweetman, Quincy Chau, M Paul Williamson, Michael Vinegra, Tufia C. Haddad, Matthew P. Goetz
Journal: Journal of Clinical Oncology (2018)

e18598 Background: IBM Watson for Clinical Trial Matching (CTM) is a cognitive computing solution that uses natural language processing to match patients to clinical trials through analysis of structured and unstructured data from a patient's Electronic Medical Record (EMR) against protocol eligibility criteria. This pilot was conducted collaboratively by Mayo Clinic, IBM Watson Health and Novartis to develop enhanced CTM functionality, allowing a global evaluation of patients at a site to determine the feasibility of accrual to individual clinical trials. Methods: We identified 7 ongoing or completed Novartis protocols1 (breast n = 4; lung n = 3) and obtained EMR patient data from a date-specific sampling of 376 breast and lung cancer patients seen at the Mayo Clinic in 2017. Using trial eligibility criteria and filters for patient setting (metastatic vs. non-metastatic), tumor stage, genetic markers and histology, Mayo nurse abstractors manually reviewed charts and assigned patients as potentially eligible or ineligible for each protocol. Time to complete this review per patient was recorded. Overall predictive accuracy, sensitivity, specificity, and related metrics were derived. Results: Overall eligibility accuracy of the breast protocols was 87.6% Patient attribute accuracy included: metastatic, 90.4%; neoadjuvant, 87.2%; HER2 status, 93%; and hormone receptor status, 88.6% For lung protocols, overall eligibility accuracy was 74.9%. Patient attribute accuracy included: metastatic, 87.7%; stage IIIB, 74.1%; ALK mutation, 72.6%; EGFR mutation, 75.9%; and subtype (NSCLC or SCLC), 91.4%. Manual screening time for 376 patient cases totaled 441 minutes (7.4 hours). Conclusions: Using Watson CTM to evaluate clinical trial criteria against a pool of institutional patients is a rapid and effective way to assess site feasibility and identify cohorts of potentially eligible patients. Further development and deployment of volume-based screening is highly desirable given the increasing complexity of clinical trials. The overall higher eligibility accuracy observed for breast trials compared to lung may be related to an increased number of breast training iterations prior to the pilot study.
Prognostic factors, treatment, and survival in dermatofibrosarcoma protuberans: A population-based cohort study.
Authors: Maressa C Criscito, Kathryn J Martires, Jennifer A Stein
Journal: Journal of Clinical Oncology (2016)

9584 Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue sarcoma that carries a 2-5% risk of distant metastasis. There is limited information on the influence of patient demographics, tumor characteristics, and treatment type on the survival of patients with DFSP. Methods: We performed a population-based cohort study in which we examined DFSP using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Registry from 2004-2011, with linkage to the US Census Bureau for median household income (MHI). DFSP patients with unknown information regarding race, anatomic site, tumor size, and/or treatment modality were excluded. Chi-square, t-tests, ANOVA with Tukey, and simple linear regressions were used to calculate univariate differences. Survival analyses were conducted using Kaplan-Meier method with log-rank statistic and Cox proportional Hazards modeling. Results: There were 461 cases of DFSP examined. Black (OR 2.275, CI 1.450-3.569, p < .001) and male (OR 0.414, CI 0.281-0.608, p < .001) DFSP patients were more likely to present with larger tumors, however race (p = 0.357), sex (p = 0.080), and MHI (p = 0.404) did not independently influence survival. Patients with larger tumors (OR 1.025, CI 1.010-1.039, p = 0.001) and tumors of the head and neck (OR 6.994, CI 2.545-19.224, p < .001) were more likely to receive both surgery and radiation. Females (OR 2.339, CI 1.213-4.511, p = 0.011) and patients with higher MHI (OR 1.361, CI 1.067-1.735, p = 0.013) were more likely to receive Mohs surgery than surgical excision. Larger tumor size was the only prognostic factor independently associated with worse survival (p = 0.029). Conclusions: While black and male DFSP patients were more likely to present with larger tumors, neither race nor gender were significantly associated with worse survival. Patients with large tumors located on their head or neck were most likely to receive radiation in addition to surgery. Furthermore, female DFSP patients and patients with a higher MHI had a greater likelihood of receiving MMS. While these clinical differences were significant, treatment modality did not influence all-cause mortality.
A real-world experience of palbociclib-induced adverse events in women with HR-positive/Her2-negative metastatic breast cancer.
Authors: Geoffrey Alan Watson, Oana Deac, Razia Aslam, Richard O'Dwyer, Sue Sukor, Michael John Kennedy
Journal: Journal of Clinical Oncology (2018)

e13061 Background: Palbociclib is a novel small molecule inhibitor of cyclin dependant kinases 4 and 6, and has been shown to improve progression free survival in HR positive metastatic breast cancer patients when used in conjunction other endocrine therapies, with a manageable safety profile. The aim of our study was to provide a real world experience of the adverse events (AEs) reported on this treatment. Methods: We performed a retrospective, single centre audit of HR positive metastatic breast cancer patients treated with Palbociclib over a six month period in an Irish tertiary hospital. Results: 64 patients were included in the analysis. Median age was 62.5 years. Palbociclib was most commonly used in combination with Letrozole (n = 40). 10 patients received Palbociclib as 1st line treatment. The median number of cycles completed was 5 (range 1-9). 28 patients (44%) had treatment deferrals due to neutropenia, with a median time to first deferral of 4 weeks. Only one patient developed febrile neutropenia. 16 patients (25%) required dose reductions, however there was no association with an increased risk of progressive disease (p = 0.56). Only 3 patients discontinued treatment due to poor tolerance. AEs reported included fatigue (n = 28), gastrointestinal complaints (n = 17), infection (n = 11), thrombocytopenia (n = 7), anaemia (n = 7), alopecia (n = 3), deranged liver function tests (n = 3) and decreased appetite (n = 2). Of note 7 thromboembolic events (TEs) were recorded, with one patient suffering from a saddle pulmonary embolus. Conclusions: To our knowledge this is the largest real world analysis of the AEs associated with Palbociclib therapy. While a significant proportion may experience neutropenia, this is often uncomplicated. If dose reductions due to neutropenia are warranted this is not associated with an increased likelihood of progression. While the PALOMA III trial reported a 2% incidence of TEs, we observed a 9% incidence rate. It is difficult to ascertain whether these events were palbociclib related or disease related, thus clinical suspicion and awareness are paramount and further studies are recommended to determine if prophylactic anticoagulation may benefit these patients.
Differences between gene mutation profile and outcome of Merkel cell polyomavirus (MCPyV) positive and negative Merkel cell carcinoma (MCC).
Authors: Guilherme Rabinowits, Anita Giobbie-Hurder, Christina Marcelus, Jingwei Cheng, Manisha Thakuria, Jonathan Daniel Schoenfeld, Charles H. Yoon, Lynette M. Sholl, Hailey Becker, Laura Ma, Nicole R. LeBoeuf, Robert I. Haddad, James A DeCaprio
Journal: Journal of Clinical Oncology (2016)

9577 Background: Despite its rising incidence and aggressive behavior, MCC remains an orphan disease with no active agents. Immunosuppression, UV exposure and MCPyV are known risk factors. A better outcome for those associated with MCPyV has been suggested, but the reasons for that remain unclear. MCPyV LT antigen is known to suppress RB1 gene. We correlated RB1 and p53 mutation status to tumor and clinical characteristics to better elucidate the field. Methods: Oncopanel, a multiplexed targeted assay that surveys exonic DNA sequences of 309 cancer genes was performed in MCC tumors of 35 patients. Sex, age, immune status, primary tumor site, disease stage, sentinel lymph node biopsy, extra-capsular extension, lymphovascular invasion (LVI), type of treatment and outcome were analyzed. Comparisons according to mutation status for the categorical characteristics were based on Fisher’s exact tests. Kaplan-Meyer estimates were used for survival analysis. Results: Analysis has been completed for 30 patients. Median f/u was 23 months (95% CI 10-36 months). The majority was male and older than 70 years. Only 2 patients were immunosuppressed. Head and neck and extremities were the primary site in 63% of the patients. Disease stages: I (9), II (2), III (11), IV (7), unknown (1). 70% underwent surgery, 60% radiation therapy, 63% systemic therapy. RB1 and/or p53 mutation was seen in 40% of the tumors. Tumors without the mutations more often had LVI (44% vs 0%). Best overall response was reported for 29 of 30 patients. The overall CR rate was 80% (95% CI 61-92%), with no differences noted according to mutation status. There were 16 (53%) recurrences and 8 (27%) deaths. Kaplan-Meier estimates of 2-year OS was 80% (95% CI 49-93%) vs 57% (95% CI 17-84%), and 2-year recurrence-free survival was 43% (95% CI 17-67%) vs 18% (95% CI 1-53%) for those without mutations vs those with mutations, respectively. Conclusions: RB1 and p53 mutations are common in patients with MCC. Survival for those without the mutations was better than those with the mutation. Final results of all 35 patients, including analysis of MCPyV status and correlation with the RB1 and p53 mutation status will be presented at the time of the meeting.
Stereotactic body radiotherapy to extend the clinical benefit of PD-1 inhibitors in recurrent/metastatic nasopharyngeal carcinoma.
Authors: Yu Chen, Qiaojuan Guo, Jin Lin, Gang Chen, Leong Kin Pan, Yuqi Wang, Shaojun Lin, Mei Chen, Chuanben Chen, Lurong Zhang, Yunbin Ye, Jian-ping Lu, Jingfeng Zong, Tian Zhu Lu, Lina Tang, Li Zhang, Ya Lin, Fang Guo, Zeng-qing Guo, Jian-ji Pan
Journal: Journal of Clinical Oncology (2018)

e18013 Background: Emerging evidences have showed that immune checkpoint inhibitors lead to durable responses in a variety of advanced cancers, including recurrent/metastatic nasopharyngeal carcinoma(RM-NPC), however, combination approaches are required to extend this benefit beyond a subset of patients. This study retrospectively evaluated 9 RM-NPC patients, to investigate how stereotactic body radiationtherapy(SBRT) could potentiate programmed cell death protein 1(PD-1) checkpoint inhibition. Methods: Between September, 2016 and July, 2017, 9 consecutive RM-NPC cases were treated at our institution and Macau Clinics, for which prior standard therapy was ineffective(4 patients), had disease progression within 6 months of completion of definitive chemo-radiation(2 patients), or was considered inappropriate(3 patients), all except one received full-dose PD-1 inhibitors(either nivolumab or pembroizumab) combined with SBRT. Due to economic burden, most patients could not receive PD-1 inhibitors according to the recommended regimen of Food and Drug Administration. Treatment was discontinued as long as patients were experiencing clinical benefit in the opinion of the physicians and at least 5 cycles were given before stoppage. Results: After a median following-up time of 398 days, the confirmed objective response and complete responses rate based on RECIST1.1 was 88.9%(8/9) and 44.4%(4/9), respectively. The median progression free survival 1(PFS1) and PFS2 were 239 and 145 days, respectively, with the median overall survival(OS) was not reached at the time of censorship. Series biopsy was performed in patients with disease progression, we discovered that immune microenvironment, in terms of the expression amount and location of CD3, CD8, PD-1 and PD-L1, had not change significantly after drug resistance. Two in 9(22.2%) patients occurred grade 3~4 treatment-related adverse events(i.e. nausea and vomiting). Conclusions: PD-1 inhibitors combined with SBRT demonstrated promising antitumor activity and manageable safety profile in RM-NPC patients, and it may maximize clinical benefit beyond progression after PD-1 inhibitors treatment in a subset patients.
Correlation between platelet/lymphocyte ratio, neutrophil/lymphocyte ratio and response to neoadjuvant chemoradiation therapy in rectal cancer.
Authors: Sarah Louise Picardo, MinYuen Teo, Khairun Izlinda Abdul Jalil, Syed Yaseen Naqvi, Patrick G. Morris, Oscar S. Breathnach, William Grogan, Gregory D. Leonard, Bryan Hennessy
Journal: Journal of Clinical Oncology (2016)

e15140 Background: Locally advanced rectal cancer is treated with neoadjuvant chemoradiation, but biomarkers are lacking to predict response to this therapy. Neutrophil/lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) have been studied in many cancers as possible predictors of response. Both NLR and PLR have been shown to predict poorer outcomes including disease-free survival (DFS) and overall survival (OS) in rectal cancer after neoadjuvant treatment, but measures of response such as pathological complete response (pCR) and tumor regression grade (TRG) were not evaluated. Therefore, we aimed to determine the correlation between hematological parameters and responsiveness to chemoradiation in locally advanced rectal cancer. Methods: One hundred and twenty two patients with locally advanced rectal cancer undergoing preoperative chemoradiation were identified retrospectively and full blood count parameters including neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratios (PLR) were recorded at baseline and weekly during chemoradiation. Outcome measures were pCR, TRG, DFS and OS. Results: The overall rate of pCR was 27%. Baseline NLR did not correlate with pCR (p = 0.365) or TRG (p = 0.119). NLR changes from pre-treatment to weeks 2 or 3 did not predict pCR or TRG either, when examined as continuous variable, categorical change or percentage change. There was no correlation between NLR baseline or changes and DFS, although there was a trend towards poorer OS with baseline NLR > 4 (p = 0.051). Baseline PLR did not correlate with pCR (p = 0.476), TRG (p = 0.292) or OS (p = 0.73). The percentage change in PLR between weeks 1 and 2 correlated with TRG (p = 0.038) and also correlated with DFS (HR 3.67, p = 0.03). Conclusions: Changes in PLR with neoadjuvant chemoradiation may be a potential biomarker for response to treatment and disease free survival in locally advanced rectal cancer, while NLR does not appear to correlate with tumour response. Prospective studies may help to further evaluate the correlation between pre-treatment hematological parameters and outcomes.
Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
Authors: Giuseppe Lo Russo, Massimo Moro, Michele Sommariva, Valeria Cancila, Mattia Boeri, Giovanni Centonze, Simona Ferro, Monica Ganzinelli, Patrizia Gasparini, Veronica Huber, Massimo Milione, Luca Porcu, Claudia Proto, Giancarlo Pruneri, Diego Signorelli, Sabina Sangaletti, Lucia Sfondrini, Chiara Storti, Elena Tassi, Alberto Bardelli, Silvia Marsoni, Valter Torri, Claudio Tripodo, Mario Paolo Colombo, Andrea Anichini, Licia Rivoltini, Andrea Balsari, Gabriella Sozzi, Marina Chiara Garassino
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutational subsets, were assessed for tumor growth after treatment with antibodies against mouse and human programmed death receptor-1 (PD-1). The immune microenvironment was evaluated by flow cytometry and IHC. Results: Among 187 patients, 152 were evaluable for clinical response. We identified four categories: 32 cases were defined as responders (21%), 42 patients with stable disease (27.7%), 39 cases were defined as progressors (25.7%), and 39 patients with HP (25.7%). Pretreatment tissue samples from all patients with HP showed tumor infiltration by M2-like CD163+CD33+PD-L1+ clustered epithelioid macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even in tumor nodules from immunodeficient mice injected with human lung cancer cells and with PDXs. In these models, tumor growth was enhanced by treatment with anti–PD-1 but not anti–PD-1 F(ab)2 fragments. Conclusions: These results suggest a crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually inducing HP and provide clues on a distinctive immunophenotype potentially able to predict HP. See related commentary by Knorr and Ravetch, p. 904
Outcomes of EGFR-TKI therapy in EGFR mutated metastatic lung adenocarcinoma in an inner city population.
Authors: Romy Jose Thekkekara, Rohit Kumar, Thomas E. Lad
Journal: Journal of Clinical Oncology (2017)

e20635 Background:Metastatic lung cancer with systemic chemotherapy has a median progression-free survival (PFS) of 5-6 months and median overall survival time (OS) of around 12 months. In Epidermal Growth Factor Receptor gene (EGFR) mutated metastatic lung cancer the use of EGFR Tyrosine Kinase Inhibitors (EGFR-TKIs) has increased the median PFS to12 months and the median OS to 30 months. The objective of this study is to evaluate the response to TKIs in EGFR mutated metastatic lung cancer in racially diverse inner city population with high smoking rates. Methods:Consecutive patients diagnosed with EGFR mutant metastatic lung adenocarcinoma and treated with TKIs in John H. Stroger Jr. Hospital of Cook County in Chicago, IL between January 2009 to June 2016 were retrospectively evaluated. Demographic data was collected and PFS and OS were analyzed. Results:35 patients with EGFR mutated metastatic lung cancer received EGFR-TKI during the study period. There was a female preponderance (63%). Hispanics formed the most common racial group (37%), followed by Asians (26%), African Americans (AA) (20%) and Caucasians (17%). Mean age of diagnosis of metastatic disease was 56.5± 11.5 years. 20% of the patients were ever smokers. Stage 4 disease at presentation was seen in 88.6 %. Sites of metastatic disease included lungs/pleura (60%), bone (60%), brain (22.9%) and liver (14.3%). 82.9% had TKI as first line treatment. Median PFS and OS were 9.89 (95% CI: 7.8-11.9) months and 19.3 (95% CI: 1.9-36.8) months respectively. The median PFS and OS were 12.88 and 17 months for Asians, 10.8 and 24.4 months for Caucasians and 9.2 and 33 months for Hispanics respectively. Among AA, PFS at 19 months and OS at 35 months was 0.58%, not reaching the median. Patients who continued to smoke had a median OS of 8.5 months vs 19.3 months in nonsmokers/ex-smokers. Conclusions: In an underserved population, patients treated with EGFR mutated metastatic lung adenocarcinoma with EGFR-TKI have similar survival compared previously known data. Race of the patient does not appear to alter response to EGFR-TKI therapy. Active smokers had a lower OS. Studies in minority populations with larger samples are required to further validate the above findings.
Effect of time to resection of colorectal liver metastases on recurrence risk.
Authors: Emerson Yu-sheng Chen, Skye C. Mayo, Kevin G. Billingsley, Gina M. Vaccaro, Matthew Kearney, Charles D. Lopez
Journal: Journal of Clinical Oncology (2018)

3541 Background: Resection of colorectal liver metastases (CRLM) with perioperative chemotherapy is curative in only 20-30% of patients. There are no biomarkers or robust clinical predictors that can effectively select patients curable by resection. The time interval from diagnosis of liver metastasis to hepatic resection (time to resection, or TTR) has not been studied to risk-stratify patients who would benefit. Methods: A retrospective analysis of patients who underwent resection for CRLM from 2003 to 2017 was conducted at our institution. Patients were categorized as: 1) no evidence of disease (NED) or 2) disease relapse or death. NED patients with < 1 year follow-up were excluded. Factors including TTR (short = < 3 months; intermediate = 3-6 months; and long = > 6 months) were compared between the two groups (all p < 0.05 unless noted). Logistic regression was used to identify factors associated with NED. Results: We identified 264 patients with a median follow-up of 30 months. Of these, 60% presented with synchronous liver metastases, 42% had bilateral liver disease, and 76% received preoperative chemotherapy. Preoperative MRI was performed in 19% of patients. R0 resection was achieved in 88%. Overall, 27% of patients were NED at one year. Patients with intermediate TTR had a higher proportion of NED compared to short TTR and long TTR (45% vs. 27% vs. 28%). Primary tumor location, grade, metachronous CRLM, and response to chemotherapy were not associated with NED. Long TTR was associated with synchronous CRLM, bilateral disease, and more liver lesions compared to intermediate and short TTR. On multivariate analysis, patients with long TTR (OR: 0.65), older age (OR: 0.97), more liver lesions (OR: 0.80), and positive resection margin (OR: 0.08) were less likely to achieve NED. Preoperative MRI use was predictive of NED (OR: 2.6). Conclusions: Intermediate TTR is associated with NED status at > 1 year when compared to short TTR. This suggests liver resection should wait 3-6 months to assess for more indolent tumor biology. Lack of benefit seen with long TTR was likely due to high tumor burden in our dataset. Use of preoperative MRI may better quantify extent of liver involvement to help select patients who will benefit from resection. Analysis is ongoing.