tbuckley/cabot-search huggingface dataset:
A three-year epidemiological profile of cancers managed by a Haitian cancer program from 2016 to 2018.
Authors: Joseph Bernard, Lynn Gabrielle Alexis, Lenz Sacha Christyl Pierre, Vincent DeGennaro
Journal: Journal of Clinical Oncology (2019)

e13079 Background: The recent epidemiology of cancers in Haiti is poorly understood, since there is no functional national cancer registry. The data from GLOBOCAN 2012 and 2018 are estimations that do not reflect the actual cancer burden in Haiti. The aim of this study was to present the three-year epidemiology of cancer cases managed by a cancer program in Port-au-Prince, Haiti. Methods: A retrospective study was conducted on patients aged 15 years old or more with pathological and/or clinical diagnosis at the cancer clinic of Innovating Health International (IHI) from January 2016 to December 2018. The chart review collected variables such as age, gender, date of diagnosis, cancer type and outcome to present this epidemiological profile of cancers. Results: One thousand four hundred and eighty-one (1481) cancer cases were managed during this study period, respectively 282 in 2016, 513 in 2017 and 686 in 2018 (p &lt; 0.001). 84% of the patients were female and 16% male. The mean age of the study population was 51.8 years [15 –92], ranging from 51.7 years in 2016 to 52.1 years in 2018 (p = 0.56). Adolescents and young adults (15-39 years old) represented 20.9% of this cohort and geriatric cases (≥ 65 years old) 19.6%. Breast cancer was the most common type (n = 686, 46.3%), followed by gynecological cancers (n = 330, 22.3%) with cervical cancer representing 70.9% of the cases, gastrointestinal cancers (n = 138, 9.3%), hematological malignancies (n = 75, 5.1%), head and neck cancers (n = 64, 4.3%), sarcomas (n = 40, 2.7%), urological cancers (n = 32, 2.2%), skin cancers including melanoma (n = 29, 2%), lung cancer (n = 13, 0.9%), thyroid cancer (n = 10, 0.7%) and central nervous system (CNS) cancers (n = 2, 0.1%). 4.2% of the patients (n = 62) had a cancer of unknown primary (CUP). Breast cancer was the most common type among women (54.7%) and gastrointestinal cancers the most diagnosed among men (25.3%). There was a predominance of women for most of the cancer types. The overall mortality rate was 31% and 8.6% of the patients were lost to follow-up. Conclusions: There was a significant increase of cancer cases in our cancer clinic from 2016 to 2018, likely due to a combination of our cancer awareness campaign, increased diagnosis and referral. Cancer mainly affects Haiti’s young, feminine and active population. Breast and cervical cancers were the most prevalent in this retrospective cohort. The under-representation of prostate and other urological cancers, lung cancer, acute leukemias and CNS cancers was likely due to underdiagnosis, misdiagnosis, under-referral or early mortality.
The Occupational Burden of Nonmalignant Respiratory Diseases. An Official American Thoracic Society and European Respiratory Society Statement
Authors: Paul D. Blanc, Isabella Annesi-Maesano, John R. Balmes, Kristin J. Cummings, David Fishwick, David Miedinger, Nicola Murgia, Rajen N. Naidoo, Carl J. Reynolds, Torben Sigsgaard, Kjell Torén, Denis Vinnikov, Carrie A. Redlich
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.
Impact of antibiotics (ABX) on overall survival (OS) in patients (pts) with advanced non-small-cell lung cancer (aNSCLC) and melanoma (aMel) treated with first-line immune checkpoint inhibition (ICI).
Authors: Stephen Joseph Bagley, Neil Dhopeshwarkar, Vivek Narayan, Neal J. Meropol, Ronac Mamtani, Ben Boursi
Journal: Journal of Clinical Oncology (2019)

e20643 Background: Recent data suggest that modulating the microbiome may affect response to ICI. Using electronic health record (EHR) data, we examined whether use of ABX influences OS in pts with aNSCLC and aMel treated with ICI. Methods: We performed two retrospective cohort studies (aNSCLC, aMel) of pts who received ICI +/- chemotherapy as first-line treatment in the nationwide Flatiron Health EHR-derived database. The impact of ABX exposure on OS was assessed using Cox regression, adjusting for age, sex, body mass index (BMI), performance status (ECOG PS), Elixhauser Comorbidity Index, glucocorticoid (GC) use, and smoking. In the primary analysis, ABX exposure was defined as use from -6 to +4 weeks around start of ICI. In secondary analyses, we separately evaluated ABX use within 6 weeks pre- and 4 weeks post-initiation of ICI. Results: Baseline characteristics are displayed (Table). In the primary analysis, there was no association between ABX use and OS in aNSCLC (HR 1.16, 95% CI 0.54-2.47, p = 0.7) or in aMel (HR 0.70, 95% CI 0.17-2.81, p = 0.6). The only secondary analysis to reveal a negative impact of ABX on OS was the time window of 0 to +4 weeks after ICI start in aNSCLC (HR 3.41, 95% CI 1.38-8.39, p = 0.008). Conclusions: In this large, real-world dataset, ABX exposure around the start of front-line ICI did not influence OS in pts with aNSCLC or aMel. However, ABX exposure was associated with inferior OS in the subgroup of aNSCLC pts who received ABX within 4 weeks following start of ICI. Further characterization of completeness of ABX exposure data in the oncology EHR will assist with interpretation of these results. [Table: see text]
Transducer array layout optimization for the treatment of pancreatic cancer using Tumor Treating Fields (TTFields) in the phase 3 PANOVA-3 trial.
Authors: Ariel Naveh, Hadas Sara Hershkovich, Eilon David Kirson, Uri Weinberg, Zeev Bomzon
Journal: Journal of Clinical Oncology (2019)

e15766 Background: TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz), which are delivered in two orthogonal directions using 2 pairs of transducer arrays. Based on favorable results in a Phase 2 study in locally-advanced pancreatic cancer (LAPC), an ongoing Phase 3 PANOVA-3 trial [NCT03377491] is investigating the efficacy of adding TTFields to nab-paclitaxel and gemcitabine in LAPC. Preclinical studies show that the effect of TTFields is intensity-dependent with a therapeutic threshold of 1 V/cm. The field distribution within the body is known to changes with array placement. The current study was designed to develop clinical practice guidelines for optimizing the layout of arrays applied to patients participating in the TTFields arm of the PANOVA-3 study. Methods: Three realistic computerized models of a male, a female and an obese male were used to simulate delivery of TTFields to the abdomen. For each model, 6-8 different layouts utilizing combinations of arrays with either 13 or 20 disks per-array were tested. The arrays were placed over the upper 6 standard abdominopelvic regions, and field intensity distributions within these regions were evaluated. Results: In all simulations, the large arrays generated higher field intensities than the smaller arrays. However, models with lower BMI were almost covered entirely using large arrays, increasing the potential of skin toxicity from TTFields. However, these Low BMI models were able to receive TTFields at an anti-mitotic intensity with smaller arrays. The clinical guidelines were formulated based on the following principles: the target tumor region should be directly between the arrays, (b) the extent of disease as well as the anatomy of the patient determines the size of arrays determined using waist circumference measurements. Conclusions: A matrix for selecting between 8 individual array layouts was generated based on these principles. The clinical practice guidelines allow the optimization of TTFields delivery to individual patients treated in the PANOVA-3 Study.
Is a clinical biomarker predictive of outcomes with immune checkpoint inhibitor (ICI) therapy in a phase I patient population.
Authors: Ulka N. Vaishampayan, Seongho Kim, Jaswinder Karwa, Hirva Mamdani, Lisa Lange, Danielle Harfoot, Andrea Jamison, Lindsay Williams, Kelley Wilson, Amy M. Weise
Journal: Journal of Clinical Oncology (2019)

e14136 Background: NLR is reported to be a prognostic marker in multiple malignancies and has reported potential predictive value with ICI. We evaluated NLR as a predictor of response and time to treatment failure (TTF) in a phase I patient population treated with ICI. Methods: Regulatory approval was obtained. A retrospective chart review of patients treated on phase I trials with ICI based therapy at Karmanos Cancer Institute, was conducted. Data were collected on demographics, performance status, tumor type, response rate, TTF and NLR pre and post therapy. Associations with clinical benefit (response rate and stable disease) and TTF were conducted by univariable logistic and Cox regression analyses. Results: 100 pts; 52 female and 48 male were evaluated. Median age was 62 years (range 22-84 years). 11 were African American (AA) and all patients were pretreated with standard therapy and had progressed prior to enrollment. Median pretherapy NLR was 3.31 (range 0.91-25.5). 26 patients showed clinical benefit with ICI based therapy; 6 partial responses and 20 with stable disease. Univariable Cox analysis for baseline continuous NLR associated with TTF showed a significant relation between NLR and TTF (p = 0.023). Univariable logistic and Cox analyses for dichotomized baseline NLR with optimal cut-off values, resulted in low NLR favoring higher chance of clinical benefit (Odds ratio = 0.169 95% CI 0.028,1.013, p = 0.043) and longer TTF (Hazard ratio = 1.841, 95% CI 1.188,2.854 p = 0.006). Conclusions: Pretherapy NLR was a statistically significant predictor of clinical benefit with ICI therapy in a phase I patient population. NLR is an easily applicable clinical predictive biomarker that may help guide clinical trial choice, especially in a patient population with limited life expectancy.
Rethinking about the dose limiting toxicities (DLTs): They can be equivocal!
Authors: Wei Zhong, Roberto Bugarini, Ling Wang, Cynthia Basu, Darrin M. Beaupre
Journal: Journal of Clinical Oncology (2019)

3064 Background: The primary goal of oncology phase I trials is to determine the maximum tolerated dose (MTD) in a small number of patients. Within the standard design methodology currently employed there remains many challenges and one pertains to the variability around defining dose limiting toxicities (DLTs). The pre-specified DLT criteria may not well reflect the clinician’s practical experience with some adverse events, while others may actually be related to the disease status more than the investigational drug and could be misclassified. DLT misclassification seen in testing a small sample size from each dose group could generate a large bias on dose finding and the MTD estimation. Methods: To mitigate the risk of dichotomizing and misclassifying DLTs, we proposed a strategy that introduced the new concept of “equivocal” DLT or AE. A novel dose escalation approach is applied to increase the variability associated with less interpretable AEs so that the model recommendations are more weighted towards the unequivocal AEs/DLTs. To evaluate this novel approach, we established a framework incorporating two types of systematic measurement errors on DLT misclassification, one for the misclassified DLT that is not related to the drug treatment while the other for the non-DLT AE that should be considered severe and relevant to dose finding. In our simulation studies, the Bayesian logistic regression model (BLRM) was used to guide dose escalation in simulated trials to compare the novel weighting approach with the traditional approach. A few numerical examples were also included for method illustration. Results: For different types of measurement errors, simulation studies showed that the weighting approach could successfully improve the trial performance, with higher chance of finding the correct MTD and treating more patients at the MTD level. Conclusions: The DLT weighting strategy provides a flexible but powerful tool that may incorporate the clinician’s valuable experience on some specific DLTs/AEs and improve MTD estimation in oncology phase I dose-escalation trials.
Case 49-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, E. Gonzalez, F.J. Guillén
Journal: New England Journal of Medicine (1985)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 49-1985 — A 25-Year-Old Haitian Man with Hansen's Disease, Painful Subcutaneous Nodules, Fever, and Hypesthesia
HER2 targeted therapy and outcome in HER2-equivocal cases after 2018 ASCO/CAP HER2 guideline modification.
Authors: James Crespo, Hongxia Sun, Jimin Wu, Qingqing Ding, Guilin Tang, Melissa Robinson, Hui Chen, Aysegul A. Sahin, Bora Lim
Journal: Journal of Clinical Oncology (2019)

e14729 Background: The best targeted therapeutic approach for HER2-equivocal cases remains unclear. New ASCO/CAP HER2 guidelines are intended to decrease this ambiguity by combining immunohistochemistry and in situ hybridization to resolve equivocal cases as positive or negative. However, the benefit of anti-HER2 therapy in HER2-equivocal cases is unknown. Methods: We retrospectively reviewed patients who visited MD Anderson from April 2017 to March 2018 with equivocal HER2 results based on the 2013 ASCO/CAP guidelines. The population was divided into 2 cohorts according to biopsy origin (primary cohort: biopsy from breast or axilla; recurrent/metastatic cohort: biopsy from recurrent or metastatic site). HER2 status was redefined using the 2018 ASCO/CAP guidelines. OS and PFS were calculated (Kaplan-Meier method) based on redefined HER2 status and use of HER2 targeted therapy. Results: A total of 139 equivocal results were found. Primary cohort had 90 patients (33 received neoadjuvant and 57 adjuvant therapy). HER2 IHC results were 0 (6.6%), 1+ (37.7%), 2+ (50%), 3+ (1.1%), and no IHC (4.4%). 94% of HER2-equivocal results became HER2 negative. Only 5 patients received anti-HER2 therapy, all of them in the HER2-negative group. After median follow-up of 1.91 yrs, 3 deaths and 8 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.67) or PFS (p = 0.49). The recurrence/metastatic cohort had 49 cases with equivocal results. HER2 IHC results were 0 (6.1%), 1+ (22.4%), 2+ (26.5%), and no IHC (44.9%). 55% of HER2-equivocal results became HER2 negative, and only 1 patient received anti-HER2 therapy. After median follow-up of 2.96 yrs, 15 deaths and 35 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.61) or PFS (p = 0.78). Conclusions: Most HER2-equivocal results were redefined as HER2 negative using the new ASCO/CAP guidelines. Association between anti-HER2 therapy and OS or PFS according to the new HER2 status was not observed. Although this is a small sample with short follow-up, patients with HER2-equivocal breast cancers seem to have clinical behavior similar to HER2-negative breast cancer.
Estimation of U.S. patients with cancer who may respond to cytotoxic chemotherapy.
Authors: Edward Maldonado, Scott Parsons, Emerson Yu-sheng Chen, Alyson Haslam, Vinay Prasad
Journal: Journal of Clinical Oncology (2019)

e18228 Background: Oncology drug development has shifted away from cytotoxic agents, while they remain widely used in clinical practice. We sought to estimate the proportion of U.S. patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy alone based on National Comprehensive Cancer Network (NCCN) treatment guidelines. Methods: This retrospective review used publicly available annual mortality data from the American Cancer Society to estimate the number of patients who would have presented with advanced or metastatic disease. Published clinical trials of first-line cytotoxic-only regimens as advised by the NCCN were used to calculate overall response rates (complete plus partial response) for each cancer type. Chemotherapies in combination with immunotherapy or biologic agents were excluded. Mean response rate was used when there was more than one recommended regimen. The main outcome was to identify the proportion of patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy regimens based on cancer type. Results: We identified 92 different cytotoxic chemotherapy regimens used in 25 cancer types. Among an estimated 609,640 cancer-related deaths in 2018, 479,823 (78.7%) would be eligible to receive standard first-line cytotoxic chemotherapy. We estimated 189,159 of 609,640 (31.0%) patients to achieve at least partial response. The median objective response rate was 48.6% (range 9.2%-90.6%). The following cancers had the highest response rate to cytotoxic chemotherapy: acute lymphoblastic leukemia (90.6%), acute myeloid leukemia (76.7%), and uterine cancer (75%). The following had the greatest number of patients who may respond to cytotoxic chemotherapy: lung cancer (60,234 of 609,640; 9.9%), colorectal cancer (23,138; 3.8%), and non-Hodgkin lymphoma (14,773; 2.4%). Conclusions: Given the large proportion of patients who may benefit from cytotoxic agents, drug development in this space may warrant continued interest in specific cancer types. Also, the regulatory approval of novel oncology drugs may justify head-to-head comparison against modern chemotherapy regimens.
Diagnostic accuracy of imaging studies for initial staging of T2b to T4b melanoma patients: A cross-sectional study
Authors: Constanza Riquelme-Mc Loughlin, Sebastian Podlipnik, Xavier Bosch-Amate, José Riera-Monroig, Alicia Barreiro, Natalia Espinosa, David Moreno-Ramírez, Priscila Giavedoni, Ramon Vilana, Marcelo Sánchez, Sergi Vidal-Sicart, Cristina Carrera, Josep Malvehy, Susana Puig
Journal: Journal of the American Academy of Dermatology (2019)
Case 18-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Marvin D. Berman, Austin L. Vickery
Journal: New England Journal of Medicine (1985)

Presentation of CaseAn 18-year-old man was admitted to the hospital because of abdominal pain and an eating disorder.He was well until six years earlier, when he began to notice a persistent sore throat and dysphagia. He was admitted to another hospital, where he was transferred to the psychiatric unit because of a "psychogenic" problem. After three months the sore throat disappeared, but he began to have occasional mild epigastric pain and vomiting after eating solid food and thereafter limited his food intake to liquids. After seven months in the psychiatric unit he was discharged. During the next five . . .
Efficacy of PD-1/PD-L1 inhibitor-based therapies in refractory microsatellite instability (MSI)-unselected metastatic colorectal cancer (mCRC): A network meta-analysis (NMA) of randomized controlled trials (RCTs).
Authors: Zi-xian Wang, Yu-tong Chen, Yi-xin Zhou, Hao-xiang Wu, Zhan-Hong Chen, Tian-tian Wang, Xiangyuan Wu, Feng Wang, Rui-hua Xu
Journal: Journal of Clinical Oncology (2019)

e15048 Background: PD-1/PD-L1 inhibitor-based monotherapies and combination therapies are being investigated to challenge microsatellite stable (MSS) mCRC. This NMA aimed to assess the efficacy of anti-PD-1/PD-L1-based therapies against active comparators (regorafenib, trifiuridine+tipiracil, and fruquintinib [R/T/F]) and negative controls (placebo and best supportive care [P/BSC]) in patients with refractory MSI-unselected mCRC, which are predominantly MSS. Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and major oncology websites for relevant RCTs comparing the above therapies with each other up to Feb 15, 2019. We used the frequentist NMA to evaluate hazard ratios (HRs) for pairwise treatment comparisons in terms of overall survival (OS). Results: Seven RCTs were included, totaling nine comparisons between five therapies (durvalumab+tremelimumab [anti-PD-L1+Tre] vs. P/BSC [n = 1], atezolizumab+cobimetinib [anti-PD-L1+Cobi] vs. R/T/F [n = 1], atezolizumab [anti-PD-L1-only] vs. R/T/F [n = 1], anti-PD-L1+Cobi vs. anti-PD-L1-only [n = 1], and R/T/F vs. P/BSC [n = 5]). No significant heterogeneity was detected in the NMA (P = 0.340 in Q test; I 2 = 11.6%). Compared to P/BSC, OS was significantly improved with anti-PD-L1+Tre (fixed-effects model HR, 0.72 [95% confidence interval, 0.54-0.96]; P = 0.014) and anti-PD-L1+Cobi (HR, 0.70 [0.50-0.98]; P = 0.018), but not with anti-PD-L1-only (HR, 0.83 [0.57-1.21]; P = 0.172). OS with anti-PD-L1+Tre and anti-PD-L1+Cobi did not significantly differ from that with R/T/F (P = 0.565 and P = 0.500, respectively). Conclusions: In refractory MSI-unselected mCRC, anti-PD-L1 monotherapy was ineffective but anti-PD-L1+Tre and anti-PD-L1+Cobi therapies exhibited efficacies comparable to that of R/T/F.