tbuckley/cabot-search huggingface dataset:
Morbidity and mortality of pelvic exenteration for cervical cancer at a German referral center.
Authors: Jelena Boekhoff, Luisa terGlane, Uwe Wagner, Axel Hegele
Journal: Journal of Clinical Oncology (2021)

e17505 Background: The purpose of this study was to evaluate data regarding the outcome of pelvic exenteration (PE) when performed for advanced or recurring cervical cancer. Methods: A total of 24 patients underwent PE for cervical cancer at the University Hospital Marburg between 2011 and 2016. Their data were retrospectively assessed and statistically analyzed. Survival was evaluated using the Kaplan-Meyer method. Results: Mean age was 52.2 years (29.7 to 72.6 years), mean BMI was 23.4 kg/m 2 . Most common indication was squamous cell carcinoma, whereas 3 patients underwent PE for adenocarcinoma. The majority of the tumors (62.5%) were stage pT4. Negative margins could be achieved in 70.8%. Lymph nodes could be assessed in 55% and were tumor-afflicted in 20.8%. 45.8% were treated for recurrent cancer; median recurrence free time between previous treatment and PE was 16 months. Up-front PE was performed in 20.8%. Another 79.2% received treatment prior to PE: 20.8% received all 3 treatment modalities whereas 37.5% had two treatments before (29.2% underwent chemo- and radiotherapy, 8.3% had surgery and radiotherapy) and 20.8% underwent one type of treatment. Anterior PE (APE) and total PE (TPE) were performed in 62.5% and 37.5%, respectively. Median operation time was 324min. Blood products were administered perioperatively in 75%; 37.5% needed 2 or more. Median hospital stay was 25 days. Major complications (Clavien Dindo≥3) were observed in 41.7% and 16.7% had no complications. Overall Survival (OS) was 29.2%; median overall survival was 19.1 months. 2- and 3-year survival rates for curative PE were 50% and 35% respectively. 4 patients underwent PE with palliative intent. Overall survival correlated significantly with R1- (p = 0.012), N1- (p = 0.047) and M1-status p &lt; 0.01), TPE (p = 0.034) and surgical time &gt; 6 h (p = 0.003). Conclusions: In cases of advanced or recurrent cervical cancer gynecologists struggle to find suitable therapeutic options, especially since most patients have already received radio- and/or chemotherapy. PE is a valid option for selected patients that may represent a cure with tolerable complication rates.
Germline HLA-B evolutionary divergence to influence efficacy of immune checkpoint blockade therapy in gastrointestinal cancer.
Authors: Zhihao Lu, Lin Shen, Henghui Zhang, Huan Chen, Xi Jiao, Yujiao Wang, Lijia Wu, Huaibo Sun, Shuang Li, Jifang Gong, Jian Li, Jianling Zou, Keyan Yang, Beibei Mao, Lei Zhang, Xiaotian Zhang, Zhi Peng, Ming Lu, Zhenghang Wang
Journal: Journal of Clinical Oncology (2021)

e16101 Background: To date, although a number of biomarker-related investigations have focused on the intrinsic properties of tumor cells and immune microenvironment, how germline genetics influences efficacy of immune checkpoint inhibitors (ICIs) immunotherapy in gastrointestinal (GI) cancer is scarcely understood. Methods: Our investigation enrolled 94 metastatic GI cancer patients treated with ICIs recruited from Peking University Cancer Hospital (PUCH) between August 1, 2015, and May 24, 2019. A publicly available dataset from the Memorial Sloan Kettering (MSK) Cancer Center (MSK GI cohort) was used for validation. For the PUCH cohort, we performed HLA genotyping by whole exome sequencing (WES) analysis on the peripheral blood mononuclear cell (PBMC) from all 94 patients. Tumor tissues from 86 patients were subjected to WES analysis and immune oncology-related RNA profiling. Results: We assessed the clinic relevance of germline HLA heterozygosity and evolutionary divergence (HED, a quantifiable measure of HLA-I evolution) to immunotherapy in patients with advanced GI cancers from the PUCH cohort. Our data showed that neither HLA heterozygosity nor mean HED correlated with the overall survival (OS) in the PUCH cohort. However, patients with high HLA-B HED showed a better OS and durable clinic benefit (DCB) rate compared with the lower subgroup (p &lt; 0.05 for all comparison). The prognostic value of HLA-B HED was consistently validated in the MSK GI cohort (N = 84). Notably, a combinatorial biomarker based on HLA-B HED and tumor mutation burden (TMB) could better stratify potential responders (86 patients with tumor samples). Survival analysis performed on the PUCH and MSK GI cancer datasets further demonstrated the potential joint utility of HLA-B HED and TMB for prognosis stratification. Moreover, HLA-B HED high subgroup was characterized with a lower prevalence of TP53 mutation and enrichment of multiple immune related pathways, indicating an immune-inflamed phenotype of this subgroup. Conclusions: Taken together, our data create an intriguing argument for the germline HLA-B sequence divergence and TMB as complementary biomarkers in guiding patient selection for GI cancer immunotherapy. Further investigation revealed a potential HLA-B restricted mutational pattern of TP53, and can be indicative of tumor immune microenvironment in GI cancer.
Cachexia is an independent factor for negative clinical and functional outcomes in lymphoma patients receiving CART therapy.
Authors: Ishan Roy, Gordon John Smilnak, Madelyn Burkart, Corinne Williams, Elizabeth Hamilton, Sarah Miyata, Katherine Thorp, Shuo Ma, Jane N. Winter, Barbara Pro, Leo I. Gordon, Reem Karmali
Journal: Journal of Clinical Oncology (2021)

e19504 Background: Cachexia is a known independent factor for negative outcomes in several cancer populations at early and late stages, but has not been in investigated in cancer patients receiving Chimeric Antigen Receptor T-cell therapy (CART). Our objective was to evaluate the relationship between cachexia and clinical and functional outcomes in patients with lymphoma receiving CART. Methods: Design: Retrospective cohort study including 70 adult patients with aggressive B-cell lymphomas (Diffuse Large B-cell or Mantle Cell Lymphoma) who received CART. Cachexia markers: body weight loss (BWL), BMI, albumin, creatinine, and neutrophil-to-lymphocyte ratio (NLR) – each captured at diagnosis, pre-collection, CART initiation, and through day 360 post-CART. Outcome measures: Primary outcomes: Disease relapse after CART and 90-day mortality. Secondary outcome: Need for rehabilitation services post-acute care (inpatient rehabilitation or home physical therapy). Statistical analyses: Linear regression modeling, area under the curve analysis, and multivariate modeling (any univariates with p &lt; 0.25). Co-variates: age, ECOG PS, IPI, cell of origin, MYC status, number of prior cancer therapies, time from diagnosis to CART, and need for bridging / steroid pre-CART. Results: In longitudinal modeling from diagnosis to day 360, CART patients who relapsed had linear associations over time with BWL since diagnosis (p &lt; 0.01), NLR (p &lt; 0.0001), creatinine (p = 0.045), and albumin (p &lt; 0.001). In univariate analyses (see table): at pre-collection, high NLR and BWL increased odds of relapse; at treatment, high NLR and CRP increased odds of mortality; and at D30, and BWL and high NLR increased odds of relapse and mortality, respectively. In multivariate analyses (see table, # = independent association), BWL and high NLR independently associated with relapse and mortality, respectively. Significant covariates included need for bridging (p = 0.02), steroid therapy pre-CART (p &lt; 0.01), and time from diagnosis to CART (p = 0.02). Secondarily, BWL and low albumin pre-CART increased odds of needing rehabilitation services, with BWL independently associating in multivariate models (OR = infinity, p &lt; 0.001). Conclusions: Cachexia markers, such as BWL from diagnosis and NLR, are candidate predictors of relapse and mortality after CART. Specific markers could also assign patients to neo/adjuvant rehabilitative and medical therapies targeted towards cachexia. Overall, this study suggests that cachexia may alter the clinical and functional trajectory of lymphoma patients receiving CART.[Table: see text]
Oral Glucose Tolerance Test Results in Pregnancy Can Be Used to Individualize the Risk of Future Maternal Type 2 Diabetes Mellitus in Women With Gestational Diabetes Mellitus
Authors: Liran Hiersch, Baiju R. Shah, Howard Berger, Michael Geary, Sarah D. McDonald, Beth Murray-Davis, Ilana Halperin, Ravi Retnakaran, Jon Barrett, Nir Melamed
Journal: Diabetes Care (2021)

OBJECTIVE We aimed to quantify the risk of future maternal type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) based on the type and number of abnormal 75-g oral glucose tolerance test (OGTT) values and the diagnostic criteria used for the diagnosis of GDM. RESEARCH DESIGN AND METHODS We conducted a population-based retrospective cohort study of all nulliparous women with a live singleton birth who underwent testing for GDM using a 75-g OGTT in Ontario, Canada (2007–2017). We estimated the incidence rate (per 1,000 person-years), overall risk (expressed as adjusted hazard ratio [aHR]), and risk at 5 years after the index pregnancy of future maternal T2DM. Estimates were stratified by the type and number of abnormal OGTT values, as well as by the diagnostic criteria for GDM (Diabetes Canada [DC] vs. International Association of the Diabetes and Pregnancy Study Groups [IADPSG] criteria). RESULTS A total of 55,361 women met the study criteria. The median duration of follow-up was 4.4 (interquartile range 2.8–6.3; maximum 10.3) years. Using women without GDM as reference (incidence rate 2.18 per 1,000 person-years), women with GDM were at an increased risk of future T2DM; this risk was greater when using the DC compared with the IADPSG criteria (incidence rate 18.74 [95% CI 17.58–19.90] vs. 14.07 [95% CI 13.24–14.91] per 1,000 person-years, respectively). The risk of future maternal T2DM increased with the number of abnormal OGTT values and was highest for women with three abnormal values (incidence rate 49.93 per 1,000 person-years; aHR 24.57 [95% CI 21.26–28.39]). The risk of future T2DM was also affected by the type of OGTT abnormality: women with an abnormal fasting value had the greatest risk, whereas women with an abnormal 2-h value had the lowest risk (aHR 14.09 [95% CI 12.46–15.93] vs. 9.22 [95% CI 8.19–10.37], respectively). Similar findings to those described above were observed when the risk of T2DM at a fixed time point of 5 years after the index pregnancy was considered as the outcome of interest. CONCLUSIONS In women with GDM, individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.
Intensity-Modulated Radiation Therapy and Intensity-Modulated Proton Therapy—2 Effective Treatment Modalities for Nasopharyngeal Cancer
Authors: Aaron Falchook
Journal: JAMA Network Open (2021)

Xingzhe Li, MD, MPH; Sarin Kitpanit, MD; Anna Lee, MD, MPH; Dennis Mah, PhD; Kevin Sine, BS; Eric J. Sherman, MD; Lara A. Dunn, MD; Loren S. Michel, MD; James Fetten, MD; Kaveh Zakeri, MD, MAS; Yao Yu, MD; Linda Chen, MD; Jung Julie Kang, MD, PhD; Daphna Y. Gelblum, MD; Sean M. McBride, MD, MPH; Chiaojung J. Tsai, MD, PhD; Nadeem Riaz, MD; Nancy Y. Lee, MD
Genetically Predicted Adiposity, Diabetes, and Lifestyle Factors in Relation to Diverticular Disease
Authors: Shuai Yuan, Susanna C. Larsson
Journal: Clinical Gastroenterology and Hepatology (2021)

Adiposity, type 2 diabetes, alcohol and coffee consumption, and smoking have been examined in relation to diverticular disease in observational studies. We conducted a Mendelian randomization study to assess the causality of these associations.Independent genetic instruments associated with the studied exposures at genome-wide significance were obtained from published genome-wide association studies. Summary-level data for the exposure-associated single nucleotide polymorphisms with diverticular disease were available in the FinnGen consortium (10,978 cases and 149,001 noncases) and the UK Biobank study (12,662 cases and 348,532 noncases).Higher genetically predicted body mass index and genetic liability to type 2 diabetes and smoking initiation were associated with an increased risk of diverticular disease in meta-analyses of results from the two studies. The combined odds ratio of diverticular disease was 1.23 (95% confidence interval [CI], 1.14-1.33; P < .001) for a 1-standard deviation (~4.8 kg/m2) increase in body mass index, 1.04 (95% CI, 1.01-1.07; P = .007) for a 1-unit increase in log-transformed odds ratio of type 2 diabetes, and 1.21 (95% CI, 1.12-1.30; P < .001) for a 1-standard deviation increase in prevalence of smoking initiation. Coffee consumption was not associated with diverticular disease, whereas the association for alcohol consumption largely differed between the 2 studies.This study strengthens the causal associations of higher body mass index, type 2 diabetes, and smoking with an increased risk of diverticular disease. Coffee consumption is not associated with diverticular disease. Whether alcohol consumption affects the risk of diverticular disease needs further investigation.
Anticoagulation outcomes in patients with venous thromboembolism following Whipple surgery for pancreatic cancer: Single center experience.
Authors: Nino Balanchivadze, James P Purtell, Philip Kuriakose, Julie Clark, Kylie Springer, George Divine, David S. Kwon, Irina Y. Dobrosotskaya
Journal: Journal of Clinical Oncology (2021)

e16255 Background: Venous thromboembolism (VTE) is a common complication in patients with pancreatic cancer (PC). Incidence of major bleeding and clinically relevant non-major bleeding is 14%-20% in patients with cancer who receive anticoagulation therapy (AT). Whipple procedure is a complex surgical intervention offering potential cure in patients with resectable PC; however, surgery can affect drug absorption, which may reduce effectiveness of AT or exacerbate drug related adverse events. Our aim was to assess incidence of bleeding in PC patients who had whipple procedure with subsequent VTE. Methods: Retrospective analysis of medical records for all adult patients with PC who underwent whipple procedure and developed VTE (between July 1, 2010, and July 1, 2020) at Henry Ford Hospital was performed. Multiple variables and outcomes were analyzed by two-group comparisons, univariate analysis, and Cox regression. Results: A total of 32 patients were included in the analysis. The mean (standard deviation [SD]) age was 67.4 (11 y) years, 16 (50%) patients were men, and 16 (50%) were women, (20 [63%] White; 11 [34%] Black; 1 [3%] Asian). The median Khorana score was 3 (range, 2–4). Of the 32 patients, 6 (19%) had upper extremity VTE, 11 (34%) had lower extremity VTE, 10 (31%) had a pulmonary embolism, 7 (22%) had intra-abdominal VTE, and 7 (22%) had recurrent VTE. All patients with upper extremity VTE had a peripherally inserted central catheter (PICC) or a venous port at the time of VTE diagnosis. Most of the patients (28 or 88%) received AT. Whereas 13 (41%) patients had at least one bleeding episode, 19 (59%) had no bleeding. Twenty-two (68%) patients did not need PRBC transfusion, while 4 (13%) patients required &gt; 4 units packed red blood cell transfusion. No significant association between bleeding and AT was observed ( p = .590). Patients with a bleeding event had lower hemoglobin levels ( p = .030) and were more likely to receive blood transfusion ( p = .005). Cox regression analysis did not show patient age, ethnicity, type of AT used, recurrent VTE, and neoadjuvant chemotherapy treatment to be significantly associated with bleeding or death. A total of 14 (44%) patients were alive at the time of analysis. Conclusions: In patients with PC and VTE who received AT after whipple procedure, the incidence of bleeding was higher than what has been reported in patients with cancer in general, regardless of type of AT administration. Patients with central venous catheters might be at increased risk of upper extremity VTE and this subset of patients may benefit from various risk reducing strategies. Caution is recommended while managing AT in this complex patient population, and more studies are needed to assess factors specifically associated with AT and bleeding after whipple procedure.
Multicancer hereditary syndrome testing: Genetic counselors’ perspectives.
Authors: Christine B. Weldon, Su-Ying Liang, Kathryn A Phillips, Michael P Douglas, Maren Theresa Scheuner, Allison W. Kurian, Kendra Schaa, Breanna Roscow, Deanna Erwin, Julia Rachel Trosman
Journal: Journal of Clinical Oncology (2021)

10594 Background: The accessibility of cancer hereditary syndrome testing has increased, and the cost has declined significantly in the past few years. We conducted a national, quantitative survey of genetic counselors (GCs) to assess their perspectives on what influences hereditary cancer genetic testing decisions and practices, with a focus on cost. This survey was funded by NIH, conducted by UCSF TRANSPERS, and supported by the National Society of Genetic Counselors (NSGC). Methods: The survey was developed through literature review, expert interviews, and a pilot. Sent to the NSGC Cancer Special Interest Group via email. Chi-square tests were used to examine variability. Results: The survey response rate was 56% (202/363). Multiple hereditary cancer syndrome tests are discussed often/always by 86% of genetic counselors (GCs). The existence of an institutional protocol on multiple hereditary cancer syndrome testing was reported by 35.4% of GCs. When asked about GC counseling encounters, GCs report insurance rarely/never pays for: 25.2% pre-test in-person, 39.7% for pre-test tele-genetics, 35.4% post-test in-person, and 52.9% post-test tele-genetics. GCs rated clinical factors higher than cost as influencing decision for multiple hereditary syndrome cancer testing (table); the total cost of the test was least important. These patterns were similar across the GCs institution types and years in practice. Conclusions: We found consistent use of multiple hereditary cancer syndrome tests, with less focus on cost, out-of-pocket, and insurance coverage and more of a focus on clinical indicators. GCs reported challenges with reimbursement for GC counseling encounters. The shift toward more genetic counseling encounters via tele-genetics necessitates evaluation of insurance reimbursement.[Table: see text]
Psychometric properties of patient reported outcome (PRO) instruments in patients with small cell lung cancer (SCLC) in RESILIENT part 1.
Authors: Jaba Kokhreidze, Veleka Allen, Cristina Ivanescu, Xiaopan Valerie Yao, Bin Zhang, Brooke Harrow
Journal: Journal of Clinical Oncology (2021)

e24027 Background: The ongoing two-part phase 2/3 RESILIENT study (NCT03088813) is investigating the efficacy and safety of liposomal irinotecan monotherapy in patients with SCLC who have progressed on or after first line platinum-based chemotherapy. This exploratory analysis from RESILIENT part 1 was conducted to confirm the psychometric properties of established PRO instruments that had not previously been validated in patients with SCLC. Methods: Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (C30) and the EORTC QLQ Lung Cancer 13 (LC13) before treatment assignment (baseline), every 6 weeks thereafter, at treatment discontinuation and at the 30-day follow-up visit. Psychometric methods included descriptive statistics (items and scales), correlations (item-to-item and item-to-total), internal consistency (Cronbach’s α), test-retest reliability (intraclass correlation coefficient [ICC], two-way random effects model), construct validity and sensitivity to change. The analysis included patients who received at least one dose of study drug and completed at least one PRO assessment. Results: Thirty patients were enrolled in RESILIENT part 1 and included in the analysis. At baseline, 68% of patients reported ‘not severe’ or ‘mild’ symptoms. Floor effects (i.e. more than 25% of responses of ‘not at all’) were observed for several of the functioning/impact and symptom scales of the EORTC QLQ C30 and LC13. Moderate to strong correlations were found among most questionnaire items within their respective scales. Acceptable evidence for internal consistency and good test-retest reliability were observed. Selected results for the EORTC QLQ LC13, including dyspnea scales, are shown in the Table. The magnitude of correlations among PRO instruments supported evidence for convergent validity in this sample. Conclusions: In RESILIENT part 1, patients experienced low and tolerable symptoms at enrollment, limiting the potential for further improvement. Overall, these PRO instruments had acceptable psychometric properties (e.g. construct validity, reliability and ability to detect change) in this sample. However, these analyses should be repeated in a larger sample using data from RESILIENT part 2. Clinical trial information: NCT03088813. [Table: see text]
Genomic landscape of malignnant mesothelioma by site and histology.
Authors: Elio Adib, Elie Akl, Amin Nassar, Talal El Zarif, Sarah Abou Alaiwi, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2021)

8559 Background: Malignnant mesothelioma (MM) is a highly lethal tumor that can develop in the pleura, the peritoneum, the pericardium or the testes. While the genomic features of pleural MM have been well-described overall, less is known about the distribution of genetic alterations (GAs) according to histology. In addition, few reports comparing genetic features according to disease site are available. Methods: We identified patients with pleural or peritoneal mesothelioma with mutational analysis through the GENIE registry. Patient tumor genetic data were provided by Memorial Sloan-Kettering Cancer Center (MSK)-IMPACT and Dana-Farber Cancer Institute (DFCI)-Oncopanel NGS initiatives. Patients with more than one sequenced sample were excluded. We limited our analysis to genes common to all versions of both panels and that were significantly mutated in the TCGA mesothelioma cohort. Mutation and copy number variant (CNV), collectively called GAs, were determined, and were compared using the Fisher’s Exact test and Kruskal-Wallis Test. Comparisons were made both by disease site (pleural vs. peritoneal) and histology for the pleural samples (epithelioid vs. biphasic vs. sarcomatoid). Nominal p-values were obtained, and FDR correction was employed (q&lt;0.1). Results: We identified 439 patients with MM in the GENIE registry who fit the inclusion criteria. The median age was 70.5 years for pleural MM and 60 years for peritoneal MM (Wilcoxon-rank sum test p-value = 3e-9). 72% of patients were male. CDKN2A/CDKN2B GAs (97% and 100% being deletions in CDKN2A and CDKN2B respectively), a described prognostic marker in MM, were more common in pleural than in peritoneal MM. Among pleural MMs, tumors of epithelioid histology had less NF2 GAs than biphasic or sarcomatoid tumors, whereas sarcomatoid tumors had the lowest frequency of BAP1 GAs (Table). Conclusions: Malignnant mesotheliomas of different disease sites and/or histologies display distinct patterns of GAs. These findings may contribute in part to differences in response to treatment and survival among these subsets of MM.[Table: see text]