tbuckley/cabot-search huggingface dataset:
Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study
Authors: Nikhilesh R. Mazumder, Dinee Simpson, Kofi Atiemo, Kathryn Jackson, Lihui Zhao, Amna Daud, Abel Kho, Lauren G. Gabra, Juan C. Caicedo, Josh Levitsky, Daniela P. Ladner
Journal: Hepatology (2021)

Background and Aims Estimates of racial disparity in cirrhosis have been limited by lack of large‐scale, longitudinal data, which track patients from diagnosis to death and/or transplant. Approach and Results We analyzed a large, metropolitan, population‐based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End‐Stage Liver Disease‐Sodium (MELD‐Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD‐Na, and proportion of alcohol‐associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all‐cause mortality and non‐liver‐related death and were less likely to be listed or transplanted ( P &lt; 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver‐related death (subdistribution HR, 1.26; 95% CI, [1.15‐1.38]; P &lt; 0.001). Conclusions Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.
Patient-reported outcomes (PROs) from a phase II trial of pembrolizumab for HPV-associated papilloma patients with laryngeal, tracheal and/or pulmonary involvement.
Authors: Sara I. Pai, Ramon Franco, Ashok Muniappan, Aaron D Friedman, Jong Chul Park, Nicholas Paul Campbell, Seth B. Krantz, Phillip C Song, Cheryl Nocon, Thomas L Carroll, William C Faquin, Kee-Young Shin, Anne M. O'Neill, Lori J. Wirth
Journal: Journal of Clinical Oncology (2021)

6080 Background: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 &amp; 11. RRP proliferates in the respiratory tract impacting breathing, swallowing, and voice and carries a 1-4% risk of malignant transformation.There is no curative therapy for RRP. Given the tolerized host immune response against HPV, the safety and efficacy of pembrolizumab (pembro) as an alternative treatment for this patient population was evaluated in a phase II clinical trial. Patient reported outcomes (PROs) were assessed during the trial to capture the patient perspective of pembro as an alternative to surgery or in office procedures, both standard of care (SOC). Methods: RRP patients who had previously undergone &gt;3 procedures in any year, or with known tracheal or pulmonary involvement prior to study entry were treated with pembro 200mg every 3 weeks. The primary endpoint of the trial was best ‘overall response rate’ (ORR) measured by an endoscopic-based disease burden score (lower score reflects better ‘response’) and/or RECIST 1.1, secondary endpoint included PROs. Twenty-one patients were required to assess the primary endpoint. Most of the QoL surveys used Likert scale to assess PROs (‘never, sometimes, often, most of the time, always’). The percentage reporting ’never’ having an issue with symptom or activity at baseline, 6 months, and at time of ORR (nadir disease burden score) is reported here. Results: Twenty-one patients were accrued. Median age (range) was 45 (19-68), 57% (12/21) were male and 67% (14/21) were white. Questionnaire completion rates were 100% at baseline, 90% at 6 months, and 85% at ORR. Improvement in: social interactions (less difficulty with: physical intimacy [38%,56%,65% reporting ‘never’ at baseline, 6 months, and at ORR respectively]), discussing disease diagnosis [19%,21%,39%]); personal feelings (less depression [14%,32%,33%], less anxiety [5%,16%,22%], less embarrassment [19%,37%,50%]), and work-related absences (less frequently fabricating reasons for work absence due to disease-related treatment [57%,78%,56%] and less utilization of family vacation or FMLA for disease treatment [29%,53%,56%]) were reported. At ORR, 72% (13/18) patients reported that IV infusion was not emotionally burdensome and 78% (14/18) reported it as the preferred treatment relative to their perceived experience with SOC surgery or in office procedures. Conclusions: PRO results show consistent benefit in key aspects of the patient experience with pembro over procedure based SOC further supporting its overall clinical benefit in patients with HPV-associated RRP. Clinical trial information: NCT02632344.
Immunotherapy toxicity in patients over 65 years.
Authors: Miriam Mendez, Blanca Cantos, Beatriz Nuñez García, Juan Cristobal Sanchez, Fernando Franco, Constanza Maximiano, Lourdes Gutiérrez, Blanca De La Puente, Ana Ruíz Casado, Mariano Provencio
Journal: Journal of Clinical Oncology (2021)

12027 Background: Cancer patients increasingly present an advanced age at diagnosis; 50% of the new cases are over 65 years old, being underrepresented in clinical trials. The safety of immunotherapy has not been adequately evaluated in the subgroup of elderly patient. In this population, with more comorbidities, adverse events may be less well tolerated and have more serious consequences. Methods: A retrospective observational study was developed, including all patients treated with immunotherapy at our center between January 2015 to February 2020. Of the total (279 patients), the analysis was performed with the 105 patients ≥65 years of age who had received at least one cycle (in routine clinical practice or within an unblinded clinical trial). All clinical and radiological data of the patients were collected. Results: From the total, the majority had a lung carcinoma or melanoma, treated with nivolumab or pembrolizumab either in first or second line. 63% had died at the time of the analysis. The frequency of toxicities: digestive (15%), pneumonitis (12%) and endocrine (9%). We divided the population into 65-75 years (76 patients) or &gt; 75 years (29 patients), analyzing the frequency of toxicity and deaths secondary to it. Those &gt; 75 years had more digestive toxicity (25% vs 11%), but less pneumonitis (3% vs 15%). There were 7 deaths (6%) related to treatment: 2 patients with ipilimumab-nivolumab (28%), 2 nivolumab (28%), 2 pembrolizumab (28%), and 1 ipilimumab (16%). 5 patients were &gt; 75 years old (median 78 years) presenting a higher mortality rate in relation to toxicity (4% vs 20%, p 0.02) and a worse median survival (29 vs 23 months). The fatal toxicities were: 3 neurological (2 meningoencephalitis and 1 acute diffuse axonal denervation), 2 hepatic, 1 hemophagocytic syndrome and 1 myocarditis. Conclusions: The most frequent toxicity was digestive, but those that led to death were neurological, hepatic, hematological and cardiac. In our series, neurological and cardiac adverse events accounted for 57% of immunotherapy deaths in older patients. Our data warn that patients over 75 years have a higher risk of death from immune-mediated events. In addition, these would be mainly neurological and cardiac, which represents a diagnostic and treatment challenge for oncologists.[Table: see text]
Comprehensive or specialty-specific cancer care in the United States: A story of continuing underperformance.
Authors: Christopher Thomas Aquina, Adan Z. Becerra, Aslam Ejaz, John R.T. Monson, Fergal J. Fleming
Journal: Journal of Clinical Oncology (2021)

6577 Background: “Textbook oncologic outcome” (TOO) is a composite measure representing the “ideal” outcome for patients undergoing cancer surgery and is associated with improved survival. Using TOO as the primary outcome, we asked whether hospitals are high-performing across multiple cancer types. Methods: Patients undergoing potentially curative breast, colon, rectal, lung, or pancreatic cancer resection were identified within the National Cancer Database (2010-2016). Organ-specific TOO was defined as: adequate lymph node yield, R0 resection, non-length of stay outlier, no hospital readmission, no 90-day postoperative mortality, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the risk-adjusted TOO rate for each hospital stratified by cancer type. Results: Among 1,094,550 cancer resections (breast = 690,442; colon = 213,918; lung = 121,771; rectum = 40,315; pancreas = 28,104), 434 hospitals performed ≥10 resections for each cancer type. Only 11 hospitals (2.5%) ranked in the top quartile for adjusted TOO rate for all five cancer types. Of the 323 hospitals (74.4%) that ranked in the top quartile for one cancer type, 149 hospitals (46.1%) also ranked in the bottom quartile for another cancer type. There was a weak correlation between hospital rankings across cancer types with the strongest correlations between colon and rectal cancer (R 2 = 0.148) and lung and pancreatic cancer (R 2 = 0.098). Conclusions: Most U.S. hospitals do not provide high-quality care across cancer types with respect to TOO. Perhaps this knowledge should be used to guide referral for oncology care.
Concurrent chemoradiotherapy with weekly cisplatin in stage III unresectable non-small cell lung cancer (NSCLC): A local experience with LATAM patients.
Authors: Carlos Salinas, Felipe Eduardo Pinto Negrete, Maria Paz Saavedra, Francisco J Orlandi
Journal: Journal of Clinical Oncology (2021)

e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is expected in Chile in 2021 accoding to Globocan, with a 12.4% mortality rate last year. Among NSCLC, 35 to 40% present as locally advanced disease, most of them non surgical candidates. Current standard of treatment is platinum-based doublet with concurrent Radiotherapy plus adyuvant durvalumab since 2018. Still many controversies related to different approaches are not settled. Few literature is available concerning a less aggressive approach in order to achieve a more tolerable treatment for the patient preserving effectiveness. Many patients compromise the treatment compliance due to early toxicities. We present our preliminary results of local data consisting in weekly cisplatin plus concurrent standard dose of radiotherapy. Methods: We performed a retrospective review of local database for stage III unresectable NSCLC between 2013 to 2019. Baseline clinical data , treatment modality, toxicities and response rates were recorded for all patients. Outcomes were analyzed by measuring overall response rate (ORR) , progression free (PFS) and overall survival (OS). Toxicities were assessed by CTCAE v5.0 and treatment response by RECIST 1.1 criteria. Results: 54% of the patients were men, 68%ECOG 0 and 32% ECOG 1. Mean BMI of 26 kg / m2. 100% smokers with average 39 packages per year and 71% had some other comorbidity;. 26% had emphysema. Histologic confirmation of 74%adenocarcinom and as. 26% squamous cell carcinoma. Staging analysis showed 23% stage IIIA, 54% stage IIIB, and 23% stage IIIC. Only 6 patients received adjuvant treatment before being diagnosed with stage III disease. Chemoradiotherapy is carried out as follows: 86% cisplatin (median 54.4 mg/m2) as a single weekly dose combined with standard radiotherapy of 60 Gy /30 Fr in a concurrent modality in ???. 74.2% completed follow up after CRT and the remaining 50% received adyuvant durvalumab. 71% of the patients reported some degree (mild, moderate or severe?) of toxicity related to the treatment; 37.1% grade 2 actinic pneumonitis, 11.4% grade 2 actinic esophagitis and 11.4% grade 1 acute renal failure among the most significant. No CTCAE 5.0 grade 4 and 5 toxicities were reported. 82.8% progressed in 15 months average (mean??); with 17% with current stable disease. The ORR was 48,5%. The mOS was 23 months (95% CI [16,7-29,3]) and the mPFS was 10 months (95% CI [8.25-11.75]. Conclusions: Since PACIFIC trial, stage III unresectable NSCLC have experienced a pivotal change in management. Unfortunately, our Public Health Insurance System does not cover access for all pts. This approach reaches similar results described in earlier trials published in the area and could be an option in certain clinical settings.
Dual immune checkpoint blockade in advanced well-differentiated neuroendocrine tumors, a phase II clinical trial.
Authors: Susan Combs Scott, Ana De Jesus-Acosta, Chen Hu, Benjamin Philip Levy, Valsamo Anagnostou, Julie R. Brahmer, Peter Bela Illei, Elizabeth M. Jaffee, Kristen Marrone, Patrick M. Forde, Christine L. Hann
Journal: Journal of Clinical Oncology (2021)

e16201 Background: Limited systemic treatment options are available for progressive well-differentiated neuroendocrine tumors (NET), also called carcinoid tumors. Given emerging evidence for immunotherapy response in high grade NET including small cell lung cancer, we sought to determine the efficacy of combination immunotherapy with ipilimumab and nivolumab in patients with advanced, progressive, well-differentiated NET in an open label phase II clinical trial. Methods: Eligible patients had well-differentiated, nonfunctional NET of lung, pancreas, or GI origin that had progressed within the past 12 months after at least one line of prior therapy. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1mg/kg every 6 weeks for up to 2 years. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Using a Simon’s 2-stage design, the study planned to accrue up to 56 patients. Based on published response rates to everolimus of 5%, we hypothesized that this regimen would be considered promising if the true ORR is &gt; 15%. Results: Nine patients were enrolled prior to study closure due to funding, including 6 patients with NET of lung origin, 2 pancreatic, and 1 small bowel (Table). Median age was 71 years. All patients had distant metastatic disease at enrollment, with an average of 2 prior lines of therapy. Four of 9 patients achieved the primary endpoint of confirmed objective response, all of whom have ongoing response with a median duration of 15.4 months. Five of 9 patients, including all 4 responders, experienced immune-related toxicity requiring treatment modification or discontinuation. The trial did not accrue the target of 56 patients, however, objective response in 4 of 9 patients (ORR 44.4%, 90% CI: 16.9-74.9%) excluded the response rate target (15%). Conclusions: The impressive ORR of 44% with a median duration of response exceeding 15 months in this small clinical trial warrants further study of combination CTLA-4 and PD-1 inhibition in previously treated well-differentiated NET. Our ongoing immunologic and genomic correlative analysis in responders and non-responders will help inform future study of immunotherapy in this patient population in need of new systemic therapy approaches. Clinical trial information: NCT03420521. [Table: see text]
Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study
Authors: Richard S. Finn, Masatoshi Kudo, Ann-Lii Cheng, Lucjan Wyrwicz, Roger K.C. Ngan, Jean-Frederic Blanc, Ari D. Baron, Arndt Vogel, Masafumi Ikeda, Fabio Piscaglia, Kwang-Hyub Han, Shukui Qin, Yukinori Minoshima, Michio Kanekiyo, Min Ren, Ryo Dairiki, Toshiyuki Tamai, Corina E. Dutcus, Hiroki Ikezawa, Yasuhiro Funahashi, Thomas R. Jeffry Evans
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT. Experimental Design: Serum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated. Results: Four hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33–0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16–0.91; P = 0.0253). Conclusions: Higher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.
Definition and validation of serum biomarkers for optimal differentiation of hyperferritinaemic cytokine storm conditions in children: a retrospective cohort study
Authors: Christoph Kessel, Ndate Fall, Alexei Grom, Wilco de Jager, Sebastiaan Vastert, Raffaele Strippoli, Claudia Bracaglia, Erik Sundberg, AnnaCarin Horne, Stephan Ehl, Sandra Ammann, Carine Wouters, Kai Lehmberg, Fabrizio De Benedetti, Carolin Park, Claas Hinze, Helmut Wittkowski, Katharina Kessel, Karin Beutel, Dirk Foell, Dirk Holzinger
Journal: The Lancet Rheumatology (2021)
Limitations of direct-to-consumer (DTC) genetic testing for hereditary breast and ovarian cancer.
Authors: Neelam Vijay Desai, Elizabeth Dominic Barrows, Sarah M. Nielsen, Kathryn E. Hatchell, Edward D. Esplin, Nadine M. Tung, Claudine Isaacs
Journal: Journal of Clinical Oncology (2021)

10515 Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant (PLPV) in BRCA1/2 or other cancer-risk genes. Methods: Multi-panel genetic testing was performed in 348,692 individuals for a clinical indication of hereditary breast/ovarian cancer (Clinical cohort) and 7,636 self-referred ostensibly healthy individuals (Healthy cohort) by a clinical testing laboratory. The primary analysis evaluated PLPVs for Group 1 genes: BRCA1/2 AJ founder variants and Group 2: full sequence BRCA1/2. Secondary analyses assessed PLPVs in Group 3: high-risk breast cancer genes ( BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53), Group 4: all breast or ovarian cancer-risk genes (Group 3 genes plus ATM, BARD1, BRIP1, truncating CHEK2, EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D) and Group 5: 41 cancer-risk genes; these analyses were limited to participants who tested for all 41 genes. Potentially mosaic variants were excluded. Results: Table illustrates PLPVs found in both cohorts. The BRCA1/2 AJ founder variants account for only ̃11% (1513/13,987) and ̃30% (19/64) of the BRCA PLPVs in the Clinical and Healthy cohorts, respectively. Even among AJ individuals, testing only for the 3 founder variants will miss ̃10% (52/513) of all BRCA1/2 PLPVs. Evaluating only the BRCA AJ founder variants missed a higher percentage of PLPVs in other cancer-risk genes. Conclusions: The 3 BRCA1/2 AJ founder variants analyzed by DTC testing account for a small fraction of PLPVs in cancer-risk genes in the general population, and miss 10% of BRCA PLPVs even among AJ individuals. Greater public education is needed to dispel the misconception that DTC tests are equivalent to clinical assessment and comprehensive genetic testing. PLPVs identified in Clinical and Healthy Cohorts.[Table: see text]
Harnessing EV communication to restore antitumor immunity
Authors: Crescenzo Massaro, Wei Min, D. Michiel Pegtel, S. Rubina Baglio
Journal: Advanced Drug Delivery Reviews (2021)

Restoring effective anti-tumor immune responses to cure cancer is a promising strategy, but challenging to achieve due to the intricate crosstalk between tumor and immune cells. While it is established that tumor cells acquire traits to escape immune recognition, the involvement of extracellular vesicles (EVs) in curbing immune cell activation is rapidly emerging. By assisting cancer cells in spreading immunomodulatory signals in the form of (glyco)proteins, lipids, nucleic acids and metabolic regulators, EVs recently emerged as versatile mediators of immune suppression. Blocking their action might reactivate immune cell function and natural antitumor immune responses. Alternatively, EV communication may be exploited to boost anti-tumor immunity. Indeed, novel insights into EV biology paved the way for efficient ex vivo production of 'rationally engineered' EVs that function as potent antitumor vaccines or carry out specific functional tasks. In this review we discuss the latest findings on immune regulation by cancer EVs and explore how EV-mediated communication can be either targeted or harnessed to restore immunity as a means for cancer therapy.