tbuckley/cabot-search huggingface dataset:
A phase 2 study of cabozantinib in combination with atezolizumab as neoadjuvant treatment for muscle-invasive bladder cancer (HCRN GU18-343) ABATE study.
Authors: Deepak Kilari, Aniko Szabo, Kathryn A. Bylow, Robert S. Alter, Ariel Ann Nelson, Emily Lemke, William Adrian Hall, Scott Johnson, Peter Langenstroer, Kenneth Jacobsohn, Nancy B. Davis, Chunkit Fung, Matthew I. Milowsky
Journal: Journal of Clinical Oncology (2021)

TPS4591 Background: ABACUS and PURE-01 trials demonstrated the activity of single agent atezolizumab and pembrolizumab respectively as neoadjuvant therapy for muscle invasive urothelial carcinoma (MIUC). However, downstaging to non-muscle invasive disease was noted in only 50 percent of patients. Resistance to programmed death (PD)- 1/L-1 antibodies is likely to include factors such as impaired dendritic cell maturation/function, infiltration of T-Regs and myeloid derived suppressor cells, impaired T-cell priming and T-cell trafficking in tumors. Cabozantinib is a tyrosine kinase inhibitor which targets MET, AXL, MER, Tyro3 and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical activity as monotherapy and in combination with PD-1/L1 antibodies in various solid tumors including UC, renal cell cancer, castrate- resistant prostate cancer, and non-small cell lung cancer. We hypothesize that the combination of cabozantinib and atezolizumab as neoadjuvant therapy for MIUC would improve rates of pathologic downstaging compared to single-agent checkpoint inhibitors. Methods: ABATE(NCT04289779) is an open-label, single arm, multi-center study to assess the efficacy and safety of cabozantinib with atezolizumab as neoadjuvant therapy for cT2-T4aN0/xM0 MIUC. An estimated 38 patients will be enrolled and receive cabozantinib 40 mg PO daily with atezolizumab 1200mg every 3 weeks for a total duration of 9 weeks followed by radical cystectomy. Adults (≥18 years) with resectable UC who are either cisplatin-ineligible or decline cisplatin are eligible. Patients are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 analysis. UC should be predominant component (≥ 50%). Previous systemic anticancer therapies for MIUC are not permitted. CT/MRI will be performed before investigational therapy and cystectomy. Primary endpoint is pathologic response rate defined as the absence of residual muscle-invasive cancer in the surgical specimen ( &lt; pT2). Secondary endpoints are safety and toxicity, pathologic complete response rate and event-free survival. Exploratory end points include patient-reported outcomes and outcome associations with biomarkers. Accrual began May 2020. Clinical trial information: NCT04289779.
Mortality in adult patients with solid or hematological cancers and SARS-CoV-2 infection with a specific focus on lung and breast malignancies: A systematic review and meta-analysis.
Authors: Marco Tagliamento, Elisa Agostinetto, Marco Bruzzone, Marcello Ceppi, Kamal S. Saini, Evandro de Azambuja, Kevin Punie, Benedikt Westphalen, Gilberto Morgan, Paolo Pronzato, Lucia Del Mastro, Francesca Poggio, Matteo Lambertini
Journal: Journal of Clinical Oncology (2021)

e18608 Background: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a diagnosis of cancer are at high risk of severe symptomatic disease (COVID-19) and death. We performed a systematic review and meta-analysis of published studies, to estimate the case-fatality rate (CFR) of patients with solid or hematological tumors and SARS-CoV-2 infection. Methods: A systematic search of PubMed library up to 31 January, 2021, was performed in order to identify publications reporting the CFR among adult patients with solid or hematological tumors and SARS-CoV-2 infection. CFR was defined as the rate of deaths among SARS-CoV-2-positive cancer patients. Moreover, we separately assessed the CFR among patients with lung and breast cancer. Studies with at least 10 patients were included. The CFR was assessed through a random effect model, and 95% confidence intervals (CI) were calculated. The Higgins I 2 index was computed to assess the heterogeneity between studies. Results: The systematic search of the literaturereturned 1,727studies. 1,551 were excluded on the basis of the title, 29 based on the abstract, and 3 were duplicates. A total of 144 studies were selected, including 35,725 patients with solid or hematological tumors and SARS-CoV-2 infection. In total, 46 and 32 studies reported the CFR among COVID-19 patients with lung (total N = 1,555) and breast (total N = 1.398) cancer, respectively. Overall, the CFR was 25.5% (95% CI 23.1%-28.1%, Egger test p &lt; 0.001). A sensitivity analysis, after excluding studies with less than 100 patients, showed a CFR of 22.1% (95% CI 19.4%-25.2%). The CFR among patients with lung cancer and SARS-CoV2 infection was 33.4% (95% CI 28.1%-39.6%) when including all studies and 26.3% (95% CI 17.6%-39.2%) at the sensitivity analysis after excluding studies with less than 100 patients. The CFR among patients with breast cancer and SARS-CoV2 infection was 13.7% (95% CI 9.1%-20.7%) when including all studies and 13.0% (95% CI 7.6%-22.1%) at the sensitivity analysis after excluding studies with less than 100 patients. Conclusions: One year after the outbreak of the pandemic, this large meta-analysis reports the impact of SARS-CoV-2 infection in patients with cancer. This population experienced a high probability of mortality, with a comparatively higher CFR in patients with lung cancer, and a comparatively lower CFR in patients with breast cancer. Patients with an underlying diagnosis of cancer require special attention with aggressive preventive measures that also include early access to COVID-19 vaccination.
Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status.
Authors: Scott Boniol, Neal E. Slatkin, Nancy Stambler, Robert J. Israel
Journal: Journal of Clinical Oncology (2021)

e24083 Background: Opioid-induced constipation (OIC) is a common side effect of opioid treatment for cancer-related pain. Methylnaltrexone (MNTX) is a peripherally active µ-opioid receptor antagonist indicated for OIC that does not affect opioid central analgesia. We assessed if baseline Eastern Cooperative Oncology Group (ECOG) status impacted the rescue-free laxation (RFL) responses among cancer patients with OIC treated with repeated doses of MNTX. Methods: This pooled post hoc analysis from 2 randomized, placebo-controlled, institutional review board–approved clinical studies included cancer patients with OIC (study 302, NCT00402038; study 4000, NCT00672477). Study 302 compared subcutaneous MNTX 0.15 mg/kg vs placebo and study 4000 compared body weight‒based subcutaneous MNTX 8 mg (38–&lt; 62 kg) or 12 mg (³ 62 kg) vs placebo. The data were stratified by baseline ECOG status (&lt; 2 vs ≥ 2). Endpoints included the number of patients with RFL responses within 4 hours after ≥ 2 of the first 4 doses and the number of patients with RFL response within 4 hours of treatment for patients who received all 7 doses. Results: The intent-to-treat analysis included 43 patients with an ECOG &lt; 2 (placebo = 20; MNTX = 23) and 187 patients with an ECOG ≥ 2 (placebo = 94; MNTX = 93). Those with an ECOG &lt; 2 were younger (mean age 58 vs 65 years), predominantly male (60.5% vs 51.3%), and used a higher daily dose of oral morphine equivalent (190.7 vs 180.0 mg/d) compared with those with an ECOG ≥ 2. Cancer patients with an ECOG &lt; 2 treated with MNTX had a significantly greater RFL response within 4 hours after ≥ 2 of the first 4 doses compared with placebo (56.5% vs 5.0%, P = 0.0003). Similar results were reported for patients with an ECOG ≥ 2 (57.0% vs 5.3%, P &lt; 0.0001). Compared with placebo, the MNTX group had a greater proportion of patients with an RFL response, whether they had at least 1 RFL response or up to 7 RFL responses out of 7 doses, with significant treatment differences with each additional RFL per 7 doses among cancer patients with an ECOG ≥ 2 (Table). Conclusions: RFL response rates in cancer patients were significantly greater in the MNTX group vs the placebo group regardless of baseline ECOG status; responses were similar between the 2 groups despite a higher daily dose of opioids in the group with an ECOG &gt; 2. Clinical trial information: NCT00402038; NCT00672477. [Table: see text]
The Medico-economic Impacts of Marijuana Use on the Outcomes and In-hospital Mortality in Patients with Atrial Fibrillation – Nationwide Database study
Authors: Hammam Shereef
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Introduction Cannabinoid users are at high risk of developing atrial arrhythmias. We sought to investigate the outcomes and the economic impact of marijuana use on patients with atrial fibrillation utilizing the National Inpatient Sample. Materials and Methods Patients with atrial fibrillation were identified in the National Inpatient Sample (NIS) database between 2012 and 2014 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), who subsequently were divided into two groups, those with and without marijuana smoking. The primary outcome was all-cause in-hospital mortality in the two groups. Secondary outcomes were in-hospital morbidities, required procedures and complications. We also evaluated the length of hospital stay and the cost of hospitalization. Logistic regression model was performed to address potential confounding factors. Results: The marijuana-users group had no significant increase of in-hospital mortality (OR: 1.24; 95% CI: 0.51 - 3.01, p = 0.632). However, marijuana users were predominantly younger males and less likely to undergo cardiac surgery (OR: 0.54, 95% CI 0.37 - 0.78, p = 0.001). Moreover, marijuana users are more likely to have a lower cost of hospitalization when compared to non-users ($28,916 vs $32,303, p = 0.001). Conclusion: Cannabinoid use was not associated with an increase in mortality among patients admitted with atrial fibrillation. However, marijuana users were younger, had fewer comorbidities, and cardiac surgeries with associated lower hospitalization costs. Admittedly, given the growing popularity of these products, further large prospective studies are needed to investigate the safety and evaluate different integral associations of cannabis use with worse cardiac outcomes in atrial arrhythmias patients, particularly those with atrial fibrillation.
Neutrophil extracellular traps (NETs) and thrombosis (Thr) in pancreaticobiliary cancer (PBC).
Authors: Christos Fountzilas, Han Yu, Anm Nazmul Khan, Thejaswini Giridharan, Alok A. Khorana, Renuka V. Iyer, Brahm H. Segal
Journal: Journal of Clinical Oncology (2021)

e16230 Background: NETs are linked to tissue damage, Thr and cancer progression. Detection of NETs in pancreatic cancer (PC) tissue and NET products in plasma, such as citrullinated Histone 3 (cit-H3) and myeloperoxidase (MPO), can predict survival. A robust biomarker to identify PC patients that may benefit from prophylactic antithrombotic interventions is still lacking. We hypothesized that NET products can predict PC patients at risk of poor outcomes. Methods: Frozen plasma collected on diagnosis from a cohort of 117 patients with HPBC (69% with PC) with known tissue factor (TF) levels was analyzed for MPO and cit-H3 by ELISA. Plasma MPO is a marker of neutrophil degranulation while cit-H3 is a more specific marker of NETosis. Univariate association of clinical variables, TF, cit-H3, MPO with overall survival (OS) was performed. For multivariable analysis, Cox proportional hazards regression model and backward stepwise selection based on the Bayesian information criterion (BIC) were used. Results: We observed a strong correlation between MPO and cit-H3. MPO also correlated with TF. Only TF showed a trend with association with the risk of Thr (p=0.053). Results of the multivariable model for OS are presented in the table (all patients and stratified by Thr status). High absolute neutrophil count (ANC) predicted worse OS only in patients without Thr. Increased cit-H3 was associated with worse OS. Higher MPO predicted worse OS in stage IV patients, which is in contrast to their relationship in stage I-III patients, where increased MPO was associated with improved OS. This interaction effect is stronger in patients with thrombosis. Conclusions: Plasma cit-H3, a systemic marker of NETosis, was associated with worse OS in PBC. Significant MPO by stage interaction implies a differential association of MPO with the OS among patients in different cancer stages. The activation status of neutrophils, including degranulation and NETosis, may be an important predictive biomarker for OS in patients with HPBC with interactions with both stage and Thr. Prospective studies to confirm and extend our findings are ongoing.[Table: see text]
Association of Granuloma Annulare With Type 2 Diabetes, Hyperlipidemia, Autoimmune Disorders, and Hematologic Malignant Neoplasms
Authors: John S. Barbieri, Misha Rosenbach, Olaf Rodriguez, David J. Margolis
Journal: JAMA Dermatology (2021)

Although granuloma annulare (GA) has been associated with several other conditions, these studies have been limited by single-center designs and small sample sizes.
Association of <i>TP53</i> mutation status and <i>GATA6</i> amplification with clinical outcome of pancreatic cancer.
Authors: Jung-In Yang, Taehoon Ha, Edward Zhou, Chris Tzanavaris, Craig E. Devoe, Xinhua Zhu, Jeff Boyd
Journal: Journal of Clinical Oncology (2021)

e16224 Background: Recent advances in pancreatic adenocarcinoma (PDAC) research unveiled that molecular subtypes reflect cancer prognosis and chemosensitivity. Here, we examined the possible use of genomic profiling of PDAC in the clinic by assessing retrospective clinical outcomes and treatment responsiveness based on genetic alterations. Methods: All patients treated for PDAC with Next-Generation Sequencing (NGS) data available between 2014 to 2020 at Northwell Health Cancer Institute were included in a retrospective analysis. Patients were subdivided into resectable and unresectable cancer. Genetic findings frequently reported in NGS were used to compare progression-free survival (PFS) and overall survival (OS) within subgroups. Survival probability was compared using Peto-Peto’s modified survival estimate followed by pairwise comparisons using Peto-Peto’s modified survival estimate. Family-wise error rate was adjusted using Benjamini &amp; Hochberg method. Results: A total 115 patients were qualified for the evaluation. In all cases of PDAC, TP53 mutation (n = 89) was associated with poor OS compared to the wild-type TP53 gene (n = 19) (median OS 20.2 months, 95% CI 10.2 to 39.7, vs. 41.1 months, 95% CI 20.9 to 81.0, HR 1.98, p = 0.028). In unresectable PDAC, tumors with GATA6 amplification (n = 11) were associated with a significantly better OS over patients whose tumors harbored a TP53 mutation (n = 57) (median OS 22.9 months, 95% CI 9.6 to 54.5, vs. 10.0 months, 95% CI 4.2 to 23.8, HR 0.48, p = 0.048) . Within the TP53 mutation group, FOLFIRINOX (n = 21) did not show improved OS compare to Gem/NabP (n = 30) (mean OS 13.8 months, 95% CI 6.8 to 28.2, vs. 8.5 months, 95% CI 4.17 to 17.4, HR 0.84, p = 0.25). Other genetic alterations were not associated with OS. There was no difference in PFS in all PDACs. Conclusions: Our retrospective analysis showed that genetic changes in TP53 and GATA6 were significantly associated with the clinical outcome for PDAC. Mutation of TP53 was associated with poor OS in general. However, in unresectable PDAC, GATA6 amplification was associated with better clinical outcome than tumors with TP53 mutation. In contrary to general belief, FOLFIRINOX did not result in better OS than Gem/NabP.
Efficacy of HPV vaccination among seropositive, DNA negative cohorts.
Authors: Colm Mac Eochagain, Robert Power, Imelda Parker
Journal: Journal of Clinical Oncology (2021)

10552 Background: Prophylactic HPV vaccination of naïve cohorts is known to be highly effective in the prevention of incident HPV infection and HPV-associated cervical premalignancy. Conversely, vaccination of women with active (DNA+) HPV infections has been demonstrated to be ineffective. Vaccine efficacy among previously exposed, but currently uninfected women, i.e. those who have serological evidence of a prior HPV infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to RCTs of HPV L1-based vaccines. Methods: The study protocol was prospectively registered on PROSPERO (CRD42020206888). Searches were conducted on 08/16/20 on MEDLINE, EMBASE, SCOPUS and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Two authors independently screened studies, extracted data and assessed for bias. Data for SPDN women were extracted from subgroup analyses within primary and secondary publications, publication supplements, and manufacturers' clinical study reports. Relative risks (RR) of 6-month persistent infection (6mPI), 12-month persistent infection (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. Results: A total of 1727 citations were reviewed. 8 studies, with a total of 9569 SPDN participants, met all eligibility criteria. The relative risk of 6mPI (RR: 0.22, 95% CI 0.08-0.61, p = 0.018), 12mPI (RR: 0.20, 95% CI 0.05-0.80, p = 0.035), CIN1+ (RR:0.13, 95% CI 0.05-0.30, p = 0.003) and CIN2+ (RR: 0.15, 95% CI 0.04-0.59, p = 0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. The number needed to vaccinate (NNV) to prevent one case of CIN1+ and CIN2+ was 152 and 208 respectively. Conclusions: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV 16/18 infections. Women without DNA evidence of active infection may be seronegative, implying naïve status and &gt; 99% efficacy; or seropositive, implying SPDN status and 87% efficacy against CIN1+ for HPV 16/18. Women without DNA evidence of HPV 16/18 infection should be offered prophylactic HPV vaccination regardless of prior exposure history.
Pediatric cancer registry in Turkey 2009-2020 (TPOG &amp; TPHD).
Authors: M. Tezer Kutluk, Akif Yeşilipek
Journal: Journal of Clinical Oncology (2021)

e22519 Background: Global actions on pediatric cancer control is targeting to improve the survival rates in low and middle income countries which already exceeded 80% in high income countries. Almost 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Pediatric cancer registry must be a priority within the pediatric cancer control programs. Here, we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2020 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 12 years from 2009 to 2020, 21792 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 12198/9584, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.9%; 5-9 yrs, 23.7%; 10-14 yrs, 23.4%; 15-19 yrs, 12.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5208, 23.9%, 5.5, 3004/2204); Lymphoma &amp; other RES tumors (4103, 18.8%, 9.8, 2733/1367, 1 hermaphrodite &amp; 2 unknown); CNS [brain &amp; spinal] (3269, 15.0%, 6.8, 1794/1474, 1 unkown); Symphatetic system (1794, 8.2%, 2.4, 933/861); Retinoblastoma (610, 2.8%, 1.4, 339/271); Renal (1079, 5.0%, 3.1, 524/553, 1 hermaphrodite &amp; 1 unknown); Liver (376, 1.7%, 2.2, 216/160); Malignant bone (1448, 6.6%, 12.5, 787/661); Soft tissue sarcomas (1554, 7.1%, 7.6, 888/666); Germ cell (1461, 6.7%, 9.3, 547/910, 2 hermaphrodite, 2 unknown); Carcinoma &amp; other malignant epithelial (745, 3.4%, 13.5, 362/383); Other/non-specific malignant (145, 0.7%, 7.9, 71/74). Five year survival rate was found as 72%. Conclusions: This registry shows the imrovement of survival rates to 72% in Turkey which is comparable with middle income countries. The pediatric cancer control community is investing on the control of childhood cancer for further improvement and this registry became a valuable source for pediatric oncology community at national and international level.
Pathology of durable stable disease in melanoma patients treated with ipilimumab, nivolumab, or ipilimumab, and nivolumab combination therapy.
Authors: Elizabeth Iannotti Buchbinder, Kathleen L. Pfaff, Michael P. Manos, Olivia Ouyang, Patrick Alexander Ott, Scott J. Rodig, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2021)

9567 Background: As immunotherapy with checkpoint blockade becomes the backbone of melanoma treatment there is a need to better understand the biology associated with long term benefit. One particularly interesting set of patients are those with prolonged stable disease or response with residual findings on imaging. It is unknown if immunotherapy has led to scarring at the site of prior disease or if there are residual tumor cells being controlled by an ongoing immune response. Evaluating tissue from patients with prolonged responses provides a unique opportunity to determine the composition of residual lesions. Correlation with PET/CT helps determine if this is an accurate modality to reflect presence of residual viable tumor tissue. Methods: Metastatic melanoma patients that have attained long term stable disease after treatment with ipilimumab, nivolumab, or ipilimumab plus nivolumab were identified. Patients must have received ipilimumab, nivolumab or combination therapy 2+ years prior to enrollment and must have had stable disease for ≥ 6 months. Patients were consented and underwent PET/CT scans and biopsies of residual areas of stable disease. Pre- and post-treatment tissue samples underwent pathologic assessment to look at tumor cell content, fibrotic content, and inflammation. Results: Ten patients were consented for evaluation but only 7 met the screening criteria and underwent PET/CT and tissue biopsy. Six patients had FDG avid lesions on PET/CT which ranged in intensity from SUV 2.4-22. One patient had no FDG avidity in the areas of residual disease observed on CT. Biopsies from the residual stable lesions demonstrated predominantly necrosis and fibrosis with prominent pigment containing macrophages. One patient with an axillary nodal lesion with an SUV of 22 had active melanoma on pathology which was resected, and the patient has subsequently remained without progression of disease. Conclusions: Patients with durable stable disease after treatment with ipilimumab, nivolumab or ipilimumab and nivolumab combination therapy represent a unique population of melanoma patients treated with immune checkpoint inhibition. An examination of the residual lesions observed in these patients demonstrated predominantly necrosis and fibrosis consistent with resolving lesions. The presence of melanophages in these samples may suggest some ongoing immune surveillance. One patient did demonstrate residual melanoma suggesting the need for ongoing monitoring of this patient population.