tbuckley/cabot-search huggingface dataset:
Clinically advanced pelvic squamous cell carcinomas (pSCC) in men and women: A comprehensive genomic profiling (CGP) study.
Authors: Philippe E. Spiess, Petros Grivas, Douglas A. Mata, Gennady Bratslavsky, Joseph M Jacob, Andrea Necchi, Natalie Danziger, Douglas I. Lin, Brennan Decker, Ethan Sokol, Richard S.P. Huang, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2021)

3130 Background: Given that the clinical manifestations, disease course, and treatment options for pSCC differ between tumor types, we performed CGP to examine possible genomic differences. Methods: 1,741 clinically advanced pSCCs including 230 penile (penSCC), 17 male urethral (murthSCC), 125 male anal (manSCC), 7 female urethral (furthSCC), 263 vulvar (vulSCC), 822 cervical (crvSCC), and 277 female anal SCCs (fanSCC) underwent hybrid capture-based CGP to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: HPV-16/18 detection was lowest in murthSCC and vulSCC and highest in manSCC, fanSCC, and crvSCC. TP53 GAs were inversely associated with HPV status. PIK3CA GA frequency varied (22-43%). DNA-damage response (DDR) GAs (e.g., BRCA1/2, ATM, others) were low ( &lt; 1-3%) throughout. Cell-cycle GAs were most frequent in external cases (penSCC, furthSCC, vulSCC). MTOR pathway GAs ( PTEN, FBXW7) were the most frequently identified “actionable” GAs. FGFR3 GA were present in &gt;5% of murthSCC, crvSCC, and fanSCC; other receptor-tyrosine kinase (RTK) targeted options were 1% in BRAF/ ERBB2. NOTCH1 GAs were present in &gt; 15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was &gt;15% in manSCC, fanSCC, and crvSCC. PD-L1 low expression was &gt; 25% in all pSCC except crvSCC and high expression was &gt; 18% in all pSCC except urthSCC and manSCC. Conclusions: Despite similar histology, pSCC differ widely in GAs and HPV status. PIK3CA is the most frequent “targetable” GA followed by MTOR pathway and cell cycle; RTK targets are extremely rare. PARP inhibitor options appear low given the infrequent finding of DDR GAs. Anti-PD(L)1 could be considered in a number of cases based on TMB&gt;10 mut/Mb and PD-L1 expression.[Table: see text]
Durvalumab and pazopanib in patients with advanced soft tissue sarcoma: A single-center, single-arm, phase 2 trial.
Authors: Hyo Song Kim, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Sung Hyun Kim, Wooyeol Baek, Min Kyung Jeon
Journal: Journal of Clinical Oncology (2021)

11551 Background: Based on the central role played by the vascular endothelial growth factor receptor (VEGFR) in immunosuppression, we assessed the activity and safety of VEGFR inhibitor pazopanib plus anti-PD-L1 blockade durvalumab in soft tissue sarcoma (STS). Methods: We did a single-arm, single-center, phase 2 study that enrolled patients with metastatic or locally advanced STS aged 19 years or older, ECOG PS 0-1, with at least one measurable lesion, and received at least one previous line of systemic therapy. Patient were given pazopanib 800 mg orally daily and durvalumab 1500 mg intravenously for 60 min every 3 weeks. The primary endpoint was investigator-assessed objective response. Results: Between September 2019 and October 2020, 47 participants were enrolled, of whom 46 (97.9%) were evaluable for the efficacy analyses. With a median follow up of 12.3 months, complete and partial response (PR) was achieved in 1 (2.2%) and 12 (26.1%) patients, resulting in 28.3 % of objective response rate. Median time to achieve PR was 1.4 months and median duration of response was 11.0 months. The most common treatment-related adverse events of any grade include fatigue (20 [42.6%]), anorexia (17 [36.2%]), diarrhea (17 [36.2%]), and AST elevation (16, [34.0%]). Thirty-one patients (67.3%) had progressive disease, and the median progression free survival was 8.6 months (95% CI 3.6-13.6). Conclusions: Durvalumab and pazopanib showed encouraging activity in patients with advanced STS. Molecular predictors with whole exome and RNA sequencing will be presented. Clinical trial information: NCT03798106.
Efficacy and safety of anti-EGFR monoclonal antibody (SCT200) as third-line or further treatment in advanced lung squamous cell cancer.
Authors: Xiaorong Dong, Lin Wu, Dingzhi Huang, Ying Cheng
Journal: Journal of Clinical Oncology (2021)

e21070 Background: Treatment strategies for advanced lung squamous cell cancer (LSCC) of third-line or further-line are limited. We assessed the efficacy and safety of recombinant anti-EGFR monoclonal antibody SCT200 in patients with advanced LSCC in a phase 1b study. Methods: Advanced LSCC Patients previously treated with at least two chemotherapy regimens were randomly assigned to intravenous injection of SCT200 9 or 12 mg/kg every week (QW) for a maximum of 6 cycles, followed by 12 or 15 mg/kg every two weeks (Q2W). The primary endpoint was objective response rate (ORR). The secondary endpoint was progression free survival (PFS), overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT03808701). Results: Between March 19, 2019 and October 19, 2019, a total of 25 patients were enrolled and 23 were included in the final analysis (10 low dose [9mg/kg] and 13 high dose [12mg/kg]). The median age was 57 years old, and 21 (91.3%) patients were males. 22 patients (95.6%) had ECOG performance status of 1, and 17 (74%) were stage IV. The baseline characteristics were similar between the two dose groups. While no patients were evaluated as complete response or partial response, 5 and 6 patients achieved stable disease in the 9mg/kg and 12mg/kg dose groups respectively. However, the mOS was 5.96m (2.14 ̃ NR) and 9.59m (2.86 ̃ NR) in the low and high dose groups respectively. The mPFS was 2.23 (0.23 ̃ 5.26) and 1.38 (1.25 ̃ 3.02) in each group. The most common grade ≥3 treatment-related AEs were hypomagnesemia (13%), rash (13%) and anemia (4.3%). Conclusions: In this trial, a clinical benefit in OS was observed in the high dose group. SCT200 was shown to be safe and well tolerated in all patients. Our study indicated that SCT200 could serve as a potential single treatment or in combination with other therapy for advanced LSCC. Clinical trial information: NCT03808701. [Table: see text]
EMBR-17. DE-INTENSIFICATION OF RADIOTHERAPY IN RIGOROUSLY DEFINED LOW-RISK WNT-SUBGROUP MEDULLOBLASTOMA IS ASSOCIATED WITH UNACCEPTABLY HIGH RISK OF NEURAXIAL FAILURE: RESULTS FROM THE PROSPECTIVE FOR-WNT STUDY
Authors: Tejpal Gupta, Shizan Pervez, Archya Dasgupta, Abhishek Chatterjee, Rahul Krishnatry, Jayant GodaSastri, Maya Prasad, Girish Chinnaswamy, Sridhar Epari, Ayushi Sahay, Neelam Shirsat, Prakash Shetty, Aliasgar Moiyadi, Farnaz Shaikh, Nazia Bano, Rakesh Jalali
Journal: Neuro-Oncology (2021)

Abstract Background Medulloblastoma is a heterogenous disease comprising four molecular subgroups (WNT, SHH, Group 3, and Group 4) with varying outcomes. Excellent long-term survival (&amp;gt;90%) has prompted de-intensification of therapy in WNT-subgroup medulloblastoma globally. FOR-WNT is one such prospective study (CTRI/2017/12/010767) testing the hypothesis that focal conformal radiotherapy (RT) (54Gy/30 fractions/6-weeks) with avoidance of upfront craniospinal irradiation (CSI) followed by standard adjuvant chemotherapy significantly reduces RT-related late toxicity without unduly compromising survival in low-risk WNT-subgroup medulloblastoma (residual tumor &amp;lt;1.5cm2 with no evidence of metastases in children aged between 3–16 years). Methods Patients with low-risk WNT-subgroup medulloblastoma were enrolled after written informed consent/assent. To ensure patient safety, stopping rules were devised according to group-sequential method. Results Between July 2017 till Feb 2019, seven children of WNT-pathway medulloblastoma were treated with focal conformal RT followed by 6-cycles of adjuvant chemotherapy (cisplatin, cyclophosphamide, and vincristine). One child succumbed to acute renal failure during chemotherapy, while the other 6 patients completed all 6-cycles as planned. Three children were detected with neuraxial failure (supratentorial brain and/or spine) without synchronous local recurrence in the treated tumor-bed on surveillance neuro-imaging between 1.5–2 years from index diagnosis following which the study was terminated prematurely. All 3 children with relapse were treated with salvage CSI (35Gy/21 fractions) with (conformal avoidance of previously treated tumor-bed) plus boost irradiation (10.8-18Gy/6–10 fractions) of metastatic deposits resulting in complete/near complete response and are alive with controlled disease. The other 3 children have not shown any evidence of relapse for over 2-years from index diagnosis and remain on active clinico-radiological surveillance. Conclusion In rigorously defined low-risk WNT-subgroup medulloblastoma, avoidance of upfront CSI is associated with unacceptably high risk of neuraxial failure. A successor study (FOR-WNT 2) incorporating low-dose CSI (18Gy/10 fractions) with similar tumor-bed dose and adjuvant systemic chemotherapy is currently underway.
Tumor PD-L1 expression and gene panel mutational profile as outcome predictors of PD-1-based checkpoint inhibition therapy in metastatic melanoma: A prospective multicenter DeCOG study.
Authors: Selma Ugurel, Klaus Griewank, Susanne Horn, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Elke Meier, Edgar Dippel, Antje Sucker, Jan-Malte Placke, Eva Hadaschik, Jürgen C. Becker, Michael Weichenthal, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2021)

9568 Background: PD-1 checkpoint inhibition (CPI) has recently advanced to one of the most effective treatment strategies in melanoma. However, since a considerable proportion of patients shows upfront therapy resistance, baseline predictive biomarkers of therapy outcome are needed. Methods: This prospective multicenter study included metastatic melanoma patients whose formalin-fixed paraffin-embedded tumor tissue samples taken prior to the start of a systemic non-adjuvant therapy of any line were analyzed for PD-L1 expression on tumor cells by immunohistochemistry (clone 28-8, DAKO) and for COSMIC-annotated oncogenic mutations by 29-gene panel sequencing (MiSeq, Illumina). Clinical baseline and follow-up data were collected within the DeCOG multicenter skin cancer registry ADOREG. Results: From 09/2015 until 10/2020, 706 enrolled patients from 15 centers were evaluable for the endpoints best overall response (BOR), progression-free (PFS) and overall survival (OS). Thereof, 540 patients received PD-1-based CPI as first systemic treatment after tumor tissue analysis. 197/540 patients tested positive for PD-L1 (cut-off = 5%) in pre-treatment tumors, and revealed a favourable BOR (objective response 34.4% versus 19.1%; p &lt; 0.0001), PFS (median 10.4 versus 4.2 months; p &lt; 0.0001) and OS (median 45.1 versus 18.8 months; p = 0.001) compared to patients with PD-L1 negative tumors. 47/540 patients presented oncogenic mutations of three or more genes in pre-treatment tumors, and revealed a favourable BOR (objective response 46.8% versus 32.1%; p = 0.041), PFS (median 15.1 versus 6.1 months; p = 0.008) and OS (median not reached versus 25.2 months; p = 0.027) compared to patients whose tumors showed mutations in two or less genes. Multivariable Cox regression including sex, primary site, non-adjuvant systemic pre-treatment, serum LDH, and ECOG performance state demonstrated tumor PD-L1 expression and gene panel mutational profile as independent predictors of survival upon treatment with PD-1-based CPI. In contrast, in 106/706 patients treated with BRAF/MEK inhibitors as first systemic treatment after tumor tissue analysis, no association was found between tumor PD-L1 expression or gene panel mutational profile and therapy outcome. Conclusions: PD-L1 expression quantification and gene panel mutational profiling provide useful outcome predictors of PD-1-based CPI therapy in metastatic melanoma patients.
Prevalence of HBV Infection, Vaccine‐Induced Immunity, and Susceptibility Among At‐Risk Populations: US Households, 2013‐2018
Authors: Henry Roberts, Kathleen N. Ly, Shaoman Yin, Elizabeth Hughes, Eyasu Teshale, Ruth Jiles
Journal: Hepatology (2021)

In the USA, HBV is one of the leading causes of chronic liver disease and cirrhosis and is a major cause of liver cancer. We aimed to estimate the prevalence of past and present HBV infection, susceptibility to HBV infection, and vaccine-induced immunity to hepatitis B among the US population during 2013-2018.Prevalence estimates and 95% CIs were analyzed using 2013-2018 data from the National Health and Nutrition Examination Survey. Serologic testing among noninstitutionalized persons aged ≥ 6 years was used for classifying persons as total hepatitis B core antibody (anti-HBc), indicative of current or previous (ever having had) HBV infection; HBsAg, indicative of current HBV infection; and antibody to ABsAg (anti-HBs), indicative of immunity attributable to hepatitis B vaccination. Persons who tested negative for anti-HBc, HBsAg, and anti-HBs were considered susceptible to HBV infection. Non-US-born residents accounted for 69.1% of the population with chronic HBV infection and were 9.1 times more likely to be living with chronic hepatitis B, compared with US-born persons. Among adults aged ≥ 25 years who resided in US households, an estimated 155.8 million persons (or 73.4%) were susceptible to HBV infection, and an estimated 45.4 million had vaccine-induced immunity to hepatitis B. Men who have sex with men (MSM) were 3.6 times more likely to have ever been infected with HBV; however, MSM were just as likely to have vaccine-induced immunity to hepatitis B as non-MSM.Despite increasing immune protection among young persons vaccinated after birth, the estimated prevalence of persons living with chronic hepatitis B in the USA has remained unchanged at 0.3% since 1999.
Breast cancer as seen at the Nairobi Hospital.
Authors: Nicholas Anthony Othieno-Abinya, Gladwell Wanjiru Kamere Kiarie, Alice Musibi, Amina Habib Kidee, Tom Nyaboga, Ruth Wanjohi, Richard Baraza
Journal: Journal of Clinical Oncology (2021)

e12514 Background: Breast cancer is the most common cancer and the second leading cause of death among women globally. The Nairobi Hospital has a comprehensive cancer centre, with various practitioners treating cancer patients individually. To document breast cancer diagnosis, treatment and outcome at the Nairobi Hospital. Methods: A retrospective cohort study involving records of breast cancer patients between Jan 2014 and Dec 2019 inclusive. Details included, demographic details, comorbidities, pathology, stage, treatment and outcome. The study was approved by the hospital’s Ethics and Research Committee. Results: 591 patients; 580 (98.1%) women and 11(1.9%) men. Age group 41-60 years had 330 patients(57.2%). Mean parity was 3. Fifteen (2.5%) were smokers, 73 (12.4%) took alcohol, 159 (12.4%) used hormonal contraceptives, 4(0.7%) had been exposed to iatrogenic radiation. Family history of cancer was present in 112 (19%), 25 (4.2%) had personal history of cancer, breast cancer in 8 (1.4%). Diagnosis was by core needle biopsy in 301 (50.9%), excision biopsy in 238 (40.3%), and fine needle aspiration cytology in 52 (8.8%). Pathology was invasive ductal carcinoma in 502(84.9%), invasive lobular in 12(2%). Oestrogen receptors were expressed in 329 (55.7%), progesterone receptors in 264 (44.7%), and Her2 in 129(21.8%). Triple negative were 86( 18%). T1 tumors were 84 (14.2%), T2 were 197 (33.3%), T3 were 126 (15.9%,) and T4 in 94 (15.9%), 126 (21.3%) had distant metastases. Neoadjuvant combination of doxorubicin and cyclophosphamide (AC) was in 109(18.4%) of patients, a taxane following AC (AC-T) in 79 (13.4), and 5-FU with doxorubicin and cyclophosphamide (CAF) in 105 (17.8%). Adjuvant AC was administered to 59 (10%), AC-T to 65 (11%), and CAF to 105 (17.8%), adjuvant tamoxifen to 160 (27.1%). Overall 93 patients (15.7%) received trastuzumab. Adjuvant radiotherapy was completed in 367 (62.1%). At a median follow-up of 36 months, patients 33 (5.6%) were recorded dead. The younger patients had worse survival. Conclusions: Ductal carcinoma constituted 85% of cases and metastatic disease was in 21.3 %. Triple negative cancer were 18%. Younger patients had higher risk of early death.
Comparing the clinical impact of pancreatic cyst surveillance programs: A trial of the ECOG-ACRIN cancer research group (EA2185).
Authors: David Weinberg, Jon Steingrimsson, Herbert Zeh, Ruth Carlos, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2021)

TPS10608 Background: The optimal surveillance strategy for pancreatic cysts, which occur in up to 20% of the adult population, is ill defined. Although risk of malignant degeneration of these cysts is low, pancreatic cancer mortality remains high. Two cyst surveillance guidelines, one proposed by an international consensus group (Fukuoka) and the other by the American Gastroenterological Association (AGA), are accepted standards. Both rely on radiographic and endoscopic ultrasonographic imaging. They differ in indications for, and intervals between, imaging tests, with the Fukuoka guideline advocating more intensive imaging. Clinical guidelines that provide discordant recommendations may undercut the quality and/or value of care, and have implications for societal health care costs. The primary objective of this prospective trial is to compare the clinical effectiveness and associated resource utilization of the Fukuoka and AGA guidelines for pancreatic cyst surveillance. Secondary objectives include a comparison of resource utilization and patient reported outcomes. We are also collecting and banking radiomics data and biospecimens to identify novel methods that might improve cancer risk stratification. Methods: 4606 asymptomatic patients with newly identified pancreatic cysts ≥1cm in diameter are being randomized 1:1 to high intensity (Fukuoka) or low intensity (AGA) surveillance. The primary endpoint is a composite of any pancreatic cancer without surgery, unresectable pancreatic cancer or cancer &gt; T1a, N0 at surgery, and benign disease at surgery. This sample size will provide 90% power to identify a 30% relative difference in the primary outcome at 5 years between the two study arms. Study duration is 8 years in total, allowing for 2 years of cohort enrollment, 5 years of prospective follow-up, and six months reserved for study initiation and close out. Study participants must be ≥ 50 years and ≤ 75 years with an ECOG Performance Status 0-1 at baseline. Participants must have received a CT or MRI within 6 months of registration that identifies a new ≥1 cm pancreatic cyst. Patients with a prior diagnosis of a pancreatic cyst, pancreatic malignancy or a history of pancreatic resection are not eligible. Additional exclusion criteria include a history of acute or chronic pancreatitis, a family history of pancreatic adenocarcinoma in 1 or more first degree relatives, imaging findings or clinical signs that would prompt immediate surgical consideration (enhancing mural nodule, solid component in cyst, pancreatic duct &gt; 10mm, cyst causing obstructive jaundice), a comorbid illness that precludes pancreatic cyst resection, pregnancy or current participation in an established surveillance program. As of February 4, 2021, thirty three (33) participants have been enrolled from two hundred (200) potential sites. Clinical trial information: NCT04239573 .
Anaesthetist training: UK “must double numbers” to combat NHS waiting lists
Authors: Clara Munro
Journal: BMJ (2021)

Anaesthetic training places must be doubled to enable the NHS to deal with the huge backlog of surgical procedures created by the covid pandemic, the Association of Anaesthetists has said.

In open letters to the UK’s four health secretaries,1 the association called for the number of higher specialty training posts (ST3) in anaesthetics to be doubled in 2021, from around 350 to 700, and to remain at that level for two subsequent …
18F-FDG-PET/CT response assessment in patients with advanced melanoma treated with combination of low-dose ipilimumab and anti-PD1: A real-world experience.
Authors: Caio Dabbous Liz, Marcos Rezende Teixeira, Luciana Beatriz Mendes Gomes Siqueira, Jose A. Rinck, Joao Paulo S. N. Lima, Monique Celeste Tavares, Daniel Garcia, Thiago Bueno Oliveira, Marcelo Cavicchioli, Eduardo Lima, Joao Duprat, Milton Jose De Barros E. Silva
Journal: Journal of Clinical Oncology (2021)

e21533 Background: Combination therapy with anti-PD1 and low-dose ipilimumab has shown reduced rate of immune-related adverse effects compared with standard dose used in the Checkmates studies 067 and 204. However, the discussion whether low-dose ipilimumab may hamper the response rate in advanced melanoma is still open. Methods: We conducted a retrospective analysis of response evaluation based on 18F-FDG PET/CT for patients with advanced melanoma treated with combination of nivolumab 3mg/kg plus ipilimumab 1mg/kg for 4 cycles (N3+I1) followed by anti-PD1 maintenance therapy and compared the results to RECIST 1.1 response criteria in the same population. Results: Between December 2017 and August 2020, 45 patients with advanced melanoma treated with N3+I1 in first-line setting were identified. Unresectable stage III/stage IV were 2/43 patients, respectively. Among stage IV patients, 60.5% were M1c, 23.3% had elevated LDH and 28% had brain metastasis (3 or more brain lesions: 58%). At a median follow-up of 16.7 months, 11 patients (24.4%) had G3/G4 toxicity. During induction phase, three patients (6.6%) discontinued all drugs and 2 other patients (4.4%) interrupted only ipilimumab. Review of response evaluation by RECIST was possible in 36 patients and showed an objective response of 50%. Complete response (CR): 11% and partial response (PR): 39%. Eight percent presented progressive disease (PD). In 37 patients, review of response evaluation using 18F-FDG PET/CT was possible. Twenty-four patients (65%) achieved metabolic CR, 5 (13.5%) PD and 8 (21.5%) were classified as non-CR non-PD. Median progression-free survival (PFS) and overall survival(OS) were not reached. 12-month PFS and OS were: 72.5 and 89%, respectively. During the study follow-up, only 1 patient with metabolic complete response relapsed and 3 out of 8 with non-CR non-PD progressed. Conclusions: Using low-dose ipilimumab combination does not hamper the response rates and, possibly due to fewer protocol interruptions, these patients may achieve more complete responses as showed by 18F-FDG PET/CT evaluation.