tbuckley/cabot-search huggingface dataset:
Integrated immune-related gene signature to predict clinical outcome for patients with luminal B breast cancer.
Authors: Xiaying Kuang, Du Cai, Ying Lin, Feng Gao
Journal: Journal of Clinical Oncology (2021)

e12526 Background: Luminal B breast cancer is always routinely treated with chemotherapy and endocrine therapy but heterogeneous with respect to sensitivity to treatment, identification of patients who may most benefit remains a matter of controversy. Immune-related genes (IRGs) was found to be associated with the prognosis of breast cancer. The aim of this study is to evaluate the impact of IRGs in predicting the outcome of luminal B breast cancer patients. Methods: According to the Metabric microarray dataset also as a training cohort, 488 luminal B breast cancer patients were selected for generation of immune-related gene signature (IRGS). Another independent dataset (n=250) of patients with complete prognostic information was analyzed as a validation cohort. Prognostic analysis was assessed to test the predictive value of IRGS. Results: A model of prognostic IRGS containing 12 immune-related genes was developed. In both training and validation cohorts, IRGS significantly stratified luminal B breast cancer patients into immune low- and high-risk groups in terms of disease free survival (DFS, HR=4.95, 95% CI=3.22-7.62, P&lt;0.001 in training cohort, HR=2.47, 95% CI=1.29-4.75, P&lt;0.001 in validation cohort). Multivariate analysis revealed IRGS as an independent prognostic factor (HR=4.96, 95% CI=3.00-8.18, P&lt;0.001 in training cohort, HR=2.56, 95% CI=1.28-5.09, P=0.007 in validation cohort). Furthermore, those 12 genes mostly related with response to chemical, and the expression levels of them were completely opposite in patients of immune low- and high-risk groups. Conclusions: The proposed IRGS is a satisfactory prognostic model for estimating DFS of luminal B breast cancer patients. Further studies are needed to assess the clinical effectiveness of this system in predicting prognosis and treatment options for luminal B breast cancer patients. This work was supported by National Natural Science Foundation of China (No. 81602520), Natural Science Foundation of Guangdong Province (No. 2017A030313596).
<i>PALB2</i> mutation as a predictive biomarker for immunotherapy in patients with advanced melanoma: Results from (a pooled analysis of) five multicenter, randomized clinical trials.
Authors: Changxuan You, Yating Zheng, Mengli Huang
Journal: Journal of Clinical Oncology (2021)

e21537 Background: PALB2, a gene in the homologous recombination repair (HRR) pathway, has been shown to be associated with the efficacy of platinum based chemotherapy, and PARP inhibitor therapy in breast, prostate, ovarian, and pancreatic cancers. However, their predictive value of PALB2 remained unknown in patients with advanced melanoma. Methods: Five independent cohorts (Miao2018, Samstein2018, Allen 2015, Hugo2016, and Synder2014. study cohort) with data from 672 patients with advanced melanoma were used to analyze the correlation with immunogenic marker, and the prognostic effect of PALB2 on immunotherapy. Results: A pooled analysis of five independent cohorts of 672 advanced patients melanoma show that 31 (4.6%) harbored PALB2 mutation ( PALB2 mut ). PALB2 mut (72.63Muts/Mb) was associated with higher tumor mutation burden (TMB) (P &lt; 0.001) than PALB wild-type ( PALB2 wt ) (19.71Muts/Mb). The same phenomenon has also been observed in TNB, PALB2 mut (1983 counts) was associated with higher tumor neoantigen burden (TNB) than PALB2 wt (603.5 counts) (P = 0.0147). The objective response rate (ORR) of immunotherapy was 53.33% for the patients with PALB2 mut and 24% for the PALB2 wt subgroup (P = 0.027). The PALB2 mut patients had significantly improved median overall survival (mOS) than the PALB2 wt group (Not reach versus 29 months, hazard ratio (HR) = 0.38, 95%CI 0.19−0.73, P = 0.003). A subgroup analysis of CTLA4 inhibitor treatment found that PALB2 mut was associated with better ORR (50% versus 18.3%, P = 0.016) on immunotherapy, and mOS in the PALB2 mut group was significantly better than that in the PALB2 wt group (Not reach versus 21 months, HR = 0.3, 95%CI 0.13−0.68, P = 0.002). However, in the subgroup receiving PD-L1 inhibitor treatment, no ORR benefit was found in the PALB2 mut group (66.67% versus 56.76%, P = 1), and there was no difference on mOS between PALB2 mut and PALB2 wt (Not reach versus 31 months, HR = 0.45, 95%CI 0.11−1.8, P = 0.254). Conclusions: PALB2 mutations was associated with a higher TMB and TNB level. PALB2 may serve as a positive predictor of immunotherapy (CTLA4 inhibitor therapy) in patients with advanced melanoma and their clinical value warrants further investigation.
A phase II study investigating biological effects of maintenance usage of hydroxychloroquine on Par-4 levels in patients with resected tumors.
Authors: Peng Wang, Ravshan Burikhanov, Heidi Weiss, Rani Jayswal, Susanne M. Arnold, John L. Villano, Vivek Rangnekar
Journal: Journal of Clinical Oncology (2021)

3085 Background: Hydroxychloroquine (HCQ) is an inducer of the tumor suppressor Par-4 (prostate apoptosis response-4) secretion from normal cells. Secreted Par-4 causes paracrine apoptosis of tumor cells in mice. Established dosing of HCQ 200 mg bid induces Par-4 secretion but not the autophagy-inhibition marker p62 and correlates with apoptosis induction in patients' tumors. Methods: This is a single-arm, single institute phase II study to characterize the biological effects of 3-months of HCQ at fixed-dose (200 mg p.o. twice a day) on plasma Par-4 levels in adults with resected solid tumors. The primary endpoint is proportion of patients who will exhibit a two-fold increase in Par-4 levels from baseline compared to 3 months of follow-up. 12-month progression free survival (PFS) is one of the secondary endpoints. A Simon's two-stage design was used to test the null hypothesis that the proportion of patients exhibiting a two-fold increase in Par-4 is equal to 50% compared to 70% using a one-sided alternative. These hypothesized assumptions are based on a small pilot human data and from a phase I clinical trial on a small number of patients (n = 9). The first stage of interim analysis will be performed after a total of 15 patients have been accrued. If there are eight or fewer responses occurred, the study will be stopped. Otherwise, 28 additional patients will be accrued for a total of 43 subjects. Results: A total of 19 patients were enrolled in the trial. Per protocol, the interim analysis and stopping boundary is based on the first 15 patients. A total of 4 out of 15 patients (26.7%) 95% CI: 8% - 55% exhibited a &gt;2-fold increase in Par-4 levels at 3 months. This did not surpass the stopping bound for futility and thus indicates stopping of patient accrual based on the assumptions used for the Simon's two-stage design. 7 out of 19 patients (36.8%) 95% CI: 16% - 62% who exhibited at least a 2-fold increase at either 2 or 3 months of follow-up, 50% (95% CI: 26% - 74%) and 56% (95% CI: 31% -79%) exhibited a 1.5-fold and 1.25-fold increase respectively. To date, 10/19 patients finished 12-month follow-up, 4/19 and 5/19 finished 6-month and 3-month follow up respectively. 2 of 12 patients with less than 2-fold increase of Par-4 developed disease progression. None of 7 patients with 2-fold increase of Par-4 showed disease progression. Conclusions: Despite that the study was terminated prematurely, to our knowledge this is the first study in human to identify dynamic changes of serum Par-4 while on long-term of usage of HCQ. We also demonstrate trend of PFS benefit especially for subjects having 2-fold increase of Par-4 induction. Identification of tumors more Par-4 sensitive and predictive biomarkers of Par-4 induction are necessary to continue our investigation. Clinical trial information: NCT02232243.
An online pilot survey to assess collateral damage related to male breast cancer treatment.
Authors: Deanna J. Attai, Leah Eshraghi, Susan M. Love
Journal: Journal of Clinical Oncology (2021)

e24046 Background: Fewer than 1% of all cases of breast cancer occur in men, and little is known about the late effects of the disease and its treatment in this population. We developed a pilot survey with the aim of identifying primary areas of concern among men who have been treated for breast cancer. The findings will be used to develop a more comprehensive survey assessing the late effects or collateral damage of male breast cancer treatment. Methods: An anonymous survey was developed with the assistance of patient advocates from the Male Breast Cancer Coalition (MBCC). The survey asked for the men’s current age and contained five open-ended questions. Respondents were asked to (1) describe the most significant types of collateral damage they had experienced; (2) share the effects of disease and treatment on areas of their lives (physical, emotional, psychological, financial); (3) identify resources they had found to be helpful; and (4) provide advice to other men with breast cancer. The fifth question allowed for additional free-text entry. The survey, distributed by the Dr. Susan Love Foundation for Breast Cancer Research and MBCC via social media postings and email, was open from January to February 2021. Results: Sixty-eight men responded to the survey. Mean age of respondents was 62.9 (range 34 - 87). Sexual dysfunction, peripheral neuropathy, musculoskeletal complaints, and fatigue were the most commonly reported collateral damage symptoms. In their open-ended answers, many respondents expressed anxiety about and fear of recurrence, being self-conscious regarding their appearance, and negative effects on sexual function and intimacy. Some described the social isolation of being a man with breast cancer, and several discussed job loss and financial hardship as a result of their diagnosis and treatment. Online resources, including MBCC, were popular sources of support, as were family, friends, and faith. The respondents’ advice to other men with breast cancer included many recommendations to “be your own advocate,” seek out others for support and networking, and “prepare for a pink world.” Conclusions: This pilot study provides important preliminary information regarding late effects and collateral damage of male breast cancer and its treatments, as well as insights into the male breast cancer experience not captured in prior work. This information will be used to inform a more comprehensive project that assesses collateral damage and quality of life among men who have been treated for breast cancer. The findings also will be used to develop recommendations on how to educate clinicians about the needs of male breast cancer survivors and how to better alleviate the late effects and collateral damage they experience.
SHARED: Efficacy and safety of sintilimab in combination with concurrent chemoradiotherapy (cCRT) in patients with locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Jia Wei, Xiaofeng Lu, Qin Liu, Yao Fu, Song Liu, Ju Yang, Meng Wang, Liming Zheng, Yang Yang, Xiangshan Fan, Yang Zhao, Wenxian Guan, Baorui Liu
Journal: Journal of Clinical Oncology (2021)

4040 Background: PD-1 inhibitor and chemotherapy have shown significant clinical benefits in 1L-treatment of G/GEJ. While it is not clear for locally advanced stage. The aim of this single-arm phase Ib trial is to assess the feasibility of sintilimab (PD-1 inhibitor) in combination with cCRT in locally advanced GC. Methods: Patients (pts) with initial histopathologically confirmed G/GEJ adenocarcinoma, diagnosed as locally advanced III-IVA per AJCC 8 th and ECOG PS of 0-1 were eligible. Sintilimab (200mg, iv, Q3W) was given with CRT sandwich in sequence of one induction chemotherapy (S-1+Nab-PTX), weekly Nab-PTX(80-100mg/m 2 , d1, d8, d15, d22), concurrent radiotherapy (45Gy/1.8Gy*25f), and one consolidation chemotherapy (S-1+Nab-PTX). Pts received three additional combinations of sintilimab and chemotherapy after surgery or investigator’s best choice for unresectable pts after planned therapy. The primary endpoint was pCR and a Simon two-stage was employed at first 9 pts. This interim analysis was pre-planned after finishing stage I assessment. Accrual is ongoing with another 25 in next stage. Results: In the first stage, 5 out of 9 pts achieved pCR and passed to next stage. As of 7th Feb 2021, 28 pts met inclusion criteria with median age 67 yrs (range 47-81), men 86%, PS 1 25%, cT3/4a/4b 28%/54%/18%, cN1/N2/N3 7%/50%/43% and Borrmann II/III/IV 57%/18%/25%. The location on GEJ and G was 14% and 86%. Of 23 pts completed neoadjuvant, all were evaluated as D2-surgery feasibility. 19 pts had completed gastrectomy (4 pts waiting for surgery) with pCR 42.1% (8/19), MPR (≤10% viable tumor cells) 73.7% (14/19) and R0 resection 94.7% (18/19). Down-staging to pT0 and pN0 were both observed in 42.1%. The median follow-up was 5.8m unavailable for survival evaluation at present. Grade (gr) 3-4 TRAE occurred in 39.3% (11/28) pts with most common events as myelosuppression (39.3%) and increased transaminase (10.7%). IrAEs occurred in 21.4% (6/28) pts with one gr 4 hepatitis and others gr 1-2. Peri-operative complications occurred in 3 pts with gr 1-2 pneumonia, increased transaminase, and ileus. No death or unexpected toxicity observed. Conclusions: SHARED interim analysis demonstrated a promising feasibility of sintilimab in combination with cCRT with preliminary impressive pCR &amp; MPR and acceptable toxicity in phase III-IVA G/GEJ cancer. These results warrant further accrual and evaluation. Clinical trial information: ChiCTR1900024428.
Evaluation of telehealth based nutrition counselling to improve dietary compliance and nutritional status of cancer patients.
Authors: Amit Kumar Jotwani, Krishna Priya NG, Arun AK, Rashie Jain
Journal: Journal of Clinical Oncology (2021)

e13619 Background: According to published literature, regardless of the cancer type, the overall prevalence of malnutrition in cancer is about 40% (range 30%-70%). Malnutrition is known to adversely affect the treatment compliance, quality of life and survival outcomes for cancer patients. Onco.com provides telehealth based nutrition care support (NCS) as a part of cancer care management program. We sought to evaluate impact of telehealth based nutrition counselling on diet compliance and overall nutritional status of patients. Methods: NCS includes virtual nutrition screening, nutrition diagnosis and nutrition intervention. Virtual nutrition screening was done using modified patient generated subjective global assessment (PG-SGA) tool developed by Ottery. An initial nutrition screening was initially performed for 165 patients. After nutrition screening, patients were divided as malnourished (category 1- 47%), nutritionally at risk (category 2- 34%) and well nourished (category 3- 19%). Patients in category 1 &amp; 2 were analysed for the purpose of study. Diet counselling and customized diet plans were provided to the patients between the age group of 12 to 83 years for a period of 3 months from October to December 2020. On follow up, 24 hour diet recall method and food frequency method were used to assess the compliance to the diet plan. One day prior 24 hour diet recall and food frequency method for two weeks was used to analyse the adherence to the plan. If the patient consumed ≥75% of the recommended diet for a minimum of 5 days in a week, he/she was considered a ‘compliant’, while those who consumed &lt; 75% of the recommended diet were considered to be ‘non-compliant’. Data on body weight and performance status (PS) was documented during follow up to track changes. Results: Of 134 study participants, 35.1% were in the early (I &amp; II) stage, 38.7 % were in the locally advanced (III) stage, 21.2 % were in the metastatic stage, and 4.8 % were in the recurrent stage of disease. After 3 months of initiation of the nutrition counselling, 40% of the patients had gained weight, whereas 38% could maintain the body weight and 22 % had lost weight. Change in physical activity, appetite, management of side effects after diet plan initiation were also assessed during the reassessment calls. Overall, 67% patients showed improvement in diet compliance across all stages of disease. Majority of dietary non-compliance was noted in patients with head and neck, upper GI cancers or those with poor PS. Conclusions: Telehealth based nutritional counselling is an effective tool to help cancer patients achieve better diet compliance and nutrition outcomes across all stages of disease. Dietary non-compliance in head and neck cancers and upper gastrointestinal cancers or poos PS could correlate with difficulty in oral intake. Getting accurate information could be one of the challenges in virtual mode of counselling.
Phase I study of a DNA-based vaccine targeting prostatic acid phosphatase (PAP) in patients with clinical stage D0 prostate cancer
Authors: Edward Dunphy, Mary Jane Staab, Dorothea Horvath, Jane Straus, Dona Alberti, Glenn Liu, George Wilding, Douglas McNeel
Journal: Cancer Research (2007)

1858  Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, however, tumor vaccines may be most effective in the setting of minimal residual disease. We have investigated plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8+ T cells and observed evidence of anti-tumor efficacy. We report here the initial clinical and immunological results from a dose-escalation phase I trial evaluating a DNA vaccine encoding PAP in patients with minimal residual prostate cancer, clinical stage D0.  Methods: Patients with clinical stage D0 prostate cancer with rising serum PSA were vaccinated over a 12-week period, six times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP) in a dose-escalation trial. Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. The primary endpoints of the trial were safety and immunological response, antigen-specific IFNγ-secreting CD8+ T cells as measured by ELISPOT. Other immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion and by ELISA for PAP-specific IgG.  Results: Nine patients were enrolled and all completed the immunization series. No serious adverse events were observed, and no events greater than grade 2 were identified. Antibody responses to PAP were not observed, however 4/9 developed PAP-specific CD4+ or CD8+ proliferative T cell responses. 2/9 patients developed PAP-specific IFNγ-secreting CD8+ T cells, detectable without in vitro stimulation, as measured by ELISPOT, the primary immunological endpoint of the trial. 2/9 patients also demonstrated a marked increase in PSA doubling time, one of whom was found to have an ELISPOT response.  Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP resulted in no significant adverse events in doses up to 1500 mcg. CD4+ and CD8+ T cell responses were elicited, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. The development of an antigen-specific CD8+ T cell response in conjunction with an increase in PSA doubling time in some patients suggests that further clinical evaluation is warranted.
Abstract 10597: Analysis of the Factors Associated With Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease
Authors: Taichi Kato, Tohru Kobayashi, Mamoru Ayusawa, Ryuji Fukazawa, Shigeto Fuse, Keiichi Hirono, Yoshihide Mitani, Kenji Suda, Jun Maeda, Masaru Miura
Journal: Circulation (2019)

Background: In the patients with coronary arterial aneurysm (CAA) due to Kawasaki disease (KD), the clinical course of CAA regression is not well described. We analyzed the factors associated with ...
Alternative ways to improving the quality of life in combination treatment for high-grade glioma.
Authors: Ivan A. Popov, Alla I. Shikhlyarova, Elena M. Frantsiyants, Eduard E. Rostorguev, Marina A. Engibaryan, Dmitriy P. Atmachidi, Natalya S. Kuznetsova, Irina V. Kaplieva, Valeria A. Bandovkina, Natalia D. Cheryarina, Olga V. Pandova
Journal: Journal of Clinical Oncology (2021)

e14031 Background: The steady increase in the rates of high-grade gliomas (HGG) and poor results of antitumor therapy actualizes the problems of improving surgical and chemoradiation treatment, as well as accompanying therapy technologies for managing secondary disorders of neurological, cognitive, and adaptive status of neurooncological patients. Transcranial magnetotherapy (TMT) helps managing disorders of brain activity at the level of systemic and local regulation, including the mechanisms of formation of general anti-stress reactions of the body, as the basis for improving the quality of life. The purpose of the study was to improve the quality of life of patients with HGG receiving surgical and radiation treatment with TMT. Methods: Neurological and cognitive functions were analyzed in 50 patients with HGG after TMT (1 - ultra-low-frequency magnetic field on the projection of the hypothalamus, 0.3-3.0-9.0 Hz, induction 3 mT; 2 - pulsed magnetic field on the tumor bed, 0.3-3.0-9.0 Hz, induction 15 mT) in the early postoperative period and with radiation therapy, total boost dose 60 Gy, 30 fractions. The results were evaluated with the Bartel, Karnofsky, MoCA and NIHSS scales. Types of general adaptive reactions were identified according to the criteria of the cellular composition of blood by Garkavi. Results: 84% patients after TMT had no neurological symptoms (NIHSS scale), vs. 48% in controls. The number of patients without cognitive dysfunctions (MoCA scale) before radiation therapy was 3.4 times higher than the control values and exceeded them by 4.0 times after radiotherapy. Similar positive dynamics was observed when testing with the Bartel scale, with mild (88.0±4.7% vs. 45.5±10.6% in controls; p &lt; 0.05) and moderate (12±6.5% vs. 45.5±10.6% in controls; p &lt; 0.05) dependence on others in everyday life, and testing with the Karnofsky performance status in patients with the index 90 (60±7.1% in the main group vs. 27.3±9.5% in controls; p &lt; 0.05), in which the symptoms of the disease were insignificant. A 3.4-fold decrease in the frequency of acute stress (S) development was registered, with increased coefficient (C) of antistress (AS) reactions (C = AS/S) by 3.0 times relative to the control values. Conclusions: Antistress mechanisms of the integral response to TMT involved neurological and cognitive recovery, contributing to early rehabilitation and improving the quality of life. The reported study was funded by RFBR, project number 19-315-90082\19.