tbuckley/cabot-search huggingface dataset:
Vaccine titers in lymphoma patients receiving chimeric antigen receptor T-cell therapy.
Authors: Radhika Bansal, Paschalis Vergidis, Pritish Tosh, John W. Wilson, Matthew Hathcock, N. Nora Bennani, Jonas Paludo, Jose Caetano Villasboas, Yucai Wang, Stephen M. Ansell, Patrick B. Johnston, Catherine M. Freeman, Yi Lin
Journal: Journal of Clinical Oncology (2021)

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG&lt;400 mg/dl received IVIG supplement for prophylaxis. Among the 23 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (2/3, 67%), rubella (2/3, 67%), varicella-zoster (VZV, 3/3, 100%), hepatitis A (6/6, 100%), hepatitis B (6/7, 86%) and Strep PNA (0/10, 0%). For patients who did not receive IVIG prophylaxis, there was one loss of seropositivity for Strep PNA (1/4, 25%). Conclusions: The presence of protective vaccine titers is variable for patients receiving CAR-T, regardless of recent ASCT. The loss of protective titers post CART was low. IVIG variably impacted vaccine titer status. Immunization remains important for patients with ASCT prior to CART, without completion of post ASCT immunization protocol. Further study is needed to inform the need for immunization and optimal timing post CART.[Table: see text]
Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome
Authors: Ryotaro Nakamura, Wael Saber, Michael J. Martens, Alyssa Ramirez, Bart Scott, Betul Oran, Eric Leifer, Roni Tamari, Asmita Mishra, Richard T. Maziarz, Joseph McGuirk, Peter Westervelt, Sumithira Vasu, Mrinal Patnaik, Rammurti Kamble, Stephen J. Forman, Mikkael A. Sekeres, Frederick Appelbaum, Adam Mendizabal, Brent Logan, Mary Horowitz, Corey Cutler
Journal: Journal of Clinical Oncology (2021)

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined.
Author Correction: Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation
Authors: Zhaogang Yang, Junfeng Shi, Jing Xie, Yifan Wang, Jingyao Sun, Tongzheng Liu, Yarong Zhao, Xiuting Zhao, Xinmei Wang, Yifan Ma, Veysi Malkoc, Chiling Chiang, Weiye Deng, Yuanxin Chen, Yuan Fu, Kwang J. Kwak, Yamin Fan, Chen Kang, Changcheng Yin, June Rhee, Paul Bertani, Jose Otero, Wu Lu, Kyuson Yun, Andrew S. Lee, Wen Jiang, Lesheng Teng, Betty Y. S. Kim, L. James Lee
Journal: Nature Biomedical Engineering (2021)
The PATH score based on pathological grade predicts survival of patients with advanced hepatocellular carcinoma after hepatic arterial infusion chemotherapy.
Authors: Jinfa Lai, Ning Lyu, Ming Zhao
Journal: Journal of Clinical Oncology (2021)

e16134 Background: Hepatic arterial infusion chemotherapy (HAIC) is an emerging and effective therapeutic strategy for advanced hepatocellular carcinoma (HCC). We developed a practical prognostic score for patients undergoing HAIC to determine who can benefit from it. Methods: Between 2014 and 2019, 482 treatment-naïve patients with advanced HCC undergoing HAIC were included from two independent treatment departments. Patients were randomly divided into training (n = 337) and validation (n = 145) cohorts. Pathological grade, ALBI grade, and TNM stage were selected and developed a simple score to evaluate HAIC treatment (PATH) by Cox regression model, subsequently confirmed in the validation cohort and compared with other prognostic scores. Results: According to the PATH score, patients were divided into three groups; low-risk (0-1 point), moderate-risk (2-3 points), and high-risk (4-6 points). The median survival in the low-risk group was significantly longer than those in the other two groups (34.9 [95% CI: 25.8-44.0] vs. 13.6 [95% CI: 11.3-15.9] vs. 8.0 [95% CI: 6.8-9.2] months; p &lt;0.001). The PATH score was fairly confirmed in the validation cohort and consistently performed better than other existing models in the training and validation cohorts. Conclusions: PATH score may be a simple and practical tool, which has good discrimination ability to screen HAIC sensitive populations and effectively predict individual survival outcomes. Calculation method of the PATH score.[Table: see text]
Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy
Authors: Yancheng Tang, Liming Wang, Tao Yi, Jun Xu, Jigang Wang, Jiang-Jiang Qin, Qilei Chen, Ka-Man Yip, Yihang Pan, Peng Hong, Yingying Lu, Han-Ming Shen, Hu-Biao Chen
Journal: Acta Pharmaceutica Sinica B (2021)

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal Magnolia officinalis. First, we found that magnolol induces mitochondrial depolarization, causes excessive mitochondrial fragmentation, and increases mitochondrial reactive oxygen species (mtROS). Second, magnolol induces PTEN-induced putative kinase protein 1 (PINK1)‒Parkin-mediated mitophagy through regulating two positive feedforward amplification loops. Third, magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis pathway. Moreover, magnolol prolongs the survival time of tumor-bearing mice. Finally, inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol's anticancer efficacy, both in vitro and in vivo. Altogether, our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis, whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol, suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.
Safety of same day HD-MTX with induction therapy for DLBCL with concurrent CNS disease or as prophylaxis for high risk of CNS relapse.
Authors: Brett Barlow, Haris Hatic, Charles Douglas Bodine, Amitkumar Mehta, Gaurav Goyal, Mayur Narkhede
Journal: Journal of Clinical Oncology (2021)

e19545 Background: High-dose methotrexate (HD-MTX) at a dose between 2.5 to 5 gm/m2 is commonly administered in conjunction with standard induction chemotherapy to patients with Diffuse Large B Cell Lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse, as defined by the Lymphoma International Prognostic Index (CNS-IPI). Optimal timing of HD-MTX in relation to induction chemotherapy is unknown. A recent study suggested that HD-MTX intercalated with R-CHOP cycles was associated with increased toxicity and treatment delays without improvement in survival or CNS relapse compared with end of treatment MTX (Wilson et al 2020). This retrospective study evaluates the toxicities and treatment delays associated with HD-MTX administered on day 1 of cycles of chemo-immunotherapy. Methods: This single center retrospective cohort study included 45 patients (pts) with DLBCL with concurrent CNS disease or at high risk of CNS relapse who received HD MTX on day 1 of chemo-immunotherapy at our center. Data was abstracted from chart review and included variables describing clinical and treatment characteristics, time to MTX clearance, toxicities experienced and treatment delays. Results: 31 pts received HD-MTX on the day of R-CHOP chemotherapy, 6 pts received HD-MTX on the day of R-EPOCH (Rituximab, Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, and Prednisone), and 8 pts received HD-MTX with R-MiniCHOP (dose reduced R-CHOP). Same day HD MTX with chemo-immunotherapy was associated with acute kidney injury (AKI; 17-25%), treatment delays &gt;7 days (13-17%), and grade 2 mucositis (11-50%). The burden of toxicities was numerically higher in patients treated with R-EPOCH vs. R-CHOP (Table). Clinical outcomes are summarized in table below. Conclusions: In our heterogeneous population of pts, we describe that the incidence of toxicities and treatment delays experienced with same day HD-MTX are higher with R-EPOCH than with R-CHOP. Comparative studies with intercalated or end of treatment MTX will determine if the incidence of treatment delays, toxicities and de-escalations are higher with same day HD-MTX administration. [Table: see text]
Clinicopathological characteristics of exceptional responders who achieve durable remissions beyond five years (DR5) in HER2+(H+) metastatic breast cancer (MBC).
Authors: Darko Skrobo, Naomi Walsh, Jose Berenguer, Janice Maria Walshe, Michaela Jane Higgins, David William Fennelly, Jo Ballot, Cecily Quinn, Giuseppe Gullo, John Crown
Journal: Journal of Clinical Oncology (2021)

1046 Background: The introduction of anti-H2 targeted therapies has resulted in substantially improved outcomes for patients (pts) with H+MBC, yet despite survival prolongation, most patients so-treated will still ultimately die from MBC. Some patients do however, achieved prolonged remissions. In this report we outline the long-term outcomes of patients with H+MBC who were treated in our institution, with at least five-year follow-up from the diagnosis of MBC. Methods: As part of our larger single-institution “Thousand Patient HER-2 Database”, we conducted a retrospective review of all patients in whom a diagnosis of H+MBC was made prior to December 2015 (range 2000-2015 years). The DR5 category included only those who had never experienced relapse or progression following initial anti-H2 therapy for MBC, and who were alive at 5 years. Patients were designated as (1) DR5, defined as never relapse with an overall survival (OS) &gt; 5 years; (2) nonDR, which included those who had no or shorter remission, but also included nine pts who did achieve a 5 year CR, but who subsequently relapsed. OS was calculated from the date of diagnosis of MBC. The frequency distribution was assessed by Fisher’s Exact Test or Chi-Square Test, as appropriate. OS and PFS were calculated according to Kaplan Meier method, and evaluated by Log-rank test. Univariate and multivariate Cox proportional hazards regression analysis was used to evaluate the effect of clinicopathological features on OS and PFS. Results: A total of 245 patients diagnosed with advanced H+MBC were identified. The median survival was 38 months, (range 0.3 – 248 months). Among these, 85 patients (35%) experienced an OS &gt; 5 years, with 34 designated as DR5. The median OS for DR5 was 117 months, whereas nonDR (n = 211) had median OS of 33 months. The median age was similar between groups (DR5 53 yrs vs nonDR 56 yrs). A higher incidence of visceral disease was present in nonDR compared to DR5 (69% vs 44%). Of all patients diagnosed with de novo H+MBC, 23% achieved DR5. Presence of visceral disease, number of metastases and site of metastases were statistically significant negative predictors of achieving DR5 (P &lt; 0.05). Presence of ER positive disease was not associated with OS. Conclusions: A meaningful subset of patients (14%) with advanced H+MBC achieve prolonged remission beyond five years with H2 targeted therapy. Nearly one quarter of those with de novo H+MBC achieve DR5. As de novo H+MBC now constitutes a higher proportion of all H+MBC than it did in the pre-trastuzumab era, an increasing proportion of H+MBC may now be achieving DR5. Prospective identification of variables to predict DR5 could assist in the stratification of patients for whom additional therapy is needed.
Disparate Use of Chemoradiation in Elderly Patients With Localized Anal Cancer
Authors: Eric D. Miller, Ansel P. Nalin, Dayssy A. Diaz Pardo, Andrea L. Arnett, Emily Huang, Alessandra C. Gasior, Pannaga Malalur, Hui-Zi Chen, Terence M. Williams, Jose G. Bazan
Journal: Journal of the National Comprehensive Cancer Network (2021)

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly among the elderly (age ≥65 years). We sought to compare patterns of care for the treatment of SCCA in elderly versus nonelderly patients.Data for patients with stages I-III SCCA diagnosed from 2004 through 2015 were obtained from the National Cancer Database. Patients were categorized as having received standard-of-care (SOC) chemoradiation (CRT) with multiagent chemotherapy, non-SOC therapy, palliative therapy, or no treatment. Differences in treatment groups were tested using the chi-square test. We used logistic regression to identify predictors of SOC CRT and multiagent versus single-agent chemotherapy in patients receiving CRT. Propensity score matching was used to compare overall survival (OS) in elderly patients receiving multiagent versus single-agent chemotherapy for those receiving CRT.We identified 9,156 elderly and 17,640 nonelderly patients. A lower proportion of elderly versus nonelderly patients (54.5% vs 65.0%; P<.0001) received SOC CRT than other treatments or no treatment. In multivariate analysis, elderly patients were 38% less likely than nonelderly patients to receive SOC CRT (odds ratio, 0.62; 95% CI, 0.58-0.65; P<.0001). A higher proportion of the elderly were treated with single-agent versus multiagent chemotherapy (16.9% vs 11.8%; P<.0001), which resulted in a >1.5-fold increase in the likelihood of elderly patients receiving single-agent chemotherapy (odds ratio, 1.52; 95% CI, 1.39-1.66) in multivariate analysis. After propensity score matching, 3-year OS was higher in elderly patients who received CRT with multiagent versus single-agent chemotherapy (77.1% vs 67.5%; hazard ratio, 0.78; 95% CI, 0.68-0.89; P=.0002).In this comprehensive study of patients with stages I-III SCCA, elderly patients were less likely than nonelderly patients to receive SOC CRT. The low proportion of elderly patients receiving SOC CRT with multiagent chemotherapy for localized anal cancer suggests that the optimal treatment approach for this vulnerable population remains undefined.
Long-term outcomes and predictors of recurrence in patients with early-stage node negative breast cancer.
Authors: Izzet Dogan, Esra Aydin, Nail Paksoy, Ferhat Ferhatoglu, Naziye Ak, Kamuran Ibis, Semen Onder, Mustafa Tukenmez, Neslihan Cabioglu, Mahmut Muslumanoglu, Pinar Saip, Adnan Aydiner
Journal: Journal of Clinical Oncology (2021)

e12597 Background: In this study, we aimed to assess the outcomes, and predictors of recurrence in patients with early-stage node-negative breast cancer. Methods: We evaluated data of the patients who were treated between 1988 and 2018 years retrospectively. Demographical, clinical, pathological, and treatment features of the patients were recorded. SPSS 25 version was used for statistical analysis. We used Kaplan-Meier and Cox regression analysis to assess survival analysis. Also, we performed logistic regression and ROC analysis for recurrence predictors. Results: In total, 347 patients were included in the study.The median age was 50 (range, 18-81) at diagnosis. The percent of the patients who had stage 1 and 2 were 86.6% and 13.4%, respectively. The most common histopathological type was invasive ductal carcinoma (71.6%). Estrogen receptor and progesterone receptor positivity were 80.3% and 62.1%, respectively. Her2 receptor positivity was 15.9%. The number of patients who had undergone lumpectomy and mastectomy was 85.5% and 14.5%, respectively. Sentinel lymph node biopsy was performed on 78.7% of the patients, and axillary lymph node dissection 21.3%. Also, the patients received adjuvant radiotherapy (88.7%), adjuvant chemotherapy (48.5%), and adjuvant hormonotherapy (82.1%). Tumor recurrence was occurred in 31 (8.7%) patients (local recurrence-45.2% and metastasis-54.8%). Five-, ten- and twenty-years recurrence ratios were 4.3%, 8%, and 23%. Also, contralateral breast cancer has occurred in 19 (5.3%) patients. During the study period, 30 (8.4%) patients died. Ten-years and twenty-years survival ratios were 91.6% and 76.6%, respectively. In univariate analysis, aged over 65 years (p = 0.004), nuclear pleomorphism (p = 0.049), mitosis (p = 0.003), and necrosis (p = 0.002) were statistically significant for recurrence. In ROC analysis, the tumor's longest size was not statistically significant for recurrence (for over 1.45 cm, p = 0.07). Conclusions: In this study, we determined thirty-years outcomes in patients with early-stage node-negative breast cancer. In the follow-up, we detected the recurrences ratios, between ten and twenty years, were more common than the first ten-years. Despite a small number of patients who had a recurrence, we showed that being age over 65 years and pathological features (nuclear pleomorphism, mitosis, and necrosis) were statistically significant for disease recurrence in univariate analysis.
Impact of universal health care on trends of incidence and mortality of cancers with screening recommendations in North America. A GLOBOCAN 2020 study.
Authors: Mounika Addula
Journal: Journal of Clinical Oncology (2021)

e18513 Background: Cancers with screening recommendations in general population include breast, colorectal, cervical and prostate cancers. Our study is aimed at comparing the current and future trends in incidence and mortality amongst two biggest countries in North America (United States of America and Canada) with and without universal health care. Methods: Incidence and mortality data, their trends were obtained from the GLOBOCAN 2020 database. Crude rate and age standardized rate (ASR) data on incidence and mortality was obtained to minimize population-based distribution errors. Age groups were divided as 20-40, 40-49, 50-65 and above 65. Current incidence, mortality and future trends were obtained for both USA and Canada and compared. Results: Breast cancer incidence is higher in USA in all age groups. Mortality in the age groups of 20-39 and 50-64 is comparable in Canada and USA with ASR of 9.6 (Canada), 9.5 (USA) 197.2 (Canada), 195 (USA) respectively. Future trends predict higher increase in incidence and mortality in Canada in age groups of 40-49 (I: Canada +22.5% USA +19.2%. M: Canada +22.8% USA +19.3%) above 65 (I: Canada +52.3% USA +40.8%. M: Canada +70.9%. USA +57.3%). In age group above 65 the mortality is significantly higher in USA compared to Canada (p=0.001). The incidence of colorectal cancer is higher in USA compared to Canada. The ASR mortality of above 65 age group is significantly higher in Canada (p=0.0009) (M: Canada: 835.6 USA: 713.9). Mortality trends for the 2040 year are higher in the age groups of 50-64 and above 65 in Canada (50-64 M: Canada: +25.9% USA: +21.2%) (above 65: M: Canada +70.9% USA: +57.3%). Prostate cancer has higher incidence in 50-64 age group. The mortality is higher in 40-49 age group. The predicted incidence for 2040 is also higher in Canada in above 65 age group (Canada +48.3%, USA: 39.9%). Similarly, mortality is higher in Canada for the above 65 age group (Canada: +112.7%, USA: +90.2%). Both USA and Canada have higher mortality for prostate cancer in age group 40-49 than 50-64. Cervical cancer incidence and mortality ASR are higher in USA for age groups of 20-39 and 40-49. For ages 50-64, while the incidence is higher in the USA, mortality is higher in Canada. For ages above 65 the mortality is significantly higher in Canada (p=0.0022) compared to USA. The predicted percentage change in 2040, incidence and mortality of age group 40-49 is higher compared to 50-64. Conclusions: Though both health care systems have screening recommendations for breast, CRC, prostate and cervical cancers, mortality appears to be higher compared to the world population suggesting need for improvement in screening access/awareness. Younger adults (20-39) and middle age adults (40-49) appear to be more vulnerable population and need for improvement in identifying high risk population.
Abstract 15858: Exploring Novel Risk Factors in Hypertrophic Cardiomyopathy Sudden Cardiac Death Risk Stratification
Authors: Kristin Boulier, David Hsu, Matthew T Wheeler
Journal: Circulation (2019)

Introduction: Sudden cardiac death has been extensively studied in hypertrophic cardiomyopathy. The current ACC/AHA recommendation is to consider primary prevention ICD in anyone with one or more r...