tbuckley/cabot-search huggingface dataset:
Treatment of advanced mucosal melanoma in the immunotherapy era: A joint institutional case series.
Authors: Abigail Gee, Hannah Taylor, Christopher Herbert, Tania Tillett, Helen Winter
Journal: Journal of Clinical Oncology (2021)

e21503 Background: Treatment pathways for malignant melanoma have changed dramatically in recent years, with the advent of immunotherapy. Mucosal melanoma is a rare subtype, representing 1-2% of melanomas in Caucasians, with higher incidence reported in other populations. They commonly present at an advanced stage due to their occult, UV naïve location. Rarity limits adequate trial exposure and the literature offers contradictory data on the benefits of immune checkpoint inhibitor (ICI) therapy in this group. Methods: Patient databases at two specialised treatment centres were searched to identify all patients with mucosal melanoma treated with ICI therapy between 01.10.15 and 30.09.19. All patients were reviewed at the regional multi-disciplinary team meeting. Patient demographics, pathology reports, mutation status, stage at start of treatment and prior treatment modalities were noted. Results: Ten patients were identified with a median age 73 years (range 32-80) and M:F ratio of 4:6. The site of the primary cancer was head and neck in 5 cases, gastrointestinal in 3 cases and genitourinary in 2 cases. All patients were BRAF wild type. C-Kit was wild type in 3 patients tested. The median number of cycles of first line ICI was 5.5 (range 1 – 45). At first radiological assessment 7 patients had progressive disease (PD), 2 patients had stable disease and one patient had a complete response (CR). Two patients progressed to second line therapy with a second ICI. One of these demonstrated a partial response after a further 9 months of treatment and had a progression-free survival (PFS) of 30.1 months on second line treatment. One patient received 3 cycles of dual ICI therapy (ipilimumab/nivolumab) but demonstrated PD after 1.5 months. The longest surviving patient currently has a PFS of 43 months. He achieved a CR after just 3 months of pembrolizumab and completed a total of 18 cycles before switching to surveillance. Conclusions: The joint institutional case series demonstrates a poor response to ICI therapy in the majority of patients, yet as commonly reported, response when it occurs can be remarkable. Recent studies have shown increased overall response rate when anti-vascular endothelial growth factor therapies are added to cytotoxics or ICI. Further investigation of this rare subtype is required to identify predictive biomarkers of response to ICI therapy and other targeted and combination treatments.
Somatic and germline mutation profiles of Chinese young colorectal cancer patients.
Authors: Hongxia Li, Qianqian Duan, Yuan Tan
Journal: Journal of Clinical Oncology (2021)

e15522 Background: In recently years, although CRC morbidity and mortality can be mitigated through appropriate screening and surveillance, the incidence rate of colorectal cancer (CRC) younger than 50 years old increased annually. Limited studies have investigated the underpinnings driving CRC development in Chinese younger population. In our study, we aim to explore the comprehensive mutational profile of Chinese CRC patients old (＞50) and young (≤50) diagnosed with CRC. Methods: Targeted sequencing with a 539 cancer-related genes panel was performed on 235 patients diagnosed with CRC. We investigate the landscape and difference of old and young CRC somatic and germline mutations in our Chinese cohort and compare with TCGA CRC cohort (N = 592). Results: Analysis revealed an overall 20.9% (49/235) mutation detection rate of young CRC in our Chinese cohort, which is higher than TCGA cohort (13.9%, 82/592). In our cohort, all Chinese young CRC patients can detect mutation and median mutation count is 10 mutations which is similar to old CRC patients (11 mutations). Comparing high frequency somatic mutations (young group with top 20), we found that BRCA2 mutation in young CRC group is significantly higher than old group (18.4% vs 7.0%, P = 0.025). In TCGA cohort, there is no difference between two groups with top 20 mutations and frequency of BRCA2 is 13.4% (11/82) in young CRC. For germline mutation, 12.29% (29/236) patients in our Chinese cohort harbored pathogenic and likely pathogenic (P/LP) germline mutations and 24.1% (7/29) CRC with P/LP germline mutations is young patients. In these seven P/LP mutation young patients, three patients have MMR gene mutation, two patients harbor ATM mutation, one patient has APC and another has SLX4 mutation. Moreover, young CRC have higher frequency MSI-H than old CRC patients (28.6% vs 18.2%). Conclusions: Our study has identified that young CRC patients account for a higher proportion in Chinese population and BRAC2 mutation may be an important factor in the early development of colorectal tumors in younger patients. In addition, our results also support the role of MSI statues in tumor oncogenesis in Chinese patients with early-onset CRC, indicating the need to include a more comprehensive germline mutation and genetic screening in our population.
Immune related biomarkers in biliary tract cancers (BTC).
Authors: Zoya Sandhu, Jorge Sanchez-Garcia, Tyler Barker, Sharanya Raghunath, Katherine Shortt, Su-Ho Hwang, Gail Fulde, Ivan R Zendejas-Ruiz, Derrick S. Haslem, Timothy Joseph Yeatman, Ramya Thota
Journal: Journal of Clinical Oncology (2021)

e16191 Background: Biliary tract cancers are aggressive tumors with limited treatment options. Several ongoing clinical trials are currently exploring role of immune therapy in advanced BTC. Programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), and microsatellite instability (MSI) are commonly used immune related-biomarkers. Herein, we analyzed the TMB, MSI and PD-L1 expression in advanced BTC. Methods: We retrospectively evaluated the association of TMB, MSI and PD-L1 expression with survival and related treatment outcomes. Results: The immune mediated biomarkers were reported in a total of 62 BTC patients (pts). The mean age of the pts is 73 (range 32-83) years, with predominant females (59%) and Caucasians (82%). The most common histology noted was intrahepatic cholangiocarcinoma (67%) followed by extrahepatic cholangiocarcinoma (18%) and gallbladder carcinoma (15%). Approximately, 40% received 2 or more lines of therapy while 20% of patients didn’t receive any treatment and over. The treatment regimen included gemcitabine-based regimen (35%), 5FU based regimen (18%), immune therapy (15%) and targeted therapy (6%). The TMB was low in 52 pts (83%), intermediate 7 pts (11%) and high in 2 pts (3%). MSI is stable in 55 pts (89%) and PD-L1 expression is negative in 29 pts (47%) and positive in 23 pts (37%). Conclusions: Our data suggests the BTC’s have in general low TMB, are microsatellite stable and have low PD-L1 expression. The potential prognostic and predictive value of these immune related- biomarkers need to be validated in larger studies.
A nomogram to predict the value of mammary adipose index (MAI) for prediction of response to neoadjuvant chemotherapy in breast cancer patients.
Authors: Wenxiu Xu, Jinhai Tang
Journal: Journal of Clinical Oncology (2021)

e12607 Background: Breast cancer (BCa) is the most common malignancy in females on a global scale. Neoadjuvant chemotherapy (NACT) is a promising therapeutic approach for the treatment of locally advanced BCa, which result in primary tumor regression and optimal surgical planning. Cumulative evidence has identified a deleterious crosstalk between cancer cells and the surrounding mammary adipose tissue during tumor progression. Mammary adipose index (MAI) is a novel indicator defined by us, which represents the percentage of adipose tissue in breast. Therefore, this study aims to investigate the correlation between MAI and NACT efficacy of BCa by establishing an intuitive nomogram. Methods: Clinical data of 221 BCa patients who received NACT at the First Affiliated Hospital of Nanjing Medical University from January 1, 2018 to May 31, 2020 were retrospectively collected. Besides, patients were divided into major histological response and non-major histological response group in line with Miller-Payne pathology grading. The level of MAI was collected from magnetic resonance imaging of breast, and was divided into two groups according to the cut-off value. The level of MAI and clinicopathological characteristics were collected to assess the predictive roles of NACT response. Univariate analysis was performed by Chi-square test or Fisher’s exact test. Indicators with P &lt; 0.05 were included in multivariate binary logistic regression analysis. The nomogram was constructed based on results of multivariate logistic analysis. The predictive accuracy and discriminative ability were evaluated by C-index and the calibration curve. Results: Among the 221 patients enrolled, 77 cases (34.84%) were represented by major responses of pathologic histology. In univariate analysis, the level of MAI, tumor size, node status, ER status, PR status HER-2 status and Ki-67 status were correlated with NACT. Multivariate Logistic regression analysis showed that tumor size, HER-2 status and the level of MAI were independent influencing factors for the response to NACT in BCa patients. The patients with a high level of MAI (≥0.6916) were more likely to have a worse NACT response. MAI was an independent predictor for NACT efficacy, and area under the curve of ROC, specificity and sensitivity of the predictive model were 0.805, 0.632 and 0.774 respectively. The nomogram established based on these factors showed its discriminatory ability, and the C-index for prediction was 0.881. The calibration curve indicated that the predictive ability of the nomogram was a good fit to actual observation. The difference was statistically significant (P &lt; 0.05). Conclusions: The nomogram constructed in the present study indicated that the level of MAI could predict the efficacy of NACT in BCa patients, which might provide clinical guidance for the selection of appropriate treatment decisions.
Phase II clinical trial using anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) consolidation therapy for HER2 negative (0–2+) metastatic breast cancer
Authors: Lawrence G. Lum, Zaid Al-Kadhimi, Abhinav Deol, Vidya Kondadasula, Dana Schalk, Elyse Tomashewski, Patricia Steele, Kristie Fields, Melissa Giroux, Qin Liu, Lawrence Flaherty, Michael Simon, Archana Thakur
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Metastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2–4 months with the secondary endpoints of increasing overall survival (OS) and immune responses. Methods HER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks. Results This phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6–21.8) and 8.6 (3.3–17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th 1 cytokines, Th 2 cytokines, and chemokines after HER2 BATs infusions. Conclusions In heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.
Less is more: Postoperative pain management using restrictive opioid protocols in all surgical services in a comprehensive cancer center.
Authors: Jason Ricciuti, Steven Gallo, Deanna Argentieri, Paul Visco, Kristopher Attwood, Wenyan Ji, Andrew J. Fabiano, Mark Hennon, Eric Kauffman, Kimberly Wooten, Jessica S. Young, Steven J. Nurkin, Oscar de Leon-Casasola, Emese Zsiros
Journal: Journal of Clinical Oncology (2021)

103 Background: Opioids are routinely given for postoperative pain management with limited evidence on the amount needed to be dispensed. Prescribed opioids increase the risk of chronic use, abuse, and diversion, which contribute to the opioid epidemic. We sought to demonstrate that postsurgical acute pain can be effectively managed across different surgical specialties with a markedly reduced number of opioids. Methods: A prospective case-control study of restrictive opioid prescription protocol (ROPP) was implemented in all surgical services from February 2019 through July 2019 at a tertiary comprehensive cancer center for all patients undergoing a surgery for which opioids would be routinely prescribed at discharge (n = 2,015). Data from surgeries performed by the same services from August 2018 through January 2019 were used for comparison (n = 2,051). At discharge, patients did not routinely receive opioids unless they had a maximally invasive procedure or if they required multiple doses of opioids during hospitalization (maximum 3-day supply). Compliance with the protocol was tracked by pharmacists daily. Patient demographics and surgical details were collected. State-run opioid prescription database was used to determine the number of opioids prescribed to all surgical patients within a 120-day surgical window. Validated patient satisfaction surveys were used at postoperative visits to assess patient experience. Results: After implementation of the ROPP, 45% less opioids were prescribed after surgery for all participating patients (323,674 morphine milligram equivalents (MME) vs 179,458 MME, p &lt; 0.001). The majority of services complied with the ROPP in more than 95% of cases. There was no difference in postsurgical pain intensity between cohorts. Patients in the ROPP cohort had less refill requests compared to the control group (20.9% vs 17.9%, p value = 0.016). Surveys were completed by 338 patients in the control group (16.5%) and 360 in the ROPP group (17.9%). There was no significant difference in patient reported satisfaction with postoperative pain control or on the impact of pain on daily activities between the cohorts. Conclusions: Implementation of a ROPP by multiple surgical services at a tertiary cancer center was feasible and resulted in substantial decrease in the number of opioids prescribed while not compromising patient experience. Patients did not require more prescription refills despite being provided no opioids or a limited supply. This study provides evidence to support reducing the number of opioids routinely prescribed after surgery.[Table: see text]
Prevalence and risk factors for vasomotor symptoms in Hispanic female breast cancer survivors, 0-3 years post-treatment: Results of a single-center retrospective analysis.
Authors: Lisellet Morin, Noah Zanville, Rosalind Guest, Muni Rubens, M. Beatriz Currier
Journal: Journal of Clinical Oncology (2021)

e24038 Background: Early detection and a growing complement of treatment options have led to improved survival among women with breast cancer in the U.S. Vasomotor symptoms (VMS) such as hot flashes and night sweats are among the most common side effects reported by breast cancer survivors (BCS) following treatment. These symptoms may affect quality of life and increase the risk of non-adherence to anti-hormonal therapies. Hispanics are one of the fastest growing ethnic populations in the U.S. However, research exploring whether Hispanic BCS report VMS at similar rates as their non-Hispanic counterparts remains an important gap in the science. The purpose of this study was to compare the prevalence and risk factors for VMS between Hispanic and non-Hispanic BCS following cancer treatment. Methods: Data for this single-center, retrospective study came from a database of self-reported symptom data collected at survivorship visits. Results: Over a 2.8-year period, 815 female BCS were evaluated for VMS (Hispanic: 63.0% (n=513) vs. Non-Hispanic: 37.0% (n = 302)). Mean age of the sample was 58.4 + 11.7 (range 24.2 - 91.8).Approximately four in ten (42.9%) BCS reported VMS at their initial survivorship visit, 0-3 years post-treatment. Results found virtually no difference in VMS prevalence between Hispanic and non-Hispanic BCS, (42.5% vs 43.7%, p = 0.735). BCS who reported VMS after treatment were 6.5 years younger, on average, than BCS who did not report VMS (54.7 ±11.0 vs. 61.2 ±11.3, p &lt; 0.001). Multivariate logistic regression models using age, race, stage of cancer, chemotherapy, radiation and hormone therapy as predictors showed that only age was associated with reporting VMS. For every one-year increase in age, the odds of reporting VMS fell by approximately 5.3% (OR: 0.947, 95% CI: 0.933-0.963, p &lt; 0.0001). Conclusions: Results found no difference in VMS prevalence between Hispanic and non-Hispanic BCS. VMS were reported by over 40 % of BCS in the study. In addition, symptoms were more prevalent in younger BCS. Given the potential impact of VMS on quality of life and mediation adherence, studies validating these findings as well as exploring the prevalence and risk factors for VMS in Hispanic BCS from distinct nationalities and cultures are needed.
Feasibility of RECIST-based real-world tumor response assessment in metastatic non-small cell lung cancer patients.
Authors: Nguyet Tran, Alan Fu, Monika A. Izano, Liz Toland, Ryan Hilbelink, Huakang Tu, Hil Hsu, Chris Sommers, Matthew J. Rioth, Thomas D. Brown
Journal: Journal of Clinical Oncology (2021)

e21121 Background: Treatment response to anti-cancer therapies for advanced lung cancer is usually assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), which is not generally applied in real-world settings. With real-world evidence increasingly being used to support promising treatment, this study evaluated the feasibility of assessing real-world lung cancer response by RECIST-based measurement of lesions on archived radiologic films and assessed its concordance with treatment response based on oncologist narratives in electronic health record (EHR). Methods: This retrospective study included 30 randomly selected metastatic non-small cell lung cancer (mNSCLC) patients diagnosed between January 2015 and December 2019 from the Syapse Learning Health Network of US community health systems. Eligible patients were ≥18 years, histologically confirmed mNSCLC; no other malignancy within 2 years prior to diagnosis; initiated index systemic treatment subsequent to progression on a platinum or anti-PD(L)-1-containing therapy; and had a baseline scan followed by at least one additional scan during the index period. Patients were followed from the initiation of index treatment until the initiation of a post-index line of treatment, death, or date of last contact, whichever occurred first. Tumor response was established using response documented in the medical oncologists’ narratives and compared to a radiologist’s assessment of archived images using RECIST v1.1 criteria. Best overall response was characterized as complete or partial response (CR/PR), stable disease (SD), progressive disease (PD), and not evaluable (NE). Results: The median age at mNSCLC diagnosis was 62 years; 22/30 (73%) were male; 28/30 (93%) were White and 2/30 (7%) were Black. Of the 22/30 (73%) patients with a documented Eastern Cooperative Oncology Group performance status, 21 (95%) had a status of 0 or 1. Patients had a median of 8 months follow-up with the majority surviving (63%) until the end of study. Table shows good concordance of best overall response between medical oncologist-reported and radiologist re-assessed responses; CR/PR was 67%, SD 79% and PD 80%. Causes of discordance were lack of CR/PR confirmation in medical oncologists’ narratives, absence of narratives, or presence of clinical symptoms. Conclusions: This study is an important step in demonstrating the potential to approximate real-world RECIST-based treatment response using EHR abstraction of oncologists’ documentation. Future studies should validate this approach, and improve upon it, by exploring additional real-world data elements as surrogates for clinically relevant responses to anti-cancer therapies. [Table: see text]
Delayed Large Local Reactions to mRNA Covid-19 Vaccines in Blacks, Indigenous Persons, and People of Color
Authors: Upeka Samarakoon, Santiago Alvarez-Arango, Kimberly G Blumenthal
Journal: New England Journal of Medicine (2021)

ing, Covid-19 had not developed in any of the patients after they received the three vaccine doses.No serious adverse events were reported after the administration of the third dose, and no acute rejection episodes occurred.This study showed that administration of a third dose of the BNT162b2 vaccine to solidorgan transplant recipients significantly improved the immunogenicity of the vaccine, with no cases of Covid-19 reported in any of the patients.However, a large proportion of the patients remain at risk for Covid-19.Barrier measures should be maintained, and vaccination of the relatives of these patients should be encouraged.