tbuckley/cabot-search huggingface dataset:
An internal review of chemotherapy toxicities in patients with pancreatic cancer.
Authors: Karthik Shankar, Deanna Huffman, Chelsea Peterson, Khaled Alhamad, Thejus Thayyil Jayakrishnan, Abraham Attah Attah, Nada Alrifai, Nkechi Onokwai, Adriani Cherico, Palash Asawa, Pragnan Kancharla, Srividya Srinivasamaharaj, Yazan Samhouri, Saleha Rizwan, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2021)

e16258 Background: Cytotoxic chemotherapy remains the standard of care in the treatment of pancreatic ductal adenocarcinoma (PDAC). There is more excitement in the last few years regarding the use of neoadjuvant chemotherapy even when the disease is resectable. In this analysis, we sought to study the different regimens used in our institutions, in regards to setting and toxicity. Methods: We retrospectively reviewed all patients diagnosed with pancreatic adenocarcinoma at Allegheny General Hospital between 2009-2020. Data was extracted from electronic medical records and de-identified. Institutional Review Board approval was obtained. Descriptive analysis was undertaken and multivariate analysis was performed to compare differences in the prevalence of toxicity across the regimens and demographics using Stata version 16. The primary outcome was the rate of toxicity that prompted dose adjustment, stratified by the setting chemotherapy was administered (neoadjuvant, adjuvant, or palliative). Results: Of the 121 patients studied, 88 patients received chemotherapy. Median age was 69 years. 66 patients (55%) were females. 40 patients suffered from adverse effects requiring a dose adjustment. 85% of the adverse effects occurred in Caucasians. 15 out of 37 patients (42.9%) who received Folfirinox, 15 out of 31 patients (48.4%) who received gemcitabine and nab-paclitaxel, 6 out of 10 patients (60.0%) who received gemcitabine and capecitabine, 3 out of 4 patients (75.0%) who received gemcitabine monotherapy required dose adjustment (table). Folfirinox and gemcitabine with nab-paclitaxel were statistically compared and found to be not significant (p-value=0.12). No significant impacts of race, gender, or age were noted in a multivariate model. Conclusions: Approximately 42% of patients receiving chemotherapy suffered from toxicities that required dose adjustments. We found a trend toward more use of neoadjuvant chemotherapy in resectable PDAC with a similar toxicity rate compared with other settings.[Table: see text]
Closing the gap: Trends in inconclusive rates on hereditary cancer testing across racial/ethnic groups.
Authors: Foluso Olabisi Ademuyiwa, Carrie Horton, Holly LaDuca, Timothy Komala, Jessica Profato, Tina Pesaran, Fergus Couch
Journal: Journal of Clinical Oncology (2021)

10525 Background: Several groups have described disparities in genetic test results for inherited breast cancer predisposition, with a disproportionate number of variants of unknown significance (VUS) reported in non-Caucasian individuals. These disparities are due in part to the underrepresentation of non-Caucasians in reference databases and clinical genetic testing cohorts. Over the past few years, diversification efforts have been made however, little data exists on how ethnicity- and gene-specific VUS rates have changed over time and whether such disparities have improved or worsened. Methods: We retrospectively reviewed demographic information and test results for individuals who underwent hereditary cancer multigene panel testing between March 2012 and September 2020 at a single laboratory. Individuals who self-reported as African American, Asian, Caucasian, or Hispanic on the test requisition form and whose testing included ATM, BRCA1, BRCA2, CHEK2 and PALB2 (five commonly tested breast cancer predisposition genes with management guidelines) were included in the study (n = 284,130). The frequency of germline variants of unknown significance (VUS) in the five genes was assessed in September 2015 and September 2020. Results: Amongst patients tested between March 2012 and September 2015, 82.8% of the study cohort self-reported as Caucasian and 17.2% were not Caucasian (6.5% African American, 6.0% Hispanic, and 4.6% Asian). The proportion of non-Caucasian individuals in the study cohort increased slightly by September 2020 to 22.8% (77.2% Caucasian, 9.2% African American, 8.4% Hispanic, and 5.3% Asian). Consistent with previous reports, Caucasians had the lowest VUS rate overall in both 2015 and 2020. This was also true at the individual gene level, with the exception of CHEK2. Over time, we observed a relative decrease in VUS rates across all ethnicities. Between 2015 and 2020, the overall VUS rate for the five included genes in non-Caucasian individuals was reduced by 32.0% in non-Caucasians compared to 23.6% in Caucasians. The absolute difference in VUS rate between non-Caucasians and Caucasians decreased from 7.9% in 2015 to 4.5% in 2020. Conclusions: While VUS rates for commonly tested breast cancer predisposition genes remain higher in non-Caucasians relative to Caucasians, our results demonstrate that this gap has been reduced over a five-year time period. These findings may be indicative of efforts by clinicians and laboratories to reduce these disparities. Further studies are necessary to improve the clinical utility of genetic testing in under-represented populations.[Table: see text]
Patterns of knowledge and use of medical cannabis among Brazilian oncologists and palliative care physicians.
Authors: Júlia Maria Mathias Pedreira de Freitas, Daniela Oliveira de Almeida, Luciana Castro G. Landeiro, Tércia Vilasboas Reis, Thomas Azevedo de Carmo, Clarissa Mathias
Journal: Journal of Clinical Oncology (2021)

e24099 Background: Medical cannabis (MC) emerged as an important complementary therapy in the context of oncological diseases. In 2019, the Brazilian Health Regulatory Agency (Anvisa) approved use of MC, which can be produced in the country and sold in pharmacies under medical prescription. Previous investigations have extensively correlated MC effectiveness, over management and support of symptoms caused by the disease and/ or its treatment. However, studies evaluating knowledge and patterns of MC use in oncology patients MC are lacking. In the present study, we assessed the perception of oncologists and palliative care physicians on MC as a complementary therapy for cancer patients, and their personal experiences in clinical practice in Brazil. Methods: In October 2020 an online survey was sent via e-mail by the Brazilian Society of Clinical Oncology and the National Academy of Palliative Care for physicians with expertise in oncology and/or palliative care. Outcomes measured included knowledge and opinions about MC, prescription experience and impressions about the Brazilian legislation. Data analysis was performed with descriptive statistics, comparison tests and the Poisson regression model with robust variance, using the IBM Statistical Package for the Social Sciences software, version 25. Results: A total of 124 physician participated in the study and, of those, 58.1% were oncologists, and 82.3% believed that MC has application as a complementary therapy in cancer. In contrast, only 52.4% of the participants felt comfortable recommending its use and only 15.3% have ever prescribed MC for their patients with cancer. Further, among those who have never prescribed, 71% have already referred patients to other professionals to prescribe, and 61% indicated lack of knowledge as the main factor for not prescribing. In addition, more than half of participants claimed not knowing Brazilian legislation regarding MC use. Nausea and vomiting were mentioned by 73.4% of physicians as the major indication for MC. Conclusions: Oncologists and palliative care physicians agree with the applicability of MC use for the management of symptoms related with or caused by cancer. However, our findings infer that factors such as lack of knowledge, legislation barriers and lack of robust scientific evidence, lead to its limited use among Brazilian oncologists and palliative care physicians.
Standardization of fertility preservation discussion amongst pediatric oncology and bone marrow transplant patients.
Authors: Chandni Dargan, Sarah Mc Dermott, Shelby Chesbro, Joy M. Fulbright
Journal: Journal of Clinical Oncology (2021)

10051 Background: As treatment for pediatric malignancies improves long term survival, physicians are shifting focus to late effects of therapy such as infertility. Currently, options for fertility preservation include cryopreservation of mature oocytes, sperm, and gonadal tissue, although barriers remain present. Within our division, we lacked a standard approach to discussing fertility preservation options. Methods: Records from 474 pediatric patients with new oncologic diagnoses at CMH from 2014-2020 were retrospectively reviewed. We evaluated the frequency that reproductive health discussions were documented in pubertal males and females requiring chemotherapy or radiation treatment. We implemented a standard fertility preservation note and patient handouts, then surveyed our department to identify diagnoses that place patients at risk for infertility and barriers to formalized fertility consultations. We then provided educational sessions to address these barriers with pre- and post-evaluation to measure efficacy. Our longitudinal assessment, encompassing multiple points of intervention, was compared to results from previous chart review (2010-2013). Results: Of 474 patients diagnosed between 2014-2020, 175 (90 females, 85 males) warranted a fertility discussion per inclusion criteria. 61 (67.8%) females received a fertility discussion and of those 8 (8.9%) completed oocyte or gonadal tissue preservation, all between 2017-2020. 52 (61.2%) males received a fertility discussion and 20 (23.5%) completed sperm cryopreservation, with even distribution pattern between 2014-2020. Following implementation of an electronic fertility consult process and standardized fertility preservation documentation, there was an increase in documented fertility discussions from 30% in 2014 to 63.6% in 2020. Internal department survey responses identified a lack of comfort with knowing fertility preservation options available and diagnoses that should prompt this conversation. Education sessions with pre- and post-provider assessment demonstrated more comfort discussing fertility preservation (average score increase from 3.44 to 4.33) and knowledge regarding diagnoses at higher risk of infertility (average score increase from 3.67 to 4.33). Conclusions: Integration of a standardized fertility preservation process and addressing barriers identified within our division have led to a 33.6% increase in fertility discussions over the last 6 years. While the data shows a promising increase in oocyte and ovarian tissue preservation, sperm banking completion rates remained unchanged. Further steps include incorporation of an automated fertility consultation order into electronic chemotherapy orders, hospital-wide identification of other high-risk patient populations, and continued education of patient, families, and the health care team.
Histone deacetylase inhibitors for cardiovascular conditions and healthy longevity
Authors: João Pedro Ferreira, Bertram Pitt, Faiez Zannad
Journal: The Lancet Healthy Longevity (2021)

Histone deacetylase inhibitors (HDACi) regulate gene expression via epigenetic mechanisms. Accumulating evidence suggests that HDACi exert antiproliferative, antioxidant, antineoplastic, and proapoptotic effects through epigenetic mechanisms. Furthermore, HDACi also exert antithrombotic and antifibrotic effects through regulation of thrombotic and fibrotic transduction mechanisms. One of the oldest HDACi is valproic acid, which was first synthesised in 1882. After the discovery of its anticonvulsant properties for the treatment of epilepsy, the use of valproic acid was extended to other conditions, such as bipolar disorder and migraine. Given the accumulating evidence supporting the role of HDACi in the treatment of multiple medical conditions beyond epilepsy, the interest in novel potential indications for HDACi has been renewed. Considering the pleotropic epigenetic effects of HDACi, future studies could assess their efficacy and safety for cardiovascular disease prevention and treatment; treatment of venous thrombosis, Alzheimer's disease, autoimmune and proinflammatory conditions, chronic thromboembolic pulmonary hypertension, and pulmonary arterial hypertension; and as a coadjuvant therapy for cancer. Adequately designed and powered clinical trials are required to assess the efficacy and safety of HDACi before their clinical repurposing.
Rate of seroconversion for routine vaccinations in patients with chronic lymphocytic leukemia on ibrutinib.
Authors: Mohammad Ammad Ud Din, Saad Jamshed
Journal: Journal of Clinical Oncology (2021)

e19509 Background: It is unclear whether Bruton tyrosine kinase inhibitors (BTKi) contribute to the humoral dysfunction in chronic lymphocytic leukemia. Methods: A literature search of PubMed, EmCare, and Google Scholar was performed on December 5, 2020. Five studies met inclusion criteria out of 249 studies per PRISMA guidelines (n = 244). Results: Pleyer et al. and Zent et al. showed an adequate recall humoral response to the shingle vaccine (41.5% and 75% seroconversion rate respectively), however, de novo response to hepatitis B vaccine was greatly reduced. Conflicting results were seen for the influenza vaccine as Sun et al. showed a significant increase in post-vaccination geometric mean titers for all three strains while only 7% of patients demonstrated seroconversion in the study by Douglas et al. None of the patients responded to the pneumococcal conjugate vaccine in a study by Andrick et al, though the results were not statistically significant (p = 0.029) (Table). Conclusions: Treatment with BTKi may not cause significant detrimental response to immunization but further studies are needed to elucidate longterm effects especially in patients with prior exposure to anti-CD20 antibodies.[Table: see text]
Comparison of fusions detection by next generation sequencing between malignant pleural effusion and tumor tissue in lung cancer.
Authors: Yurong Xu, Yingxue Qi, Ningning Luo, Qin Zhang, Yaqing Wu, Chuang Qi
Journal: Journal of Clinical Oncology (2021)

e21059 Background: Anaplastic lymphoma kinase ( ALK), c-ros oncogene 1 receptor tyrosine kinase ( ROS1), ret proto-oncogene ( RET) and neurotrophic receptor kinase ( NTRK) are important driver genes in lung cancer. Each of these four genes fusions as therapeutic targets have been recommended by the national comprehensive cancer network (NCCN) guidelines for non-small cell lung cancer (NSCLC). Malignant pleural effusion (MPE) is observed in multy types of malignancies, especially in lung cancer. Studies have indicated that next generation sequencing (NGS) detection of somatic mutations by MPE is reliable. Nevertheless, the distribution and comparison of fusions in lung cancer between malignant pleural effusion and tumor tissue specimen have not been well characterized yet. Methods: In this study, 9-gene, 69-gene and 539-gene panel NGS profiling were performed by MPE and tumor tissue in 640 and 10013 patients with lung cancer respectively. The variation analysis between patients with or without gene fusion in different sample groups were calculated by fisher exact test via SPSS v26.0. Results: In lung cancer patients using MPE detection, 59 of 640 (9.22%) were found harboring at least one of the four gene fusions, and the ratio of ALK, ROS1, RET and NTRK fusion was 6.25% (40/640), 1.41% (9/640), 0.63% (4/640) and 0.47% (3/640) respectively. Meanwhile, we found gene fusions in 6.25% (626/10013) lung cancer patients using tumor tissue detection, including 3.66% (366/10013) ALK fusion, 1.07% (107/10013) ROS1 fusion, 1.09% (108/10013) RET fusion and 0.22% (626/10013) NTRK fusion. Significant differences of gene fusion frequency between different sample groups were found via fisher exact test ( p = 0.005), especially ALK fusion ( p = 0.001). Conclusions: The frequency of fusion in MPE was significantly higher than in tumor tissue, especially ALK fusion. However, as a retrospective study, the conclusions and the specific mechanisms are needed to be verified.
Neoadjuvant camrelizumab combined with chemotherapy and apatinib for locally advanced thoracic esophageal squamous cell carcinoma (ESCC): A single-arm, open-label, phase Ib study.
Authors: Zhen Wang
Journal: Journal of Clinical Oncology (2021)

4047 Background: Neoadjuvant therapy with PD-1 blockade plus chemotherapy has been found to be effective in the first-line treatment of advanced esophageal cancer. However, evidence of PD-1 blockade combined with chemotherapy as neoadjuvant treatment is limited. This study was designed to investigate the safety and efficacy of camrelizumab, a PD-1 blockade combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: A regiment of 2–4 cycles of neoadjuvant camrelizumab (200 mg, intravenous, day 1), nab-paclitaxel (150 mg/m 2 , intravenous, day 1), nedaplatin (50 mg/m 2 , intravenous, day 1), and apatinib (250 mg, orally, day 2–4) was given to the treatment-naive patients with resectable locally advanced ESCC. The treatments were repeated every 14 days. In this study, six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment, and then 24 patients received four cycles of neoadjuvant therapy, followed by esophagectomy after 4–8 weeks. The primary end points were safety and feasibility. The secondary end points were the rate of major pathologic response (MPR) and pathologic complete response rate (pCR). Results: A total of 30 patients were enrolled, among them, five patients received two planned cycles of neoadjuvant therapy, and one patient missed the second cycle of therapy due to grade 3 ALT elevations. Further, all other 24 patients received four planned cycles of neoadjuvant therapy. A total of 11 patients (11/30, 36.7%) experienced grade 3 neoadjuvant treatment-related adverse events (TRAEs). No grade 4 and grade 5 TRAEs were reported. The most frequent grade 3 TRAEs was neutropenia (7/30, 23.3%). Twenty-nine patients underwent minimally invasive esophagectomy (McKeown procedure) after neoadjuvant therapy. The reason for not undergoing surgery was due to bone metastasis. There were five treatment-related surgical delays that were caused by adverse reactions (hyperglycemia, arthritis, anemia, leukopenia, capillary endothelial proliferation in oral mucosa). Among the 29 patients undergoing esophagectomy, 15 patients (15/29, 51.7%) achieved MPR, including 7 patients with pCR (7/29, 24.1%). Among the 24 patients who received four cycles of neoadjuvant treatment, there were 7 patients with pCR (7/24, 29.2%), and 14 patients with MPR (14/24, 58.3%). No surgery related mortality was documented. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy plus apatinib is a safe and tolerable treatment for patients with locally advanced ESCC, and the MPR and pCR rate are promising. Clinical trial information: ChiCTR1900023880.
Retrospective pilot study of regorafenib combined with ICIs in the third-line treatment of advanced colorectal cancer.
Authors: Hangyu Zhang, Yi Zheng, Zhou Tong, Lulu Liu, Xudong Zhu, Qihan Fu, Xuanwen Bao, Xiaomeng Dai, Weijia Fang, Peng Zhao
Journal: Journal of Clinical Oncology (2021)

e15582 Background: An increasing number of patients with advanced colorectal cancer tend to receive third-line treatment. Although there are several treatment options, concerns about efficacy and adverse events still remained. Regorafenib seems to enhance the effect of immune checkpoint inhibitors (ICIs) by modulate tumor microenvironment. In the absence of stage III clinical trial data, the real-world study might show certain clinical value. Methods: From Aug 2019 to June 2020, 23 advanced MSS colorectal cancer patients underwent third-line treatment of regorafenib combined with ICI. All patients received regorafenib 80 mg QD for 21 days, as a 28-day cycle, combined with ICIs until disease progression or intolerable adverse events. We retrospectively collected the overall response data, survival data and adverse events data from these patients. Results: The characteristics of all 23 patients is shown in the table. All patients had received at least 2 lines of prior systemic chemotherapy, the median time from diagnosis to third-line treatment was 31 months. The overall response rate was 26% (6/23), including one complete response. Almost all the responders were male (5/6) and with pulmonary metastasis (5/6). The disease control rate was 60% (14/23). The progression free survival ranges from 0.69 month to 19.3 months (median 4.8 months), with 6 patients continued response and constantly treatment. Duration of response range from 6.4 months to 19.4 months. Serious adverse events were hepatitis occurred in two patients and lead to the termination of subsequent anticancer therapy, which was considered to be related to immunotherapy. Conclusions: Regorafenib combined with ICIs might favor a certain group of advanced colorectal cancer patients, with a acceptable response rate and comparatively long duration of response. Interestingly, this retrospective pilot study was in consistence with that of REGONIVO trials to some extent for that the male patients with pulmonary metastasis appeared to response better. Key words: colorectal cancer; regorafenib; immune check point inhibitors Clinical characteristics of 23 patients.[Table: see text]