tbuckley/cabot-search huggingface dataset:
Cannabis use for cancer-related symptoms in rural versus urban Minnesota.
Authors: Maria Borrero, Patricia Jewett, Dylan M. Zylla, Helen M. Parsons, Jeanette Y Ziegenfuss, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2024)

12078 Background: Minnesota currently has a medical cannabis program and recently legalized recreational cannabis in 2023. Evidence suggests that cannabis may have positive effects on various aspects of a cancer patient's quality of life. However, little is known about any differences in cannabis use between rural and urban cancer patient populations. We compared cannabis use, behaviors, attitudes, access, and associations with cancer-related symptom burden in rural versus urban Minnesotans with cancer. Methods: We conducted a cross-sectional survey between 2021 and 2022. Study participants were adults diagnosed in 2018-2019 with cancer and treated at an academic cancer center and its community clinic affiliates in Minnesota. Participants were sent self-administered surveys. 775 surveys were completed and returned. Analysis was restricted to 688 who reported residential ZIP codes to classify them as living in urban versus rural areas based on ZIP-code level Rural Urban Commuting Area codes. Our primary outcomes were cannabis use and perceptions. Secondary outcomes included patterns of use, behavior, attitudes, and self-reported symptom burden. Results: Of 688 participants, 54% were classified as rural and 46% as urban. Of all respondents across both groups, 60% reported never using cannabis, 56% reported cannabis use during cancer treatment, and 21% reported use since cancer diagnosis. The majority of respondents in both groups believed there are potential benefits of cannabis. Those in the urban group reported greater interest in trying medical cannabis in the future compared with rural group. The majority of respondents reported never discussing cannabis use with their healthcare provider, and even fewer reported their provider recommending cannabis to them. Both urban and rural groups reported improvement in pain, stress, insomnia, appetite, and digestion. The rural group experienced more improvement in fatigue and stress compared to the urban group. Nearly no one reported worsening of any symptoms measures after the use of cannabis. Conclusions: Cannabis use, perceptions, and attitudes were overall similar in a cohort of rural and urban patients with cancer. Both groups experienced significant cancer related symptom burden improvement after use of cannabis. While the urban cohort showed greater interest in future cannabis use, the rural cohort reported greatest benefits in relief of stress and fatigue after cannabis use, two important measures of quality of life. Our data suggest that providers rarely recommend or talk about cannabis use to cancer patients. [Table: see text]
Enhancing WHO Prescription writing guideline adherence through an educational intervention – a quality improvement study of Azad Jammu and Kashmir
Authors: Mushood Ahmed, Areeba Ahsan, Muhammad Selal Zia, Qura Tul Ain, Salwa Khurshid, Jawad Basit, Tagwa Kalool Fadlalla Ahmad
Journal: International Journal of Surgery (2024)

Background: Prescription writing is an important component of healthcare delivery and can directly influence patient safety and treatment outcomes. Prescription errors are common in developing countries because of the lack of national guidelines. This two-cycle clinical audit assessed the impact of educational interventions on improving prescription writing practices. Methods: A cross-sectional prospective clinical audit was conducted in the Out Patients Department (OPD) of the District Head Quarters (DHQ) Hospital in Bhimber, Azad Jammu, and Kashmir. A total of 100 randomly selected prescriptions were reviewed for each cycle from July to August 2023. We recorded compliance with WHO guidelines for prescription writing before and after the educational intervention. Microsoft Excel and SPSS version 25.0 were used for statistical analysis. Categorical variables were analyzed using frequencies and percentages. Results: An improvement in compliance was observed during the 2 nd audit cycle, after the educational intervention. The greatest improvement was observed in documenting the allergic status of patients (62%) and the direction of drug administration (40%). We also observed improvements in the treatment duration (&gt;10%), patient weight, physician registration number, diagnosis, and follow-up advice. The legibility of prescriptions also improved during the 2nd audit cycle. Conclusion: This study shows that integrating an educational intervention into a clinical audit can improve prescription writing practices and ultimately result in better quality of care for patients.
Accuracy of medical oncology prognosis for patients with metastatic cancer evaluated for enrollment onto an ongoing randomized clinical trial.
Authors: Shearwood McClelland
Journal: Journal of Clinical Oncology (2024)

12063 Background: For patients with metastatic cancer, a key aspect of interdisciplinary care has involved the overall prognosis provided by Medical Oncology, which often dictates the intensity and direction of further care while impacting all other disciplines, most prominently Radiation Oncology, Surgical Oncology and Palliative Medicine. Despite the millions of patients for whom such prognoses have been ascribed, the success rate of Medical Oncology prognosis has been sparsely described. This study represents prospective evaluation of Medical Oncology prognosis accuracy for patients having been considered for enrollment onto an ongoing Phase 2 randomized controlled oncology trial. Methods: The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic MEtastatic Neoplasms (SPORTSMEN) clinical trial (clinicaltrials.gov number NCT05617716) is a Phase 2 randomized clinical trial examining optimal radiation therapy treatment of symptomatic spinal metastases with a primary endpoint of pain freedom at 3 months post-treatment. A key eligibility criteria for trial enrollment is overall prognosis exceeding 3 months, typically provided by Medical Oncology. During the first year of trial enrollment, Medical Oncology prognosis for patients considered for SPORTSMEN inclusion was prospectively assessed for accuracy. Results: From January 2023 through December 2023, a total of 27 patients with documented Medical Oncology prognosis were considered for SPORTSMEN enrollment. Medical Oncology administered a prognosis exceeding three months in 26 patients, and less than three months in one patient. Of patients with a prognosis exceeding three months, 12 (46%) succumbed to death or hospice care prior to three months; the patient ascribed a prognosis of less than three months did not survive to exceed this threshold. The Medical Oncology prognosis overall was proven correct for 15 of 27 patients (56%). Medical Oncologist prognostic accuracy was 13/19 (68.4%) for outpatients, and 2/8 (25%) for inpatients; this difference was statistically significant (p=0.0381). Conclusions: In patients with symptomatic metastatic spine disease, the estimated prognosis provided by Medical Oncology is often optimistic, as nearly half of patients assigned a prognosis of greater than three months failed to reach this threshold before experiencing death or hospice. These findings indicate that providers considering enrolling patients on clinical trials should expect a prognosis overestimation rate exceeding 40%. Consequently, a more heuristic approach to assessing patient prognosis may be necessary to avoid unwarranted prognostic optimism, particularly for inpatients. Such an approach could potentially provide a more compassionate and cost-effective management of these patients’ remaining lifespan thereby optimizing quality-of-life.
Walking dose required to achieve a clinically meaningful reduction in cancer-related fatigue among patients with breast cancer receiving chemotherapy: A URCC NCORP nationwide prospective cohort study.
Authors: Lindsey Jean Mattick, Po-Ju Lin, Karen Michelle Mustian, Luke Joseph Peppone, Umang Gada, Stephen Rajan Samuel, Viktor Clark, Sule Yilmaz, Jeremy McGuire, Alison Katherine Conlin, Lora Rose Weiselberg, Jerry W. Mitchell, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2024)

12008 Background: Exercise is recommended by ASCO as a treatment for cancer-related fatigue (CRF) - one of the most pervasive toxicities patients with breast cancer experience. Current oncology guidelines recommend aerobic exercise (e.g., walking) at a weekly dose of 150 minutes of moderate intensity or 75 minutes of vigorous intensity. While these recommendations exist and are effective for treating CRF, patients with breast cancer struggle to achieve these levels of exercise, especially at a vigorous intensity during chemotherapy. The purpose of this study was to determine the doses of low and moderate intensity walking required to elicit a clinically meaningful reduction in CRF. Methods: As part of a nationwide prospective cohort study, 580 female breast cancer patients (stage I-IIIC; receiving chemotherapy) were recruited from 19 University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base locations. CRF (Multidimensional Fatigue Symptom Inventory) and exercise dose (i.e., walking via ACLS Physical Activity Measure) were measured at pre-chemotherapy, 1-month post-chemotherapy, and 6-months post-chemotherapy. Exercise dose was measured in METs (energy expenditure normalized for body weight and time; 1 MET = 1 kcal/kg/hr) and converted into walking time (minutes) and intensity (mph). A low-intensity walking pace is &lt; 2.5mph (&lt; 3 METs), and a moderate-intensity walking pace is 2.6-4.5mph (3.1-6 METs). Results: Pre-chemotherapy, patients with breast cancer averaged walking 40-60 minutes/week at a low intensity or 20-38 minutes/week at a moderate intensity (median: 2.0 MET hrs/wk). Linear mixed modeling demonstrated a higher amount of walking significantly predicts lower CRF at all three time points (β: -0.26, SE: 0.08; p &lt; 0.001). Logistic regression identified that patients who increase their walking by 111-162 minutes at a low-intensity pace or 54-108 minutes at a moderate-intensity pace (i.e., 1 SD) are 43% more likely to experience a clinically meaningful reduction in CRF (- 4.5 MFSI total) from pre-chemotherapy to 1-month post-chemotherapy (SD: 5.4 MET hrs/wk; OR: 1.43, 95% CI: 1.19-1.72; p &lt; 0.001). Conclusions: Over the course of chemotherapy, patients with breast cancer who can increase their walking at a low intensity pace (&lt; 2.5 mph) up to 151-222 min/wk or at a moderate intensity pace (2.6-4.5 mph) up to 74-146 min/wk are 43% more likely to have clinically meaningful lower levels of CRF post-chemotherapy.
Double-stranded RNA to mimic viral infection for cancer immunotherapy
Authors: Ana Martínez-Riaño, Laura Mosteo, Paula Molero-Glez, Iván Márquez-Rodas, Ignacio Melero
Journal: Clinical Cancer Research (2024)

The presence of moieties denoting viral infection is crucial to mount powerful cytotoxic T-cell immune responses acting through innate receptors such as Toll-like receptor 3. For cancer immunotherapy, several safe analogues of viral double-stranded RNA are under clinical development following compelling evidence for efficacy in mouse models. See related article by van Eijck et al., p. 3447.
A phase II study of an oncolytic herpes simplex virus 2 and an anti-PD-1 antibody in patients with advanced sarcoma.
Authors: Zhichao Tan, Jiayong Liu, Tian Gao, Sijuan Ding, Liang Han, Suxia Luo, Qingxia Fan, Jianhua Shi, Xiangyong Gu, Binlei Liu, Nassos Alevizopoulos, Zhengfu Fan, Jing Huang
Journal: Journal of Clinical Oncology (2024)

11571 Background: OH2 is an attenuated oncolytic Herpes Simplex-2 Virus expressing GM-CSF. In a phase I/II open-label clinical trial OH2 was safe and efficacious as monotherapy. When combined with HX008, a humanized anti-PD-1 antibody, OH2 demonstrated a disease control rate of 50% in solid tumors (1). Here, we present the efficacy results observed in a sarcoma-specific expansion cohort of the trial. Methods: Patients refractory to ≥1 prior line of systemic therapy were allocated to a monotherapy group receiving intratumoral OH2 once every 2 weeks and a combination group receiving i.t. OH2 and HX008 (i.v) every 3 weeks. The primary endpoint was best objective response rate (ORR, per RECIST v 1.1). Secondary endpoints were disease control rate (DCR), progression free survival (PFS), overall survival (OS), duration of response (DOR) and adverse effects (AEs). Results: 26 patients were enrolled in the phase II trial, 7 in the monotherapy group and 19 in the combo group. Median age was 52 years, with 65.4% females. 50% had received ≥3 prior lines of therapy, whereas 30.7% had prior lines of immunotherapy. 25 patients were evaluable for efficacy (1 withdrew). ORR was 0% and 16.7%; DCR 14.3% and 50.0%; median PFS 1.4 and 2.1 months, and median OS 4.5 and 22.3 months, for the monotherapy and combo groups, respectively. In the combo group we observed 1 CR and 2 PRs, in which the DOR was 4.2, 5.6 and 11.1 months (Table). Angiosarcoma and fibrosarcoma patients experienced clinical benefit with durable disease control, with one angiosarcoma patient remaining in study for &gt;1 year. Treatment was well tolerated with most common AEs being grade I and II, including GGT elevation (26.9%), fever (23.1%), neutropenia (19.2%), weight loss (15.4%), LDH elevation (15.4%), and anemia (15.4%). Conclusions: OH2 and HX008 demonstrated goodsafety and encouraging anti-tumor activity in a phase II sarcoma cohort. Further clinical investigation of this combination is warranted. 1. Zhang et al, 2021; PMID: 33837053. [Table: see text]
Phase IIA study of high-affinity TCR-T (TAEST16001) targeting NY-ESO-1 in soft tissue sarcoma.
Authors: Jiayong Liu, Tian Gao, Qiuzhong Pan, Chujie Bai, Zhaosheng Han, Zhichao Tan, Ruiqing Peng, Bushu Xu, Xizhi Wen, Huafang Cen, Chaoxian Yan, Johnson Yiu-Nam Lau, Lun Zeng, Xueyun Wu, Yusheng Ou, Haiping Gong, Yingjie Huang, Zhengfu Fan, Xing Zhang
Journal: Journal of Clinical Oncology (2024)

11548 Background: TAEST16001 cells are genetically engineered autologous T cells expressing high-affinity NY-ESO-1-specific T-cell receptor (TCR) targeting NY-ESO-1 (expressed in a wide range of tumors) positive soft tissue sarcoma (STS) in the context of HLA-A*02:01. A phase I study of in patients with advanced STS (NCT04318964) demonstrated safety and preliminary indication of efficacy at ASCO 2022. Here, we will present our encouraging phase IIa results. Methods: This is an open-labeled, single arm study to evaluate efficacy and safety of TAEST16001 cells in patients with advanced STS (NCT05549921). Enrolled patients underwent apheresis, their isolated T cells expanded in vitro after transduction with a lentiviral vector expressing high affinity NY-ESO-1 TCR. Patients received 3-day lymphodepleting chemotherapy (cyclophosphamide 15 mg/kg/day and fludarabine 20 mg/m 2 /day). TAEST16001 cells were administered at 1.2 × 10 10 ± 30% cells (determined through our phase I data) and they also received 14-day IL-2 s.c. injection. Target efficacy ( per RECIST 1.1) was set at overall response rate (ORR) =25% for the first stage cohort of 12 patients. Results: As of January 2024, 8 patients were enrolled (M:F 4: 4; mean age: 40 yrs.; median prior regimens: 3 (range:2-5)). TAEST16001 cells demonstrated a manageable safety profile consistent with previous phase I study. The common (n&gt;1) reported grade (G) 3 adverse events were lymphocytopenia (n=8), decreased WBC count (n=7), neutropenia (n=6), elevated γ-GT (n=3), hypokalemia (n=2). Six patients had cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), and 2 patients also experienced G1 ICANS, all resolved completely after symptomatic treatment. Importantly, after at least two tumor assessments, 4 had confirmed partial response, 3 had stable disease, and 1 had progressive disease. The ORR at cut-off date was 50%. The median time to initial response was 1.1 months (1.1 to 2.2) and median duration of response was 5.0 months (1.5 to 8.8). Most patients are still being follow-up. When pooling the data for the same dose in phase I part, ORR at dose of 1.2 × 10 10 was 54.5% (6/11). Conclusions: TAEST16001 demonstrated an acceptable safety profile. The encouraging efficacy data (ORR=50%) exceeded our pre-specified target efficacy (ORR=25%). The review committee has recommended TAEST16001 to proceed early to the next stage of clinical development. Clinical trial information: NCT05549921 .
Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo
Authors: Emmanuel Hasivirwe Vakaniaki, Cris Kacita, Eddy Kinganda-Lusamaki, Áine O’Toole, Tony Wawina-Bokalanga, Daniel Mukadi-Bamuleka, Adrienne Amuri-Aziza, Nadine Malyamungu-Bubala, Franklin Mweshi-Kumbana, Léandre Mutimbwa-Mambo, Freddy Belesi-Siangoli, Yves Mujula, Edyth Parker, Pauline-Chloé Muswamba-Kayembe, Sabin S. Nundu, Robert S. Lushima, Jean-Claude Makangara-Cigolo, Noella Mulopo-Mukanya, Elisabeth Pukuta-Simbu, Prince Akil-Bandali, Hugo Kavunga, Ombotimbe Abdramane, Isabel Brosius, Eugene Bangwen, Koen Vercauteren, Nadia A. Sam-Agudu, Edward J. Mills, Olivier Tshiani-Mbaya, Nicole A. Hoff, Anne W. Rimoin, Lisa E. Hensley, Jason Kindrachuk, Cheryl Baxter, Tulio de Oliveira, Ahidjo Ayouba, Martine Peeters, Eric Delaporte, Steve Ahuka-Mundeke, Emma L. Mohr, Nancy J. Sullivan, Jean-Jacques Muyembe-Tamfum, Jean B. Nachega, Andrew Rambaut, Laurens Liesenborghs, Placide Mbala-Kingebeni
Journal: Nature Medicine (2024)

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.
Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-VEGFR targeted therapy: A Phase 2 Trial of Regorafenib combined with avelumab.
Authors: Antoine Italiano, Jean-Philippe Guegan, Thibaud Valentin, Rastilav Bahleda, Jean Philippe Metges, Philippe Alexandre Cassier, Maud Toulmonde, Mariella spalato-Ceruso, Florent Peyraud, Jean Palussière, Michèle Kind, Coralie Cantarel, Carine A. Bellera, Alban Bessede
Journal: Journal of Clinical Oncology (2024)

11516 Background: Vascular Endothelial Growth Factor (VEGF)-driven angiogenesis is a pivotal factor in creating an immunosuppressive tumor microenvironment. Approximately 80% of Soft Tissue Sarcomas (STS) are characterized by a 'cold' microenvironment, lacking tertiary lymphoid structures (TLS). While the efficacy of VEGF pathway and PD-1/PD-L1 axis blockade has been established in various tumor types, their impact on 'cold' STS remains unexplored. This study aims to evaluate the synergistic effect of anti-angiogenesis and PD-1 blockade in altering the microenvironment of cold STS, potentially enhancing immune response and therapeutic efficacy. Methods: In this phase II, single-arm, open-label, multicentric trial, we explored the efficacy and safety of combining regorafenib (R) and avelumab (A) in advanced TLS-negative STS patients. Patients were administered 160 mg of R daily for 3 weeks in a 4-week cycle, alongside 10 mg/kg of A biweekly. Endpoints included high-throughput analysis of tumor and plasma samples, response rate, progression-free survival (PFS), overall survival (OS), and safety, as per the NCI-CTCAE v5.0 guidelines. Results: From May 2019 to August 2021, 49 TLS-negative STS patients were enrolled, including leiomyosarcoma (45%), synovial sarcoma (18%), and other subtypes. The median age was 57.1 years, with patients having undergone an average of 2 prior treatment lines. High-throughput analysis of sequential plasma samples indicated an upregulation of immune-inducing protein biomarkers such as CXCL10 and soluble CD8 antigen. Multiplex immunofluorescence analysis of sequential tumor samples revealed significant increase in CD8 T cell infiltration on-treatment. The most common severe adverse events were grade 1 or 2 palmar-plantar erythrodysesthesia, fatigue, and diarrhea. The median follow-up was 7.1 months, with 32.6% of patients experiencing tumor shrinkage, and a clinical benefit rate of 48.8%. The 6-month PFS was 22.1%, with a median OS of 15.1 months. Conclusions: The combination of regorafenib and avelumab demonstrates a marked mobilization of antitumor immunity in patients with TLS-negative STS. The observed efficacy appears superior to that of single-agent immune checkpoint inhibition in 'cold' STS, and higher than the 6-month PFS benchmark of 14% set by EORTC. This indicates the potential effectiveness of this treatment combination in managing advanced cold STS, marking a significant stride in precision immunotherapy for this group of tumors. Clinical trial information: NCT03475953 .
Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals
Authors: So-Young Kim, June-Young Koh, Dong Hyeon Lee, Hyung-Don Kim, Seong Jin Choi, Yun Yeong Ko, Ha Seok Lee, Jeong Seok Lee, In Ah Choi, Eun Young Lee, Hye Won Jeong, Min Kyung Jung, Su-Hyung Park, Jun Yong Park, Won Kim, Eui-Cheol Shin
Journal: Journal of Hepatology (2024)