tbuckley/cabot-search huggingface dataset:
Romiplostim for chemotherapy induced thrombocytopenia in solid tumors: A meta-analysis.
Authors: Chiranjeevi Sainatham, Sahib Singh, Shubham Agrawal, Aravind Dilli Babu, Sailaja Vinnakota, Jayanth Reddy Tallapalli, Vishal Jindal, Pallavi P. Kumar, Forat Lutfi, Rushad Patell, Sonal Paul
Journal: Journal of Clinical Oncology (2024)

e24137 Background: Chemotherapy-induced thrombocytopenia (CIT), defined as platelets &lt; 100,000/mcL persisting for ≥3-4 weeks post-chemotherapy affects 20-25% of cases necessitating platelet transfusions or dose reductions leading to treatment delays and impacting patient outcomes. (1,2) Despite multiple studied agents, there are no established guidelines. Romiplostim, a thrombopoietin receptor agonist approved for immune thrombocytopenic purpura, stands out. NCCN suggests its use, but pooled analyses are lacking. Our meta-analysis addresses this gap, exploring romiplostim's efficacy in CIT management. Methods: We performed a systematic search of PUBMED, EMBASE, and COCHRANE databases for studies that evaluate the use of romiplostim in the setting of CIT for solid tumors. The primary endpoint was the proportion of patients that showed improvement in platelet counts in response to romiplostim. Secondary endpoints were the proportion of patients that continued full dose chemotherapy dose on romiplostim and incidence of thromboembolic events. Pooled proportions were calculated along with 95% confidence intervals (CI) using a random-effects model. I2 statistic was used to depict inter-study heterogeneity. Results: A total of 10 single arm studies - 3 prospective studies, 3 case series, and 4 retrospective studies were included. The pooled outcomes were: significant improvement of platelet count above 100K with response to romiplostim therapy in 80.53% patients [95 % CI 72.47 - 87.48, I2 = 69%], proportion of patients that continued full dose chemotherapy on romiplostim was 70.89% [95% CI 63.40 - 77.84, I2 = 0%], and incidence of thromboembolic events was 6.81% [ 95% CI 3.64 – 10.89, I2 = 35%]. Variables like platelet transfusions, bleeding events, type and stage of cancer were not reported uniformly and hence subgroup analyses could not be performed. Conclusions: Our analysis reveals that romiplostim improved the platelet counts in majority of patients with underlying CIT associated with solid tumors. It also shows that a majority of the patients were able to resume their full dose chemotherapy when maintained on romiplostim. The incidence rate of thromboembolic events with romiplostim believed to be consistent with what expected of this population with majority having advanced/high-risk malignancies. Given its efficacy, romiplostim may be used for routinely managing CIT in solid tumors. This analysis is limited by lack of comparative studies and warrant further randomized trials to confirm the safety and efficacy of romiplostim in this patient population.
Risk score stratification of cutaneous melanomas based on whole slide images using deep learning.
Authors: Céline Bossard, Yahia Salhi, Gaelle Quereux, Amir Khammari, Sanae Salhi, Eric Lavoine, Jérôme Chetritt
Journal: Journal of Clinical Oncology (2024)

e21573 Background: Predictive and prognostic biomarkers represent the cornerstone of clinical oncology. Improving the prognostication of melanoma is needed to select patients for effective adjuvant therapies. Taking into account that tumor tissue contains a large amount of clinically relevant hidden information that is not fully exploited, we applied a weakly-supervised deep-learning approach on H&amp;E-stained whole-slide image (WSI) to directly predict 5-year survival outcomes in melanoma patients. Methods: We designed a deep neural (DL) network that extracts features from no-padding patches of WSI (tiles of size 512x512 pixels) using a self-supervised learning framework as well as from the tumor region. These features are then fed along with survival information into the deep learning fusion network assigning a survival risk score to each WSI. The model was trained and validated on 195 cases of primary melanoma diagnosed between 2015 and 2017 originating from the IHP Group and the French RICMel melanoma database. Performance was evaluated using a cross-validation and cross-testing framework as well as on an external set of 238 cases from the TCGA database. Concordance index (c-index) was used as a metric to assess the performance of the proposed algorithm. Results: For the prediction of survival, the proposed pipeline yielded c-index of 0.76 and 0.66 for the IHP Group cohort and TCGA dataset respectively. Furthermore, the model is able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p-value &lt; 0.001 for IHP and p-value = 0.01 for TCGA). Also, the proposed score is statistically significant when added to a multivariate cox model incorporating the classic prognosis factors (p-value &lt; 0.005) and allows to reach a c-index of 0.81 over the discovery cohort. Conclusions: This infrequent weakly-supervised deep-learning approach to HE images analysis has the advantage of leaving the feature selection entirely to the deep network, and so discover new morphological biomarkers. By this way, it could have in the near future the potential to accelerate and improve the clinical decision-making process in the field of melanoma. Also, these findings will undoubtedly open room for substantial applications with economic and treatment delay fallouts.
Immunosuppressant drug-associated skin cancer: A real-world pharmacovigilance database analysis.
Authors: Anil Ananthaneni, Sarah Jones, Daniyal Nadeem, Sydney Moore, Mohamed Ghoweba, Poornima Ramadas
Journal: Journal of Clinical Oncology (2024)

e21575 Background: The association between immunosuppressant drugs and skin cancer has been frequently reported; however, the precise relationship remains uncertain. Skin cancer is among the most common cancers associated with long-term immunosuppressant drug use. The FDA Adverse Event Reporting System (FAERS) is a publicly available tool that collects reports of adverse events related to the use of certain drugs and biologic agents, thereby generating real-world data. Methods: The FAERS database was searched for skin cancer as an adverse event. Nine drugs belonging to different immunosuppressant classes were shortlisted. Reporting odds ratio (ROR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When skin cancer was analyzed as a percentage of all cancers reported as an adverse event for a particular drug,sirolimus had the highest percentage (30.11%) followed by infliximab (23.91%), azathioprine (23.69%), cyclosporine (19.71%), adalimumab (16.79%), mycophenolate (16.77%), etanercept (15.69%), tacrolimus (14.07%) and methotrexate (10.95%). Drugs with highest ROR for skin cancer included sirolimus (2.12, 1.88-2.39) followed by infliximab (1.68, 1.62-1.75) and azathioprine (1.54, 1.44-1.66). Drugs with lowest ROR for skin cancer included methotrexate (0.55, 0.52-0.57) followed by tacrolimus (0.78, 0.74-0.83) and etanercept (0.89, 0.85-0.93). Conclusions: Although all immunosuppressive drugs have been associated with an increased risk of developing skin cancer, it is advisable to exercise caution with prescribing sirolimus, infliximab and azathioprine in patients with preexisting risk. While methotrexate use is known to possess an increased risk, it had the lowest odds of skin cancer compared to other drugs in the study. Prospective studies are needed to understand the true incidence of skin cancer associated with the use of immunosuppressant drugs. [Table: see text]
Association between immunotherapy and hypothyroidism in a Latin American population: An analytical study of cases and controls from 2019 to 2023.
Authors: Ivan Camilo Triana, Erick Andres Cantor Rizo, Javier Segovia, Henry Vargas, Andres Jaramillo, Laura Kattah, Isabel Hernandez, Luis Eduardo Pino, Lizeth Bustamante, Daniela Sanabria, John Alejandro Murillo Silva, Andres Felipe Bejarano
Journal: Journal of Clinical Oncology (2024)

e24135 Background: In different clinical studies worldwide, the use of immunotherapy has been related to the development of hypothyroidism; However, there is no data on this association in Latin American population. Methods: An analytical observational case-control study conducted in a 3-year follow-up cohort at an oncology institute of cancer patients treated with immunotherapy who developed hypothyroidism in Colombia. The aim of the study was to evaluate the development of new hypothyroidism cases after immunotherapy. Cases and controls were randomized in a ratio of 1:3. A multivariate analysis was performed to identify risk factors for developing hypothyroidism and an inferential analysis was performed over time between levothyroxine dose vs TSH levels. Results: 112 patients were included, 57% men and 42% women with a mean age of 63 years. 21% developed hypothyroidism after immunotherapy, while 12% presented with thyrotoxicosis as first alteration and 9% with central hypothyroidism. During the first semester 54% of patients developed hypothyroidism, 84% in the first year and 100% at 2 years . Pembrolizumab and nivolumab were used most frequently with 58% and 29% respectively developing hypothyroidism. The most common underlying pathology was lung cancer with 33% and kidney at 38%. In the multivariate analysis, female were found as a protective factor compared to men (OR:0.10 CI: 0.05-0.63 95% p = 0.02), and the use of pembrolizumab was associated with a higher risk trend, but this result was not statistically significant (OR:2.49 CI: 0.5-2.7 p = 0.2). The average initial dose of levothyroxine was 1.4 mcg/kg, at 3 months of 1.2 mcg/kg and 6 months of 0.82 mcg/kg. Average TSH levels at diagnosis were 23.3, uUI/ml, achieving target values for 100% of patients after 9 months of substitution. After two years of follow-up, patients continued with an average dose of levothyroxine of 0.8 mcg/kg. Conclusions: The incidence of hypothyroidism in our population is similar to that reported worldwide. Male patients who start immunotherapy should have their thyroid profile monitored strictly given that they present a higher risk. Additionally, monthly monitoring of the thyroid profile should be done within the first year. In Latin American population, more conservative initial doses of levothyroxine (1.0 - 1.1 mcg/kg) could be used and titrated.
A randomized trial of topical cannabis balms for the treatment of aromatase inhibitor–associated musculoskeletal syndrome (AIMSS).
Authors: Dylan M. Zylla, Dame Idossa, Maria Borrero, Char Napurski, Stephen Dahmer, Jordan Cowger, Grace Gilmore, Xianghua Luo, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2024)

e24129 Background: Aromatase inhibitors (AIs) are commonly used for postmenopausal women with hormone receptor positive breast cancer. Nearly 2 of 3 women on AIs complain of AIMSS leading to poor adherence. Preclinical and clinical pilot data suggest topical cannabinoids can reduce inflammation in arthritis. Methods: We conducted a randomized controlled trial assessing the feasibility and acceptability of two different topical medical cannabis balms for AIMSS. Women with stage 1-3 breast cancer with AIMSS [scoring 4 or higher on at least one of the four screening Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affectations of the Hands (M-SACRAH) questions] were eligible. Patients with skin lesions, use of any cannabis in prior 4 weeks, acupuncture, or plans to increase doses of other analgesics were excluded. Women were randomized 1:1 to cannabidiol (CBD) (2210mg CBD/ &lt; 0.3% THC) vs delta-9-tetrahydrocannabinol (THC) (375mg THC/ &lt; 20mg CBD) predominant balm. Participants enrolled in the Minnesota Medical Cannabis Program and were dispensed balms at state-registered dispensaries. 125cc of balm was applied 3 times daily to hands for 2 weeks. M-SACRAH, brief pain inventory (BPI), and NCI Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures were captured weekly. Results: 20 women were enrolled from one academic and one community oncology practice in Minnesota over a 10-month period. Reasons patients with AIMSS did not enroll included patient/clinician not interested, AIMSS not meeting M-SACRAH severity, and patient already using cannabis. Adherence to study protocol through week 2 was 85%. Mean age was 54 years, 85% White/15% Asian, 45% received adjuvant chemotherapy, and 50% reported no lifetime cannabis use. Participants reported improvement in M-SACRAH, BPI, and PRO-CTCAE pain scores from baseline to week 2 (Table 1). No skin toxicity was reported by patients. One patient discontinued balm due to greasy texture. Conclusions: Conducting a randomized trial of topical cannabis using state approved dispensaries is feasible. Both THC and CBD predominant topical balms are well tolerated and appear to reduce AIMSS severity in this pilot study of breast cancer survivors. Further confirmatory studies are warranted. Clinical trial information: NCT05935891 . [Table: see text]
Comparison of adjuvant targeted and anti-PD1 immunotherapy in BRAF-mutated stage III cutaneous melanoma: Retrospective, single center cohort study.
Authors: Angelina Akhmetianova, Kristina V. Orlova, Valery V. Nazarova, Kirill A. Baryshnikov, Igor Samoylenko, Kirill Ivanilov, Lev V. Demidov
Journal: Journal of Clinical Oncology (2024)

e21558 Background: Targeted therapy (TT) and anti-PD1 immunotherapy (IT) are standard of adjuvant stage III melanoma treatment. However, no comparative prospective randomized trials (head-to-head) were conducted. Data limited to a few retrospective studies. Both treatment regimens were registered in Russia in 2019. We aimed to compare adjuvant options in Russian melanoma pts. Methods: We conducted a single-center retrospective observational study approved by the IRB. We included all pts age 18 and older (one patient, female, was 14) with BRAF-mutated stage III melanoma who were treated at the N.N.Blokhin NMRC of Oncology MoH and received adjuvant therapy between Jan 2019 and Dec 2022. The primary endpoint was RFS, the secondary endpoint - OS. Cox regression analysis was used to identify prognostic factors for RFS (including substage, thickness and ulceration of primary tumor). Results: A total of 209 pts were included, mostly BRAF V600E/K, 92 (44%) male and 117 (56%) female. Median age was 50,6 years (range: 14-81). 93 (44,4%) pts received TT, 103 (49,3%) pts received IT and 13 (6,3%) didn’t receive adjuvant therapy (observation only). The observation group wasn’t analyzed due to a small number of pts. At a median follow-up of 27 mo, median RFS was 30 mo (95% CI 23-56) in TT group and wasn’t reached in IT group; median OS wasn’t reached in both groups. There weren’t statistical differences between TT and IT groups in RFS (HR 0,84, 95% CI 0,53-1,34, p = 0,47) and OS (HR 0,59, 95% CI 0,26-1,34, p = 0,21), even though at 12 mo, the rate of RFS was higher in the TT group (91.4%) compared IT group (67%), at 18 mo – 79,5% and 63,1%, 24 mo – 68,8% and 61,1% respectively. TT group had numeric but not significant RFS benefit in most subgroups. HR values for substage, thickness and ulceration are presented in the table below. Tx+T0 pts (TT, n = 7; IT, n = 13) and unknown status of ulceration (TT, n = 7; IT, n = 16) was not presented for some pts. Conclusions: Differences between TT and IT wasn't reached at a median follow-up of 27 mo. But IT-treated pts had more and earlier recurrences than TT pts. In BRAF mutated pts, adjuvant TT might prevent early recurrences more effectively than IT. These results need to be interpreted with caution given its retrospective and non-randomized nature and potential selection biases. Additional time to follow-up and biomarker analysis was planned. [Table: see text]
Immune-related adverse events associated with nivolumab: Analysis of the FAERS database in the United States.
Authors: Yi Liu, 亚宁 朱
Journal: Journal of Clinical Oncology (2024)

e24126 Background: To describe the risk of nivolumab adverse events (AEs) and to provide a reference for the safe clinical to use this drug. Methods: Nivolumab AE reports from January 2014 to December 2023 were collected from the FDA Adverse Event Reporting System, with a total of 133,12811 background patients (3,853,1848 occurrences of adverse events) included in the analysis, of which the number of patients in the target drug population was 60,625 (16,512 occurrences of adverse events). The number of patients in the target drug population was 60625 (161512 adverse events). Signals were detected using the Reporting Odds Ratio (ROR) method in conjunction with the Proportional Reporting Ratio (PRR), with signal judgment thresholds typically using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1, The ROR and PRR (using a ≥ 3, and the lower limit of the 95% confidence interval for the ROR being greater than 1) were compared to the PRR. When ROR and PRR (using a ≥ 3, PRR ≥ 2 and chi-square ≥ 4 as thresholds) were used in combination, signal crossover between the two methods was defined as a positive risk signal. The preferred system organ classification (SOC) and preferred terminology (PT) of the current version of the MedDRA dictionary were used to classify AEs, and the top 30 PTs in terms of AE signal intensity were selected for analysis. Results: A total of 161,512 reports of AE with nivolumab as the first suspected drug were collected, involving 5174 PTs. A total of 995 positive PT signals were calculated using the combined ROR and PRR assay. The top 5 risk signals induced by nivolumab were immune-mediated small bowel colitis (ROR (95% CI) 114.42 (103.26-126.79), PRR (Chi-Square) 114.04 (40959.8)), pituitary gland inflammation (ROR (95% CI) PRR (Chi-Square) 88.60 ( 79.17-99.15)PRR(Chi-Square)88.37(26256.6)), fulminant type 1 diabetes mellitus (ROR(95% CI)213.73(183.24-249.30),PRR(Chi-Square)213.33(34295.5)) immune-mediated pneumonias (ROR(95% CI) 114.08 (99.42-130.89),PRR(Chi-Square) 113.87 (22764.4)), immune-mediated hepatitis (ROR(95% CI) 86.09 (75.08-98.71),PRR(Chi-Square) 85.94 (17262.8)).The top 5 SOCs were systemic diseases and various reactions at the site of administration in 25447 cases (15.76%), gastrointestinal disorders in 25447 cases(15.76%), gastrointestinal disorders 16,282 cases (10.08%), various types of injuries, poisoning and operational complications 12,510 cases (7.57%), respiratory, thoracic and mediastinal disorders 11,572 cases (7.16%), as well as benign, malignant, and tumors of undetermined nature (including cystic and polypoid) 10,486 cases (6.49%). Conclusions: The risk signal of autoimmune diseases caused by nivolumab is relatively strong, and it is recommended that clinicians should pay attention to the possible autoimmune diseases of various systems during the use of the drug.
Cold prevention of alopecia during chemotherapy: Real clinical practice.
Authors: Denis Fedorinov, Marina Lyadova, Veronika Tuleiko, Evgenia Kuzmina, Anastasia Zhuravleva, Olesya Bikmurzina
Journal: Journal of Clinical Oncology (2024)

e24132 Background: Alopecia is one of the most common visible adverse effects of anticancer drug therapy. The incidence of grade 2 alopecia can be as high as 90% in patients getting anthracyclines or taxanes. Decreased scalp temperature causes vasoconstriction which limits the flow of chemotherapeutic agents into the scalp and reduces the metabolism of hair follicle cells at the time of maximum concentration of cytotoxic agents in plasma. This leads to a decrease in the antimitotic and antimetabolic effects of chemotherapy. ORBIS II scalp cooling device has been successfully implemented in comprehensive oncology centers. However, the results of large-scale studies are still lacking which delays application of this technology in clinical practice. The aim of our study was to evaluate the efficacy and safety of alopecia cold prophylaxis using ORBIS device in a regional referral center in Russia. Methods: Between 22 June 2022 and 13 December 2023 101 patients (100 women and 1 man) were treated using ORBIS II in the Department of Chemotherapy N1, City Clinical Cancer Hospital N1, Moscow. Various combinations of chemotherapeutic agents depending on cancer type were administered. Breast cancer was the most common type (63), followed by ovarian (15), uterine (9), lung (6) and cervical cancer (3). Other primaries were represented by 1 patient each: pancreatic, rectal, gastric, fallopian tube and colon cancer. Totally 431 scalp cooling procedures were performed including 261 (61%) in breast cancer and 78 (18%) in ovarian cancer patients. Outcomes were evaluated using the CTCAE/CTCAE V5.0 toxicity criteria. We evaluated the development of 1 grade alopecia (hair loss of less than 50% and not requiring a wig) as a positive result. On the contrary, a negative result was registered in patients with grade 2 alopecia, namely hair loss of 50% or more and/or requiring a wig. Results: Grade 1 alopecia was experienced by 61% of patients and the other 39% had grade 2 alopecia. Notably, the highest incidence of grade 2 alopecia was observed in patients who received doxorubicin 60 mg/cm 2 + cyclophosphamide 600 mg/cm 2 once every 21 days (9.9%). Taxane-based regimens had a 21% incidence of grade 2 alopecia, while platinum-containing regimens had a 11% incidence. No serious adverse events occurred during the application of cold prophylaxis. The procedure was well-tolerated by all patients. Conclusions: The use of a cold helmet is an effective method of preventing chemotherapy-induced alopecia. Our analysis yielded a success rate of 61%, which is comparable to the worldwide data range of 50% to 80%.