bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and confidence gaps in differentiating PARP inhibitors among community oncology providers.
Authors: Robinson Katie J.H. , Scully Emily , Rose Kristin R. , Esgro Robert A. , Lee Nita Karnik
Published: July 2024

e21002

Background: Data and professional recommendations regarding the use of Poly(ADP-ribose) polymerase inhibitors (PARPis) for patients with ovarian cancer have evolved rapidly, challenging providers who manage patients with ovarian cancer (OC). Coupling confidence-based learning with continuing education (CE) is a proven tool to address such challenges towards enhanced patient care. Methods: A confidence-based continuing education (CE) activity was developed to address the evolving landscape of PARPi use in patients with OC. Pre-, intra-, and post-test assessment was used to quantify baseline parameters as well as the impact of education on knowledge and behaviors. The CME activity was available for credit from October 31, 2022 to October 30, 2023. Results: In total, 354 community oncology physicians or advanced practice providers (APPs) who see an average of 6 patients with OC per month completed the education. Baseline knowledge and confidence was low on topics related to strategies for molecular testing (29% correct) as well as the use of PARPis (27% correct). Moreover, on average, only 3% of those who answered correctly were confident in their response, highlighting a lack of confidence even in those who were correct. These knowledge and confidence gaps translated to only 24% of providers who use appropriate testing to determine BRCA1/2 and HRD status and only 16% feeling comfortable in differentiating PARPis. Additionally, while providers showed slight preference for olaparib in patients with homologous recombination deficiency (HRD) and niraparib in patients without HRD, on average 30% of providers were unsure of which agent to use in each clinical context. Overall, at baseline only 24% of providers reported individualizing the use of PARPis based on patient and tumor characteristics. Post-learning, there was a 46% increase in knowledge, and while the percentage of those who were confident and correct increased 21%, 76% remained unconfident. Still, these gains in knowledge and confidence resulted in two-thirds of providers making practice improvements in their use of PARPis, which resulted in improvements in patient health. Conclusions: The rapid evolution of the PARPi therapeutic landscape has caused gaps in knowledge, confidence, and behaviors. Ongoing and rapidly developed CE is a critical tool to address these challenges as data and recommendations for use continue to evolve rapidly.[Table: see text]
Behavioral analysis of social media and email usage among hematology-oncology fellowship applicants: A national survey.
Authors: Thakur Rahul Kumar , Vegivinti Charan Thej Reddy , Yusuf Hasiya , Gor Rajvi , Ray Barun , Thakur Monika , Deshpande Shweta , Kumar Abhishek
Published: July 2024

e21003

Background: The advent of digital communication has transformed the landscape of fellowship programs, with social media(SoMe) emerging as pivotal platforms for information dissemination and engagement between applicants and programs. Despite its proven influence in surgical and urological specialty, the role of SoMe in Hematology-Oncology (HO) fellowships remains to be elucidated. This pioneering survey evaluates the utility and impact of SoMe alongside traditional email among Internal Medicine residents applying the fellowship application process in the era of virtual interviews. Methods: An anonymous, cross-sectional survey was administered via SurveyMonkey to residents applying to U.S. HO fellowships in the 2023-2024 cycle. Outreach methods included emails to all internal medicine program directors, SoMe, and online forums. The questionnaire probed the frequency of SoMe and email usage, types of content accessed, and the influence of these platforms on applicants' strategic choices and program preferences. Results: Analysis from 33 respondents revealed a demographic predominance of individuals aged 26-35 years, with an equal gender distribution and significant representation from the Middle Atlantic region. The majority were non-U.S. graduates (51.5%), predominantly identifying as Asian (54.5%). While 67% of respondents used Twitter/X, but only 13.6% used it for direct program contact, resulting in a minimal 4.5% receiving interview offers. Twitter/X was acknowledged as a useful information source by 55% of respondents, and 20% felt it influenced their program ranking decisions. Conversely, 70% and 45% used Instagram and LinkedIn respectively, but usage for fellowship applicants was minimal, with no respondents utilizing it for program outreach or reporting any increase in interview offers because of its use. Notably, 25% felt pressured to use SoMe to boost their application prospects. In contrast, 74% approached program directors through personalized emails, attributing a 34% increase in interview offers to this method. Conclusions: Our findings emphasize the enduring prominence of email in fellowship applications while illuminating the evolving but significant presence of SoMe. This divergence highlights a potential big change where SoMe particularly Twitter/X, begins to complement traditional methods. Such insights suggest that fellowship programs should strategically integrate digital tools into their application processes and actively improve their online engagement to align with applicant behaviors.
Effectiveness of online activities to reinforce multidisciplinary management of advanced soft tissue sarcoma and extend education globally.
Authors: Heller Elizabeth Jean , Smith Keira P. , Brook Lyn , Maack Eden , Karfonta Amy J.
Published: July 2024

e21013

Background: Soft tissue sarcoma is a heterogeneous group of rare tumors. The multidisciplinary team is integral to optimize patient care and prolong survival. Online video platforms provide a convenient and costless method to deliver content, but their ability to reach and teach clinicians has not been studied extensively. We investigated usage and pre/post-survey data from viewers of a continuing medical education (CME)/nursing continuing professional development (NCPD) Virtual Tumor Board (VTB) video activity. Methods: We developed Virtual Tumor Board: Multidisciplinary Management of Advanced Soft Tissue Sarcoma, for oncologists, pathologists, nurse practitioners, physician assistants, and nurses. The VTB discussed strategies to optimize treatment outcomes of patients with soft tissue sarcoma using case studies. It was made accessible on August 10, 2023, on the i3 Health website, YouTube, and VuMedi. Viewers can receive CME/NCPD. Responses were analyzed, with Fisher’s exact test used to compare responses. Results: At the 5-month follow-up, the VTB has been viewed 1,547 times: 459 views on i3 Health, 988 views on YouTube, and 150 views on VuMedi, representing viewers from across the US and internationally. Baseline assessment data revealed gaps in knowledge in areas addressed by the VTB. For learners who completed the assessments (N=422), the mean score for all topics combined rose by 56% (33% vs 89%). The activity resulted in significant gains in knowledge and competence, with P < 0.001 for all learning gains (Table).Upon completion, 92% of learners self-reported that knowledge acquired from this activity would be utilized to improve the outcomes of their patients, and 91% self-reported that, based on the information learned during the activity, they felt more confident in treating patients with soft tissue sarcoma. Conclusions: Over 1,500 viewers from both rural and urban areas have viewed this lecture, primarily on YouTube. Learners of i3 Health’s accredited activities have grown from 100,000 YouTube viewers in 2021 to over 600,000 by the end of 2023. In 2023, viewership extended to 60 countries, including 30 countries classified as low-to-middle income by The World Bank. The post-activity knowledge gains and improvements in competence show significant impact and the educational benefits of online video viewing. [Table: see text]
Descriptive and content analysis of breast cancer vlogs on YouTube.
Authors: Morena Nina , Htite Elly , Ahisar Yitzchok , Hayman Victoria , Rentschler Carrie A. , Meguerditchian Ari N.
Published: July 2024

e21016

Background: Vlogs, or “video blogs,” are personally-created experiential videos based on wide-ranging topics, usually posted to YouTube. Many women with breast cancer (BC) document their cancer experiences in YouTube vlogs. These may have the potential to serve as peer-to-peer support and provide community. This study provides a descriptive and content analysis of vlogs by women with BC. Methods: YouTube was searched in incognito mode in 11/2023 using the search terms “breast cancer vlog.” A maximum of 10 videos/creator were included based on viewership and date created. Video characteristics collected included: title, length, number of views, likes, comments, and playlist inclusion. Videos were assessed for sponsorship, presence of explanation and discussion on BC, type of content, and themes. Creator characteristics included age, location, and engagement approaches. Descriptive and content analysis were performed to assess and analyze video content and potential areas where peer-to-peer support may be provided. Results: 90 vlogs by 13 creators were included, all originating from personal accounts. Mean video length, number of views, and number of comments were 21.4 minutes (SD 9.1), 266,780 (SD 534,465), and 1485 (SD 3422), respectively. 38.9% included hashtags. 12.2% included paid sponsorships. Most common filming location was at home (96.7%), followed by the hospital (31.1%), or in the car (21.1%). Home vlogs were most often set in the living room (44.3%), bedroom (33.0%), or kitchen (20.6%). 56.7% included visuals of treatment as well as physical findings. Creators addressed motivation for vlogging in 48.9%; the two most common reasons were wanting to build a community and helping others in a similar situation. In 46.7%, creators explicitly expressed emotion. Most common themes were treatment (85.6%), mental health (81.1%), side effects (72.2%), appearance (63.3%), and family relationships (36.7%). Subthemes included young age, finances, and the importance of online community support. Patient-directed advice was offered in 60.0%, mostly on treatment-related issues. In 56.7%, creators provided explicit treatment definitions. Chemotherapy was discussed in 70.0%; surgery in 57.8%, primarily mastectomy; radiation in 30.0%; general side effects in 71.1%. 24.4% were about a new diagnosis. When mentioned (44.4%), most common creator location was the USA. When mentioned (30.0%), most common age demographic was 20-29 years old. Conclusions: Vlogs by women with BC receive significant levels of engagement. The dedication to building community demonstrated by vlog creators, and the personal nature of their storytelling, advice, and suggestions, may make these vlogs a potential resource for peer-to-peer support.
Clinical and epidemiological profile of patients with atypical melanomas treated with immunotherapy.
Authors: Cicilini Andre Luiz , Saruwatari Thamilyn , Tavares Monique Celeste
Published: July 2024

e21532

Background: Atypical melanomas, such as acral lentiginous, uveal, mucosal, spitzoid, desmoplastic, meningeal, and primary occult site, represent less than 5% of melanoma cases. Due to their different biological tumor behavior from cutaneous melanomas, their treatment is still challenging. Currently, checkpoint inhibitors are the main treatment based on extrapolations or data from small surveys. Methods: This study aims to describe the epidemiological profile, clinical and pathological characteristics, and treatment of patients with atypical melanomas treated with immunotherapy. It is an observational, descriptive, retrospective study that analyzed 72 medical records of patients with atypical melanomas, ECOG 0-1, > 18 years old, treated with immunotherapy (neo, adjuvant, and palliative lines), between January 2015 and December 2023 at the A.C. Camargo Cancer Center, São Paulo, Brazil. Results: We gathered 72 patients, 61% male and 39% female, with an average age of 58.89 (±13.63) years; 57% were white, 15% African-descendant (black and brown), 8% Asian, and 20% not specified. Regarding primary site, 26% were acral, 24% mucosal, 24% occult primary site, 15% uveal, 8% desmoplastic, 1% amelanocytic, 1% spitzoid, and 1% cauda equina meningeal. Regarding staging, (3%) were stage I, (15%) stage II, (25%) stage III, (47%) stage IV, and (10%) unknown. LDH: 372.5 (±360) mg/dL. Metastases: lymph node 29%; hepatic 23%; pulmonary 21%; bone 18%; central nervous system 15%; peritoneal carcinomatosis 5%; stomach 3%; cauda equina 3%; adrenal 1%; in transit 1%; intestine 1%; bone marrow 1%; parotid 1%. BRAF mutations were present in 23% of cases (variants V660E, V600K, V660R, and G469R); NRAS 6% (codons 13 and 61); KIT 1% (exon 11) and NTRAK 1% (S701F). In relation to treatment, 5 received neoadjuvant anti-pd1 + anti-ctla4 combination, 13 adjuvant with anti-pd1+/- anti-ctla4. About 50 patients received systemic treatment for metastatic disease anti-pd1+/- anti-ctla4. Overall survival: 26 (±14.8) months. Conclusions: Atypical melanoma primary occult site is the most prevalent, with the majority diagnosed at stage IV, with high LDH levels and lymph nodes as the main sites of metastases. Twenty-three percent had a BRAF gene mutation. The majority were treated palliatively with first-line immunotherapy, with median survivals of 14.8 months.
Dendritic cell vaccine as a strategy to prevent melanoma recurrence after local resection: A systematic review and meta-analysis.
Authors: Silva Raquel Oliveira de Sousa , Freitas João Luís Reis , Gonçalves Ocílio de Deus da Rocha Ribeiro , Melão Bárbara , Neto Edgar Paulo da Silva , De Paiva Reis Camila Mariana de Paiva , Lech Gabriele Eckerdt , Viana Patricia , Morriello Rafael
Published: July 2024

e21561

Background: Melanoma has a high risk of recurrence and death even following complete surgical excision, specially in stages III and IV. Immunotherapy with checkpoint inhibitors, among other treatments, has been employed as adjuvant therapy in an effort to improve overall survival (OS) and disease free survival (DFS) in these patients. Cancer vaccines, particularly those based on dendritic cells loaded with tumor lysate particles (TLPLDC), have been investigated as new adjuvant therapy, these vaccines utilize autologous tumor lysate from an individual tumor, captured by dendritic cells to generate a personalized vaccine that stimulates an active cellular immune response. We conducted a meta-analysis to assess the effectiveness of these vaccines in patients with melanoma following complete resection. Methods: We searched in Pubmed, Cochrane and Embase in December 2023 for articles evaluating the effectiveness of TLPLDC vaccines on the recurrence and survival of patients with locoregional melanoma completely resected. The outcomes of interest included DFS for 3 years and OS for 2 and 3 years, comparing TLPLDC against the control. Additionally, we performed a subgroup analysis comparing an alternative TLPLDC technique named TLPLDC+G against the control. Random-effects models were employed to pool hazard ratios from studies using R software version 4.3.1. Results: We included 4 randomized controlled trials comprising 564 patients. The OS at the 3-year follow-up favored TLPLDC against control (logHR = -1.718[-2.697,-0.740], p = 0.0006,I² = 0%). In the 2-year comparison, treatment was also favored (logHR = -1.511,CI[-2.743,-0.279],p = 0.0162,I² = 36%). However, TLPLDC+G did not exhibit a statistically significant difference from the control in the 3-year long comparison (logHR = 0.043[-0.504,0.590],p = 0.8780,I² = 0%). Regarding the DFS in 36-month comparison, TLPLDC was favored with a 95% CI (logHR = -0.419,[-0.831,-0.006],p = 0.0468,I² = 48%). For TLPLDC+G, there was no statistical difference (0.269[-0.07,0.609],p = 0.1201,I² = 0%). Conclusions: Our results suggests that TLPLDC had a significant impact on OS at 2 and 3-year follow-up with a relatively low heterogeneity between the studies. Regarding the DFS, the TLPLDC group showed a significant difference favoring the vaccine; however, it presented higher heterogeneity. The TLPLDC+G subgroup did not exhibit a significant difference from control in both OS and DFS. Despite the favorable outcomes associated with the TLPLDC vaccine it is important to consider the potential effects of curve reconstruction, the limited number of studies, individual variations in patients immune responses, and differences in vaccine protocols between institutions as limitations of our analysis.
Mucosal melanoma treatment patterns and outcomes in real clinical practice: Single institution experience.
Authors: Samoylenko Igor , Stroganova Anna , Orlova Kristina V. , Kuzmenko Angelina , Martynova Margarita , Kogai Ekaterina , Nazarova Valery V. , Petenko Natalia N. , Demidov Lev V.
Published: July 2024

e21571

Background: Mucosal melanoma (MM) is a challenging malignancy to diagnose and treat, even with the advent of modern drug therapies. There is a lack of established surgical, radiological, or pharmacological treatment approaches for locally advanced or metastatic mucosal melanoma. This study analyzes the treatment practices and clinical outcomes at a single institution over a five-year period to understand real-world clinical practices. Methods: A сomprehensive, continuous, retrospective study analyzed medical records of adults with histologically confirmed MM at the N.N. Blokhin Russian Cancer Research Center from January 2018 to December 2023. Data was digitized into an electronic questionnaire, with patient follow-up conducted via telephone. Results: A total of 87 patients were identified, comprising 72 females (82.8%) from 31 regions of Russia. The median age was 67.8 years (ranging from 29.5 to 90.1 years). The patient breakdown was as follows: 6 with head&neck MM (6.9%), 41 with vulvovaginal MM (47.1%), 5 with penile MM (5.7%), 27 with anorectal MM (31.0%), and 8 with gastrointestinal MM (9.2%). A significant portion of the patients presented with locally advanced (22.9%) or metastatic disease (67.8%), while 9.2% of the patients had undergone surgery and were being considered for adjuvant treatment. The most common sites of metastasis were regional lymph nodes (23%), liver (14%), and lungs (11.5%), with one patient having CNS metastasis. Mutational status was determined for 48 of the 87 patients, revealing driver mutations in 12 patients (Table). The majority of patients were initially treated with immunotherapy. The most frequently used therapies included monotherapy with anti-PD-1 agents (nivolumab or pembrolizumab, accounting for 41.6%) and a combination of ipilimumab and nivolumab (33.3%). After a median follow-up of 17.7 months, the median overall survival (OS) for the entire cohort was 18.1 months (with a 95% confidence interval ranging from 6.8 to 23.2 months), showing no significant statistical differences in outcomes based on the location of the mucosal melanoma or the type of treatment received. Conclusions: Mucosal melanoma remains an under-researched malignancy. There is a critical need for prospective, randomized trials to explore more effective treatment options for patients with this condition. [Table: see text]
Immunosuppressant drug-associated skin cancer: A real-world pharmacovigilance database analysis.
Authors: Ananthaneni Anil , Jones Sarah , Nadeem Daniyal , Moore Sydney , Ghoweba Mohamed , Ramadas Poornima
Published: July 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: Triana Ivan Camilo , Cantor Rizo Erick Andres , Segovia Javier , Vargas Henry , Jaramillo Andres , Kattah Laura , Hernandez Isabel , Pino Luis Eduardo , Bustamante Lizeth , Sanabria Daniela , Murillo Silva John Alejandro , Bejarano Andres Felipe
Published: July 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.
Romiplostim for chemotherapy induced thrombocytopenia in solid tumors: A meta-analysis.
Authors: Sainatham Chiranjeevi , Singh Sahib , Agrawal Shubham , Dilli Babu Aravind , Vinnakota Sailaja , Tallapalli Jayanth Reddy , Jindal Vishal , Kumar Pallavi P. , Lutfi Forat , Patell Rushad , Paul Sonal
Published: July 2024

e24137

Background: Chemotherapy-induced thrombocytopenia (CIT), defined as platelets < 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.
Serial testing to assess cognitive function in patients with cancer being treated with immunotherapy.
Authors: Shahani Shobha , Ajrouch Ali , Hanna Nasser H.
Published: July 2024

TPS1644

Background: The advent of immunotherapy (IT) has revolutionized lung cancer treatment, becoming a primary modality from Stages Ib to IV. While the short-term side effects of IT are well documented, its long-term impact on cognitive function are under explored. This is a crucial area of investigation given the significant impact of cognitive health on the quality of life in cancer survivors. Preclinical investigations suggest neurocognitive alterations in IT-treated patients, evidenced by increased microglial activation and cytokine release, contributing to observed cognitive deficits such as impaired cued fear memory and object recognition. This study leverages the Montreal Cognitive Assessment (MoCA) to investigate these potential cognitive changes in a clinical setting, aiming to provide crucial insights into the long-term effects of IT. Methods: This single-center, open-label pilot study enrolls patients with various cancer types and stages undergoing IT. Exclusion criteria include prior history of underlying cognitive dysfunction, dementia, depression or psychiatric illness, history of brain metastasis or radiation. The study compromises three cohorts: those receiving IT alone, those undergoing chemo-immunotherapy, and a control group with no active treatment (in remission with prior history of cancer and have received IT in the past). Each of the IT and chemo-immunotherapy groups will include 72 patients, while the control group will consist of 40 participants. Baseline cognitive function is assessed using the MoCA scale, with follow-up assessments at 3 and 6 months from baseline. Patient enrollment commenced in April 2022, with 4 patients enrolled in the IT group, 16 in the chemo-IT group, and 32 in the control group. The primary objective is to assess the Cognitive function change in each individual group of patients. The secondary objective is to assess change of MoCA scores after 3 months and 6 months in patients receiving immunotherapy alone in lung cancer patients. The changes in MoCA scores will be plotted and summarized with mean change, standard deviation of change and standard errors of mean change. MoCA scores at baseline and at 6 months will be compared using paired t-tests. The study will analyze the rate of change in MoCA scores over time, comparing outcomes across the treatment cohorts. Clinical trial information: NCT06160700 .
ESORES-Trial: Surgery as needed versus surgery on principle in patients with postneoadjuvant clinical complete tumor response of esophageal cancer.
Authors: Hipp Julian , Bruns Christiane J. , Schmoor Claudia , Weis Joachim , Hoeppner Jens
Published: July 2024

TPS4185

Background: A substantial fraction of patients with esophageal cancer (EC) shows post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients. Active surveillance (AS) and surgery as needed may be a treatment alternative for patients with clinical complete response (cCR). Methods: ESORES is a multicenter randomized controlled parallel-group non-inferiority trial. Patients are randomized either to surgery on principle and subsequent follow-up (Arm B) or clinical response evaluation (CRE) and surgery as needed (Arm A). CRE consists of esophagogastroscopy with deep biopsies (EGD), endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) of suspicious lymph nodes, and F18-FDG-PET CT. In case of residual tumor (non-CR) after CRE, treatment is surgery. Patients with cCR will proceed with AS and surgery only if local regrowth occurs. AS comprises EGD, EUS-FNA and CT-Thorax/Abdomen at 3/6/9/12/18/24 months and yearly thereafter. A sample size of 670 patients is needed to demonstrate non-inferiority of Arm A vs. Arm B with regard to overall survival (OS) at a one-sided significance level of 5%, choosing a hazard ratio of 1.325 as non-inferiority margin which corresponds to a difference in 3-year OS rates of 8%. Superiority with regard to quality of life will be evaluated hierarchically only after non-inferiority with respect to OS has been shown. Key inclusion criteria: histologically verified EC, TNM stage ycT0-3 ycN0 ycM0, completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT) (irrespective of specific protocol), no visible lymphatic or distant metastasis in routine postneoadjuvant CT. Key exclusion criteria: postneoadjuvant dysphagia and/or esophageal obstruction, tumors of the cervical esophagus, tumors with direct proximity to the membranous part of the central airways (if regrowth is suspected to evoke locally irresectable ryT4b-stage), TNM stage cT4/ycT4 and/or cM1/ycM1, tumor progression during/after nCT/nCRT, and nCRT with >50 Gy radiation dose. Primary endpoints (hierarchically tested): 1) OS, 2) EORTC QLQ C30 global quality of life subscale. Secondary endpoints: Efficacy: long term tumor control, disease free survival, distant metastasis/local recurrence/regional recurrence; quality of life: EORTC QLQ C30, QLQ OES18, fear of progression: FoP-Q-12, surgery-free survival time in Arm A, patients’ satisfaction: EORTC OUT-PATSAT7; economic impact: days and costs of hospitalization; Safety: Interventional Safety: 3-Year-Comprehensive Complication Index, Oncological Safety (diagnostic accuracy of CRE, resection status (R0/R1/R2), irresectable regrowth during AS). Enrollment of patients started on January 30th, 2024. Clinical trial information: DRKS00032613 .
QUIC: Phase 2 study of gemcitabine, cisplatin, quemliclustat (AB680), and zimberelimab (AB122) during first-line treatment of advanced biliary tract cancers (BTC)—Big Ten Cancer Research Consortium study BTCRC-GI22-564.
Authors: Ebben John , Eickhoff Jens C. , Deming Dustin A. , Hochster Howard S. , Turk Anita Ahmed , Sahai Vaibhav , Uboha Nataliya Volodymyrivna
Published: July 2024

TPS4195

Background: Despite recent approvals of immune checkpoint inhibitors with chemotherapy in the first-line setting, the median overall survival (mOS) for patients with advanced biliary tract cancer (BTC) remains less than 15 months. CD73 is a key enzyme responsible for the conversion of extracellular adenosine 5’-monophosphate into adenosine and may play an important role in creating an immunosuppressed tumor microenvironment. High expression of CD73 in BTC is associated with decreased OS. Quemliclustat (Q) is a potent, selective, reversible inhibitor of CD73. Q in combination with chemotherapy has demonstrated promising activity in patients with advanced pancreatic cancer without significant increase in adverse events. The BTCRC-GI22-564 study evaluates safety and preliminary efficacy of Q in combination with zimberelimab (Z), a monoclonal antibody targeting human PD-1, with gemcitabine and cisplatin (GC) as first-line therapy for patients with advanced BTC, QUIC (Q and Immunotherapy in Cholangiocarcinoma). Methods: This is an open label, single arm, phase II multi-site trial, evaluating Q and Z in combination with GC in patients with advanced BTC who have not received systemic treatment for advanced disease or who completed adjuvant therapy > 6 months prior to development of recurrent disease. Chemotherapy is given on days 1, 8, 22 and 29 of each 42-day cycle as per local standards. Z is administered at a fixed dose of 360 mg via IV infusion every 3 weeks. Q is administered via IV infusion on days 1, 15, and 29. A safety run-in portion built into the study is planned to enroll 6 subjects to ensure there are no dose limiting toxicities (DLT). If a study defined DLT is observed, Q, gemcitabine and cisplatin will be reduced by 1 dose level, and an additional 6 subjects will be enrolled in the safety run-in portion. The primary efficacy endpoint is median progression free survival (mPFS) with null and alternative survival of 6.0 and 10.0 months, respectively. Based on an accrual rate of 3 patients per month, we expect to accrue 33-39 patients which will provide at least 83% power with a one-sided alpha of 0.1. Secondary endpoints include mOS, disease control rate, overall response rate, and duration of response. Correlative endpoints will assess clinical outcomes with immune infiltration within tumor microenvironment, CD73 and PD-L1 expression. The QUIC study is currently open to enrollment through BTCRC. Clinical trial information: NCT06048133 .
VIRAGE: A phase IIb, open-label, randomized study of nab-paclitaxel and gemcitabine plus/minus VCN-01 in patients with metastatic pancreatic cancer.
Authors: Garcia-Carbonero Rocio , Pazo Cid Roberto , Macarulla Teresa , Nguyen Alana , Kim Edward , Laquente Berta , Seery Tara Elisabeth , Cazorla Mireya , Guillen-Ponce Carmen , De Castro Eva Martinez , Anton-Pascual Beatriz , Muñoz Martín Andrés J. , Lobo Miriam , Garrido-Laguna Ignacio , Le Charles , Kaleko Michael , Shallcross Mary Ann , Blasco Carmen , Cascallo Manel , Hidalgo Manuel
Published: July 2024

TPS4210

Background: VCN-01 is a modified oncolytic adenovirus type 5 (Ad5) designed to replicate selectively in cancer cells with a dysfunctional RB1-E2F pathway and express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. Results obtained in a previous phase I trial in patients with solid tumors, including metastatic pancreatic cancer, showed that a single systemic administration of VCN-01 is feasible and has an acceptable safety profile alone or when combined with standard of care chemotherapy (SoC) nab-paclitaxel plus gemcitabine (NCT02045602). VCN-01 reached and replicated in tumors and encouraging biological and clinical activity was observed when administered in combination with SoC to patients with metastatic pancreatic adenocarcinoma (mPDAC). Based on the promising phase I results, a phase IIb, open-label, randomized study was initiated to evaluate treatment with two doses of VCN-01 in combination with nab-paclitaxel and gemcitabine in patients with mPDAC. Methods: VIRAGE is a multi-center, open label, randomized, 2-parallel arm, phase IIb trial that evaluates the safety, tolerability and efficacy of two separate VCN-01 intravenous administrations (1x1013 vp/dose) in combination with SoC (nab-paclitaxel at 125mg/m2 and gemcitabine at 1000mg/m2 ) as first line treatment in chemonaïve mPDAC patients. A total of 92 subjects in North America and European Union will be recruited and randomized (1:1) to receive either SoC nab-paclitaxel and gemcitabine (on days 1, 8 and 15 of each 28-day cycle) (Arm I), or doses of VCN-01 administered 1 week prior to SoC nab-paclitaxel and gemcitabine in each of cycle 1 (week 1) and cycle 4 (week 14) (Arm II). Cycles 1 and 4 of Arm II will be 35-day cycles to accommodate VCN-01 dosing, while all other SoC cycles will be 28 days. Patients will continue study treatment until progressive disease (PD), unacceptable toxicity or patient’s/investigator’s decision. The primary endpoint is overall survival (OS) and the assessment of safety and tolerability of two intravenous doses of VCN-01 added to SoC. The secondary objectives include time-to-progression (TTP), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of the response (DoR), 1-year OS and PFS rates, and serial changes in tumor markers (Ca19.9). At 31 Jan 2024, the enrollment is ongoing in US and Spanish sites. Clinical trial information: NCT05673811 .
Phase 2 randomized study of rintatolimod following FOLFIRINOX in patients with locally advanced pancreatic adenocarcinoma.
Authors: Klute Kelsey , Picozzi Vincent J. , Gabrail Nashat , Hollingsworth Michael A. , McAleer Christopher , Young Diane , Strayer David Rodney
Published: July 2024

TPS4214

Background: The immunosuppressive microenvironment of pancreatic ductal adenocarcinoma (PDAC) is a driver of its lethality and resistance to immunotherapy. Strategies which modulate the immunosuppressive milieu have the potential to improve the anti-tumor response and improve outcomes in patients with PDAC. Rintatolimod is a synthetic double-stranded RNA molecule that activates the toll-like receptor 3 (TLR3) present on dendritic cells, B-cells, natural killer cells and pancreatic epithelial cells. TLR3 stimulation may increase cytotoxic T-cell activity in PDAC through dendritic cell maturation, antigen priming and downstream proliferation of cytotoxic T-cells. Twenty-seven patients were treated with rintatolimod in a single center Named Patient Program at Erasmus University Medical Center in Rotterdam between January 2017 and February 2019. All had locally advanced or metastatic PDAC which had not progressed on FOLFIRINOX (median 8 cycles). Maintenance rintatolimod, administered intravenously twice weekly for up to 18 weeks, was generally well tolerated. The most common toxicities were grade 1-2 myalgia (30%), chills (52%) and fatigue (30%); no toxicities ≥ grade 3 were observed. Progression-free and overall survival (from cycle 1 FOLFIRINOX) were 13 and 19 months. Methods: This is a phase 2 randomized, open-label, multicenter clinical trial. The primary objective is to assess the efficacy of rintatolimod compared to observation in subjects with locally advanced PDAC which has not progressed after FOLFIRINOX. Eligible patients have completed at least 4 months of FOLFIRINOX, have no evidence of progressive disease, have measurable disease by RECIST v1.1, Karnofsky Performance Status ≥80 and have adequate organ function. Subjects with resected PDAC or metastatic disease are not eligible. Subjects are randomized 2:1 to rintatolimod vs. observation. Rintatolimod is administered intravenously twice weekly until disease progression in the experimental arm. Cross-sectional imaging is performed every 8 weeks in both arms. The primary endpoint is progression-free survival, as assessed by the investigator. Secondary endpoints include overall survival, objective response rate, duration of response and safety, as assessed by CTCAE v5.0. Exploratory endpoints include quality of life and changes in immune cell composition and T-cell response in the peripheral blood to characterize the immunomodulatory effects of rintatolimod. The planned sample size is 90 subjects. The final analysis will be performed after 64 events (disease progression or death) have been observed. The study is powered to detect a hazard ratio of 0.47 for median PFS with 80% power and significance level of 5%. Clinical trial information: NCT05494697 .
A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in patients with metastatic appendiceal adenocarcinoma.
Authors: Shen John Paul Y.C. , Ito Ichiaki , Yousef Abdelrahman M.G. , White Michael , Fournier Keith F. , Helmink Beth A
Published: July 2024

TPS4215

Background: Appendiceal cancer is a rare, orphan disease, that is unfortunately becoming more common. There is growing data from our lab and others that particular subtypes of AA do not respond to CRC chemotherapy. The use of CRC chemotherapy to treat patients with AA tragically results in many patients enduring side effects from chemotherapy that is ineffective; however, this practice will likely continue unless AA-specific treatments are developed. The Shen lab has recently tested IP paclitaxel (PTX) in orthotopic PDX models of AA. After allowing implanted tumors to grow for four weeks to simulate diffuse peritoneal metastases, baseline MRI was performed and mice were randomly assigned to treatment groups of four mice and intraperitoneally (IP) administered increasing doses of PTX. Marked response was seen in all three models at dose of 25 mg/kg IP weekly, with a near complete response in model AAPDX-10. This dose given IP was well tolerated by the mice, notably this dose exceeds the know lethal IV PTX dose. Methods: The Phase I component of this study will be a prospective single-arm intervention trial giving IP PTX every 2 weeks for a total of 5 doses with primary endpoint of safety and tolerability (MTD determination). Each patient will have an initial diagnostic laparoscopy where PCI score will be calculated and IP catheter placed, dx lap is repeated at the end of study after 5 biweekly doses. For the Phase 1 portion of the trial a Bayesian Optimal Interval (BOIN) approach will be used to determine recommended phase 2 dose (RP2D). All patients treated at that dose or higher will be included in Phase 2 component of the study where the primary objective is response, determined by change in PCI score. With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going on trial is 0.05, i.e., the null hypothesis is a 0.05 ORR. Treatment is expected to raise this proportion to 30%. Using an exact binomial test with one-sided type I error of 0.05, we will reject the null if at least 3 patients achieve response. This test has power of 87%. Secondary end points include pathologic, biochemical and radiographic response, PFS, OS, and the influence of KRAS/GNAS/TP53 mutation on response. PK measurements will also be performed during the Phase 1 portion of the trial to determine the degree to which the IP injected PTX enters the blood stream. Patients will be followed for up to 1 year. Adverse events (AEs) will be captured and graded using the National Cancer Institute’s (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 (or latest version) and will include the event term, grading, duration and attribution. Attribution to the study agent or intervention will be determined by the PI, Co-PI or treating physician. Clinical trial information: NCT06207305 . [Table: see text]
Open-label, phase 2 study of adebrelimab combined with fuzuloparib in the treatment of patients with HRD-positive, recurrent platinum-resistant ovarian cancer.
Authors: Chen Jian , Zou JianPing , Yu Haijuan , Liu Li , Zang Lele , Sun Yang
Published: July 2024

TPS5634

Background: Adebrelimab, a humanized anti-PD-L1 monoclonal antibody, selectively targets PD-L1 molecules to inhibit the PD-1/PD-L1 pathway, reversing tumor-induced immune tolerance and revitalizing the immune system's capacity to combat tumors. Fuzuloparib, a novel PARP inhibitor, impedes the activity of poly (ADP-ribose) polymerase, halting the DNA repair mechanism for single-stranded breaks, resulting in DNA damage accumulation and consequent cancer cell apoptosis. Emerging evidence strongly supports that PARP inhibitors significantly extend progression-free survival in homologous recombination-deficient (HRD)-positive ovarian cancer. The TOPACIO study demonstrated that the combination of niraparib and pembrolizumab for platinum-resistant ovarian cancer achieved an objective response rate (ORR) of 18%, with durable responses in patients. This underscores the potential of integrating PARP inhibitors with immune checkpoint inhibitors in clinical protocols. For platinum-resistant recurrent ovarian cancer, known for its challenging prognosis, we propose conducting exploratory clinical trials on the combination of adebrelimab and fuzuloparib, aiming to establish robust evidence for future clinical applications. Methods: This open-label, single-arm, Phase 2 study aims to evaluate the anti-tumor activity and safety of adebrelimab in combination with fuzuloparib in approximately 37 patients with HRD-positive, recurrent platinum-resistant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (hereinafter referred to as ovarian cancer). The primary endpoint is to determine the objective response rate of the combined treatment regimen, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints encompass disease control rate, progression-free survival overall survival, along with the assessment of safety and tolerability. Patients must be aged 18-70 years with an Eastern Cooperative Oncology Group performance status of 0–1 and have recurrent histologically confirmed ovarian cancer with HRD-positive tumor. Patients must have progressed within less than 6 months after the last treatment with platinum-containing chemotherapy. HRD status confirmed by testing BRCA gene, loss of heterozygosity, telomeric allelic imbalance and large-scale transition. Adebrelimab (20 mg/kg) is administered intravenously every 3 weeks and fuzuloparib (100mg) is administered orally twice daily as until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met. This clinical trial is in progress and 7 patients have been enrolled. Clinical trial information: NCT05753826 .