bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermatologic adverse events in EGFR-TKIs: A real-world analysis.
Authors: Paton Emily , Friedman Ryan Jeremy , Cetnar Jeremy Paul
Published: July 2024

e20572

Background: Dermatologic adverse events (DAEs) affect a significant number of patients with non-small cell lung cancer (NSCLC) who are treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). While many DAEs have been identified during clinical trials and included in FDA drug labels, patients have raised concerns about experiencing unexpected DAEs. This study reviews the FDA Adverse Events Reporting System (FAERS) to identify DAEs in EGFR TKIs approved in NSCLC that are not included in drug labels. Methods: FAERS was queried for DAEs between 2003 – 2023 for osimertinib, afatinib, ertlotinib, gefitinib and mobocertinib. The reporting odds ratio (ROR) was calculated to compare DAEs between these EGFR-TKIs and all other drugs in the database. DAEs were considered statistically significant if the lower limit of the ROR 95% confidence interval (CI) was > 1 and if there were ≥ 3 reported adverse reactions. Results: 67,480 adverse events were reported for the 5 EGFR-TKIs studied. DAEs constituted 30.3% (20,426) of all adverse event reports. We identified skin (skin fissures, eczema, lip swelling, and skin infection), nail (onychalgia and onychomadesis), and hair (abnormal hair growth and hair disorder) DAEs not previously included in EGFR-TKI drug labels. RORs with 95% CIs are summarized in the table. Conclusions: Real-world FAERS data complements clinical trial data in identifying specific DAEs affecting NSCLC patients treated with EGFR TKIs. Our findings highlight DAEs that were previously not described, aiding clinicians in educating patients about side effects and giving patients a more nuanced understanding of what to expect before undergoing treatment. [Table: see text]
PD-(L)1 inhibitors plus bevacizumab and chemotherapy as first-line therapy in PD-L1 negative metastatic lung adenocarcinoma: A real-world data.
Authors: Ge Yihui , Sun Yuping , Gao Aiqin , Li Juan , Wang Dahai , Wu Jiake , Sun Yanxin , Sun Haifeng , Sun Haodong , Li Jie
Published: July 2024

e20577

Background: Chemotherapies combined with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC and IBC respectively) are the preferred first-line options for PD-L1 negative and oncogenic driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined. Methods: This retrospective real-world study enrolled PD-L1 negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated. Results: A total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. Patients receiving IBC obtained the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those receiving IC (40.4%, 84.2%) or BC (40.5%, 96.2%). Compared with the IC (6.74m) or BC (8.28m) group, IBC group improved significantly median progression-free survival (mPFS) (9.53m, P = 0.005). However, the difference in overall survival (OS) were not observed among the three groups. When analyzed based on different clinical and molecular information, we found that male gender, ever smoking, wild-type genes, and adrenal metastasis predicts superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment achieved better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups. Conclusions: Combined IBC treatment achieved superior DCR and PFS compared with IC or BC treatment in patients with PD-L1 negative metastatic lung adenocarcinoma, while did not increase the adverse events.
Pre-treatment CT radiomics for predicting immunotherapy response in non-small cell lung cancer(NSCLC): RECIST vs. irRECIST criteria.
Authors: Yadav Monica , Lee Jeeyeon , Kim Haseok , Lee Seyoung , Um Taegyu , Lee Salie , Djunadi Trie Arni , Chung Liam IL-Young , Yu Jisang , Rodrigues Darren , Gennaro Nicolo , Kim Leeseul , Nam Myungwoo , Kim Yuchan , Hong Ilene , Jang Jessica , Kang Grace , Cho Amy , Velichko Yury , Chae Young Kwang
Published: July 2024

e20613

Background: Accurate prediction of how patients with non-small cell lung cancer (NSCLC) will respond to immunotherapy is essential for customizing individual treatment plans. This research explores the use of radiomics analysis from pre-treatment CT scans as a method to predict the effectiveness of immunotherapy in individuals with NSCLC. Methods: This IRB-approved retrospective study investigated radiologic and clinical data from 159 patients with stage III-IV NSCLC treated with immunotherapy. Imaging responses were assessed according to RECIST 1.1 and immune-related RECIST (irRECIST) criteria at least twice during a 24-week period. Responses were categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). 3D radiomics features were extracted from both the tumor and a 1 cm thick peritumoral region. A linear mixed-effect harmonization model was employed to correct for scanner-associated variations. A Random Forest algorithm was used to develop a classification model to predict response according to RECIST 1.1 or irRECIST. The dataset was split into training (70%) and test (30%) sets. The accuracy of predictions was evaluated using confusion matrix statistics and bootstrapping with 1,000 iterations for median and 95% confidence interval (CI). Results: Using RECIST 1.1 criteria, 41 patients (25.2%) achieved PR and CR(0.6), 62 (39.0%) achieved SD, and 56 (35.2%) achieved PD. IrRECIST criteria yielded slightly higher CR/PR rates with 52 patients (32.7%), while SD decreased to 65 (41.0%) and PD remained at 42 (26.4%). For predicting CR/PR and SD responses, the models achieved a sensitivity of 0.45 (95% CI: 0.38-0.50) and 0.64 (0.60-0.68) for irRECIST, compared to 0.34 (0.28-0.38) and 0.55 (0.52-0.60) for RECIST 1.1. The corresponding specificity was 0.85 (0.83-0.87) and 0.63 (0.59-0.67) for irRECIST, compared to 0.91 (0.89-0.93) and 0.67 (0.63-0.72) for RECIST 1.1. For predicting PD response, the models achieved a sensitivity of 0.49 (0.45-0.56) for irRECIST and 0.57 (0.52-0.62) for RECIST 1.1. The models' balanced accuracy for predicting CR/PR, SD, and PD were 0.65 (0.61-0.68), 0.64 (0.61-0.67), and 0.65 (0.63-0.69) for irRECIST, compared to 0.62 (0.59-0.64), 0.61 (0.59-0.64), and 0.62 (0.59-0.64) for RECIST 1.1, respectively. Conclusions: This study demonstrates the potential of pre-treatment CT radiomics to predict immunotherapy responses in NSCLC patients, offering insights into personalized treatment approaches. However, larger studies are needed to validate our findings.
Double lung transplantation in patients with recent history of malignancy.
Authors: Demir Tarik , Bharat Ankit , Chung Liam IL-Young , Woo Wongi , Moloney Carolyn , Jung Chan Mi , Tomic Rade , Chae Young Kwang
Published: July 2024

e20614

Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]
Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.
Authors: Cohen Sara Frida , Cruiziat Diane , Naimer Jeremy , Cohen Victor , Kasymjanova Goulnar , Spatz Alan , Agulnik Jason Scott
Published: July 2024

e20618

Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]
Enhancing oncologist knowledge and skills through patient-centric medical education: A collaborative approach with LUNGevity.
Authors: Wilfong Kadrin , Beyer Michael , Basu Roy Upal Kunal , Martin Nikki A. , Liu Stephen V. , Wills Dana , Drew Heather
Published: July 2024

e21007

Background: Patient centricity in healthcare delivery has evolved, driven by accumulating evidence of improved outcomes through patient empowerment. PeerView partnered with LUNGevity Foundation to develop multiple educational initiatives with a patient-centered approach to lung cancer care. Methods: 4 live events and 4 online enduring activities were developed to improve the knowledge and skills of oncologists and other healthcare professionals (HCPs) involved in the management of patients with small cell and non–small cell lung cancer. These initiatives followed a patient-centric approach, featuring: Learning objectives addressing incorporation of patient-centric approaches to provision of optimal and equitable lung cancer care in two of the activities; LUNGevity input on the co-creation and development of the activities, including curriculum planning, identifying faculty, highlighting advocacy resources, and incorporating the patient voice; Expert discussions framed with patient perspectives and illustrative case scenarios to highlight strategies for improving team-based collaboration, patient engagement, shared decision-making, and health equity in clinical care and research; Unique instructional elements, including patient focus group insights and video role play; and Tools designed to enhance clinician-patient communication, patient engagement in care, and shared decision-making Pre- and post-activity assessments included multiple choice questions to measure changes in knowledge and skills and Likert-style questions assessing intent to change practice. Responses from enduring activity participants were also compared with those from a matched sample of nonparticipants. Results: To date, 11,227 learners, including 8,112 oncologists, have participated in these activities. Substantial post-activity gains were consistent across all initiatives, with a 44-ppt average increase in knowledge and skills. Outcomes related to patient-centric care included increases of: 38 ppt in ability to implement team-based and patient-centric approaches to ensure timely and accurate diagnosis, appropriate biomarker testing, individualized treatment, and equitable care of all patients with NSCLC (43% to 81%); 44 ppt in ability to implement team-based and patient-centric approaches to ensure optimal and equitable use of immunotherapy in the care of all eligible patients with NSCLC (39% to 83%); and 15 ppt in intent to provide education, guidance, and resources to patients with lung cancer (68% to 83%). Conclusions: These initiatives demonstrated significant improvements in learner knowledge, skills, and confidence across all learning objectives. Furthermore, incorporation of patient-centric approaches represents an effective model for clinical education to increase HCPs’ compassion, empathy, and ability to provide effective and holistic patient care.
Effect on patient empowerment through the EPEP program.
Authors: Diallo Aicha , Rode Tracy T.
Published: July 2024

e21009

Background: There is a critical need to support oncology providers seeking to empower their patients and care partners by connecting them to trusted resources. To fill this gap, the Patient Empowerment Network (PEN) created the Empowering Providers to Empower Patients (EPEP) program to improve physician-patient communication and shared decision-making by creating a clear path to support providers in empowering their patients and care partners. Methods: The EPEP program, developed by an interdisciplinary team of experts for oncology health care professionals, launched in March 2023 with a focus on lung cancer resources. The program includes digital resources such as Roundtables (30-minute webinars + segments with leading experts, clinicians, and peers), an HCP Portal (a system that informs and collates vetted resources), a Resource Guide (resource guide for HCPs), and a Roundup Blog (article with key takeaways summarizing program). Following two roundtables in March 2023, we assessed initial provider engagement with EPEP using digital engagement metrics and a five-item questionnaire. Results: Since the launch, 212 oncology providers have access to the suite of digital resources. The content has been viewed and downloaded almost 13,595 times. Surveys conducted following the roundtables indicated that the program was well-received. Of 21 respondents, n=18 (86%) rated their experience as very positive; agreed or strongly agreed that the program gave them the confidence to better facilitate shared decision-making with their patients; and said they found relevant resources to share with their patients and their families. Sample feedback included, “I would say it gave me the confidence to raise the flag on timing. Sometimes we test and are not doing this in a timely way. Thanks for this program.” And “These conversations are so critical. Thank you for a great program.” And, “I thought the conversation was excellent; we need more of this. I thought the tips were spot-on and very helpful.” Providers wanted communication tools focused on the “timing of testing following the initial workup,” “pathology conversations” and “anxiety and fear after the cancer diagnosis, long-term side effects, screening and early detection of lung cancer.” Conclusions: The EPEP program serves as a trusted digital space for providers to objectively share and recommend resources to their oncology patients. The program now includes removing practice barriers that may be caused by a lack of awareness and outdated practices. The long-term goal is to improve physician-patient communication and shared decision-making while also empowering cancer patients and family members to ask informed questions based on where they are in their cancer journey.
Community oncology preparedness and perceptions of challenges in care with HER2/HER3 therapy for NSCLC.
Authors: Ackbarali Tariqa , Cohen-Solal Karine , Bazhenova Lyudmila , Janne Pasi A.
Published: July 2024

e21010

Background: The rapid pace of advances in molecular testing and targeted treatment for non-small cell lung cancer (NSCLC) can make it difficult to stay up to date with new developments. Accelerating the integration of practice-changing data requires clarification of actionable vs non-actionable mutations, relevance for therapeutic decisions, and treatment options for patients. To address this need further an educational program was designed in 2023. Methods: A one-hour online, video-based program was designed for clinicians and their teams and hosted on OMedLive from February 2023. Knowledge and competence questions were administered pre-, and immediate post-activity. and the intersection of patient and clinician perspectives, including behavioral impact, and qualitative insights. Behavioral impact, perception, and practice pattern questions were also assessed immediately post-activity. Results: More than 1,700 participants have engaged in the educational program to date. Of the participants in the clinician program, 94% were physicians and 93% noted their specialty as oncology with 67% identifying as treaters seeing an average of 8 patients with NSCLC on a monthly basis. Low baseline (8% - 40%) knowledge and competence was observed for awareness of NGS-based approaches to detect ERBB2 mutations, trial eligibility criteria and outcomes, time to onset of drug-related toxicities, and ability to identify patients who would benefit from clinical trials with HER3 investigational therapies. Only 28% were confident in their ability to appropriately test for HER2 mutational status and 47% likely to incorporate testing for HER2 expression level or amplification prior to the selection of targeted therapy. The greatest challenges in managing patients with HER2-mutated NSCLC was identified as managing side effects (33%), affordability of therapy for patients (27%), and adherence to treatment schedules (17%). Conclusions: The outcomes of this educational program demonstrate a need for greater alignment and education among pathology and oncology team members on HER2 testing for patients with NSCLC. Additional education is needed relevant to investigational HER3 therapeutics, the appropriate patient to receive these therapies, and the potential application within the current treatment landscape. As these agents deepen their impact in the NSCLC landscape, it is important to prepare teams for timely management of adverse events.
Tracking the information-seeking patterns and preferences of US-based medical oncologists (MOs): A 2-year longitudinal assessment.
Authors: Love Neil , Paley Douglas , Dvorkin Jennifer , Cerenzia Wendy
Published: July 2024

e21012

Background: The rapid pace of scientific advancement demands that community-based MOs continually access new information and effectively apply it in their clinical practices to improve long-term patient outcomes. A variety of dissemination vehicles are currently available to facilitate the transfer of knowledge, including continuing medical education (CME) activities. Despite the significant resources allocated for the development of these modalities, little definitive data is available documenting MOs’ preference for, utilization of and perspectives on the benefits and limitations of CME. This longitudinal assessment sought to establish a baseline understanding of MOs’ patterns of engagement with CME activities following the upheaval caused by COVID, and gauge if and/or how this has shifted as the pandemic has subsided further. Methods: In April 2022 a 56-question online survey was distributed to 4,623 US-based MOs from a proprietary database. A small honorarium was offered for participation. Responses were collected from 83 MOs. A 2-year follow up assessment is planned for April 2024 to track changes in preferences and participation. Results: 83% of MOs “agree” or “strongly agree” that the pace of oncology advancements is quicker now than it was in the past yet only 25% spend more time accessing CME. On average, MOs dedicate 6 hours a week to seeking oncology-related information, in which utilization of CME activities is included. MOs believe CME activities are useful for helping to stay up to date with advances in oncology (3.5 on a 1-5 scale) and 55% believe the application of new and emerging therapies within oncology would be slower if CME was no longer available. MOs are most interested in CME activities featuring practically oriented topics including recently presented clinical trial findings , molecular testing and analysis and treatment sequencing . Notably, the highest-ranking MO consideration for participation in a CME program was the topic, followed by faculty and then the length of the activity. In terms of length, MOs preferred 30-to-60-minute programs rather than shorter (15 minutes or less). All surveyed MOs utilize some form of CME with preferences varying for different virtual, live in-person and enduring formats. Despite its wide-scale proliferation, only 34% of MOs use social media for professional purposes including accessing oncology education. Conclusions: MOs value CME activities and utilize both in-person and virtual programs on a regular basis. As concerns over COVID have diminished, it is predicted that established interest in asynchronous forms of education will wane with an increased shift toward in-person meetings. The results of this longitudinal study are critical to ensure that oncology CME resources are designed to effectively convey needed information and in turn positively affect patient care.
Tucidinostat plus toripalimab in patients with unresectable or metastatic melanoma: An open-label, single-arm phase II study.
Authors: Mao Lili , Dai Jie , Bai Xue , Kong Yan , Sheng Xinan , Chi Zhihong , Cui Chuanliang , Lian Bin , Tang Bixia , Yan Xieqiao , Wang Xuan , Li Siming , Zhou Li , Wei Xiaoting , Li Juan , Li Caili , Duan Rong , Xu Huayan , Guo Jun , Si Lu
Published: July 2024

e21527

Background: Acral and mucosal melanoma respond poorly to anti–PD-1 monotherapy. Tucidinostat, a benzamide class of histone deacetylase (HDAC) inhibitor, potentially augments immunotherapy with PD-1 blockade. We therefore conducted a phase II study to investigate the safety and efficacy of tucidinostat plus toripalimab in unresectable or metastatic melanoma. Methods: This was a single center, single arm phase II clinical trial. Patients with pathologically confirmed locally advanced unresectable or metastatic melanoma were enrolled and received 30 mg tucidinostat orally twice a week and 240 mg toripalimab every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was the confirmed ORR per RECIST v1.1. Secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: Between October 2022 and May 2023, a total of 21 patients(pts) were enrolled. All pts were included in the safety analysis set and 18 pts were included in the full analysis set (FAS) for efficacy analysis. In the FAS, the median age was 56.0 years (range: 49 to 60), 6 pts (33.3%) were acral melanoma, 9 (50.0%) mucosal melanoma, 1 (5.6%) cutaneous melanoma and 2 (11.1%) unknown primary melanoma. 15 pts were treated as first-line, and 3 pts were as second-line. By Dec 2023, the median follow-up was 8.8 mo (95% CI:7.6-10.4) , Confirmed ORR was 27.8% (95% CI:9.7-53.5%). The DCR was 61.1% (95% CI:35.7-82.7%). Median progression-free survival was 4.1 months (95%CI: 1.4-NR) ,OS was not reached. Subgroup analysis showed that, in acral and mucosal melanoma pts, the confirmed ORR was 50.0%(95%CI:11.8-88.2%) and 22.2%(95%CI: 2.8-60.0%), respectively. The incidence of treatment-related adverse events (TRAEs) was 90.5% (19/21). The most common ≥3 grade TRAEs were neutrophil reduction (28.6%), white blood cell count reduction (9.5%), alanine aminotransferase increase (9.5%), platelet count reduction (9.5%), aspartate aminotransferase increase (9.5%), and γ-glutamyl transferase increase (9.5%). No treatment-related deaths occurred. Conclusions: The combination of tucidinostat and toripalimab showed acceptable safety and encouraging efficacy in patients with unresectable or metastatic melanoma. Further research is warranted. Clinical trial information: NCT05478473 .
PD-1 inhibitors versus conventional therapies for adjuvant treatment of resected acral melanoma: A systematic review and meta-analysis.
Authors: Xu Yu , Li Tong , Sun Wei , Yan Wangjun , Wang Chun-Meng , Hu Tu , Zhang Xiaowei , Luo Zhiguo , Liu Xin , Chen Yong
Published: July 2024

e21555

Background: Acral melanoma (AM) is a rare and aggressive melanoma subtype with unique characteristics in western Caucasian population, but mostly prevalent in Asian population. FDA has approved pembrolizumab and nivolumab for the adjuvant treatment of melanoma. However, its role in AM is still unclear. In US and mainland of China, high-dose interferon alfa was once approved, while in other part of the world, there was no standard treatment for adjuvant therapy of AM. Thus, we performed a meta-analysis to summarize the efficacy of anti-PD-1 monotherapy in patients with AM in adjuvant setting and derive implications for early-stage AM management. Methods: A systematic review of electronic databases was conducted to identify studies that assessed relapse-free survival (RFS) and overall survival (OS) between adjuvant PD-1 and conventional therapy (interferon (IFN) / chemotherapy) or observation alone in patients with AM. RFS was the primary endpoint, OS was the secondary endpoint. We estimated RFS/OS using the fixed-effect model. Statistical analyses in our study were carried out using Stata 12.0 (Stata Corp LP, College Station, TX, USA). Results: Five retrospective studies that totally involving 516 patients with AM were recruited, including 3 China studies and 2 non-China studies. Among them, there were 260 PD-1, 74 IFN, 178 OBS and 4 chemotherapy, respectively. Adjuvant PD-1 inhibitor achieved better efficacy than conventional therapy, showing significant improvement both in RFS (HR 0.76, 95%Cl 0.61-0.95) and OS (HR 0.57 0.37-0.88). This trend of RFS/OS benefit was observed in all subgroups, includes control treatment (OBS/IFN) or study region (China/non-China). Conclusions: Our data supports that patients with resected AM are more likely to derive benefit from adjuvant PD-1 comparing to conventional treatment or observation alone. Perspective studies are warranted to explore the role of adjuvant PD-1 in AM. [Table: see text]
Sex as a predictor of progression-free survival in sentinel node-negative stage II melanoma.
Authors: Adigbli George , Issa Fadi , Cassell Oliver
Published: July 2024

e21560

Background: Adjuvant immunotherapy can improve outcomes for resected stage IIB/C melanoma patients, but also poses challenges. Many patients are cured by surgery alone, making them susceptible to unnecessary treatment risks. Additionally, current staging may overlook some high-risk stage IIA patients who could benefit from immunotherapy. Accurate risk assessment is therefore critical to balance benefits and risks of early immunotherapy and optimise patient selection. This study sought to identify clinicopathologic predictors to refine risk stratification for sentinel lymph node-negative (SLN(-)) stage II melanoma patients, with a focus on the role of sex in prognostic accuracy and treatment personalisation. Methods: We retrospectively analysed 565 stage II melanoma patients with negative sentinel lymph node biopsies at four UK hospitals between 2004-2017. The primary outcome was progression-free survival (PFS). Analysed clinicopathologic factors included Breslow thickness, ulceration sex and tumour-infiltrating lymphocytes (TILs). Univariate and multivariate analyses were conducted. Results: Median follow-up was 9.5 years. Melanoma progression occurred in 24% of patients. Sex emerged as a significant PFS predictor. Specifically, stage IIA and IIB males had higher progression risks than females at the same stages. We also observed disparities across stages; for instance, PFS was significantly worse in stage IIA males than stage IIB females (PFS difference: χ2 = 5.629, p = 0.018), revealing gaps in the prognostic accuracy of current staging systems. Stage IIB females—identified as at risk by current standards—had 5-year PFS of 91%. This highlights potential overestimation of their treatment needs and subsequent risk of undue exposure to treatment toxicity. The sex-based discrepancies observed may be partially explained by differences in antitumor immune function, evidenced by the discovery that Non-brisk TILs-an independent predictor of high progression risk in SLN(-) stage II melanoma- were associated with a 20% reduction in PFS in males vs females (p < 0.001). Conclusions: Significant sex-based PFS disparities exist among sentinel lymph node-negative stage II melanoma patients, with implications for treatment decisions. Incorporating sex enables more refined risk assessment than current substaging alone. Specifically, stage IIA males may be under-recognised for progression risks, while many stage IIB females could face overtreatment. Our findings advocate for nuanced, sex-specific approaches to enhance prognostic accuracy and optimise patient care.
Gene signature to predict hypophysitis in patients with melanoma treated with anti-PD-1 in adjuvant setting.
Authors: Simeone Ester , Mallardo Domenico , Festino Lucia , Vanella Vito , Trojaniello Claudia , Vitale Maria Grazia , Ottaviano Margaret , Sparano Francesca , Facchini Bianca Arianna , Cioli Eleonora , Isaja Antonio , Caraco Corrado , Ascierto Paolo Antonio ,   melanoma pascale
Published: July 2024

e21562

Background: Adjuvant anti-PD-1 treatment has shown to improve recurrence free survival and distant metastases free survival in melanoma patients from stage II to IV. Until now ,we have no data about overall survival of these patients nor biomarkers to select them to the best therapy , avoiding in this way severe and some times durable toxicities.Hypophysitis is a rare immune-related adverse event (irAE) and in adjuvant setting may represent a chronic irAE that may affect quality of life , such as fertility in young people.There are no clinical factors able to predict hypophysitis due to adjuvant anti-PD-1 therapy. Methods: Gene profiling analysis was performed using NanoString IO360 panel from basal PBMCs of patients treated with anti-PD1 in adjuvant setting. Patient’s characteristics are reported in table1. ROC curves were used to determine the best cut off. Survival rates were evaluated and compared using the Kaplan–Meier method. Results: Eighty pts treated with adjuvant anti-PD-1were included in a retrospective analysis from December 2019 to September 2021. Among which 12 pts developed hyphosytis. Ten pts completed treatment regularly, while two were discontinued both at week 12 due to metastatic disease. A pts developed liver metastases, the other one liver, multiple lymph nodes and soft tissues metastases. Grade 2 hypophysitis was diagnosed as the only irAE in all pts (100%). Median time of onset was 3 months (9 pts ≤6 months and 7 pts ≤3 months). A specific gene signature for predicting the onset of hypophysitis has been identified and characterized with 4 genes: IFITM2,CTSS,DUSP1,HLA-B that are mainly involved in the activation of innate-like lymphocyte populations, such as natural killer (NK) cells and innate lymphoid cells (ILCs), and adaptive immune cells, such as T helper 1 (TH1) cells and CD8+ cytotoxic T lymphocytes (CTLs). High gene signature was mostly related to hypophysitis event than lower group (HR: 0.11 95%IC 0.03-0.39, p = 0,0007). Moreover, at data lock all pts who developed hypophysitis were censored with mean overall survival of 35.60 months, 95%CI 30,86-40, 41. Conclusions: A predictive gene signature of hypophysitis was found in melanoma patients treated with adjuvant anti-PD1.Moreover, hypophysitis seems to correlate to better outcome. [Table: see text]
Detection of molecular residual disease in stage II and III melanoma utilizing circulating tumor DNA.
Authors: Chen Emily , Brunsgaard Elise Kornreich , Kuzel Timothy , Tan Alan
Published: July 2024

e21564

Background: Overall survival for patients with melanoma has significantly improved with advancements in immunotherapy, especially with immune checkpoint inhibitors and BRAF/MEK inhibitors becoming standard of care for advanced melanoma. However, the decision to proceed with adjuvant therapy should be considered against the risk of adverse side effects, particularly in early-stage melanoma patients. Accurate biomarkers are needed to risk stratify patients, determine who will most likely benefit from adjuvant therapy, and identify when the ideal time is to initiate treatment. This study evaluates the prognostic value of personalized, tumor-informed circulating tumor DNA (ctDNA) testing in patients with stage II and III melanoma. Methods: In this real-world study, plasma samples (n =429) were analyzed from 90 stage IIA-IIID cutaneous melanoma patients treated at Rush University Medical Center between 03/30/2021 and 01/30/2024. A clinically-validated, personalized, tumor-informed 16-plex PCR assay (SignateraTM, Natera, Inc.) was used for detection and quantification of ctDNA in plasma samples. Results: Personalized, tumor-informed ctDNA assays were created using tissue samples from either initial biopsy or surgical excision specimen. Assay design was successful for 100% (90/90) of patients with sufficient tissue; test requests for 4 patients could not proceed due to insufficient tissue. ctDNA was detectable in 28% (25/90) of patients at one or more time points. There was a higher ctDNA-positivity rate in stage III patients (20/50, 40%) compared to stage II patients (5/40, 13%). Of the 25 patients with identifiable ctDNA during surveillance, 13 tested positive on the initial test (2 stage II and 11 stage III). Eighteen of the 25 ctDNA-positive patients received immunotherapy; eight patients achieved sustained ctDNA clearance, 2 had transient clearance, 2 have remained positive on ctDNA testing, and 6 continue to receive adjuvant IO and follow-up ctDNA testing. Clinical or radiographic recurrence occurred in 11/90 patients, 10 of whom tested positive for ctDNA. Conclusions: Personalized, tumor-informed ctDNA offers an adjunct to conventional monitoring for melanoma patients to detect molecular residual disease and was found to be prognostic in our patient cohort. Prospective studies are needed to evaluate the role of ctDNA in clinical decision making for surveillance imaging intervals and appropriate initiation, intensification, or discontinuation of adjuvant therapy.
Malignant blue nevus: Epidemiology, socioeconomic factors, and disease presentation.
Authors: Choe Sharon , Moroz Mark , Puvvadi Suraj , Chin Kat , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: July 2024

e21565

Background: Malignant blue nevus (MBN) is a rare and aggressive melanoma that arises in a blue nevus and tends to metastasize to the lymph nodes. Metastasis has been described in up to 55% of cases, and the 10-year survival rate is 51%. Current literature on MBN is limited. Data from the National Cancer Database (NCDB) on the demographic and socioeconomic characteristics of patients with MBN could provide insightful information regarding the epidemiology of this rare disease. Methods: The 2004-2020 NCDB was used to perform a retrospective cohort analysis of patients diagnosed with malignant blue nevus (N = 118) using ICD-O-3 code 8780/3. This study used descriptive statistics to analyze factors such as age, sex, income status, insurance status, Charlson-Deyo score, treatments, and survival rates. Results: A total of 118 patients diagnosed with MBN were recorded in the NCDB with an average age at diagnosis of 56.7 ± 17.2 years with a female preponderance (59%). Nearly all patients were insured (99%), mostly by private insurance (59%) or Medicare (27%). Over half of patients (54%) were enrolled in research programs, and 62% of patients comprised the top two income quartiles based on median household income. The vast majority of patients (81%) had no major comorbidities (Charlson-Deyo = 0). The top primary sites were the skin of the scalp and neck (36%) and the trunk (21%). The average tumor size was 21.2 ± 30.3 mm ranging from 2 mm-120 mm. The most frequent treatment performed was surgery, with 92% of patients undergoing surgical procedures of the primary site. Among these, the most common procedures were wide excision or re-excision (52%), excisional biopsy (14%), and shave biopsy followed by gross excision (10%). After resection, 77% of patients showed no residual tumor. In place of surgery, a smaller number of patients received alternate treatments as their main therapy, such as radiation therapy (11%), chemotherapy (6%), or immunotherapy (12%). The 2-year and 5-year survival rates were 88% and 68% respectively. Conclusions: Based on our literature review, this study is the first NCDB analysis on MBN and presents data from the largest cohort of patients to date. Patients with MBN are more likely to be female, and most lack major comorbidities. The most common sites are the scalp, neck, or trunk, in line with current literature. Review of socioeconomic factors revealed that an overwhelming majority of patients are likely to be insured and in the top two income quartiles. These findings could implicate that those who are more socioeconomically advantaged may have more resources for recognition of disease and proper diagnosis, especially considering the challenges of diagnosing MBN due to poorly defined histological criteria. Further research efforts should investigate the impacts of socioeconomic factors on diagnosis, treatments, and prognosis.
Epidemiology and clinical management of primary penile melanoma: A review of the National Cancer Database.
Authors: Choe Sharon , Griffin Julia , Silberstein Peter T.
Published: July 2024

e21570

Background: Primary penile melanoma (PPM) is an exceedingly rare variant of skin cancer, estimated to account for less than 0.18% of all melanomas. As the incidence of melanoma is projected to increase, it is crucial to further understand subtypes of melanoma like PPM. We sought to use the National Cancer Database (NCDB) to describe the epidemiology, clinical features, and treatment modalities of PPM. Methods: We conducted a retrospective review of adults diagnosed with malignant PPM between 2004 and 2021 using the NCDB. Demographic factors analyzed included age, year of diagnosis, insurance status, and facility type. Clinical features studied included regional lymph node examination and treatments. SPSS was utilized to calculate descriptive statistics and chi-square tests for differences between categorical variables. Results: A total of 137 patients met inclusion criteria. The median age at diagnosis was 73 years. The majority of patients were insured by Medicare (n = 86, 63%) or private insurance (n = 46, 34%). About 50% (n = 69) of patients received care at an academic institution with other popular care centers being comprehensive community cancer centers (n = 33, 24%) and integrated network cancer programs (n = 28, 20%). Of the 91 (66%) patients examined for regional lymph node metastasis, 46% (n = 42/91) tested positive. The treatments of choice were partial amputation (n = 70, 51%), excisional biopsy (n = 30, 22%), total amputation (n = 15, 11%), and local excision (n = 10, 7%). After surgical intervention, 74% of patients (n = 101) showed no residual margins. Immunotherapy treatment, which was typically used as an adjuvant (n = 21,15%), increased from 7% (n = 5) of 68 cases diagnosed between 2004 and 2012 to 32% (n = 22) of 69 cases diagnosed between 2013 and 2021 (p < 0.001). Only 7% (n = 9) of patients underwent chemotherapy. Conclusions: To our knowledge, we present the largest study of PPM. Most patients were of older age, covered by Medicare, and examined for regional lymph node metastasis. In line with existing literature that demonstrates increased adoption of organ-sparing procedures over more aggressive approaches for PPM, partial amputation and excisional biopsy were the most common treatments. We observed a rise in the utilization of immunotherapy in the last decade, which is consistent with the timeline of FDA approval of several immune-based therapies for advanced melanoma. Current literature regarding immunotherapy in penile melanoma is scarce. Further research should investigate patient survival and the impact of different treatment modalities on outcomes.
Immune-related gastritis: An orphan immune-related adverse event.
Authors: Etan Tal , Shachar Shlomit Strulov , Wolf Ido , Leshem Yasmin
Published: July 2024

e24138

Background: Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology with a significant impact on patients' survival. However, they are not without shortcomings, with 70-90% of patients experiencing immune-related adverse events (irAEs(. Immune-related gastritis is a relatively uncommon irAE, literature publications are scarce and limited to case reports. We aimed to investigate this rare irAE to enhance understanding and improve patient care for oncologists and gastroenterologists. Methods: We performed a retrospective review of medical records of all cancer patients treated with ICI who completed upper gastrointestinal endoscopy during ICI treatment, at a single tertiary center between 2017 and 2023. Results: Of 2553 patients receiving immunotherapy at our medical center, 64 completed upper gastrointestinal endoscopy, and 18 (0.7%) had either endoscopic or microscopic gastritis or both. Overall, 17 (94%) patients with gastritis were symptomatic compared to only 31 of 46 patients (67%) without gastritis (p = 0.025). Epigastric pain was the most common symptom and was experienced by seven (39%) patients with gastritis, and eight (17%) patients without gastritis (P = 0.068). Other symptoms in patients with gastritis were gastrointestinal bleeding (28%), nausea (17%) and vomiting (11%). However, gastrointestinal bleeding (17%), nausea (9%), and vomiting (11%) were also experienced by patients without gastritis at similar rates (P > 0.05 for all comparisons). Two patients had grade 4 and two patients had grade 3 immune-related gastritis. Symptoms resolved in all patients, though most patients continued ICI (77%). Ten patients were treated with high-dose proton pump inhibitors (PPIs), and only four were treated with corticosteroids. Overall survival in patients experiencing gastritis was 40 months and did not differ from that of patients without gastritis (p = 0.929). Conclusions: Immune-related gastritis is an infrequent and non-lethal adverse event. Diagnosis is challenging due to non-specific symptoms, that are common among cancer patients undergoing antineoplastic therapies. Nonetheless, upon diagnosis, treatment with high doses PPIs with or without corticosteroids leads to prompt resolution.
GEMINI-Gastric: A phase 2 study of novel treatment combinations in patients with locally advanced unresectable or metastatic gastric cancers.
Authors: Shen Lin , Shitara Kohei , Chen Jen-Shi , Oh Do-Youn , Jiang Anastasia , Liu Silver , Dong Zhi , Zhu Qian , Kumar Rakesh , Rha Sun Young
Published: July 2024

TPS4182

Background: A large proportion of patients (pts) with gastric cancer present with locally advanced or metastatic disease, which is linked with poor survival. Platinum- and fluoropyrimidine-based doublet chemotherapy (CTx) remains the standard of care in advanced gastric cancers. Based on recent clinical data, immuno-oncology (IO) agents plus CTx can improve overall survival (OS) in pts with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who have human epidermal growth factor receptor 2 negative/low expression (HER2–) and have not been previously treated for advanced/metastatic disease. GEMINI-Gastric (NCT05702229) is a phase 2, open-label, multidrug, multicenter, master protocol study designed to assess the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of multiple novel IO + CTx combination therapies in this setting. Methods: Adults (≥18 years) with previously untreated HER2– locally advanced unresectable, or metastatic gastric or GEJ adenocarcinoma are eligible. Pts should have measurable target disease per RECIST v1.1 and an ECOG performance status of 0–1. The GEMINI-Gastric design allows assessment of multiple novel agents plus CTx in different substudies (Table). Novel agents include: volrustomig, an anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody (mAb); rilvegostomig, an anti-PD-1/TIGIT bispecific humanized IgG1 mAb; AZD0901, a claudin18.2-targeted antibody-drug conjugate; and AZD7789, an anti-PD-1/TIM-3 bispecific mAb. Co-primary endpoints are objective response rate and progression-free survival (PFS) at 6 months by investigator assessment per RECIST v1.1. Secondary endpoints include safety, duration of response, PFS, OS, PK, and immunogenicity. Sample sizes have been selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Europe, and Asia. Clinical trial information: NCT05702229 . [Table: see text]