bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis comparing the incidence of serious adverse events, overall survival, and progression-free survival in patients with pancreatic adenocarcinoma harboring unresectable tumors treated with modified FOLFIRINOX or FOLFIRINOX regimen.
Authors: Trieu Vuong N. , Qazi Sanjive , Fein Seymour H. , Maida Anthony Ernest , Joh Tenshang
Published: July 2024

e16318

Background: The evolution of first-line treatment for advanced pancreatic adenocarcinoma (PDAC) from Gemcitabine-based therapies to FOLFIRINOX-based regimens (fluorouracil, leucovorin, irinotecan, oxaliplatin) have demonstrated significant improvements in survival outcomes, however, this was associated with increased side effects such as neuropathy, fatigue, and diarrhea due to its heightened potency. Modified versions of FOLFIRINOX (mFOLFIRINOX) have since been developed with lower doses and longer breaks between cycles to manage side effects. Methods: To systematically test the efficacy and side effects of mFOLIFINOX treatment, we conducted a meta-analysis relating FOLFIRINOX treatment with modified FOLFIROX on the frequency of Grade 3 or 4 adverse events reported in published literature (9 studies), and Serious Adverse Events (SAE) recorded from clinical trials (17 arms accessed from clinicaltrials.gov) in PDAC patients with unresectable tumors. Results: For adverse events occurring in greater than 10% of patients, significant reductions in the frequency of patients experiencing the following events were observed in PDAC patients treated with mFOLFIRINOX: Neutropenia (29.31 % (226/771 patients across 8 arms) versus 18.8% (144/766 across 8 arms; Fisher Exact test, 2-tailed, P < 0.001)), Anorexia (18.57 % (44/237 across 3 arms) versus 5.39% (18/334 across 3 arms); P < 0.001), Peripheral sensory neuropathy (10.63 % (27/254 across 2 arms) versus 3.45% (4/116 across 2 arms); P = 0.025)), and Fatigue (10.57 % (83/785 across 9 arms) versus 6.77% (55/812 across 8 arms); P = 0.007)). Examination of 8 studies (N = 635) for PDAC patients treated with FOLFIRINOX exhibited a median OS time of 11.37 (Range = 10.07 - 13.9) months. Patients treated with mFOLFIRINOX (N = 475) exhibited a median OS time of 12.8 (10.2 - 14.4) months (Two-sample Wilcoxon test, P = 0.372). Conclusions: In conclusion, modified FOLFIRINOX has maintained similar efficacy while reducing severe adverse events, making it more tolerable for adjuvant treatment after surgery.
Somatic tissue testing in prostate cancer using the Oncomine V3 panel: A single-institution retrospective analysis.
Authors: Hanna Lilian , Park Nicole , Wang Xin , Waldman Larissa , Silberman Yael , Emmenegger Urban , Downes Michelle R. , Smoragiewicz Martin
Published: July 2024

e17002

Background: Approximately 20-30% of prostate cancer (PC) patients have a mutation in the homologous recombination repair or mismatch repair genes, 50% of which are somatic. These mutations have prognostic and predictive implications. Somatic tissue testing (STT) was implemented at Sunnybrook Health Sciences Centre using the Oncomine V3 panel, which includes 161 genes, but only four genes (BRCA1/2, ATM, PALB2) are reported due to funding restrictions. We describe our centre’s testing experience and the utility of reporting beyond these four genes. Methods: Sixty-two PC patients between May 1, 2021 - January 31, 2023 were included. Clinical characteristics were gathered via chart review. Somatic variants of genes of interest (GOI) within the Oncomine V3 panel were extracted by an annotation specialist. Results: STT was ordered at diagnosis in 69.4% of cases (n=42) vs. at progression in 27.4% (n=17), 3 cases were external and lacked clinical context. Tests were ordered in the locoregional disease setting in 46.8% (n=29), 37.1% (n=23) in the metastatic castrate-sensitive setting, 8.1% (n=5) in the metastatic castrate-resistant (CR) setting and 3.2% (n=2) in the non-metastatic CR setting. Tests were ordered by Urology or Pathology (reflex testing) in 64.5% (n=40), by Medical Oncology in 16% (n=10), by Radiation Oncology in 13% (n=8) and by others in 6.5% (n=4). Fifty-one samples (82.2%) were of the prostate and 11 (17.7%) were of metastatic sites. The median sample age was 8 days (range 0-5781). The median test turn-around time was 28.5 days (range 5-57). There were 378 variants within the GOI and meeting the limit of detection [1] , of which 63 (16.7%) were tier 1 or 2 and are listed by gene in the table. Eight of 63 variants (12.7%) were within the four funded genes whereas 55/63 (87.3%) were within unfunded genes of clinical significance. CDK12, FANCA, NBN (n=7, 11.2%) are investigated in poly (ADP-ribose) polymerase inhibitor trials and PMS2 deficiency (n=1, 1.6%) can select for immune checkpoint inhibitors. PIK3R1/PIK3CA/AKT1-mutated tumors (n=11, 17.7%) have shown response to AKT-inhibitors. SPOP-mutated tumors (n=6, 9.7%) are associated with prolonged response to androgen receptor blockade whereas PTEN/TP53/RB1-negative tumors (n=12, 19.4%) are associated with anti-androgen resistance and worse prognosis. Conclusions: The majority of STT variants identified were beyond the currently funded genes in Ontario, and many have important prognostic and predictive implications. This highlights that STT early in the disease course using expanded gene panels may help in delivering personalized PC care. [Table: see text]
Effect of strong programmed cell death ligand-1 (PD-L1) expressions on clinical outcomes in advanced non-small cell lung cancer treated with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors.
Authors: Niu Jiling , Jing Xuquan , Xu Qinhao , Liu Haoyu , Tian Yaru , Yang Zhengqiang , Zhu Hui , Sun Yulan
Published: July 2024

e20500

Background: Third-generation tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. In first/second generation EGFR-TKIs, strong programmed death ligand 1 (PD-L1) expression contributes to primary resistance, significantly affecting patient prognosis. Despite this, the relationship between PD-L1 expression levels and third-generation TKIs remains unclear. Methods: This retrospective cohort study reviewed patients with advanced NSCLC who received third-generation EGFR-TKIs as first-line systemic therapy at the Shandong Cancer Hospital between March 2019 and June 2022. The EGFR status of the patients was assessed using amplification refractory mutation system fluorescence quantitative polymerase chain reaction, and the PD-L1 expression level was evaluated using Dako 22 C3 immunohistochemical staining. The Kaplan–Meier method was used for survival analysis. The log-rank test was used to compare differences in survival curves between the two groups. Results: Overall, 150 patients were included in this study. PD-L1 expression was negative (PD-L1 tumor proportion score < 1%) in 89 cases, weak (1–49%) in 42 cases, and strong (≥50%) in 19 cases. The median follow-up period for the entire cohort was 22.12 months (median progression-free survival [mPFS]: 24.33 months); the median overall survival was not reached. mPFS for patients with negative, weak, and strong PD-L1 expressions was 23.60, 26.12, and 16.60 months, respectively. The mPFS for strong PD-L1 expression was significantly shorter than that for with weak PD-L1 expression but was not associated with negativity, particularly in the 19DEL and 21L858R subgroups. PFS was significantly shorter in patients with strong PD-L1 expression in both subgroups (19DEL and 21L858R) than in those with weak PD-L1 expression. Conclusions: Strong PD-L1 expression in tumor cells influenced the clinical outcomes of patients with advanced NSCLC treated with third-generation EGFR-TKIs. Stronger PD-L1 expression in TKI-treated patients with advanced first-line EGFR-mutated NSCLC was associated with worse PFS.
PLWH and lung cancer: A single cancer center experience in Philadelphia, PA.
Authors: Bernstein Andrew , Melby Garrett , Tucker Matthew , Palecki Julia , Begun Zoe , Zhan Ting Ting , Micaily Ida
Published: July 2024

e20502

Background: Lung cancer has been identified as the leading cause of cancer-related deaths in people living with HIV (PLWH), and disproportionately affects this population independently of smoking status and CD4 count. At the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health, we serve a uniquely underserved patient population of PLWH. As PLWH were categorically excluded from most lung cancer clinical trials, we aim to study the clinical course of our patients with HIV and lung cancer. Methods: A retrospective review of 36 patients within SKCC at Jefferson Health in Philadelphia, PA from 2016 to 2023 were obtained utilizing ICD codes for lung cancer and HIV. Patients who were found to have HIV after their lung cancer diagnosis were excluded. Patient demographics, viral status, antiviral therapy, lung cancer stage, histology, molecular and fusion status, PD-L1 status, form of cancer-directed therapy, date of progression, last date of treatment, and date of death were recorded. Results: Of our 36 patients, 24 (66.7%) were male, and 20 (55.6%) racially identified as Black. 27 patients had NSCLC (20 with adenocarcinoma, 7 with squamous cell carcinoma), and 3 had SCLC. 24 (66.7%) patients had an undetectable viral load at the time of diagnosis and 35 (97.2%) were on antiviral therapy. 32 of 36 patients (88.9%) had advanced stage at the time of diagnosis; 11 had stage III disease (30.6%), and 21 (58.3%) had stage IV disease. Only 4 patients (11.1%) were diagnosed with stage I disease. The mean age of patients at diagnosis was 61.6 years (+/- 8.7 years). Of 18 patients with molecular testing performed, 4 had a KRAS mutation (22.2%) and 1 (5.6%) had a targetable EGFR mutation. Of 16 patients with PD-L1 testing, 7 (43.8%) had 0% expression, 8 (50%) had 1-49% expression, and 1 patient (6.2%) had PD-L1 expression > 50%. The OS among this cohort was 1.3 years (95% CI: 0.8-3.8 years). Conclusions: Our cohort of patients demonstrated more advanced disease at presentation, a younger mean age at diagnosis and poor OS. These trends exist despite the majority of these patients having an undetectable HIV viral load at the time of diagnosis in the setting of ongoing antiviral therapy, indicating a potential relationship between even well-controlled HIV and aggressive lung cancer that warrants further exploration.
Effect of P. gingivalis on osimertinib resistance in EGFR-mutant lung cancer.
Authors: Li Wendong , Rotter-Maskowitz Aviva , Zhang Keqiang , Massarelli Erminia , Potempa Jan , Straussman Ravid , Raz Dan
Published: July 2024

e20511

Background: While most patients with EGFR-mutant lung cancers respond to osimertinib, resistance inevitably develops. Mechanisms of osimertinib resistance remain inadequately understood. Recent studies suggest a potential link between intra-tumoral bacteria and therapy resistance in cancer. Our previous studies found that the pre-conditioned medium (PCM) of certain bacteria in the Bacteroidetes phylum conferred resistance of all EGFR-TKIs tested. In this study, we specifically investigate the effect of Porphyromonas gingivalis, a common component of the human oral microbiome and the main pathogen responsible for periodontal disease, on osimertinib sensitivity in EGFR mutant lung cancer. Methods: P. gingivalis PCM (P-CM) was applied to EGFR-mutant lung cancer cell lines for 3 days and cell viability was measured. Western blot and receptor tyrosine kinase (RTKs) assay were used to analyze the changes of cell signaling pathways, and the contribution of identified signaling pathway to P. gingivalis-mediated resistance to osimertinib were further validated by rescue experiments. To investigate the existence of P. gingivalis in human lung cancer tissues, we used Fluorescence In Situ Hybridization (FISH) probes specific to P. gingivalis and hybridized probes to a tissue microarray (TMA) containing 3 mm punches of lung adenocarcinoma tissue from 30 patients in duplicate. The underlying mechanisms of osimertinib resistance conferred by P. gingivalis were explored by a combination of bacterial genomic and cellular proteomic approaches. Results: P-PCM led to osimertinib resistance in all EGFR-mutant lung cancer cell lines tested. Both Western blot and RTKs assay showed that phosphorylated insulin-like growth factor 1 receptor (pIGF1R) level significantly increased when P-PCM was applied to PC9 EGFR mutant lung cancer cells. We found that both IGF1R inhibitor (linsitinib) and IGF1R knockdown with siRNA eliminated the effect of P-PCM-mediated osimertinib resistance. We found that two cysteine proteases secreted by P. gingivalis, lysine-specific gingipain (Kgp) and arginine-specific gingipain A (RgpA) led to osimertinib, whereas arginine-specific gingipain B (RgpB), which lacks haemagglutinin/adhesin (HA) region of RgpA had no effect on osimertinib response. We also found that gingipains-mediated osimertinib resistance is independent of enzymatic activity. We detected intra-tumoral P. gingivalis in tumor tissue of 9 (30%) patients by using FISH probes specific to P. gingivalis. Conclusions: Our studies demonstrate that P. gingivalis can induce osimertinib resistance in EGFR-mutant lung cancer cells through secreted gingipains that activate the IGF1R pathway through an enzymatic- independent mechanism. P. gingivalis is frequently detected in human lung cancer tissues , suggesting that therapies targeting P. gingivalis may improve EGFR-TKI response in certain patients with EGFR-mutant lung cancer.
Are the clinical trials in lung cancer an advantage for patients in developing countries?
Authors: Erol Cihan , Hizal Mutlu , Kahraman Seda , Bardakci Murat , Sener Dede Didem , Akinci Muhammed Bulent , Yalcin Bulent , Sendur Mehmet Ali Nahit
Published: July 2024

e20523

Background: Clinical trials are critical to developing new drugs. This study examined the characteristics of patients diagnosed with metastatic non-small cell lung cancer (mNSCLC) and who wanted to participate in clinical trials. This study aims to compare the outcomes of patients who enrolled in clinical trials or not. Methods: The data of the patients who applied to Ankara Yildirim Beyazit University Medical Oncology Department to participate in the first-line treatment-related clinical trials in mNSCLC were retrospectively reviewed. Survival outcomes of patients included in clinical trials (CT) and patients who signed informed consent for clinical trials but could not enroll (standard treatment-ST) were compared. Results: Data from 155 patients who applied to participate in clinical trials were analyzed. Patients who died during the screening process and who lacked systemic treatment information were excluded (n = 14). While 55.3% (n = 78) of the patients participated in the clinical trials, 44.7% (n = 63) could not. Not meeting the inclusion criteria (pathological and clinical) was the most common reason for screen-fail. At a median follow-up of 29 months, median overall survival was 17.1 months (95%CI, 15.1 to 19.1) in the CT group and 9.6 months (95%CI, 7.1 to 12.1) in the ST group (p = 0.015). Median progression-free survival was 11.6 (95% CI, 5.9 - 17.4) and 5.4 (95% CI, 3.7 - 7.2) months, respectively (p = 0.014). Conclusions: Being able to take part in clinical trials is not unfavorable, and it may even improve survival for patients with metastatic non-small cell lung cancer (mNSCLC), particularly in areas of the world where access to novel and effective treatments is limited.
Malignant effusion aspirate for use in constructing organoids model to assist individualized treatment of advanced non-small cell lung cancer.
Authors: He Qiong , Yu Xinmin , Chen Zhenhua , Xie Cuiwei , Xiao Hongjiang
Published: July 2024

e20526

Background: Organoids derived from cancer patients are considered to represent the overall appearance of the original tumor in lung cancer. With the in-depth study of molecular mechanisms and the development of new drugs, the survival time of advanced non-small cell lung cancer has been greatly extended. However, when it comes to the back-end treatment, they often have limited amounts of fresh tissue samples or cannot complete puncture, which affects the successfully establishment of organoids. Some patients often have malignant pleural effusion (MPE) requiring repeated aspiration, so it is clinically easy to obtain. Our goal was to culture organoids from malignant effusion of advanced NSCLC patients (LCO), and explore and analyze the consistency of drug sensitivity with clinical practice. Methods: In this study, malignant pleural effusion specimens of 39 patients with NSCLC were collected and complete clinical information was obtained.The partially paired successfully modeled organoids and the original malignant effusion were sequenced by WES(N = 7) and RNA(N = 6) for genetic background consistency.All successfully cultured organoids were subjected to drug sensitivity test, and the drug sensitivity results were compared with the actual therapeutic effect of clinical patients. Results: We successfully established 34 LCOs with a success rate of 87.2% . LCOs retained the mutation spectrum of the matching primary tumor. TP53 and EGFR were the most frequently mutated genes, occurring in 83.3% (5 of 6) and 66.7% (4 of 6) of effusion samples. On average, LCOs retained an 93.2% overlap of the most frequently lung cancer gene mutational variants from the parental MPE samples.The gene expression in the paired LCOs and effusion samples were compared, demonstrating an average 80% overlap in gene expression between the LCOs and the matching effusion samples.The clinical outcomes of the 25 patients (27 rounds of treatment) and their LCOs pharmaco-phenotyping results are analyzed. Notably, 94.7% of the treatments, which include at least one drug that was tested to be sensitive or moderately responsive by LCOs, achieved partial response or stable disease. However, 62.5% of the treatments, which do not include any drug that was tested to be sensitive or moderately responsive by LCOs, developed progressive disease. Overall, the LCO pharmaco-phenotyping results are highly correlated with clinical outcomes, with 85.2% accuracy (95% CI, 67.5–94.1%), 85.7% sensitivity (95% CI, 62.6–96.2%), and 83.3% specificity (95% CI, 36.5–99.1%). Conclusions: The effusion and LCOs have high concordance of genomic profiling. Organoid culture from malignant effusions of lung cancer can be used as a platform for drug sensitivity testing. These LCOs may be helpful in individualized treatment of NSCLC.
Efficacy and safety of second-line immunotherapy in patients with advanced non-small cell lung cancer.
Authors: Sánchez Escudero Laura , Cobelas Cartagena Stephanie S. , Sánchez Esperilla María , Bayo Juan L.
Published: July 2024

e20571

Background: Patients (Pts) with advanced non-small cell lung cancer (NSCLC) face limited treatment options. Immunotherapy (IO) has revolutionized the treatment of NSCLC in this setting. The objective of our study is to evaluate the efficacy and safety of atezolizumab (Az) in Pts with advanced NSCLC in the second-line setting following progression on platinum-based chemotherapy (CT) in the Huelva area. Additionally, we aim to compare the results with those obtained in the phase 2 POPLAR and phase 3 OAK clinical trials. Methods: This is a descriptive and observational study conducted on patients with advanced NSCLC who received second-line IO with atezolizumab 1200 mg/1680 mg every 3 or 4 weeks, from 2015 to 2023 in the Huelva area (Spain). SPSS Statistics 22 was used for data analysis. Results: 26 Pts were treated, median age 67 years and 88.5% men. ECOG PS 0-1 in 92.3%. According to smoking habits, 42.3% were ex-smokers and 38.5% were active smokers. Regarding histology, 53.8% were non-squamous. 73.1% were inicial stage IV and 23% were stage III. Depending on the expression of PDL-1, PDL-1 was < 1% in 34.6% (9 Pts) of the sample, between 1-49% in 53.8% (14 Pt) and unknown in 3 Pts. 26.9% of patients achieved disease stability and 11.5% achieved partial response. The response has not been evaluated in 38.5% because these patients maintain treatment. The adverse effects (AE) suffered by patients treated with Az in the second line were 53.8% grade (G) 1- 2 and 7.7% G 3-4. The most frequent were asthenia (48%), pruritus and arthralgia in 15.4%, both cases, and skin toxicity in 11.5%. In the case of the 2 Pts with G 3-4 toxicity, they were due to autoimmune anemia and asthenia with subsequent to grade 1, so treatment did not have to be interrupted. The median progression-free survival (PFS) was 2.7 months (m) (95% CI 0-6.8) and the median overall survival (OS) was 5.2 m (95% CI 0.5- 9-9). In both cases the results were not statistically significant. According to PDL1, no statistically significant differences were found in the subgroup analysis. Conclusions: Based on our results and those of the Phase 2 POPLAR and Phase 3 OAK studies, we consider that Az has an acceptable safety profile, with fewer G 3-4 side effects compared to CT, so a lower percentage of Pts drop out the treatment. Although the PFS was similar to the phase II-III studies, the OS was lower, probably due to the percentage of Pts with rapid progression and patients currently continuing to receive treatment, being a limitation in our study along with the small sample size. Despite this, our results are encouraging regarding the benefit of IO in Pts. Therefore, we conclude that the use of IO in these Pts falls within good clinical practice, offering them a clearly effective therapy and thus avoiding treatments with greater toxicity such as CT.
Lung cancer in females from nonsmoker families in India: Observations and inferences in 5 years.
Authors: Udupa M. S. Namratha
Published: July 2024

e20610

Background: Incidence in lung cancer in last two decades has been changing drastically in terms of gender, age, smoking behaviour of patients, stage at presentation, histopathology, genetic abnormalities, operability at presentation and survival. More perplexing is the increase in its occurrence in females from non smoker families, mitigating the sole importance of the traditional risk factors of tobacco and smoking in the recent times. This highlights the need to investigate other risk factors like radon exposure from indoor pollution where females stay most of the time, exposure to arsenic and other chemicals in daily life, particle pollution, physical inactivity and inflammatory diseases of airways. Methods: It was an observational study of patients who were diagnosed and treated at a high volume cancer centre in Karnataka state of India. 89 never smoker female patients under 50 years of age from non smoker families with no obvious exposure to second hand or third hand smoke were enrolled from October, 2018 to June, 2023. It was a longitudinal prospective cohort study where the demographic data, symptoms with duration, histopathology including genetic abnormalities, treatment details and survival were noted. Results: 89 never smoker females from non smoker families with ages ranging from 36 to 50 years had a median age of 46 years. About 70% of the ladies were from houses closely associated with farm in past or present. 55% of them had overweight and obese body habitus. Most common presenting symptom was dry cough with median duration of about 3 months in about 89%. Other symptoms were pleuritic chest pain(39%), breathlessness (19%), generalized body ache(9%) and jaundice(2%). Stage of disease was IV(69%), IIIC(12.3%), IIIB(11.2%), IIIA(5.6%) and II in just one patient. Most common sites of metastasis were contralateral lung(45%), bone(20%), liver(20%), adrenal glands(10%) and brain (15%). Most common histopathology was adenocarcinoma(87.6%), adenosquamous carcinoma(7.8%), squamous cell carcinoma(3.3%), large cell neuroendocrine carcinoma in just one patient. EGFR was mutated in 56(62.9%) with deletion 19( 33%) and L858R(21%) being the most common abnormalities. ALK rearrangements and ROS1 fusion were seen in about 9(3.3%) and 3(3.3%) patients respectively. Surgery was done in only 3 patients and chemoradiation after neoadjuvant chemotherapy was given in 8(8.9%) patients. Median overall survival was about 42 months in stage IV patients. Conclusions: Changing demographic profile of lung cancer warrants more research into the other causes of lung cancer. More stage IV disease highlights the emphasis on prevention and screening for the disease.
The impact of online CME on clinicians’ ability to utilize immunotherapy in unique populations of patients with NSCLC.
Authors: Worst Michelle Arielle , Small Andrew , Furedy Amy , Zhang Cong , Yuan Meng , Bahra Sukhbir , Liu Stephen V. , Weiss Jared
Published: July 2024

e21004

Background: Immunotherapy (IO) has become a standard of care in the management of advanced non-small cell lung cancer (NSCLC). However, treatment with IO-based regimens may not always be straightforward, particularly in unique clinical scenarios and patient populations. As such, members of the multidisciplinary care team, including oncologists and pulmonologists, may lack experience in utilizing IO in these instances. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists and pulmonologists with respect to recognizing strategies that facilitate the safe and effective use of IO in patients with advanced NSCLC. Methods: The educational analysis consisted of 2 online, CME-certified activities. Educational impact was assessed with repeated pre-/post-education including multiple choice knowledge/competence questions and 5-point Likert scale confidence questions. Data from all oncologists and pulmonologists who completed pre- and/or post-education assessments were aggregated across activities and stratified by learning theme. Relative changes in percentage of correct responses and clinicians who were confident (value of 4 or 5) were used to measure improvement in knowledge, competence, and confidence. A McNemar’s test assessed significant levels of changes reported with P values <.05 considered statistically significant. The first activity in the analysis launched October 2023 and the last launched November 2023; data were collected until January 2024. Results: The educational series resulted in improvements in oncologists’ (N=119) and pulmonologists’ (N=49) knowledge, competence, and confidence after education. Conclusions: This analysis demonstrates that oncologists’ and pulmonologists’ knowledge, competence, and confidence regarding the safe and effective use of IO in patients with advanced NSCLC improved after education. Despite these improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in these dynamic and challenging clinical settings. [Table: see text]
The effect of an online micro CE/CME on the multidisciplinary care of patients with nonmelanoma skin cancer.
Authors: Worst Michelle Arielle , Small Andrew , Middleton Deborah , Yamaguchi Yoji , Yuan Meng , Bahra Sukhbir , Patel Vishal A.
Published: July 2024

e21006

Background: Nonmelanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC), are the most common malignancies diagnosed in the US and worldwide. While most are successfully cured with local therapies or surgery alone, immunotherapy agents have been added to the arsenal for advanced tumors that are unresectable or unlikely to be cured with surgery alone. Thus, the multidisciplinary care model in this clinical setting has numerous advantages; however, many healthcare professionals (HCPs) may not fully recognize the role of their colleagues and their value in caring for affected patients. The objective of this study was to assess the educational impact of an online micro continuing [medical] education (CE/CME) activity on the knowledge and competence of HCPs’ with respect to the role and value of the multidisciplinary team in the optimal care of patients receiving immunotherapy for NMSC. Methods: The educational activity consisted of a collection of six online video-based micro-CE/CME-certified chapters, presented by six respected NMSC experts, allowing learners to choose their chapters for participation. Educational impact was assessed with repeated paired pre-/post-assessment study design, where individual participants served as their own control. A McNemar’s test assessed significant levels of changes reported with P values <.05 considered statistically significant. The activity launched September 2023; data were collected until January 2024. Results: The educational activity resulted in overall statistically significant improvements in HCPs’ knowledge and competence after education by chapter and by HCP audience type ( P < .01), including oncologists, dermatologists, surgeons, nurses, and pharmacists. Results presented below highlight the improvements in HCPs’ knowledge and competence by chapter. Conclusions: This analysis demonstrates the success of an online CE/CME activity with micro video chapters on improving HCPs’ knowledge and competence related to the value of the multidisciplinary team members in the comprehensive care of patients receiving immunotherapy for the treatment of NMSCs. Despite these significant improvements, additional educational activities are needed to address residual gaps and further increase HCPs’ ability and comfort in providing care in this clinical setting. [Table: see text]
Hidden advertisements included in cancer information posts: Insights from social listening.
Authors: Kim Dalyong , Lim Joo Han , Choi Wonyoung , Lee Hyun Woo , Yoon Ho Young , You Kyung Han , Lee Sang-Cheol
Published: July 2024

e21017

Background: Access to cancer information on the Internet has proliferated, yet ensuring the accuracy and reliability of such information remains a challenge. The abundance of online content necessitates a comprehensive understanding of the prevailing landscape of cancer information dissemination. Methods: Cancer-related information was retrieved from search engine results pages of NAVER and Google, the most frequently used websites for information search in South Korea, during September and October 2023. Promoted posts and overt advertisements were excluded from the dataset. Posts featuring more than 50% of advertising content were categorized as fully hidden advertisements (HA), while those with lesser proportions were classified as partially HA. In cases where there was no advertising content but the hospital name or contact information was indicated for promotional purposes, it was classified as a simple HA. Topic modeling techniques were employed to analyze the content of HA posts, identifying prevalent themes and keywords indicative of promotional intent. Results: Of the collected posts, 48.6% were classified as HA. The publisher of the HA was 26.8% of oriental medicine/care hospitals, followed by general hospitals (25.3%), non-professional (21.3%), and small and medium-sized private hospitals (17.4%). In HA, 40.3% were full advertisements, 36.75% were partial advertisements, and the remainder were simple displays. By cancer type, 65.3% of posts about breast cancer were advertising posts, 55.2% were about colon cancer, and 53.7% were about stomach cancer. In the topic modeling analysis of HA, despite containing basic and theoretical information about cancer, HA subtly directs users towards advertising content, featuring terms related to private insurance and complementary medicine. Conclusions: The study elucidates the prevalence and characteristics of HA within cancer-related information available online, highlighting the need for heightened awareness. While it may not be inherently wrong, HA can impact user perception and decision-making processes. Additional research is underway to determine whether information classified as HA can be trusted. Addressing issues such as HA within cancer information will likely require cooperation between search engine platforms and government agencies.
Longitudinal circulating tumor DNA kinetics and correlation with patient outcomes in metastatic melanoma.
Authors: Tummala Ramya , Tummala Sirisha , Kuzel Timothy , Tan Alan
Published: July 2024

e21538

Background: Previous studies have shown circulating tumor DNA (ctDNA) to be an accurate noninvasive method for detecting minimal residual disease and predicting therapeutic response. This study aims to investigate if positive ctDNA and subsequent clearance kinetics may be used as a predictive and prognostic tool in patients with stage IV metastatic melanoma. Non-clearance of ctDNA may be associated with poorer outcomes for progression-free survival (PFS) and overall survival (OS). Methods: In this retrospective analysis of preexisting data from a cohort of 27 patients with stage IV melanoma treated at Rush University, longitudinal ctDNA plasma samples collected between 05/01/2020 and 01/01/2024 were analyzed. A tumor-informed ctDNA assay (SignateraTM, reported in mean tumor molecules per mL (MTM/ml), low limit of detection of 0.01% variant allele frequency) was used for detection and quantification of ctDNA in plasma samples. Progression was determined based off of radiographic studies, overall survival was determined by time from stage IV diagnosis to patient death. Results: A total of 192 ctDNA timepoints were analyzed. The median number of ctDNA timepoints per patient was 5 (range 1-26). 8 patients were identified whose initial ctDNA result was negative and remained negative throughout their treatment course; 5/8 of these patients had baseline negative values available prior to the initiation of treatment. 19 patients had at least 1 positive ctDNA result at any given time; 1/19 of these patients was ctDNA-negative at baseline, 7/19 were positive at baseline, and 11/19 did not have baseline values available. The PFS rate was higher for ctDNA-negative patients compared to ctDNA-positive patients (62.5% vs. 57.9%). The OS rate was also higher for ctDNA-negative patients compared to ctDNA-positive patients (75% vs. 52.6%). Of the ctDNA-positive patients, those who achieved persistent clearance or had decreasing values of ctDNA had higher PFS rates when compared to ctDNA-positive patients who neither downtrended nor achieved clearance (71.4% and 66.7% vs. 22.9%). Patients who achieved persistent clearance or had decreasing values of ctDNA also had higher OS rates when compared to ctDNA-positive patients who neither downtrended nor achieved clearance (71.4% and 100% vs. 33.3%). Conclusions: Within the limitations of a small sample size, our data suggests that for patients with stage IV melanoma, a positive ctDNA result is associated with poorer outcomes for PFS and OS, when compared to patients with negative ctDNA results. Additionally, ctDNA-positive patients who achieved persistent clearance or downtrending ctDNA values showed more favorable outcomes for PFS and OS than ctDNA-positive patients who did not. [Table: see text]
Exploring the correlation between high HRD status and immunotherapy response in melanoma.
Authors: Nassief George , Adeyelu Tolulope Tosin , Zhou Alice Yao , Keller Jesse W. , Abdulla Farah R. , Vanderwalde Ari M. , Gibney Geoffrey Thomas , Park Soo J. , Ansstas George
Published: July 2024

e21541

Background: Homologous recombination deficiency (HRD) status demonstrates DNA instability in tumor cells and has been implicated as a response marker for immune checkpoint inhibitors (ICI). Here, we explore the correlation between high HRD status and ICI response biomarkers, homologous recombination repair (HRR) mutations, and the prognostic advantage of high HRD status following ICI in cutaneous melanoma patients. Methods: Melanoma samples (N = 2158) were profiled for genomic loss of heterozygosity (LOH) by NGS at Caris Life Sciences (Phoenix, AZ). As a surrogate for HRD, LOH-high was defined as LOH at ≥ 16% of the segments analyzed (up to 552). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS.Tumor mutational burden (TMB)-high was defined as ≥ 10 mutations/Mb. interferon gamma (IFN-g) and T-cell inflamed scores. Real-world overall survival (rw-OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from the start of immunotherapy until the last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p-values adjusted for multiple comparisons. Results: Melanoma patient samples include - cutaneous: 1853; acral: 130; mucosal: 175, with LOH-high observed in 8.3% of cutaneous specimens, 13.1% of acral, and 30.9% of mucosal. Firstly, most biomarkers associated with response to ICI (PD-L1, TMB-high, total neoantigen load, IFN-g score, T-cell inflamed level, and dMMR/MSI-H) were not significantly different between LOH-high and LOH-low cohorts in all melanoma subtypes. However, TMB-high was significantly more prevalent in LOH-low cutaneous melanoma patients (54.9% vs 63.3%, p = 0.039). Prevalence of HRR gene mutations was not significantly different between high and low LOH groups in all cohorts, except for the ATRX gene which exhibited a significantly higher prevalence in the high LOH cutaneous (8.6% vs 1.3%, p < 0.001) and mucosal (28.8% vs 2.5%, p < 0.00001) melanoma specimens. Analysis of rw-OS showed no improvement in the treatment of LOH-high cutaneous melanoma patients with ICI compared to LOH-low (HR: 1.397 [95% CI: 0.759- 2.569], p = 0.281). Conclusions: This study demonstrates that HRDness reflected by the high-LOH status in melanoma did not correlate with mutations in HRR genes. In addition, melanoma specimens with high HRD status did not exhibit an overall higher prevalence of biomarkers associated with ICI response. Our study did not demonstrate improved survival outcomes in patients with high HRD status following anti-PD1 therapies. Future investigation is needed to assess other therapeutic approaches for these patients such as PARP inhibitors.
Neoadjuvant immunotherapy in clinical stage III melanoma: Real life experience in the community setting.
Authors: Mahmoud Fade , Gimbel Mark , Toledo Ryan , Abbott Jordan , Shellenberger Thomas D. , Tomeh Chafeek , Healy Mark Andrew , Dave Vishangi
Published: July 2024

e21556

Background: There is a paradigm shift in the management of clinical stages IIIB-IIID melanoma. Results from phase II clinical trials revealed higher pathologic response rates in the neoadjuvant versus adjuvant setting. Methods: We conducted a retrospective study of patients with clinical stages IIIB-IIID melanoma who were deemed suitable for surgical resection and treated with neoadjuvant immunotherapy between January 2019 and December 2023. Patients must have had at least one cycle of neoadjuvant immunotherapy with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The primary objective was to assess pathologic and radiologic response rates and to determine the association of pathologic response with event free survival (EFS). Results: Thirty-one patients were enrolled with a median age of 60 (range: 31-84) years. 61% of patients received two cycles, 3 weeks apart, of intravenous (IV) ipilimumab 1mg/kg and nivolumab 3mg/kg, while 23% received one cycle of IV ipilimumab 1mg/kg and nivolumab 3mg/kg followed by two cycles, 2 weeks apart, of IV nivolumab 240 mg. Twenty-nine patients underwent therapeutic lymph node dissection; of those 66% had a pathologic complete response (pCR) and 79% had an overall pathologic response. Complete radiologic response using RECIST 1.1 was detected in 28% and radiologic partial response in 56%. Next gene sequencing revealed a total of 47 mutations with BRAF V600 mutation being the most frequently encountered (28%) followed by mutations in TERT promoter (21%) and CDKN2A loss (13%). Two patients died during follow up. One patient refused surgery after neoadjuvant immunotherapy and passed away 4 years later due to stage IV melanoma. The second patient died two years after his surgery due to brain metastases despite achieving a complete pathologic response to neoadjuvant immunotherapy. Any grade adverse events (AE) were detected in 76% of patients; 64% grades 1-2 and 12% grades 3-4. Colitis was the most encountered grade 3 and 4 AE. Three-year event-free survival among 23 evaluable patients who had at least 6 months of follow up after surgery was 95%. Conclusions: Neoadjuvant immunotherapy with ipilimumab and nivolumab resulted in a high pathologic response rate of 79%. A discrepancy was detected between pathologic and radiologic responses. Colitis was the most common grade 3 and 4 toxicity. Three-year event free survival was 95%. Two patients died due to development of stage IV melanoma.
Ulcer-related cutaneous squamous cell carcinoma: New kid on the block.
Authors: Miodovnik Mor , Ospovat Inna , Gutfeld Orit , Finkel Inbar , Dolev Yardenna , Leshem Yasmin
Published: July 2024

e21559

Background: Cutaneous squamous cell carcinoma (cSCC) represents a favorable tumor microenvironment with high tumor mutational burden, and infiltration of immune cells that are highly responsive to immunotherapies. Yet, we encounter tumors arising on non-exposed skin, such as those developing from chronic ulcers in which the response to anti-PD1 is unknown. Methods: The authors reviewed the medical records of consecutive cSCC patients receiving Cemiplimab or Pembrolizumab at a single tertiary center. Results: Of the 84 eligible patients, 9 (11%) had ulcer-related cSCC. six out of the nine (67%) were located on the lower extremities. Only two out of these nine patients (22%) reached partial response (PR) and none reached complete response (CR). In contrast, of the 75 patients with non-ulcer-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P < 0.001). Interestingly, two of the seven non-responders in the ulcer-related subtype received second-line chemo-immunotherapy and experienced a partial response that continued for 21 and 8 months. Patients with ulcer-related SCC had a significantly shorter median progression-free survival (PFS) (2.1 months vs. non-reached, p < 0.001). Overall survival (OS) was also shorter, but didn't reach significance (17 vs. 30 months, p = 0.02). Multivariate analysis confirmed ulcer-related SCC as an independent risk factor for shorter PFS (hazard ratio [HR], 7.56; 95% confidence interval [CI], 1.26-40.74, p = 0.027). Conclusions: This study suggests immunotherapy is less beneficial in ulcer-related SCC. More work is needed to verify our findings and explore other treatment options including chemoimmunotherapy.
A randomized, multicenter, open-label, phase 2 study of TRK-950 in combination with ramucirumab and paclitaxel as second-line therapy in patients with Caprin-1 positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Kelly Ronan Joseph , Castillo Dani Ran , Yamaguchi Kensei , Kato Ken , Kudo Toshihiro , Wainberg Zev A. , Rha Sun Young , Lee Jeeyun , Ryu Min-Hee , Okano Fumiyoshi , Shitara Kohei
Published: July 2024

TPS4181

Background: Caprin-1 is strongly expressed on the cell membrane of many cancer types including G/GEJ and on cancer stem cells. High expression is associated with enhanced in vitro colony-forming activity and in vivo tumorigenicity. TRK-950 is a first in class humanized antibody targeting CAPRIN-11). In the phase I study (NCT02990481), TRK-950 was well tolerated as monotherapy with no DLTs and MTD not reached at doses of 3-30mg/kg IV weekly. Subsequently the Phase 1b study demonstrated that TRK-950 was well tolerated with a high potential for synergistic anti-tumor activity when used in combination with standard of care treatment(s) in selected advanced solid tumors (NCT03872947). Specifically, Regimen D which evaluated TRK-950 in combination with Ramucirumab and Paclitaxel in G/GEJ showed a DCR of 100% in all nine patients receiving 10 mg/kg and partial responses were seen in 5/9 (55%) patients. Caprin-1 strong expression was observed in 4/9 patients and an ORR of 100% was seen in those patients2). A Phase II clinical trial in gastric/GEJ cancer patients with strong Caprin-1 expressions is now enrolling patients. Methods: The phase II study is a multi-national, open-label, randomized, multicenter study evaluating the efficacy of TRK-950 in combination with ramucirumab (Ram) + paclitaxel (PTX ) as compared with Ram + PTX treatment alone in patients with previously treated metastatic G/GEJ adenocarcinoma (NCT06038578). Patients enrolled across 10 sites in Japan, South Korea and the United States are randomized 1:1:1 by the permuted block method to (arm A) TRK-950 5mg/kg plus Ram + PTX, (arm B) TRK-950 10mg/kg plus Ram + PTX or (arm C) Ram + PTX alone. Inclusion criteria include patients with Caprin-1 positive (cutoff; 30% at ≥ 2+ staining) advanced/metastatic G/GEJ adenocarcinoma who have received first line therapy. Key exclusion criteria include HER2 positive disease. The primary endpoint is progression free survival (PFS) based on Independent Central Review (ICR) assessment per RECIST v1.1. Key secondary and exploratory endpoints include overall survival (OS), ORR, DoR, and biomarker evaluation. An interim analysis will be performed after 105 patients are randomized in stage 1 to determine the optimal dose of TRK-950 (5mg/kg or 10mg/kg) that will be evaluated in arm stage 2. In total 146 patients will be enrolled (40 patients in one arm and each 53 patients in two arms). This study opened in September 2023. 1. Okano F, et al. Cancer Res Commun. 2023 Apr 18;3(4):640-658. 2. Cassier P, et al. J Clin Oncol. 2023 Vol. 41, No. 4, suppl. Clinical trial information: NCT06038578 .