bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world healthcare resource utilization amongst non-small cell lung cancer (NSCLC) patients tested with a host immune classifier (HIC).
Authors: Iams Wade Thomas , Le Kimberly , Princic Nicole , Marlin Taylor
Published: June 2023

e21210

Background: The HIC is a blood-based proteomic test that measures immune response in patients with NSCLC. The test stratifies patients into two groups, HIC-H and HIC-C which helps evaluate patient prognosis and response to treatment. While clinical validity of the HIC test has been published, no real-world studies have described healthcare resource utilization (HCRU) amongst patients who have been tested with the HIC. This claims analysis describes HCRU amongst patients with NSCLC tested with the HIC. Methods: MarketScan Commercial and Medicare Supplemental Databases linked to Biodesix data files of HIC test results were retrospectively queried to identify patients who were age 18 and older on index date (date of HIC testing), underwent a HIC proteomic test, were continuously enrolled in the MarketScan database for the 6-months before index (pre-index period) and one month post-index, and had at least one non-diagnostic medical claim of lung cancer during the pre-index period. Data utilized was between January 1, 2016 to June 30, 2021. HCRU was measured per patient per month (PPPM) during the pre-index and post-index period and compared between HIC-H and HIC-C cohorts. Results: Of the 328 included patients, 260 patients were HIC-H and 68 were HIC-C. On index, 178 patients had non-metastatic lung cancer and 150 patients had metastatic lung cancer. When examining HCRU in all patients prior to the HIC test, significantly more HIC-C patients had an outpatient visit with an oncologist (40% vs 27%, P < 0.05) or a primary care physician (71% vs 56%, P < 0.05). When assessing only patients with metastatic lung cancer prior to index, significantly more HIC-C patients had inpatient admissions (57% vs 37%, P < 0.05) and more outpatient visits with a primary care physician (73% vs 50%, P < 0.05). When examining HCRU in patients after the HIC test, metastatic patients had significantly more prescriptions (4.6 vs 3.6, P < 0.05). Metastatic HIC-H patients also had significantly more visits to the emergency room (64% vs 43%, P < 0.05). Conclusions: Patients who are identified as HIC-C tend to have higher HCRU earlier in their lung cancer diagnosis and treatment course (prior to HIC testing). In the post-index period, metastatic HIC-H patients had higher HCRU with respect to prescriptions and emergency visits. Other post-index HCRU metrics such as primary care utilization and inpatient admissions were similar among HIC-C and HIC-H patients. Earlier identification of HIC-C and HIC-H patients may help identify those most likely to benefit from additional health system navigation support.
Machine learning models based on radiomics features to predict treatment response, biomarker status, and bone metastasis in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).
Authors: Yu Jisang , Velichko Yury , Kim Hyeonseon , Gennaro Nicolò , Soliman Moataz , Kim Leeseul , Oh Youjin , Djunadi Trie Arni , Lee Jeeyeon , Chung Liam Il-Young , Yoon Sung Mi , Shah Zunairah , Yang Won Jun , Kim Hye Sung , Lee Yunjoo , Lee Soowon , Kang Daeun , Agrawal Rishi , Aouad Pascale , Chae Young Kwang
Published: June 2023

e21217

Background: Radiomics can predict diagnosis, metastasis, actionable mutations and treatment response in NSCLC patients by analyzing the heterogeneity of tumors and its surrounding tissues from medical images. In this abstract, machine-learning models based on radiomic features, in patients with NSCLC, were established and evaluated. Methods: Patients with NSCLC and treated with ICIs were selected. Main tumor and peri-tumoral space were segmented on chest CT scans with contrast at the start of immunotherapy by four clinicians. Among 255 radiomic features were extracted using LIFEx software (IMIV/CEA, Orsay, France), the top 30 features with the highest Fleiss’ kappa coefficient were chosen. The Random Forest (RF) algorithm with mixed effects was utilized to develop models. We divided data into two groups as a training set (70%) and a validation set (30%) and conducted bootstrapping to evaluate the efficiency of the models. The performance of the models was determined by calculating the sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Durable disease control, progression, clinical progression, EGFR mutations, bone metastasis was evaluated by each model. Durable disease control was defined as no progression of diseases for 24 weeks or more after initiation of ICIs according to RECIST 1.1. Progression was defined by RECIST 1.1 on the first follow-up CT. Clinical progression was defined when treatment was discontinued due to disease progression. Results: Total 102 patients were analyzed; 55 (53.9%) were female and 47 (46.1%) were male. The mean age at the start of ICI treatment was 65.6 [range: 22-89]. The multi-reader radiomics-based models predicts durable disease control, progression, clinical progression, EGFR mutation, and bone metastasis with a sensitivity of 0.700, 0.714, 0.286, 0.909, and 0.810, and specificity of 0.417, 0.444, 0.778, 0.200, and 0.222 respectively. The statistical values of the models are shown in the Table. Conclusions: The machine-learning models grounded on radiomics features has limited accuracy to prognosticate ICIs treatment outcome, EGFR mutations, and distant bone metastasis. Further studies with larger sample sizes are warranted. [Table: see text]
Reality check for precision oncology in squamous cell lung cancer.
Authors: Bakhtyar Maham , Bhatti Sajjad Akbar
Published: June 2023

e21221

Background: Squamous cell lung cancer (SqCLC) is the second most common type of pulmonary malignancy after lung adenocarcinoma. Therapeutic advances in Precision Oncology have significantly improved outcomes in subsets of patients with lung adenocarcinoma. However, a significantly different mutational landscape has limited the success of Precision Oncology in SqCLC. Still, NCCN guidelines recommend considering molecular testing in SqCLC, preferably with broad-based molecular profiling like next-generation sequencing (NGS), aiming to identify candidates for FDA-approved targeted therapy. We aim to evaluate the percentage of SqCLC potentially eligible for targeted therapy using NGS by analyzing data from The Cancer Genome Atlas (TCGA). Methods: We filtered cases with a SqCLC diagnosis from the TCGA database. These cases were screened for DNA/RNA alterations in the 9 NCCN-guidelines recommended genes, including EGFR/ALK/ROS1/BRAF/MET/RET/HER2/NTRK/KRAS. Each unique alteration in the genes mentioned above was then analyzed in the oncoKB database to predict clinical benefit with level 1 and 2A evidence from FDA-approved targeted therapy. We then calculated the percentage of patients with SqCLC tested with NGS who could assess approved matched targeted therapy. Results: We identified 501 unique cases of SqCLC diagnosis in the TCGA. In the 9 NCCN-recommended actionable genes, 206 alterations were detected. We reviewed the clinical implication and utility of each of these alterations in the OncoKB database, and only 5 alterations were consistent with level 1/2A clinical benefit from a matched targeted therapy. These included 2 cases with L861Q and one each with EGFR L858R, EGFR E746_A750 exon 19 deletion, and G222C missense in the ERBB2 gene. Conclusions: The percentage of squamous cell cases which are potential candidates for FDA-approved targeted therapy was relatively low, 0.1% (5/501). While next-generation sequencing will not affect the standard of care treatment options for most SqCLC patients, clinicians can use this information to counsel patients for enrollment in clinical trials. [Table: see text]
Clinical outcomes for immunotherapy beyond progression in patients with advanced non-small cell lung cancer.
Authors: Jia Wenxiao , Wang Min , Zhu Hui , Wu Gang
Published: June 2023

e21222

Background: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP)as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore, a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles, best response and progressive mode of first-line immunotherapy could affect the results. Methods: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles, best response and progressive mode of first-line immunotherapy were also evaluated. Results: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p= 0.029), 16.1m (16.1 vs 10.8 p= 0.021), 16.3m (16.3 vs 10.9 p= 0.015) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and local progression of first-line immunotherapy. Conclusions: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and local progression in first-line was benefit.
CAROLINE study: Incidence and characterization of melanoma in French Polynesia.
Authors: Epaillard Nicolas , Auclin Edouard , Hirigoyen Elodie , Bermond Luc , Bonnet Anouck , Loiselet Pierre , Chastenet Mathilde , Herve Robert , Mengue Sylvie , Dutin Jean Philippe , Honoré Charles , Gustin Pierre , Mahjoubi Linda
Published: June 2023

e21505

Background: Epidemiology of metastatic melanoma in French Polynesia has never been described. Yet melanoma is known to be associated with sun exposure. The aim of this monocentric study was to assess the epidemiology of metastatic melanoma in French Polynesia. Methods: Here we analyzed data of all patients diagnosed with metastatic melanoma from January 2015 to December 2020 in the only public hospital in French Polynesia and described epidemiological, survival findings and molecular characteristics. Clinical, molecular and radiological data were collected. Results: Out of 69 patients, the majority were male (74%) and median age was 65 years old. Patients were more often native from French Polynesia (59%) and Metropolitan France (32%), 80% of patients were living in Tahiti Island. Most patients had metastatic cutaneous melanoma and only 3 had metastatic uveal melanoma. A total of 37 patients had an available BRAF molecular profile and 35% were BRAF mutated. 28% were metastatic at diagnosis. First line treatments were nivolumab (31%) and pembrolizumab (15%). The ORR was 45.88% (15/33) and 2 patients had CR. Overall, the median OS was 12.2 months [95% CI, 8.64- 43.27]. Conclusions: Most patients with metastatic melanoma were from Tahiti Island and there were no major disparities between the other archipelagos. Yet facilities of access to care may vary from geographical zones. Massive prevention is still crucial.
Immunotherapy and radiotherapy in metastatic uveal melanoma: Results from a single institute study.
Authors: Guan Jian , Teh Bin S. , Schefler Amy , Bernicker Eric
Published: June 2023

e21507

Background: Metastatic uveal melanoma carries a poor prognosis, especially for patients who are not eligible for Tebentafusp. Unlike cutaneous melanoma, checkpoint inhibitors have limited effect on uveal melanoma. The observation of Abscopal effect has inspired this study of adding radiotherapy to boost the efficacy of immunotherapy. Methods: We performed a retrospective study in Houston Methodist Hospital to evaluate the efficacy of combining immunotherapy with radiotherapy including either SBRT or Y-90 treatment. Clinical outcomes were determined by assessing best overall response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), progression-free survival(PFS) and overall survival. Results: A total of 8 patients were included for this study, among which one patient had previously progressed on immunotherapy. The median follow-up period was 19 months. The best overall response rate (ORR) and disease control rate (DCR) were 25% and 75% in patients received dual-modality combination treatment (including one complete response and one partial response). The PFS and overall survival in dual-modality combination treatment group were 5.4 months (95% CI, 1.1 to 14.9 months) and 18.7 month (95% CI, 11.1 to 23.9 months), respectively. Fifty percent of patients experienced grade 3-4 treatment-related adverse events. Conclusions: The combination of radiotherapy and immunotherapy is active in metastatic uveal melanoma with sustained response in selected patients. A randomized prospective trial may be required to confirm the benefits of dual-modality combination treatment.[Table: see text]
Adjuvant polypeptide vaccines for high-risk uveal melanoma.
Authors: Gaughan Elizabeth Mary , Lucchesi Nicholas , Jin Ruyun , Slingluff Craig L.
Published: June 2023

e21509

Background: Due to biologic differences, uveal melanoma patients are often excluded from clinical trials for cutaneous melanoma; however, many antigens are shared between the two melanoma subtypes. Thus, our vaccine trials at the University of Virginia (UVA) have allowed enrollment of high-risk uveal melanoma patients, who have substantial risk of relapse without FDA-approved adjuvant therapy available. For the present study, we hypothesized that the vaccines would be well-tolerated and immunogenic in this population. We examined the clinical, immunogenicity and safety outcomes of subjects with uveal melanoma enrolled in our adjuvant vaccine clinical studies. Methods: Patients were identified through participation in an adjuvant vaccine study at UVA between 2012-2022. Ten patients received the 6-Melanoma-Helper Peptide (6-MHP) vaccine through Mel-65 and Mel-66 clinical trials (NCT03617328 and NCT04364230) and one patient received the 12-peptide MELITAC vaccine through the Mel-58 clinical trial (NCT01585350). Clinical outcomes included relapse-free (RFS) and overall survival (OS) and trial toxicity reporting. Immunogenicity was assessed by ex vivo interferon-gamma ELISpot assay of peripheral T cells. OS and RFS were reported by Kaplan-Meier survival analysis and compared by log rank test between groups. Results: Of the 11 identified patients, nine were male (82%) and two were female (18%), with a median age of 64 years. All patients were high risk by molecular testing, the majority by Castle Bioscience DecisionDx-UM. Five were PRAME positive, five PRAME negative, and one not reported. In the cohort, three patients had uveal melanoma recurrence and one subject died from metastatic disease during the evaluation period. The 5-year RFS and OS were 71% (95% CI 43-100) and 80% (95% CI 52-100), respectively. Two patients experienced dose-limiting, grade 3 toxicities to the vaccine, requiring early trial discontinuation, including one grade 3 injection-site reaction and one grade 3 uveitis. Nine patients experienced grade 1-2 toxicities, mostly injection-site reactions and constitutional symptoms. Of nine patients with available immunogenicity data, five (55%) had direct antigen-mediated immune response to vaccine. Two patients’ responses are pending. Patients with immunogenic response had a non-significant trend toward better RFS and OS (both p = 0.22). The 3-year RFS and OS were 100% for subjects with T cell response and the RFS and OS were 50% (95% CI 13-100) for patients without T cell response. Two of the relapsed patients did not have an immune response to vaccine, and response data were not available for the third. Conclusions: Melanoma polypeptide vaccines are immunogenic and safe in patients with uveal melanoma. Our early data suggests the possibility of early benefit with direct antigen response, though longer follow up and further study will be needed to investigate these findings.
Patterns of care delivery and outcomes in patients with melanoma brain metastases treated with ipilimumab/nivolumab.
Authors: Haykal Tarek , Ferreira Michelle , Lowe Melissa , Hanks Brent Allen , Fecci Peter E. , Kirkpatrick John P. , Vaios Eugene John , Reitman Zach , Salama April K.S.
Published: June 2023

e21510

Background: Patients (Pts) with metastatic melanoma presenting with brain metastases (MBM) have a high morbidity and mortality risk. The combination of ipilimumab/nivolumab (I/N) has demonstrated high intracranial response rates in selected, asymptomatic pts, suggesting there is a subset of pts who may be able to forgo or delay intracranial therapies. There is currently limited real world data on how many pts with MBM are successfully treated with this approach. We sought to explore our clinical experience at Duke University with combination immune checkpoint inhibitors for pts with MBM. Methods: An electronic database search was conducted for all metastatic melanoma pts treated with PD-1 therapies between 2015 and 2021. Pts treated with combination ICIs for brain metastases were included. The primary outcome was overall survival (OS). Secondary outcomes were need for local therapies (radiation (RT): stereotactic radiosurgery or whole brain radiation therapy or craniotomy), and immune related adverse events (irAEs). Results: Between 2015 and 2021, 66 pts with MBM received I/N, with a median follow-up of 30.4 months. Median age was 68, 60.6% were male and 61% had a BRAF mutation. 38 pts were asymptomatic. Of the 28 symptomatic patients 61% were on corticosteroids at the time of I/N initiation. 56% of pts received local therapy prior to start of I/N, 17% during and 18% after discontinuing I/N. 53% of pts were initiated on I/N as first line systemic therapy for MBM. 56% of patients had to discontinue I/N after one cycle because of high-grade irAEs. 13.8% of patients that received RT to the brain developed radionecrosis. Median OS was 25.6 months in the overall cohort, with a 1 year OS of 63%. There was a trend towards a higher risk of death for symptomatic versus asymptomatic patients HR:1.96 [95% CI: 0.96, 3.97; P:0.06]. Of the 38 asymptomatic patients, only 6 patients did not receive local therapies with either RT or craniotomy. Two of these patients died from melanoma progression, one from intra-cranial progression, the other from both intra-cranial and extra-cranial progression, and 4 remain alive without evidence of progression. Conclusions: The majority of pts with MBM are ultimately treated with multimodality therapy. Advances in systemic therapies have provided meaningful clinical benefit that could allow a limited number of asymptomatic patients to forgo local therapy, but currently few pts are treated in this manner.
Predicting immunotherapy outcomes of melanoma patients before treatment by intestinal microbiota.
Authors: Wang Tao , Liu Yang , Wang Qian , Xiao Shanshan
Published: June 2023

e21512

Background: To find the appropriate patients that can benefit from immunotherapy is very important in precision medicine. Biomarkers such as PD-L1, TMB and MSI attracted a lot of attentions in immunotherapy. Emerging biomarkers such as intestinal microbiota and others also showed promising predictive/prognosis values in the clinical studies. The purpose of this study was to evaluate new prediction models based on intestinal microbiota data from the melanoma patients before treatment. Methods: This study enrolled 41 microbiome 16S patients from published datasets. Firstly, survival analysis was performed on the response group (R) and non-response group (NR). Species in all the samples were included to perform univariate cox regression analysis, and the differences of intestinal microbiota between R and NR groups were evaluated by alpha and beta diversities. The specific differential microbiota was obtained by Student's t-test and LEfSe and further screened by the best performance of the five machine learning methods. To find the minimum set of the microbiota species, logistic regression and ROC curve were used. Analyses of KO data included PCA, differential and KEGG enrichment analysis. Significantly enriched pathways were scored by ssGSEA. The spearman correlations between ssGSEA scores and final microbiota species were calculated. Results: The non-response (NR) group had shorter PFS. Univariate cox regression analysis on all the samples identified 36 species which might be associated with prognosis. Alpha and beta diversities showed the R and NR groups were significantly different. Student's t-test identified 52 differential species and LEfSe identified 72 OTUs. Most of the microbiome enriched in R group belonged to firmicutes, while those enriched in NR group belonged to firmicutes, bacteroides and proteobacteria. We then constructed five machine learning models to predict PD1 immunotherapy responses of the melanoma patients and finally identified 25 species. Logistic regression and ROC curve identified the minimum set of the microbiota species including methanobrevibacter smithii, schaalia odontolytica, cuneatibacter caecimuris. A total of 119 differentially expressed KO genes were obtained by differential analysis, and those genes were mainly enriched in 25 pathways. Spearman correlation analysis found that those three microbial species were mainly associated with 12 pathways which might influence the classification of the two groups. Conclusions: In this study we identified three microbial species which might contribute to the classification of the R and NR patient groups. The models based on intestinal microbiota data can predict immunotherapy outcomes of melanoma patients.
Intrathecal anti-PD-1 treatment in patients with metastatic melanoma (MM) with leptomeningeal disease (LMD): Real-world data and evidence.
Authors: Zhen Junjie , Zhang Xiaoshi , Cai Linbo , Chen Linbin , Lai Mingyao , Li Dandan , Wang Hui , Ding Ya , Yang Yanying , Li Jingjing , Wen Xizhi
Published: June 2023

e21516

Background: LMD is one of the most severe complications of melanoma and has an extremely poor prognosis. Over the past decade, the incidence of LMD is increasing with improved treatment strategies and prolonged survival. This real-world study aims to evaluate the safety and efficacy of intrathecal anti-PD-1 treatment in MM patients with LMD. Methods: MM patients with LMD diagnosed by MRI and/or cerebrospinal fluid (CSF) cytology were assigned to intrathecal nivolumab infusion 20mg once every 2 weeks (n = 4) or pembrolizumab 20mg once every 3 weeks (n = 3). The patients received a median of 4 cycles of treatment (range 2–7 cycles). Efficacy and safety analyses were performed on all the treated patients. Results: Between June 2022 and December 2022, 7 patients were treated, including 3 cutaneous, 2 acral and 2 primary leptomeningeal melanoma. All patients presented linear or small nodular enhancement of leptomeningeal on MRI. Four patients had concurrent parenchymal brain metastases. The tumor cells were found in 5 patients by CSF cytology, and pathologic diagnosis was obtained by leptomeningeal biopsy in 2 patients. According to RANO-LM criteria, 4 patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while 3 patients developed progressive disease. The median overall survival (OS) was 39.7 months after initial diagnosis and 24 weeks after LMD. With a median follow-up of 13.3 weeks (range 9.4–20.3 weeks), the median intracranial progression-free survival (IPFS) and median OS for intrathecal anti-PD-1 were 16.1 and 20.3 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1). Conclusions: In this real-world study, intrathecal anti-PD-1 treatment was found to be well tolerated and effective in metastatic melanoma patients with LMD.
Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: A retrospective observational cohort study.
Authors: Gupta Mehul , Stukalin Igor , Goutam Siddhartha , Meyers Daniel E. , Heng Daniel Yick Chin , Cheng Tina , Monzon Jose Gerard , Navani Vishal
Published: June 2023

e21524

Background: The association of objective imaging response with first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in a real-world context. We compared likelihood of objective response between patients receiving first line anti-programmed cell death protein 1 (anti-PD1) monotherapies (pembrolizumab or nivolumab), or combination nivolumab with the cytotoxic T-cell lymphocyte-antigen 4 inhibitor ipilimumab and outlined the association between objective response and baseline characteristics and survival outcomes. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from 2013-2020 in Alberta, Canada. Best imaging response was assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1. The primary outcome was likelihood of objective imaging response (complete or partial response) between patients receiving anti-PD1 monotherapy and those receiving combination nivolumab-ipilimumab. Secondary outcomes were the identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT) endpoints. Results: Of the 255 patients included, 49/255 (19.2%) had complete response 112/255 (43.9%) had partial response, 28/255 (11.0%) had stable disease, and 66/255 (25.9%) had progressive disease. Median OS was not evaluable (NE) (95% CI NE-NE) for complete responders, NE (95% CI 52.93 months-NE) for partial responders, 21.30 months (95% CI 15.20 months-NE) for stable disease, and 7.72 months (95% CI 5.77-10.6 months) for progressive disease (log rank p < 0.0001). A robust delineation of TTNT by imaging response was also seen. Likelihood of objective response was similar between patients treated with nivolumab-ipilimumab compared to those receiving anti-PD1 monotherapy (OR 1.87 95% CI 0.85-4.20, p = 0.124). Normal LDH level (OR 2.13; 95% CI 1.01-4.35, p = 0.047), non-mucosal primary site (OR 9.09; 95% CI 2.44-33.33, p < 0.001), and absence of BRAF V600E mutation (OR 3.23; 95% CI 1.39-7.69, p = 0.007) were independently associated with likelihood of objective imaging response in multivariable analysis. Conclusions: In this real-world analysis, we demonstrate no significant difference in likelihood of objective response between patients treated with anti-PD1 monotherapy and combination nivolumab-ipilimumab, and demonstrate that a normal LDH level, non-mucosal primary site, and absence of BRAF V600E mutation are associated with response. Imaging response was also strongly associated with both OS and TTNT irrespective of therapy received. These results may help inform treatment selection, and aid in counseling of advanced melanoma patients treated with first line ICI therapy in a routine clinical practice setting.
Cemiplimab in first line treatment for locally advanced and metastatic skin squamous cell carcinoma in Slovenia.
Authors: Ocvirk Janja , Sever Masa , Tomic Blaz , Mesti Tanja
Published: June 2023

e21531

Background: Cemiplimab is a first PD1 inhibitor for treatment of locally advanced cutaneous squamous cell carcinoma (laSCC) and metastatic SCC (mSCC). The purpose of this study is to report outcomes of patients with SCC, treated with cemiplimab in routine clinical practice in Slovenia in twenty-month period. Methods: In this retrospective cohort study we analyzed medical records of patients with laSCC and mSCC inappropriate for surgery or radiotherapy treated with cemiplimab in first line between May 2020 and November 2022. The baseline characteristics, outcomes, immune related adverse events (irAE). Results: 28 patients were included, 24 with laSCC and 4 with mSCC, with a median age of 76.1 years. Of them, 18 % (5 patients) a concomitant autoimmune disease. The estimated median progression-free survival (PFS) was 4.4 months (95% CI: 1.5–7.3). The median overall survival (OS) was 7.3 months (95% CI: 4.6–9.9). Among 27 treated patients with an evaluable response, 3 (11 %) achieved complete response, 5 (19 %) achieved partial response, 6 (22 %) had stable disease and 13 (48 %) patients experienced a progressive disease. The overall response rate (ORR) was 30 %, and the disease control rate (DCR) was 52 %. A quarter of all patients had at least one immune related adverse events (irAEs). Only one patient had grade 3 event, there were no grade 4 and no fatal events. Higher response rate was achieved in patients with irAE – ORR was 43 % and DCR was 71 %. Seven patients are still on cemiplimab. Conclusions: Cemiplimab has shown meaningful efficacy with DCR of 52 % in patients with laSCC and mSCC in Slovenia. Patients developing irAE had higher response rate.
Efficacy of nivolumab and relatlimab-rmbw in patients with advanced melanoma who were previously treated with PD-1 inhibitor: Real world experience.
Authors: Jang Sekwon , Stahl Chelsea , Al-Mondhiry Jafar , Venna Suraj S
Published: June 2023

e21533

Background: Nivolumab and relatlimab-rmbw (R/N) combination demonstrated superior efficacy to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. Sparse data exists on the efficacy of this combination in patients with melanoma that relapsed after,or was resistant to treatment with PD-1 inhibitors. Methods: We conducted a retrospective study of patients with unresectable or metastatic melanoma whose disease recurred or progressed on/after prior PD-1 inhibitor who received R/N at Inova Schar Cancer Institute. Efficacy endpoint was objective response using modified RECIST1.1. Unconfirmed complete response (CR) or partial response (PR) were included in objective response rate (ORR). Patients whose Positron Emission Tomography (PET) scan showing complete metabolic resolution of metastatic sites were also considered CR. Patients who had rapid clinical progression and didn’t have repeat radiologic studies were considered to have progressive disease (PD). Patients who underwent radiation to target lesions were considered non-evaluable (NE). Results: From Sep 2021 through Dec 2022, a total of 32 patients (19 male) received R/N including 8 unresectable stage III melanomas and 24 stage IV melanomas (M1a: 4, M1b: 4, Mc1: 5, M1d: 10). Median age was 67 (39-88), and 12 (38%) had BRAF mutation. Median number of prior therapies was 2 (range: 1-7) including anti-CTLA4 antibody in 22 and BRAF/MEK inhibitor in 8. Nine patients (28%) had ≥ 3 prior therapies. Among 30 patients evaluable for response, ORR was 33% (4 CR, 6 PR). Three had stable disease (SD), and 16 had PD including 2 with rapid clinical progression. Response by subgroup is included in table. Conclusions: R/N shows clinically meaningful antitumor activity in patients who received prior PD-1 inhibitor in real world setting. Additional clinical data of R/N in PD-1 inhibitor relapsed or refractory patients are needed to validate the results of this single-center study. [Table: see text]
Long-term outcomes of melanoma oligoprogressive metastases treated with radiotherapy combined with locoregional hyperthermia.
Authors: Borkowska Aneta , Spalek Mateusz , Teterycz Pawel , Rutkowski Piotr
Published: June 2023

e21540

Background: Oligoprogression is a limited progression after a prior response to treatment. Oligoprogression remains a major clinical challenge in patients with metastatic melanoma (MM). Local therapy for progressing metastases may enable the continuation of effective systemic therapy. Methods: We identified 77 patients treated with radiotherapy combined with hyperthermia for oligoprogressive MM in a melanoma tertiary center between 2019 and 2022. Patients without any follow-up imaging after irradiation were excluded. We assessed local control (LC), and overall survival (OS). We estimated the correlation between BRAF status, size of the irradiated lesion, radiation dose, and LC. Survival analyses were performed using the Kaplan-Meier estimator, and Log-rank tests and were used for comparison between groups. The data cut-off was 31/Aug/2022. Results: The majority of patients (83%) had one oligoprogressive lesion. At the time of analysis, 59.5% of patients had stable disease, complete or partial response, and 40.5% of patients had progression, in the total response according to RECIST (Table). Most patients (78%) were irradiated during immunotherapy whereas 12% received concomitant BRAF and MEK inhibitors (Table). There were no severe toxicities of radiotherapy nor hyperthermia. The median follow-up was 18 (95%CI: 16-24) months(m). The 12 and 24m LC rates were: 83% (95%CI: 74-94) and 54% (95%CI: 40-73), respectively. The achieved LC rate was 88.3%. The 12 and 24m OS rates were: 87% and 72%, respectively. At the time of analysis, the median of OS and LC were not reached. BRAF status, size of the lesion, or radiation dose were not associated with LC. Conclusions: Preliminary data showed that patients with MM may benefit from radiotherapy combined with hyperthermia for oligoprogressive lesions during systemic treatment. This combination enables good local control of progressive metastases with minimal toxicity. This topic requires further investigation in prospective studies. [Table: see text]
Impact of antibiotics on survival outcomes and risk of gastritis/colitis in patients with advanced-stage melanoma receiving anti-PD-1 therapy.
Authors: Bailey Shannon , Havighurst Thomas , Pozorski Vincent , Mohamoud Yusuf , Tesfamichael Dahlia , Jung Lindsey , Dow-Hillgartner Elizabeth N. , Ma Vincent T.
Published: June 2023

e21543

Background: Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, have improved survival in advanced-stage melanoma patients compared to previous treatment options. A healthy gut microbiome has been associated with a positive response to ICIs. Antibiotics are known to disrupt the gut microbiome and may have immune-modulatory effects within the tumor microenvironment. Studies have demonstrated a negative impact on survival with any antibiotic use during ICI treatment. Less information is known regarding the impact of spectrum of activity or antibiotic timing on survival and risk of ICI-associated gastritis/colitis. Methods: We conducted a single-center, retrospective review of advanced-stage melanoma patients treated with anti-PD-1-based therapy (ipilimumab/nivolumab or anti-PD-1 monotherapy) between 2014-2022. Multiple clinicopathologic variables including antibiotic use, survival outcomes, and development of colitis and/or gastritis were assessed. Antibiotic spectrum of activity was divided into two groups: with anaerobic coverage and without anaerobic coverage. Antibiotic timing was assessed as patients who received antibiotics within 30-days prior to starting ICI and/or during treatment. Univariate and multivariate analyses on PFS and OS were performed using Cox proportional hazard models. Logistic regression models were used to assess risk of gastritis and/or colitis. Multivariate analyses accounted for age, gender, melanoma primary type, BRAF mutation status, presence of brain or liver metastases, and pre-treatment LDH levels. Results: A total of 214 patients were analyzed. Multivariate analysis demonstrated any antibiotic exposure during anti-PD-1 therapy was associated with improved OS [HR 0.500, 95% CI 0.303–0.826, p = 0.007]. Although not statistically significant, there was a trend towards worse OS in patients who received antibiotic therapy 30-days prior to ICI therapy [HR 1.726, 95% CI 0.994-2.995, p = 0.052]. Use of antibiotics without anaerobic coverage was associated with improved PFS [HR 0.462, 95% CI 0.273–0.782, p = 0.004] and OS [HR 0.399, 95% CI 0.200–0.789, p = 0.009]. Antibiotic exposure 30-days prior to initiating anti-PD-1 therapy increased the risk of developing gastritis and/or colitis [OR 1.990, 95% CI 0.744–2.651, p = 0.043]. Conclusions: Antibiotic timing and spectrum of activity may be predictive of survival outcomes and risk of gastritis/colitis in anti-PD-1-treated patients with advanced-stage melanoma. Unlike previous studies, we found improved survival in patients receiving antibiotics during treatment and in those receiving antibiotics without anaerobic coverage. Our results demonstrate the need to further investigate specific antibiotic agents as well as antibiotic timing and their clinical impact on patients receiving ICI treatment.
The phase 1 clinical trial of anti–PD-1 (pucotenlimab) plus intrahepatic injection of oncolytic virus (OH2) combined with radiotherapy of liver metastasis in stage IV melanoma.
Authors: Cui Chuanliang , Wang Xuan , Wang Hongzhi , Yin Shanshan , Cong Yue , Lian Bin , Li Caili , Yu Jiayi , Si Lu , Chi Zhihong , Sheng Xinan , Kong Yan , Mao Lili , Zhou Li , Tang Bixia , Yan Xieqiao , Bai Xue , Li Siming , Wang Weihu , Guo Jun
Published: June 2023

e21545

Background: Melanoma pts with liver metastasis has poor prognosis and reduced response to systemic immunotherapy. Oncolytic herpes simplex virus 2 (OH2) is an oncolytic virus derived from herpes simplex virus type 2. PD-1 antibody combined with intrahepatic oncolytic virus intralesional injection had shown preliminary efficacy in previous clinical trial. The radiation of liver metastasis might exert action on its tumor microenvironment and get benefit from immunotherapy combination. So we perform this phase I study to assess the safety and efficacy of OH2 and pucotenlimab (a humanized immunoglobulin G4 monoclonal antibody) combine with liver metastasis radiation in melanoma pts. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous Pucotenlimab Q3W combined with ultrasound guided intrahepatic injection (metatstasis lesion) of OH2 Q2W (107CCID50/mL, 8ml per injection) after stereotactic body radiotherapy (24-30Gy/3Fx) of liver metastasis. Liver biopsy performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was ORR; secondary:toxicity, DCR, PFS and OS. Results: From Dec 2021 to Jan 2023, 10 pts were eligible and enrolled. Baseline characteristics: 70% got previous treatment; LDH＞ULN 50.0%; 90% got extra-hepatic metastasis; median size of ed lesions: 36mm(19-120mm); median number of liver metastasis: 5.5. Among these pts, 5 pts could be evaluated for efficacy (follow-up 10.0 m). The global ORR by investigator was 40.0% (2/5), DCR 80% (4/5). Biopsies of 4 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of tumor regression and TIL infiltration. Among them, 2 pts ( 1 PR and 1 SD) had no tumor cells residual by immunohistochemistry in biopsies with impressive TIL infiltration, both of them showed PFS more than12.0 months. Most adverse events (AE) were grade 1-2. Only one pts had grade 3-4 thrombocytopenia, with treatment modified. No treatment-related deaths occurred. The median PFS was not reached and now in follow up. Conclusions: Systemic anti-PD-1 plus intralesional injection of Oncolytic virus combined with radiotherapy has shown remarkable ORR and pathological response in melanoma pts with liver metastases with manageable toxicity. Clinical trial information: NCT05068453 . [Table: see text]
Correlation of patient characteristics and tumor histology in patients (pts) with locally advanced cutaneous squamous cell carcinoma (LACSCC) receiving immune checkpoint inhibitor treatment (ICI): A retrospective analysis.
Authors: Ben Haj Frej Khaoula , Kerr Phil , Stewart Campbell , Hegde Upendra P.
Published: June 2023

e21553

Background: Cutaneous squamous cell carcinoma (CSCC) arising from epidermal keratinocytes is highly curable with surgery. Functional anti-cancer immunity is protective of CSCC and high mortality due to local or systemic dissemination is seen in pts. with immune deficiency. ICI treatment is a logical FDA approved option that result in improved outcomes in affected pts. We report our experience in LACSCC pts. receiving ICI treatment and describe correlation between pt. characteristics, tumor histology and treatment outcome. Methods: Following Institutional Review Board approval, we did a retrospective analysis of LACSCC pts. receiving ICI therapy at the Neag Cancer Center who received at least one dose of ICI between 2018-2023. Analysis includes pt. demographics, relevant comorbidities, medications, and tumor histology and tumor infiltrating lymphocytes (TILs) of tumors reviewed with dermatopathologist. Results: Between 2018-2023, 12 pts. with LACSCC met the criteria for analysis. Median age 77.5 years (yrs.), (range 65-102), 9 males, 3 females, tumors sites - head and neck region 8 pts., torso 2 pts., legs 2 pts. Relevant past medical history included treatment of prostate cancer 3, chronic lymphocytic Leukemia 1, psoriasis 2 (one received anti TNF treatment), and MGUS, Parkinson’s disease and dementia in 1 each. Majority of pts. had significant smoking history (9/12), lymphopenia in 8 out of 12 pts. Tumors were poorly differentiated in 6 out of 12 pts. Brisk TILs was present in 7 and non-brisk TILs in 5 pts. 3 pts. with brisk TILs achieved complete remission (CR), one very good partial response (VGPR), 1 partial response (PR) and 2 not evaluable for response. Out of 5 pts. with non-brisk TILS, one achieved CR, one achieved VGPR, 1 PR, 1 stable disease (SD), and 1 progressive disease (PD) in a pt. who received anti TNF treatment of psoriasis. 9 patients are alive between 1 week and 50 months after initiation of treatment. 3 pts. died, one of PD, one of bacterial sepsis and one of Covid. Conclusions: High risk LACSCC affected males with smoking histories in the majority. Durable responses following ICI treatment occurred irrespective of age, while resistant disease was noted in 1 pt. with previous anti TNF treatment. Brisk TILs predicted high response rate and durable responses although some pts. with non-brisk TILs also showed favorable outcomes. Association with previous cancer and macular degeneration may reflect underlying immune deficiency. Three pts. developed infection within two weeks of ICI treatment (urinary tract infection, wound infection, Covid). More studies will shed light at factors compounding immune deficiency and safety of this treatment in a high-risk population.
Detection of ctDNA in patients with stage III cutaneous melanoma with satellite/in-transit or nodal metastases.
Authors: Al-Mondhiry Jafar , Stahl Chelsea , Venna Suraj S. , Jang Sekwon
Published: June 2023

e21559

Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker to monitor disease status in cancer patients. Limited data exists on the sensitivity of ctDNA for detection of satellite/in-transit or nodal metastases in melanoma. Methods: We conducted a retrospective study of stage III cutaneous melanomas with clinically detected satellite/in-transit and/or lymph node metastases who underwent ctDNA analysis using an mPCR-NGS-based ctDNA assay ("Signatera") prior to surgery or systemic therapy at Inova Schar Cancer Institute. Results: ctDNA was detected in 4 of 14 patients including 1 of 3 patients with both satellite/in-transit metastases and nodal metastases; 3 of 6 patients with nodal metastases only; none of 5 patients with satellite/in-transit metastases only. Nodal tumor burden (sum of short axis of involved lymph nodes) for ctDNA detected patients was greater than 1.5cm (5.0cm, 3.0cm, 3.0cm, and 1.6cm, respectively), and 1.5cm or less in patients whose ctDNA were not detected. Conclusions: ctDNA may not detect satellite/in-transit metastases or small nodal metastases in melanoma. A larger study is needed to validate this finding. [Table: see text]
Elucidating the connection between pneumonia and melanoma: Risk factors and outcomes for patients with melanoma.
Authors: Hundal Henna , Taneja Kamil , Patel Karan , Zhang Alex , Diaz Michael , Libraro Nicholas , Cohen Jules A.
Published: June 2023

e21561

Background: Pneumonia is a common cause of morbidity and mortality in patients with melanoma and leads to many ED visits per year in the US. However, there is no national-level study that has assessed factors that increase risk for melanoma patients to present to the ED with a primary diagnosis of pneumonia. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to identify melanoma patients that presented to the emergency department (ED) with a primary diagnosis of pneumonia. A multivariate logistic regression was used to identify characteristics that were significantly associated with a higher chance of pneumonia. A p-value less than 0.05 was considered significant. Results: Between 2006 and 2012, 239,956 melanoma patients presented to the ED. Amongst these patients, 3.1% presented to the ED with a primary diagnosis of pneumonia. The majority of patients were at least 80 years old (64.3%), male (61.5%), Medicare beneficiaries (73.1%), of the highest income quartile (28.7%), living in the South (35.7%), presented to non-trauma hospitals (53.1%), and presented to metropolitan non-teaching hospitals (44.9%). Factors associated with the highest risk of pneumonia in melanoma patients are the following: Medicaid patients (odds ratio (OR): 2.5, 95% Confidence Interval (CI): 1.4-4.4, p=0.003), Medicare patients (OR: 2.3, 95% CI: 1.4-3.0, p=0.002), private insurance patients (OR: 2.1, 95% CI: 1.3-3.5, p=0.005), non-metropolitan teaching hospitals (OR: 1.6, 95% CI: 1.3-1.9, p<0.001), living in the Northeast (OR: 1.3, 95% CI: 1.3-3.5, p=0.005), being male (OR: 1.3, 95% CI: 1.1-1.4,p<0.001) a high Charlson Comorbidity Index (OR: 1.3, 95% CI: 1.2-1.3, p<0.001). The majority of patients were either admitted (86.4%) or discharged home the same day (11.1%). Amongst the patients that were admitted, most patients were discharged (59.0%), transferred to a skilled nursing facility or intermediate care facility (19.2%), or given home health care (15.8%). Only 4.0% of admitted patients died in the hospital. Conclusions: A melanoma patient’s risk for developing pneumonia is depending on insurance status, the region of their hospital, their biological sex, and the presence of comorbidities. Clinicians should be aware of these risk factors to minimize the risk of pneumonia occurring in this at-risk population.