ABSTRACT
Introduction: While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Methods: Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Results: Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Discussion: Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.
ABSTRACT
While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.
ABSTRACT
BACKGROUND: Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1â¯cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. OBJECTIVE: To assess patient outcomes and complications considering different treatment regimens and clinical characteristics. MATERIALS AND METHODS: In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. RESULTS: Standard 3-4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5-6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. CONCLUSIONS: The study suggests no significant benefit from exceeding 3-4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.
