Norwegian Cancer Society

Background: Radspherin® is a novel α-emitting radiopharmaceutical administered intraperitoneally following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastases. It delivers short-range radiation aimed at eliminating residual microscopic disease. This qualitative study explored how participants with colorectal cancer experienced participating in an early-phase clinical trial involving CRS-HIPEC followed by Radspherin®. Materials and Methods: Semi-structured interviews were conducted with ten participants enrolled in a phase 1/2a trial involving CRS-HIPEC and intraperitoneal Radspherin®. The analysis was guided by a phenomenological and interpretive approach using reflexive thematic analysis. Results: Participants expressed a strong sense of motivation and hope tied specifically to receiving Radspherin®, which they perceived as an opportunity to improve their prognosis. Many also viewed participation as a contribution to future cancer research. None attributed complications or side effects to Radspherin®. Clear and supportive verbal communication from healthcare professionals was highly valued, while the written information was described as overwhelming. Despite fears of recurrence, most participants remained optimistic about regaining a meaningful life. While experiences with Radspherin® were largely positive, participants also described pain, fatigue, and prolonged recovery related to CRS-HIPEC, including ongoing functional and psychosocial challenges. Conclusions: Participants associated Radspherin® with hope and a therapeutic benefit but did not link it to their adverse events. Their willingness to participate in experimental treatment was shaped by trust in clinicians, clear communication, and a desire for extended survival. However, the burden of CRS-HIPEC-related side effects underscores the importance of tailored follow-up and support.

ObjectivesPseudomyxoma peritonei (PMP) is a rare, slow-growing cancer with few efficacious treatment options in unresectable cases. Mutations in the KRAS and GNAS oncogenes are common, but the reported frequencies vary greatly, most likely because of low tumor cellularity in peritoneal tumor samples. With treatments targeting these mutations becoming increasingly available, reliable detection of mutations is essential.MethodsThe frequency of KRAS and GNAS mutations was analyzed in tumor samples from 167 patients with verified PMP using targeted DNA sequencing and/or droplet digital polymerase chain reaction. When analysis of fresh-frozen peritoneal tumor samples did not reveal mutations, macrodissected formalin-fixed samples were analyzed.ResultsMutations in cancer-related genes were detected in 98 % of the analyzed samples, with KRAS and GNAS mutated in 148 (89 %) and 139 (83 %) cases, respectively. In 48 % of the analyzed cases, the mutational diagnosis was based on primary tumor samples.ConclusionsHigh frequencies of KRAS and GNAS mutations support the proposed role as driver mutations and as potential therapy targets. The primary tumor may serve as an alternative source of tumor material, increasing the likelihood of detecting targetable mutations. Combined with highly sensitive analytical methods, this approach facilitates selection of patients for novel targeted therapeutic strategies.

Abstract Background Adjuvant immunotherapy has significantly improved survival for patients with stage III cutaneous melanoma, yet a fraction of patients will not benefit from immune checkpoint inhibitors (ICI). The tumor microenvironment plays a pivotal role in generating durable responses to ICI. By analyzing the cellular composition of tumor-associated subsets, key immune components essential for promoting an anti-tumor environment can be pinpointed. This will allow for both patient stratification and identification of biomarkers associated with improved patient outcome. Method Regional lymph nodes were obtained from patients with stage III melanoma at surgery (n=29). Patients eligible for anti-PD-1 therapy (αPD-1; pembrolizumab or nivolumab) received adjuvant treatment for up to one year. CyTOF was used to determine cellular composition in pre-treatment surgical specimens. Bulk gene expression data generated by NanoString from patients receiving surgery without adjuvant therapy (n=125) was implemented for evaluating trends observed in the CyTOF dataset. Results Although no significant differences were observed across major hierarchical immune cell types between patients who developed distant metastasis after surgery and those that did not, an increased proportion of CD103 + PD-1 + CD8 + (T RM ) T cells and plasmablast-like CD38 hi CD19 dim cells were associated with improved prognosis in the CyTOF cohort. In the untreated cohort, a subset of patients defined as “Ultra-cold” (< 2.5 % tumor-infiltrating lymphocyte (TIL) scored by a pathologist) had significantly worse outcome than those with higher TIL infiltration. This Ultra-cold TIL group was associated with reduced B cell score, but not CD8 + T cell score, as well as reduced expression of activation genes like CD38 . Conclusion In this study, CD103 + PD-1 + CD8 + (T RM ) T cells and plasmablast-like CD38 hi CD19 dim cell populations were found to be strongly associated with prolonged distant metastasis-free survival in regional lymph nodes from patients with stage III melanoma treated with αPD-1. This suggests an association between progression and infiltration of these cell types at baseline and highlights the potential of using immune cell subsets as prognostic biomarkers. What is already known on this topic – Patients being diagnosed with stage III melanoma will receive immune checkpoint inhibitors but will often be cured by surgery alone. Selection of which patients might benefit from treatment is still unresolved. Accurate biomarkers would aid in treatment stratification, to avoid overtreatment, and unnecessary toxicities. What this study adds – This study highlights how baseline CD103 + PD-1 + CD8 + (T RM ) T cells and plasmablast-like CD38 hi CD19 dim cell populations in the regional lymph node, is strongly associated with improved outcome in patients receiving anti-PD-1 therapy. How this study might affect research, practice or policy – The strong association between baseline plasmablast-like cell infiltration in RLN and prolonged distant metastasis free- survival, highlights this cell type as a potential treatment stratification criterion to identify patients with good prognosis.