Background and purpose: Relapses, need for further treatment lines and significant treatment attrition are typical for multiple myeloma (MM). This retrospective study investigates attrition and outcomes among MM patients in Finland. Patient, material and methods: Study included all adult MM patients (n = 1733) diagnosed and treated in four hospital districts in Finland in 2013–2022. Data were collected from hospital data lakes, Statistics Finland and Social Insurance Institution. Treatment attrition was defined as death before next treatment line. Results: By the end of follow-up 31% of patients without stem cell transplantation (non-SCT) had died before initiation of second line treatment (2L), compared with 5% of stem-cell transplant (SCT) patients. The factors associating with this early attrition in the non-SCT cohort were older age (over 75 years), higher comorbidity burden, International Staging System (ISS), and (R)-ISS scores (p < 0.001). Furthermore, non-SCT patients were more likely administered less intensive therapy during 1L (p < 0.001). During the first 6 months post diagnosis in the non-SCT cohort, the most common immediate cause of death was MM. Also, during later stages MM was responsible for 54% of deaths in the non-SCT and 68% in the SCT cohorts whereas infections were linked principally with early deaths before 2L treatment. Interpretation: This study highlights significant treatment attrition across disease course and also early mortality especially in the non-SCT cohort resulting primarily from progressive MM or infections. The findings underscore the need for more tolerable and effective anti-myeloma treatments in earlier course of the disease to enhance patient survival.
Background: Approximately 30% of sinonasal and nasopharyngeal carcinoma cases are HPV-associated, yet studies investigating circulating tumor HPV-DNA (ctHPV-DNA) among these patients are scarce. The aim of this study was to investigate the sensitivity of ctHPV-DNA in pretreatment blood samples from patients with HPV-positive (HPV+) sinonasal and nasopharyngeal carcinoma. Methods: Patients with a confirmed HPV+ sinonasal or nasopharyngeal carcinoma treated at the Department of Otorhinolaryngology, Head and Neck Surgery and Audiology at Rigshospitalet, Copenhagen, Denmark in the period 2017–2025 were included in this study. Blood samples were drawn in Streck tubes before treatment initiation and analysed for the presence of ctHPV-DNA by Droplet digital PCR (ddPCR). Results: Fifteen patients with primary HPV+ sinonasal or nasopharyngeal carcinoma were included. Except for two cases of HPV-related multiphenotypic carcinoma, all cases were squamous cell carcinoma. HPV16 was most prevalent and found in 6 patients (40%). HPV18 (n = 2), HPV33 (n = 1), HPV35 (n = 3), HPV45 (n = 1), and HPV56 (n = 2) were also represented. The sensitivity of detecting ctHPV-DNA in the pretreatment blood samples of the included patients was 80%. The level of ctHPV-DNA increased significantly with increasing T-category. Conclusion: ctHPV-DNA was detected in pretreatment blood samples in 80% of patients with HPV+ sinonasal and nasopharyngeal carcinoma. This supports further investigation of ctHPV-DNA as a biomarker for post-treatment surveillance in these patients.
Context: Conventional pain therapies sometimes fail in patients with severe neuropathic pain or bone metastases. Intrathecal therapy provides an alternative but is resource-intensive, technically demanding and costly. Objective: To compare the advantages and limitations of partially implanted devices (PIDs) versus conventional medical management or totally implanted devices (TIDs) in adults with cancer-related pain. Methods: A systematic literature review up to September 2024 was conducted, with an updated search performed in August 2026. Eligible studies included those on adults with refractory cancer pain receiving PID intrathecal therapy compared with conventional therapy, and comparative studies evaluating PIDs versus TIDs. Pain intensity was analysed using a meta-analysis; a synthesis without meta-analysis was used for other outcomes. Results: Of the 1,102 records, 15 were included, evaluating pain intensity, systemic opioid dose, quality of life (QoL), depression/anxiety, functional capacity and complications in PID-treated patients. A meta-analysis of pain intensity at 4 weeks showed statistically significant reduction with intrathecal therapy, which also reduced opioid use and improved QoL. Complication rates were lower than in conventional therapy. Investigations of depression/anxiety and functional capacity were limited, with inconsistent findings. Certainty of evidence was moderate for pain intensity and QoL; low for opioid dose, depression/anxiety and complications; and very low for functional capacity. Conclusions: Intrathecal therapy for refractory cancer pain with PIDs provides superior pain relief and improved QoL compared with the conventional therapy in patients with refractory cancer pain. Evidence for psychological and functional outcomes remains limited. Overall certainty of evidence is low to moderate, but findings support intrathecal therapy as a clinically meaningful option for selected patients.
Background and purpose: Co-occurring mutations in lung cancer can influence disease progression and treatment response. Understanding these patterns may refine prognostic stratification and therapeutic decisions. Patients/materials and methods: We analysed targeted sequencing data from 528 North Swedish non-small cell lung cancer (NSCLC) patients, validating findings in 2,239 global patients. Co-mutation enrichment was assessed using the Fisher’s exact test with odds ratios, and survival associations were evaluated using Kaplan–Meier/log-rank analyses and Cox models. Results: The North Sweden cohort showed non-random co-mutation patterns shaped by pathway dependencies. The combination of Kirsten rat sarcoma virus oncogene homolog (KRAS) and STK11 co-mutation was significantly enriched in both North Sweden (p = 4.7 × 10-4) and globally (p = 2.5 × 10-22), with North Sweden co-mutants showing significantly worse survival compared with KRAS-only cases (p = 0.037). Epidermal growth factor receptor (EGFR)+phosphate and tensin homolog (PTEN) co-mutation was significantly associated with poorer survival in both cohorts (North Sweden: p = 0.013; World: p = 0.0013). EGFR+TP53 co-mutation trended towards poorer survival compared with EGFR alone, reaching significance globally (p = 1.4 × 10-5). Adenomatous polyposis coli (APC) and PTEN were positively enriched in North Sweden (p = 0.018), and co-mutants had worse survival than APC-only cases (p = 0.029), a pattern mirrored globally. KRAS+TP53 was a frequent co-mutation but not prognostically significant. KRAS and EGFR were strongly mutually exclusive in both cohorts. Interpretation: Pathway-level co-mutation interactions, rather than individual mutation burden, drive survival heterogeneity in lung cancer. Specific co-mutations, such as KRAS+STK11 and APC+PTEN, are enriched and linked to worse survival, supporting the clinical relevance of co-mutation analysis in NSCLC.
Background and purpose: Immune-checkpoint inhibitors (ICIs) improve outcomes in renal cell carcinoma (RCC) but may cause immune-related adverse events (irAEs), including cutaneous toxicity. Bullous pemphigoid (BP) is a rare but clinically significant irAE that can require ICI discontinuation. Patient/material and methods: We report two cases of BP in patients with metastatic RCC treated with ICIs at Karolinska University Hospital, Stockholm, Sweden. In addition, a systematic review was conducted in Medline, Embase, Cochrane Library, and Web of Science to identify published cases of ICI-associated BP in metastatic RCC. Data on patient characteristics, treatment, clinical presentation, diagnostics, management, and outcomes were extracted and descriptively analysed. Results: Twenty-eight publications describing 30 cases were identified. Median age at BP onset was 69 years (interquartile range [IQR] 65–73), and 86.7% were male. Nivolumab was the most commonly reported ICI monotherapy. Median time from ICI initiation to BP onset was 35 weeks (IQR 16–76). Typical manifestations included tense bullae and vesiculobullous eruptions on the trunk and extremities. Diagnosis was confirmed by skin biopsy and immunological testing in 80% of cases. Management mainly involved corticosteroids, while ICI interruption or discontinuation was required in over half the cases. Both patients from our center improved after immunosuppressive treatment. Interpretation: ICI-associated BP is a rare but important irAE in metastatic RCC, often occurring after prolonged ICI exposure and potentially requiring treatment modification. Early recognition may improve multidisciplinary management.
