Antonis Valachis

Background and Aims: Neoadjuvant immunotherapy has emerged as the preferred treatment strategy for patients with resectable stage III melanoma. However, real-world data remain limited, especially regarding patients with in-transit metastasis (ITM). The aim of this study was to evaluate neoadjuvant immunotherapy in a population-based cohort of patients with stage III melanoma with a specific focus on patients with ITM. Study Design: This population-based multicenter observational study included all patients with macroscopic stage III cutaneous melanoma treated with neoadjuvant PD-1 inhibitors at 5 academic cancer centers in Sweden from 2022 to 2025. Patients were stratified into 3 groups, LN metastasis only, ITM only, and concurrent LN and ITM involvement. The primary endpoint was major pathological response (MPR). Secondary endpoints included event-free survival (EFS), distant metastasis-free survival (DMFS), locoregional recurrence-free interval (LRFI), and safety outcomes. Results: A total of 212 patients with a median follow-up of 14.7 months were included, of whom 41 had ITM only and 12 had both LN and ITM. The MPR rate was significantly higher in patients with LN metastases (52%) compared with ITM (22%) or concurrent LN and ITM (25%) ( P P =0.028) and LRFI (HR 4.41; 95% CI: 1.76–11.02; P =0.002). Although DMFS differed between groups in unadjusted analyses, no association was observed after multivariable adjustment (HR 1.04; 95% CI: 0.46–2.33; P =0.925). Discussion: This study represents the largest real-world cohort specifically evaluating patients with ITM treated with neoadjuvant immunotherapy. The lower pathological response rate and inferior EFS observed in patients with ITM compared with LN metastases, together with an increased risk of locoregional recurrence, but no difference in DMFS, suggest that ITM may represent a biologically distinct disease phenotype with a higher propensity for locoregional treatment failure.

Background: Axillary lymph node dissection (ALND) in breast cancer causes substantial arm morbidity and long-term functional impairment. Less extensive axillary surgery, such as targeted axillary dissection (TAD), significantly reduces this risk. Although omission of ALND is standard in clinically node-negative disease with limited sentinel node involvement, this is not the case for patients with clinically node-positive disease undergoing upfront surgery. The aim of the SENOMAC-ULTRA trial is to evaluate whether TAD can safely replace ALND in patients with clinically node-positive breast cancer receiving upfront surgery. Methods: SENOMAC-ULTRA is a prospective, international, multicentre, randomized non-inferiority trial. Adults with stage II–III invasive breast cancer and axillary metastases detectable by ultrasound and confirmed by fine needle aspiration or core biopsy are eligible for inclusion. Participants are randomized 1 : 1 to TAD (removal of marked metastatic nodes plus sentinel lymph node biopsy) or standard ALND. The primary endpoint is recurrence-free survival, assessed for non-inferiority using a Cox proportional hazards model. Secondary endpoints include overall survival, locoregional recurrence, regional nodal recurrence, distant relapse-free survival, invasive breast cancer-free survival, patient-reported arm morbidity, and health-related quality of life, as well as performance measures of axillary ultrasound and marking techniques. A sample size of 1380 patients has been calculated to provide 81% power to exclude a hazard ratio > 1.47 for recurrence-free survival at 5 years, adopting a non-inferiority margin of 4.5%. Follow-up is planned for 10 years. The trial protocol has been approved by the Swedish Ethical Review Authority (Dnr 2025-07730-01); each participating country will obtain local ethics approval. Conclusion: It is anticipated that the SENOMAC-ULTRA trial will fill an important knowledge gap guiding the surgical management of patients with clinically node-negative breast cancer. Registration number: NCT06869629 (https://clinicaltrials.gov).

Background: Wound complications after breast surgery are common and contribute to morbidity and healthcare costs. The economic value of prophylactic incisional negative-pressure wound therapy (iNPWT) remains uncertain. This study evaluated the effectiveness and cost-effectiveness of iNPWT in preventing postoperative wound complications (freedom from complication) following breast surgery through a systematic review and meta-analysis. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched without any restrictions up to 5 March 2025. Randomized trials and prospective or retrospective cohort studies comparing prophylactic iNPWT with standard dressings were included. Two reviewers independently extracted data, assessed risk of bias (RoB 2, ROBINS-I), and graded evidence certainty (GRADE). Random-effects meta-analyses were performed, and cost-effectiveness modelling focused on surgical site infection (SSI). Results: Twenty-nine studies including 4904 patients (1817 iNPWT; 3087 controls) were analysed. iNPWT was associated with higher rates of wound dehiscence prevention (RR 1.07, 95% c.i. 1.03 to 1.12), SSI prevention (RR 1.05, 95% c.i. 1.01 to 1.09), and skin necrosis prevention (RR 1.07, 95% c.i. 1.01 to 1.15). No significant differences were observed for seroma, nipple–areolar complex necrosis, or haematoma. Across outcomes, heterogeneity was substantial and 95% prediction intervals crossed the null, indicating uncertainty in the direction of effect in future settings. Evidence certainty ranged from low to moderate. Cost modelling suggested that iNPWT may be cost-saving only in settings with high SSI-related costs. Conclusions: Current evidence does not establish consistent clinical benefit of prophylactic iNPWT in breast surgery. Cost-effectiveness appears limited to high-risk or high-cost contexts, supporting selective use.

As treatment strategies for early triple-negative breast cancer continue to evolve, translating clinical evidence into practice can be challenging, especially as the standard of care also shifts and may differ across studies. The management of patients with triple-negative breast cancer who have residual disease after neoadjuvant therapy exemplifies a complex clinical scenario with emerging yet sometimes difficult-to-interpret evidence. Through a critical appraisal of current data and an expert consensus discussion from the Nordic region, the authors present a perspective on postneoadjuvant treatment options for triple-negative breast cancer and discuss potential approaches based on available evidence and expert opinion.

Background and purpose: This retrospective cohort study aimed to explore the association between short-term genitourinary (GU) and gastrointestinal (GI) toxicity and oncological outcomes in high-risk prostate cancer patients treated with external beam radiotherapy (EBRT) alone or with high-dose-rate brachytherapy (HDR-BT).Patient/material and methods: High-risk prostate cancer patients treated at Örebro University Hospital (2008–2021) were divided into two cohorts based on treatment modality: EBRT-only (66 Gy/22 fractions), EBRT-BT (42 Gy/14 fractions + 14.5 Gy HDR-BT-boost).Maximum 6-month toxicity grade was categorised as: GU-low (grade 0–1), GU-high (grade ≥ 2), GI-low (grade 0) and GI-high (grade ≥ 1), respectively. Freedom from biochemical failure (FFBF), metastasis-free survival (MFS) and overall survival were compared between the low- and high- toxicity groups, using Kaplan–Meier and Cox proportional hazards regression. Prostate cancer-specific mortality was compared between the groups using the Aalen–Johansen method and Fine-Gray regression.Results: The EBRT-only cohort encompassed 114 and 162 patients for GU- and GI-analyses. The EBRT-BT cohort comprised 306 patients for GU- and 344 patients for GI-analyses. High GU-toxicity was associated with inferior FFBF (adjusted hazard ratio (aHR) = 2.57, 95% Confidence Interval [CI] = 1.32–5.00) and MFS (aHR = 2.22, 95% CI = 1.21–4.07) in the EBRT-only but not in the EBRT-BT cohort. No statistically significant associations were found between GI-toxicity and oncological outcomes.Interpretation: Early grade ≥ 2 GU-toxicity was linked to worse FFBR and MFS after EBRT alone, whereas no such association was seen after EBRT-BT. GI toxicity showed no prognostic impact. These exploratory findings warrant validation in larger studies addressing interactions between patient-, tumour- and treatment-related factors.

External comparator cohort (ECC) studies with real‐world data (RWD) may provide more reliable estimates of treatment differences compared to single‐arm trials (SAT), yet they face limitations such as selection bias and data heterogeneity. This study assessed the perceived strength of evidence of ECC studies compared to SAT and randomized controlled studies (RCT). The study included healthcare professionals (HCP) from the European Hematology Association (EHA), the European Society for Medical Oncology (ESMO), and assessors from international regulatory agencies (RA). A conjoint analysis evaluated strength of evidence ratings for establishing an effect on OS for different hypothetical scenarios, based on different designs, RWD quality, and observed OS improvement, for a new cancer treatment for advanced disease and no effective treatments. Participants from HCP organizations rated RWD studies favorably (advantages outweigh disadvantages) more frequently (47.6%; n = 103) compared to RA participants (12.9%; n = 116). Compared to a SAT, a high‐quality RWD ECC study showing a 1.5‐month and 3‐month OS improvement had 2.7 (95% CI: 1.9–3.8) and 14.7 (95% CI: 10.0–21.5) times higher odds of receiving a higher strength of evidence rating, respectively. The OR for RCT v. SAT was 36.4 (95% CI: 24.0–55.2) and 358.4 (95% CI: 217.3–591.3), respectively. Strength of evidence ratings were associated with maximum acceptable risk of severe or symptomatic toxicity. In conclusion, when evaluating the OS of new therapies, ECC studies with RWD, especially when based on high‐quality RWD or demonstrating a larger OS benefit, were rated as more convincing than SAT without a formal control.

PURPOSE: Patients with cancer receiving immune checkpoint inhibitors (CPIs) may experience immune-related adverse events (IRAEs) due to immune system overactivation. Concurrently, infections such as seasonal influenza can be more severe in cancer patients because of their compromised immune function, making influenza vaccination particularly important. In this multicenter retrospective study, we investigated whether influenza vaccination during CPI treatment influences CPI effectiveness and rates of IRAEs. PATIENTS AND METHODS: We conducted a retrospective cohort study across three Swedish centers involving patients with metastatic cancer treated with CPIs—either PD-1/PD-L1 inhibitors or combination immunotherapy—between January 1, 2016, and December 31, 2021. To address immortal time bias in time-to-event outcomes, different statistical strategies were employed including time-dependent Cox regression and landmark analyses. RESULTS: In total, 587 patients treated with CPIs during the study period were identified. The most common malignancy was non–small cell lung cancer (NSCLC; 34.4%), followed by cutaneous malignant melanoma (CMM; 32.5%). Time-dependent Cox regression analysis showed that real-world progression-free survival was significantly longer in influenza-vaccinated patients compared with unvaccinated in overall cohort (hazard ratio [HR], 0.59 [95% CI, 0.44 to 0.79]). No statistically significant differences in the occurrence of any grade IRAEs (48.4% v 51.2%, P = .455) or multiple IRAEs (15.1% v 19.2%, P = .297) between the vaccinated and unvaccinated groups were observed. The survival benefit was more pronounced in patients with CMM, whereas no statistically significant effect was observed in patients with NSCLC. CONCLUSION: Our findings suggest a potential association between influenza vaccination and improved survival in CPI-treated patients, without a corresponding increase in IRAEs, supporting current vaccination recommendations. The observed association in patients with CMM may reflect underlying biological mechanisms and is hypothesis-generating for further investigation.

Purpose: Metaplastic breast cancer (metBC) is a rare subtype of breast cancer known for its challenging management. The impact of this histological subtype on prognosis remains unclear. Methods: Data were collected from the Swedish Cancer Registry between 2008 and 2018. Patients with metBC were matched 2:1 with breast cancer cases of no special type (NST). Survival outcomes were analyzed using cause‐specific hazard models for breast cancer specific survival (BCSS) and Cox proportional‐hazards models for overall survival (OS). Results: In total, 127 metBC patients were matched 2:1 with 245 NST patients, with a median follow‐up period of 54 months. When adjusted for matching variables and treatment‐related characteristics, metBC was not significantly associated with either BCSS (cause‐specific Hazard Ratio (HR): 1.13; 95% Confidence Interval (CI): 0.66–1.92) or OS (HR: 1.23; 95% CI: 0.83–1.82). Conclusion: With appropriate treatment, metBC may have survival outcomes comparable to NST. Larger studies with longer follow‐up are needed to provide further insights.