Optimal extent of completion lymphadenectomy for patients with melanoma and a positive sentinel node in the groin

Background: The optimal extent of groin completion lymph node dissection (CLND) (inguinal or ilioinguinal dissection) in patients with melanoma is controversial. The aim of this study was to evaluate whether the extent of groin CLND after a positive sentinel node biopsy (SNB) is associated with improved outcome. Methods: Data from all sentinel node-positive patients who underwent gr

Risk Factors for Positive Deep Pelvic Nodal Involvement in Patients with Palpable Groin Melanoma Metastases: Can the Extent of Surgery be Safely Minimized?: A Retrospective, Multicenter Cohort Study

Background: Patients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient. Aim: The aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future. Methods: This study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET − low-dose CT). Results: Median age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11–46 months). Median Breslow thickness was 2.10 mm (IQR 1.

Stereotactic Body Radiotherapy for Isolated Para-aortic Lymph Node Recurrence after Curative Resection in Gastric Cancer

The aim of this study was to investigate whether stereotactic body radiotherapy (SBRT) can salvage gastric cancer patients with para-aortic lymph node (PALN) recurrence. From January 2003 to December 2006, 7 patients were treated for isolated PALN recurrence from gastric cancer after curative resection. Follow up durations ranged from 19 to 33 months (median; 26 months), and SBRT doses from 45 Gy to 51 Gy (median 48 Gy) in 3 fractions. Disease progression-free and overall survivals and toxicities were recorded. Response to treatment was assessed by computed tomography. Final patient outcomes were as follows: 2 were alive without evidence of disease, 3 remained alive with disease, and 2 patients died of disease. Five of 7 patients showed complete response and 2 patients partial response between 3 and 11 months after SBRT. Three-year overall and disease progression-free survival rates post-SBRT were 43% and 29%, respectively. No severe complication was detected during follow-up. Selected patients with isolated PALN recurrence can be salvaged by SBRT without severe complications

Surgery after treatment with imatinib and/or sunitinib in patients with metastasized gastrointestinal stromal tumors: Is it worthwhile?

Background: Standard treatment for metastatic gastrointestinal stromal tumors (GISTs) is systemic therapy with imatinib. Surgery is performed to remove metastatic lesions to induce long-term remission or even curation. In other patients, surgery is performed to remove (focal) progressive or symptomatic lesions. The impact and long-term results of surgery after systemic therapy have not been clearly defined.Methods: Between September 2001 and May 2010, all patients with metastatic GIST who underwent surgery for metastatic GIST after systemic therapy (that is, imatinib and sunitinib) at four Dutch specialized institutions were included. Primary end-points were progression-free survival (PFS) and overall survival (OS).Results: All 55 patients underwent surgery after treatment with systemic therapy. At the last follow-up, tumor recurrence or progression was noted after surgery in 48% of the patients who responded on systemic therapy, and in 85% of the patients who were treated while having progressive disease. Median PFS and OS were not reached in the group of responders. In the non-responders group PFS and OS were median 4 and 25 months, respectively. Response on systemic therapy and a surgical complete resection were significantly correlated to PFS and OS.Conclusions: Surgery may play a role in responding patients. In patients with progressive disease, the role of surgery is more difficult to distinguish in this retrospective analysis since PFS is short. Which patients benefit and whether this improves long-term outcome should be established in a multicentric randomized trial

Unraveling the heterogeneity of sarcoma survivors’ health-related quality of life regarding primary sarcoma location: Results from the Survsarc study

Sarcoma patients experience physical and psychological symptoms, depending on age of onset, subtype, treatment, stage, and location of the sarcoma, which can adversely affect patients’ health-related quality of life (HRQoL). This study aimed to unravel the heterogeneity of sarcoma survivors’ HRQoL regarding primary sarcoma location. A cross-sectional study was conducted among Dutch sarcoma survivors (N = 1099) aged ≥18, diagnosed 2–10 years ago. Primary sarcoma locations were head and neck, chest, abdominal including retroperitoneal, pelvis including urogenital organs, axial skeleton, extremities (upper and lower), breast, skin and other locations. The European Organization for Research and Treatment of Cancer—Quality of Life Questionnaire (EORTC QLQ)-C30 was used to measure HRQoL accompanied by treatment-specific HRQoL questions. Sociodemographic and clinical characteristics were collected from the Netherlands Cancer Registry. Axial skeleton sarcomas had the lowest functioning levels and highest symptoms compared to other locations. Skin sarcomas had the highest functioning levels and lowest symptoms on most scales. Bone sarcomas scored worse on several HRQoL domains compared to soft tissue sarcomas. High prevalence of treatment-specific HRQoL issues were found per location. In conclusion, sarcomas can present everywhere, which is reflected by different HRQoL outcomes according to primary sarcoma location. The currently used HRQoL mea

The perceived impact of length of the diagnostic pathway is associated with health-related quality of life of sarcoma survivors: Results from the dutch nationwide SURVSARC study

Background: Sarcoma patients often experience a long time to diagnosis, known as the total interval. This interval can be divided into the patient (time from symptoms to doctor consultation) and diagnostic intervals (time from first consultation to diagnosis). In other cancers, a long total interval has been associated with worse outcomes, but its effect on health-related quality of life (HRQoL) has never been investigated among sarcoma patients. This study investigates the association between (1) the actual time to diagnosis and HRQoL; (2) the perceived impact of the diagnostic interval length and HRQoL; (3) the actual length and perceived impact of the length and the HRQoL of sarcoma survivors. Methods: A cross-sectional study was performed among sarcoma patients aged ≥18, diagnosed 2–10 years ago in the Netherlands. The participants completed a questionnaire on HRQoL, the time to diagnosis, the perceived impact of the diagnostic interval on HRQoL, and coping. Results: 1099 participants were included (response rate, 58%). The mean time since diagnosis was 67.4 months. More than half reported a patient (60%) or diagnostic interval (55%) ≥1 month. A third (31%) perceived a negative impact of the diagnostic interval length on HRQoL. Patient or diagnostic interval length was not associated with HRQoL. By contrast, participants perceiving a negative impact (32%) had lower HRQoL scores than those perceiving a positive (11%) or no impact (58%) (p = 0.000). This association remained significant in a multivariable model, in which maladaptive coping strategies and tumour characteristics were also found to be associated with HRQoL. Participants perceiving a negative impact of the length of the diagnostic interval related this to high psychological distress levels, more physical disabilities, and worse prognosis. Conclusion: The perceived impact of the diagnostic interval length was associated with the HRQoL of sarcoma survivors, whereas the actual length was not associated with HRQoL. Maladaptive coping strategies were independently associated with HRQoL. This offers opportunities for early intervention to improve HRQoL

Response to immune checkpoint inhibitors in acral melanoma:A nationwide cohort study

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies

External validation and adaptation of a dynamic prediction model for patients with high‐grade extremity soft tissue sarcoma

Background and Objectives: A dynamic prediction model for patients with soft tissue sarcoma of the extremities was previously developed to predict updated overall survival probabilities throughout patient follow‐up. This study updates and externally validates the dynamic model. Methods: Data from 3826 patients with high‐grade extremity soft tissue sarcoma, treated surgically with curative intent were used to update the dynamic PERsonalised SARcoma Care (PERSARC) model. Patients were added to the model development cohort and grade was included in the model. External validation was performed with data from 1111 patients treated at a single tertiary center. Results: Calibration plots show good model calibration. Dynamic C‐indices suggest that the model can discriminate between high‐ and low‐risk patients. The dynamic C‐indices at 0, 1, 2, 3, 4, and 5 years after surgery were equal to 0.697, 0.790, 0.822, 0.818, 0.812, and 0.827, respectively. Conclusion: Results from the external validation show that the dynamic PERSARC model is reliable in predicting the probability of surviving an additional 5 years from a specific prediction time point during follow‐up. The model combines patient‐, treatment‐specific and time‐dependent variables such as local recurrence and distant metastasis to provide accurate survival predictions throughout follow‐up and is available through the PERSARC app.Peer reviewe

Adjuvant treatment for melanoma in clinical practice - Trial versus reality

Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade >= 3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials. (C) 2021 The Authors. Published by Elsevier Ltd

Multifocal occurrence of extra-abdominal desmoid type fibromatosis – A rare manifestation. A clinicopathological study of 6 sporadic cases and 1 hereditary case

Desmoid-type fibromatosis, also called desmoid tumor, is a locally aggressive myofibroblastic neoplasm that usually arises in deep soft tissue with significant potential for local recurrence. It displays an unpredictable clinical course. β-Catenin, the genetic key player of desmoid tumors shows nuclear accumulation due to mutations that preve