Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study.

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM.

Impaired social functioning in adolescent and young adult sarcoma survivors: Prevalence and risk factors.

BACKGROUND: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). AYAs are increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health-related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF. METHODS: AYAs from the population-based cross-sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age- and sex-matched norm data were used as reference. RESULTS: The median time since diagnosis was 6.2 years (range, 1.8-11.2). More than one-quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261-10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118-10.300) were associated with ISF; better experienced social support was associated with non-ISF (OR, 0.739; 95% CI, 0.570-0.957). CONCLUSION: More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-oriented but also focuses on the psychological and social domains. PLAIN LANGUAGE SUMMARY: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). The AYA group is increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be severely affected in AYA cancer survivors. A population-based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-orientated but also focuses on the psychological and social domains.

A Nationwide Prospective Clinical Trial on Active Surveillance in Patients With Non-intraabdominal Desmoid-type Fibromatosis: The GRAFITI Trial.

OBJECTIVE: To assess tumor behavior and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF). SUMMARY OF BACKGROUND DATA: AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking. METHODS: In this multicenter prospective cohort study (NTR4714), adult patients with non-intraabdominal DTF were followed during an initial AS approach for 3 years. Tumor behavior was evaluated according to Response Evaluation Criteria in Solid Tumors. Cumulative incidence of the start of an active treatment and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Factors predictive for start of active treatment were assessed by Cox regression analyses. RESULTS: A total of 105 patients started with AS. Median tumor size at baseline was 4.1cm (interquartile range 3.0-6.6). Fifty-seven patients had a T41A CTNNB1 mutation; 14 patients a S45F CTNNB1 mutation. At 3 years, cumulative incidence of the start of active treatment was 30% (95% confidence interval [CI] 21-39) and PFS was 58% (95% CI 49-69). Median time to start active treatment and PFS were not reached at a median follow-up of 33.7 months. During AS, 32% of patients had stable disease, 28% regressed, and 40% demonstrated initial progression. Larger tumor size (≥5 cm; hazard ratio = 2.38 [95% CI 1.15-4.90]) and S45F mutation (hazard ratio = 6.24 [95% CI 1.92-20.30]) were associated with the start of active treatment. CONCLUSIONS: The majority DTF patients undergoing AS do not need an active treatment and experience stable or regressive disease, even after initial progression. Knowledge about the natural behavior of DTF will help to tailor the follow-up schedule to the individual patient.

Health-related Quality of Life of Patients With Non-Intra-abdominal Desmoid-Type Fibromatosis During Active Surveillance: Results of a Prospective Observational Study.

OBJECTIVE: To examine the impact of an active surveillance (AS) approach on the health-related quality of life (HRQoL) of patients with desmoid-type fibromatosis (DTF). BACKGROUND DATA: AS is recommended as initial approach in DTF patients. AS might however negatively affect HRQoL due to physical symptoms or stress and anxiety. METHODS: In a prospective observational study, the GRAFITI trial (NTR4714), DTF patients were followed during an initial AS approach for 3 years. HRQoL was assessed by the EORTC QLQ-C30 at baseline, 6, 12 and 24-month follow-up. Patients who completed questionnaires at≥1-time point were included in this analysis of the secondary endpoint. A multivariable linear mixed-effects model with random intercept was conducted to assess trends of HRQoL scores over time and to explore the effect of treatment strategy on HRQoL. RESULTS: All 105 patients enrolled in the GRAFITI trial were eligible for the HRQoL analyses. During 24-month follow-up, 75 patients (71%) continued AS and 30 patients (29%) started an active treatment (AT). DTF patients who continued AS demonstrated relatively stable HRQoL scores during follow-up. HRQoL scores of patients who started AT worsened compared to patients who continued AS, although no significant changes in HRQoL score over time were found in the mixed-model analyses. Overall, DTF patients who started AT scored significantly worse on pain (ß=10.08, P =0.039) compared to patients who continued AS. CONCLUSIONS: An initial AS approach did not impair HRQoL of DTF patients who continued AS over time, therefore providing further support for AS as the frontline approach in DTF patients. Longitudinal assessment of HRQoL should be part of clinical follow-up to identify patients who may need a change in treatment strategy.

Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy? METHODS: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. Cox regression analyses were used to analyze the influence of different variables on MSS. RESULTS: In total, 2581 patients were included, of whom 1412 were treated with a WLE of the primary tumor alone and 1169 in whom this was combined with SLNB. At a median follow-up of 44 months from diagnosis of advanced melanoma, MSS was significantly longer in patients who had previously undergone SLNB {median 23 months (95% confidence interval [CI] 19-29) vs. 18 months (95% CI 15-20) for patients treated with WLE alone; p = 0.002}. However, multivariate Cox regression did not identify SLNB as an independent favorable prognostic factor for MSS after diagnosis of advanced melanoma. CONCLUSION: Prior to the availability of adjuvant systemic therapy, once patients have unresectable stage IIIC or IV (advanced) melanoma, there was no difference in disease outcome for patients who were or were not previously staged with SLNB.

Atypical fibroxanthoma and pleomorphic dermal sarcoma: Is superficial infiltration in subcutaneous tissue acceptable in AFX?

BACKGROUND: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous neoplasms forming a spectrum. Case reports with recurrences and metastasis have been published despite the current view that AFX is benign. The aim of this study was to identify clinical and histopathological features that predict tumor recurrence. METHODS: A retrospective review of AFX and PDS cases was performed. Clinical characteristics were obtained from patient records. RESULTS: A total of 29 AFX and 23 PDS cases were identified. Review led to re-classification of 12 cases (18%). In 14/50 (26.9%) cases a recurrence occurred. Recurrences were significantly more likely to occur when the tumor showed any infiltration in the subcutaneous fat (100% vs 43.2%, p = 0.000) or when the tumor diameter exceeded 2 cm (46.2% vs 16.2%, p = 0.030). CONCLUSIONS: This study shows that histopathological distinction between AFX and PDS remains difficult with reclassification in 12 out of 52 (18%) cases upon review. All AFX cases solely confined to the dermis behaved benign. We therefore advocate to classify all cases with any form of subcutaneous extension as PDS, and only lesions without as AFX. This contrasts with the current general opinion in which superficial subcutaneous invasion is still accepted in AFX.

Early Recurrence in Completely Resected IIIB and IIIC Melanoma Warrants Restaging Prior to Adjuvant Therapy.

PURPOSE: To evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy. PATIENTS AND METHODS: One hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NCT02993315). All patients underwent imaging to exclude local relapse or metastasis before entering the trial. The frequency of recurrent disease within 12 weeks after resection and the method of detection were investigated. RESULTS: Sixty-nine (58%) stage IIIB and 51 (43%) stage IIIC melanoma patients were screened. Median age was 54 (range 27-79) years. Twenty-two (18%) of 120 patients with completely resected stage IIIB/C melanoma had evidence of early recurrent disease, despite exclusion thereof by prior imaging. Median interval between resection and detection of relapse was 7.4 (range 4.3-10.7) weeks. Recurrence was asymptomatic in 17 (77%) patients, but metastasis was noticed by the patient or physician in 5 (23%). Eight patients with local relapse received local treatment with curative intent, and one was treated with systemic therapy. The remaining patients had distant metastasis, 1 of whom underwent resection of a solitary liver metastasis while 12 patients received systemic treatment. CONCLUSIONS: Patients with completely resected stage IIIB/C melanoma have high risk of early recurrence before start of adjuvant therapy. Restaging should be considered for high-risk melanoma patients before start of adjuvant therapy.

Minimum Safe Pathologic Excision Margins for Primary Cutaneous Melanomas (1-2 mm in Thickness): Analysis of 2131 Patients Treated at a Single Center.

OBJECTIVE: This study was designed to determine the minimum safe pathologic excision margin for primary cutaneous melanomas 1.01-2.00-mm thick (T2) and to identify prognostic factors that influence survival in these patients. BACKGROUND: Several studies have shown previously that "narrow" clinical excision margins (1-2 cm in vivo) are as safe as "wide" excision margins (4-5 cm) for management of primary T2 melanomas. However, pathologic margins are likely to be a better predictor of recurrence than clinical margins. METHODS: Clinicopathologic and follow-up data for 2131 T2 melanoma patients treated at Melanoma Institute Australia between January 1992 and May 2012 were analyzed. RESULTS: Of the 2131 patients, those who had a pathologic excision margin of <8 mm (equivalent to 1 cm in vivo) had poorer prognosis in terms of disease-free survival compared with the 8-16-mm group (equivalent to 1-2 cm in vivo; P = 0.044). When comparing 8-mm with 16-mm pathologic margins, no differences were observed in any of the survival outcomes. Only the deep margin proved to be an independent predictor of local and in-transit recurrence-free survival (P = 0.003) in all excision margin categories. Pathologic excision margins <8 mm were associated with worse regional node recurrence-free survival and distant recurrence-free survival compared with margins ≥8 mm (P = 0.049 and P = 0.045; respectively). However, these results failed to translate into a statistically significant difference in melanoma-specific survival. CONCLUSIONS: The results of this study suggest that if a peripheral/radial pathologic excision margin for a T2 primary cutaneous melanoma is <8 mm consideration should be given to performing a wider excision.

Myxoid liposarcoma of the foot: a study of 8 cases.

INTRODUCTION: Myxoid liposarcoma is the only translocation-associated liposarcoma subtype. It classically originates in the deep soft tissues of the thigh. At distal sites of the extremities, this tumor is exceedingly rare. We present a series of 8 cases occurring in the foot/ankle. RESULTS: Two female and 6 male patients, aged between 32 and 77 years (mean, 54.3 years), were identified. Tumor size ranged from 1.1 to 10 cm (mean, 6.8 cm). Two lesions eroded bone. All tumors were treated by excision and 7 by (neo)adjuvant radiotherapy. R0 status was reached in 2 cases with 1 case followed by metastasis in the groin. All other cases were documented with R1 (n=2) or R2 (n=4) resection status. In 1 patient, the follow-up status was unknown. All other patients were alive 15-135 (mean, 55.8) months after initial diagnosis. We conclude that myxoid liposarcoma at acral sites are exceedingly rare, and in this series, prognosis was good irrespective of resection status. Clinicians and pathologists have to be aware because this sarcoma type shows a peculiar clinical behavior with high radio- and chemosensitivity and metastatic spread to extrapulmonary sites.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial.

BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1-116·8, IQR 70·7-96·6), median overall survival was 48·6 months (95% CI 32·1-65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2-33·7) in the surgery alone group (HR 0·68 [95% CI 0·53-0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2-116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4-26·7) in the surgery alone group (HR 0·48 [95% CI 0·28-0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9-61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0-41·2) in the surgery alone group (HR 0·73 [95% CI 0·55-0·98]; log-rank p=0·038). INTERPRETATION: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

The optimum excision margin and regional node management for primary cutaneous T3 melanomas (2-4 mm in Thickness): a retrospective study of 1587 patients treated at a single center.

OBJECTIVE: To determine the optimum excision margin and nodal management for patients with primary cutaneous melanomas 2.01- to 4.00-mm thick (T3 melanomas). BACKGROUND: Currently available evidence does not reliably define the minimum safe excision margin and best nodal management for patients with primary cutaneous T3 melanomas. METHODS: A retrospective study was conducted, analyzing data on 1587 patients with melanomas 2.01- to 4.00-mm thick treated at a single center. RESULTS: A histopathologic excision margin of 8 mm or more (equivalent to a ≥1 cm surgical margin) was associated with increased local and in-transit recurrence-free survival [hazard ratio (HR) = 0.54; P = 0.008] and disease-free survival (DFS) (HR = 0.59; P = 0.001) compared with a less than 8-mm margin. The <8-mm group had reduced distant recurrence-free survival (DRFS) compared with the 8- to 16-mm group (HR = 1.63; P = 0.038). On multivariate analysis, patients with a positive sentinel lymph node (SLN) had significantly reduced melanoma-specific survival (MSS), DFS, regional node recurrence-free survival (RNRFS) and DRFS compared with patients with a negative SLN, unless an immediate completion lymph node dissection was performed. Patients in whom an SLN biopsy was not performed had significantly reduced MSS (HR = 2.10; P < 0.001), DFS (P < 0.001), RNRFS (P < 0.001), and DRFS (P = 0.010) compared with patients who received an SLN biopsy. CONCLUSIONS: A histopathologic excision margin of 8 mm or more (corresponding to a ≥1 cm surgical excision margin) combined with SLN biopsy (followed by an immediate completion lymph node dissection if positive) provided T3 melanoma patients with optimum local, regional, and distant disease control and resulted in enhanced melanoma-specific survival.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3'-fluoro-3'-deoxy-thymidine ([18F]FLT) PET imaging.

Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting. Melanoma patients with lymph node (LN) metastases received dendritic cell (DC) vaccine therapy, injected intranodally, followed by [(18)F]-labeled 3'-fluoro-3'-deoxy-thymidine ([(18)F]FLT) PET at varying time points after vaccination. Control LNs received saline or DCs without antigen. De novo immune responses were readily visualized in treated LNs early after the prime vaccination, and these signals persisted for up to 3 wk. This selective [(18)F]FLT uptake was markedly absent in control LNs, although tracer uptake in treated LNs increased profoundly with as little as 4.5 × 10(5) DCs. Immunohistochemical staining confirmed injected DC dispersion to T-cell areas and resultant activation of CD4(+) and CD8(+) T cells. The level of LN tracer uptake significantly correlates to the level of circulating antigen-specific IgG antibodies and antigen-specific proliferation of T cells in peripheral blood. Furthermore, this correlation was not observed with [(18)F]-labeled fluoro-2-deoxy-2-D-glucose. Therefore, [(18)F]FLT PET offers a sensitive tool to study the kinetics, localization, and involvement of lymphocyte subsets in response to vaccination. This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking.

Improvement of perioperative outcomes of gastric gastrointestinal stromal tumour (GIST) resections and the influence of minimal invasive surgery.

BACKGROUND: Safety of minimally invasive surgery (MIS) for gastrointestinal stromal tumours (GISTs) is still under debate since it might increase the risk of tumour rupture, especially in larger tumours. The aim of this study was to investigate trends in treatment and perioperative outcomes of patients undergoing resections of gastric GISTs over time. METHODS: This was a multicentre retrospective study of consecutive patients who underwent wedge resection or partial gastrectomy for localized gastric GIST at five GIST reference centres between January 2009 and January 2022. To evaluate changes in treatment and perioperative outcomes over time, patients were divided into four equal periods. Perioperative outcomes were analysed separately and as a novel composite measure textbook outcome (TO). RESULTS: In total 385 patients were included. Patient and tumour characteristics did not change over time, except for median age (62-65-68-68 years, p = 0.002). The proportion of MIS increased (4.0%-9.8%-37.4%-53.0 %, p < 0.001). Postoperative complications (Clavien Dindo ≥2; 22%-15%-11%-10 %, p = 0.146), duration of admission (6-6-5-4 days, p < 0.001) and operating time (92-94-77-73 min, p = 0.007) decreased over time while TO increased (54.0%- 52.7%-65.9%-76.0 %, p < 0.001). No change was seen in perioperative ruptures (6.0%- 3.6%-1.6%-3.0 %, p = 0.499). MIS was correlated with less CD ≥ 2 complications (p = 0.006), shorter duration of admission (p < 0.001) and more TO (p < 0.001). Similar results were observed in tumours ≤5 cm and >5 cm. CONCLUSION: A larger percentage of gastric GIST were treated with MIS over time. MIS was correlated with less complications, shorter duration of admission and more TO. Tumour rupture rates remained low over time.

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study.

INTRODUCTION: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. METHODS: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. RESULTS: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. CONCLUSIONS: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88-1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73-2.38; p = 0.44). Grade 3-4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed.

Surgical management of rectal gastrointestinal stromal tumors.

BACKGROUND: Five percent of gastrointestinal stromal tumors (GISTs) are primarily localized in the rectum. We analyzed the outcome of multimodality treatment for rectal GIST in a multicenter retrospective series. METHODS: All surgically treated patients with a rectal GIST were identified from four specialized centers in the Netherlands. Primary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: Thirty-two patients (22 men and 10 women) with rectal GISTs were identified. Twenty-two patients received imatinib before surgery for a median of 9 (range 2-53) months (Group 1). Ten patients received no imatinib because of small tumor size or lack of availability (Group 2). Median tumor size before treatment was 9.3 (range 6-17) cm in Group 1 and median 6 (range 4-14) cm in Group 2. A complete resection was possible in 17/22 (77%) patients in Group 1 versus 7/10 (70%) in Group 2. Median DFS was not reached in Group 1, while it was 36 months in Group 2. Median OS was not reached in both groups. CONCLUSIONS: Preoperative imatinib leads to downsizing of the tumors in Group 1. However, it has not led to less extensive surgery. The DFS is longer in patients treated with pre- and post-operative imatinib, without an effect on OS.

The Prognostic Relevance of MRI Characteristics in Myxofibrosarcoma Patients Treated with Neoadjuvant Radiotherapy.

To improve local control, neoadjuvant radiotherapy (nRT) followed by surgery is the standard of care in myxofibrosarcoma (MFS) because of its infiltrative growth pattern. Nevertheless, local recurrence rates are high. Data on prognostic factors for poor clinical outcomes are lacking. This retrospective study thus investigates the prognostic relevance of magnetic resonance imaging (MRI) characteristics before and after nRT in 40 MFS patients, as well as their association with disease-free survival (DFS) and overall survival (OS). A vascular pedicle, defined as extra-tumoral vessels at the tumor periphery, was observed in 12 patients (30.0%) pre-nRT and remained present post-nRT in all cases. Patients with a vascular pedicle had worse DFS (HR 5.85; 95% CI 1.56-21.90; p = 0.009) and OS (HR 9.58; 95% CI 1.91-48.00; p = 0.006). An infiltrative growth pattern, referred to as a tail sign, was observed in 22 patients (55.0%) pre-nRT and in 19 patients (47.5%) post-nRT, and was associated with worse DFS post-nRT (HR 6.99; 95% CI 1.39-35.35; p = 0.019). The percentage of tumor necrosis estimated by MRI was increased post-nRT, but was not associated with survival outcomes. The presence of a tail sign or vascular pedicle on MRI could support the identification of patients at risk for poor clinical outcomes after nRT.

Physical symptom burden in patients with desmoid-type fibromatosis and its impact on health-related quality of life and healthcare use.

BACKGROUND: Desmoid-type fibromatosis (DTF) has a highly variable clinical course with varying intensity of symptoms. The objectives of this study were to identify subgroups of DTF patients based on physical symptom burden and to compare symptom burden subgroups on health-related quality of life (HRQoL) and healthcare use (univariate and multivariate). METHODS: Desmoid-type fibromatosis patients from the United Kingdom and the Netherlands received cross-sectional questionnaires on HRQoL (EORTC QLQ-C30), DTF-specific HRQoL (DTF-QoL) and healthcare utilisation. Latent class cluster analysis was performed to identify subgroups based on patients' symptom burden using EORTC QLQ-C30 and DTF-QoL physical symptom items. Multivariate linear and logistic regression analyses were conducted to examine associations of symptom burden with HRQoL and healthcare utilisation, respectively. RESULTS: Among 235 DTF patients, four symptom burden clusters were identified, with low symptom burden (24%), intermediate symptom burden-low pain (20%), intermediate symptom burden-high pain (25%) and high symptom burden (31%). DTF patients with high symptom burden had clinically relevant lower HRQoL scores compared to patients with low and intermediate symptom burden (p < 0.001) and reported more general and DTF-related visits to their general practitioner compared to the low symptom burden cluster (p < 0.01). In the multivariate analyses, symptom burden was independently associated with both HRQoL and healthcare utilisation. CONCLUSIONS: This study identified four distinct subgroups of DTF patients based on their level of symptom burden, with a considerable number of patients being highly symptomatic. Knowledge of the level of symptom burden DTF patients experience can help to identify patients at risk of poorer outcomes and tailor supportive care to the individual needs of DTF patients.