Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Follow-up Schedule for Patients With Sentinel Node-negative Cutaneous Melanoma (The MELFO Study): An International Phase III Randomized Clinical Trial.

OBJECTIVES AND DESIGN: The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines. BACKGROUND: Evidence-based guidelines for the follow-up of sentinel node-negative melanoma patients are lacking. METHODS: Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared. RESULTS: At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54-1.39, P =0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P =0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49-2.07, P =0.99). CONCLUSIONS: A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node-negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients' acceptance is very high.

Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB.

BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics have prognostic value in clinical stage IB-II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB-II melanoma. METHODS: Prospectively recorded data of patients with clinical stage IB-II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox-regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow-thickness, ulceration, mitotic rate, SLN-status) and patient-related variables (gender, age, and social-economic-status [SES]) and disease-free interval (DFI), melanoma-specific survival (MSS), and overall survival (OS). RESULTS: Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6-89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98-2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97-2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85-1.85; p = 0.25). Increased age, arm location, increased Breslow-thickness, ulceration, increased mitotic rate, and positive SLN-status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated. CONCLUSION: Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB-II melanoma who underwent SLNB.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

OBJECTIVE: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. BACKGROUND: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. METHODS: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. RESULTS: SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. CONCLUSION: In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Double venipuncture is not required for adequate S-100B determination in melanoma patients.

S-100B is used in melanoma follow-up. This serum biomarker is also present in adipocytes; therefore, subcutaneous adipocytes trapped in the needle before performing a venipuncture could contaminate the serum. The aim was to study the influence of adipocyte contamination on blood samples used for S-100B analysis, possibly resulting in falsely elevated S-100B values. A total of 294 serum samples were collected from 147 American Joint Committee on Cancer staging stage III melanoma patients. The mean difference between the first (dummy) and second tubes was 0.003 µg/l (p = 0.077), with a decrease in the second tube. Compared with the second tube, the S-100B level was higher in the first tube in 33.3% of the samples, equal in 36.8% of the samples and lower in 29.9% of the samples. No significant difference between the two consecutively drawn tubes was found. There seems to be no necessity of implementing a dummy tube system for accurate S-100B determination in melanoma patients.

Posterior retroperitoneoscopic resection of recurrent nonseminomatous tumor mass: a case report of the surgical procedure.

Treatment of stage II-IV nonseminomatous testicular germ cell tumors (NSTGCTs) consists of cisplatin-based combination chemotherapy and, when present, resection of residual retroperitoneal tumor mass (RRTM) by conventional laparotomy or laparoscopy. In case of a retroperitoneal recurrence, a second conventional or laparoscopic procedure may be challenging. A case of late relapse after prior conventional resection of a RRTM and tailor-made surgical management with a posterior retroperitoneoscopic resection (PRR) is reported. A posterior retroperitoneoscopic RRTM resection was performed in a 26-year-old male with a history of stage IIC NSTGCT, presenting with a late left-sided retroperitoneal relapse, 6 years after initial treatment. Postoperative course was uneventful and at 1-year follow-up the patient had no evidence of disease. Reoperative surgery by a minimal invasive retroperitoneoscopic approach should be considered as an alternative for patients with a recurrent retroperitoneal tumor mass of a NSTGCT.

The MelFo Study UK: Effects of a Reduced-Frequency, Stage-Adjusted Follow-Up Schedule for Cutaneous Melanoma 1B to 2C Patients After 3-Years.

BACKGROUND: Evidence-based guidelines for follow-up treatment of American Joint Committee on Cancer (AJCC) stages 1B to 2C melanoma patients are lacking. The MELanoma FOllow-up study is an international phase 3 randomized trial, and the 3-year interim data were recently reported from the Netherlands. The study was undertaken concurrently with a British cohort for comparison and validation of the Dutch study. METHODS: The study enrolled and stratified 207 patients by AJCC stage. The conventional schedule group (CSG; n = 103) cohort was reviewed as per UK guidelines. The experimental schedule group (ESG; n = 104) cohort was reviewed in a reduced-frequency nurse-led, consultant-supervised clinic. Quality of life (QoL) was measured at baseline (T1), a 1 year (T2), and at 3 years (T3) using the State-Trait Anxiety Inventory, the Cancer Worry Scale, the Impact-of-Event Scale, and the Mental and Physical Component scales (PCS/MCS) of the RAND-36. RESULTS: Of the 207 QoL questionnaires, 170 (82.1%) were completed at T3. Both cohorts expressed high satisfaction (> 93%) with their regimens. At T3, no significant group effect was found on any patient-reported outcome measures scores, indicating no QoL difference between the follow-up protocols. Recurrence had developed in 33 patients Conventional follow-up (CFU), 16 [15.5%]; Experimental follow-up (EFU), 17 [16.3%]. Self-examination was the method of detection for 12 ESG patients (70.6%) and 11 CSG patients (68.8%). The melanoma-specific survival was identical. CONCLUSION: The UK 3-year data were consistent with the previous Dutch report. The reduced follow-up strategy was shown to be safe, with significant resource usage benefits for national cancer services. Patient anxiety levels were not increased by a less-intensive follow-up regimen, and acceptance was high. The study data indicate that patient self-examination is very effective for recurrence detection.

Increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvement.

AIM: To investigate implementation of the seventh American Joint Committee on Cancer melanoma staging with sentinel lymph node biopsy (SLNB) and associations with socioeconomic status (SES). PATIENTS & METHODS: Data from The Netherlands Cancer Registry on patient and tumor characteristics were analyzed for all stage IB-II melanoma cases diagnosed 2010-2016, along with SES data from The Netherlands Institute for Social Research. RESULTS: The proportion of SLNB-staged patients increased from 40% to 65% (p < 0.001). Multivariate analysis showed that being female, elderly, or having head-and-neck disease reduced the likelihood of SLNB staging. CONCLUSION: SLNB staging increased by 25% during the study period but lagged among elderly patients and those with head-and-neck melanoma. In The Netherlands, SES no longer affects SLNB staging performance.

The MELFO Study: A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB-IIC Patients-Results After 3 Years.

BACKGROUND: This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs. METHODS: Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB-IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG, n = 93) or experimental (ESG, n = 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory-State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales [PCS/MCS]). Three years later (T3), 110 patients (CSG, n = 56; ESG, n = 54) completed PROMs, while 42 declined (23%). RESULTS: Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (p = 0.001) in favor of the ESG, and on the RAND-36 PCS (p = 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio [HR] 0.71 [0.32-1.58]; p = 0.400) and disease-free survival (HR 1.24 [0.42-3.71]; p = 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG. CONCLUSION: These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB-IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline.

Regional Node Basin Recurrence in Melanoma Patients: More Common After Node Dissection for Macroscopic Rather than Clinically Occult Nodal Disease.

BACKGROUND: Recommended treatment for patients with sentinel lymph node (SLN)-positive melanoma has recently changed. Randomized trials demonstrated equivalent survival with close observation versus completion lymph node dissection (CLND), but increased regional node recurrence. We evaluated factors related to in-basin nodal recurrence after lymphadenectomy (LND) for SLN-positive or macroscopic nodal metastases. METHODS: An institutional database and the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were analyzed independently. Exclusions were multiple primaries, multi-basin involvement, or in-transit metastases. Patient demographics, primary tumor thickness and ulceration, lymph nodes retrieved, and use of adjuvant radiotherapy were analyzed. Multivariate analyses were performed to determine factors predicting in-basin nodal recurrence (significance p ≤ 0.05). RESULTS: The retrospective cohort (577 patients) showed an in-basin failure rate of 6.6% after CLND for a positive SLN and 13.1% after LND for palpable disease (p = 0.001). This recurrence risk persisted after adjustment for patient, tumor, and LND factors [hazard ratio (HR) 2.32; p = 0.004]. In the MSLT-I cohort (326 patients), the failure rate after CLND following SLNB was 6.2%, but 10.1% after LND for palpable recurrence in observation patients. After adjustment for other factors, macroscopic disease was associated with an increased risk of recurrence after LND (HR 2.24; p = 0.05). CONCLUSION: After LND for melanoma, in-basin recurrence is infrequent, but a clinically significant fraction will fail. Failure is less likely if dissection is performed for clinically occult disease. Further research is warranted to evaluate the long-term regional control and quality of life associated with nodal basin observation, which has now become standard practice.

Laparoscopic Resection of Residual Retroperitoneal Tumor Mass in Advanced Nonseminomatous Testicular Germ Cell Tumors; a Feasible and Safe Oncological Procedure.

Ten-year oncological experience of the University Medical Center Groningen with conventional laparotomy (C-RRRTM) and laparoscopy (L-RRRTM) is described concerning resection of residual retroperitoneal tumor masses (RRTM) in a large series of patients with advanced nonseminomatous testicular germ cell tumors (NSTGCT). 150 consecutive patients with disseminated NSTGCT required adjunctive surgery after combination chemotherapy. L-RRRTM was scheduled in 89 and C-RRRTM in 61 patients. Median residual tumor diameter was 20 mm in the L-RRRTM versus 42 mm in the C-RRRTM group (p < 0.001). Conversion rate was 15% in the L-RRRTM group. Perioperative complications occurred in 5 patients (6%) in the L-RRRTM and 7 (12%, NS) in the C-RRRTM group. Median duration of L-RRRTM was 156 minutes vs. 221 minutes for C-RRRTM (p < 0.001). 17/89 patients in the L-RRRTM group had postoperative complications versus 18/61 patients in the C-RRRTM group (NS). Median postoperative stay in the L-RRRTM group was 2 vs. 6 days in the C-RRRTM group (p < 0.001). During a median follow-up of 79 months, 27 patients had recurrences: 8 (9%) in the L-RRRTM group and 19 (31%) in the C-RRRTM group (p < 0.001). Laparoscopic resection of RRTM for advanced NSTGCT is feasible and an oncologically safe option in appropriately selected patients.

S-100B as an extra selection tool for FDG PET/CT scanning in follow-up of AJCC stage III melanoma patients.

BACKGROUND AND OBJECTIVES: This current study assessed the value of S-100B measurement to guide fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scanning for detecting recurrent disease in stage III melanoma patients. METHODS: This study included 100 stage III melanoma patients in follow-up after curative lymph node dissection. Follow-up visits included physical examination and S-100B monitoring. FDG PET/CT scanning was indicated by clinical symptoms and/or elevated S-100B. RESULTS: Of 100 patients, 13 (13%) had elevated S-100B without clinical symptoms, of whom 7 (54%) showed disease evidence upon FDG PET/CT scanning. Twenty-six patients (26%) had clinical symptoms with normal S-100B and FDG PET/CT revealed metastasis in 20 (77%). Three patients had clinical symptoms and elevated S-100B, and FDG PET/CT revealed metastasis in all three (100%). Overall, FDG PET/CT scanning revealed metastasis in 30 of the 42 patients (71.4%). For seven recurrences, elevated S-100B prompted early detection of asymptomatic disease; 10% of all asymptomatic patients in follow-up, 23% of all patients with recurrent disease. CONCLUSION: S-100B cannot exclude recurrent disease during follow-up of stage III melanoma. However, adding S-100B measurement to standard clinical assessment can guide FDG PET/CT scanning for detecting recurrent melanoma.

Risk factors for postoperative wound complications after extremity soft tissue sarcoma resection: A systematic review and meta-analyses.

INTRODUCTION: Advancements in imaging, surgical, and radiation techniques have made resection of larger and more extensive extremity soft tissue sarcomas (ESTS) possible but with the potential for high complication rates. This study summarizes complication and reoperation rates associated with resection of ESTS and reviews predictors for wound complications. METHODS: A systematic review of the literature on ESTS in adults was undertaken from the four databases MEDLINE, Embase, MEDLINE In-Process & Other Non-Indexed Citations, and the Cochrane Central Register of Controlled Trials (CCRCT). Meta-analyses of the complications, reoperations, and risk factors were performed. RESULTS: In the twenty-one studies included, there was an overall wound complication rate of 30.2% (95% CI 26.56-33.47) and a reoperation rate of 13.37% (95% CI 10.21-16.52) in 5628 patients. Individual studies reported that older patient age, obesity, smoking, diabetes, large tumor size, tumor site, and preoperative radiotherapy were associated with adverse outcomes. Tumors of the lower limb, diabetes, smoking, obesity, and radiation were identified as independent predictors of wound complications in meta-analysis. A high level of heterogeneity between studies limited pooled analysis for many variables. CONCLUSIONS: Despite advancements in the treatment of ESTS, postoperative complication rates remain high. Awareness of the risk factors for wound complications, especially those that may be modifiable, is essential to decrease postoperative morbidities in these patients to improve treatment outcomes and quality of life.

Four different treatment strategies in aggressive fibromatosis: A systematic review.

BACKGROUND: The treatment approach for aggressive fibromatosis is changing. Although surgery is the mainstay in common practice, recent literature is reporting a more conservative approach. We compared the local control rate for surgery, surgery with radiotherapy, radiotherapy alone and a wait and see policy in a systematic review. METHODS: A comprehensive search of the databases PubMed/Medline, Embase and Cochrane, of the medical literature published in 1999 till March 2017 was performed by two reviewers, including articles about extra abdominal aggressive fibromatosis without the genetical variants. A total of 671 studies were assessed for eligibility, and 37 studies were included for analysis, representing 2780 patients. RESULTS: The local control rates for surgery alone, surgery and radiotherapy, radiotherapy alone and observation were 75%, 78%, 85% and 78%, respectively. For patients with recurrent disease observation had a better local control rate than surgery alone (p = 0.001). In the observation group, stabilization of the tumor was seen in median 14 (range 12-35) months. The time to local recurrence in the treatment group was median 17 (range, 11-52) months. CONCLUSION: A watchful conservative first line approach with just observation and closely monitoring, by means of physical examination and MRI, appears to be justified in a subgroup of patients without clinical symptoms and no possible health hazards if the tumor would progress.

Volume of interest delineation techniques for 18F-FDG PET-CT scans during neoadjuvant extremity soft tissue sarcoma treatment in adults: a feasibility study.

BACKGROUND: This study explores various volume of interest (VOI) delineation techniques for fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) scans during neoadjuvant extremity soft tissue sarcoma (ESTS) treatment. RESULTS: During neoadjuvant treatment, hyperthermic isolated limb perfusion (HILP) and preoperative external beam radiotherapy (EBRT), 11 patients underwent three 18F-FDG PET-CT scans. The first scan was made prior to the HILP, the second after the HILP but prior to the start of the EBRT, and the third prior to surgical resection. An automatically drawn VOIauto, a manually drawn VOIman, and two gradient-based semi-automatically drawn VOIs (VOIgrad and VOIgrad+) were obtained. Maximum standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolically active tumor volume (MATV), and total lesion glycolysis (TLG) were calculated from each VOI. The correlation and level of agreement between VOI delineation techniques was explored. Lastly, the changes in metabolic tumor activity were related to the histopathologic response. The strongest correlation and an acceptable level of agreement was found between the VOIman and the VOIgrad+ delineation techniques. A decline (VOIman) in SUVmax, SUVpeak, SUVmean, TLG, and MATV (all p < 0.05) was found between the three scans. A > 75% decline in TLG between scan 1 and scan 3 possibly identifies histopathologic response. CONCLUSIONS: The VOIgrad+ delineation technique was identified as most reliable considering reproducibility when compared with the other VOI delineation techniques during the multimodality neoadjuvant treatment of locally advanced ESTS. A significant decline in metabolic tumor activity during the treatment was found. TLG deserves further exploration as predictor for histopathologic response after multimodality ESTS treatment.

Histopathological tumor response following neoadjuvant hyperthermic isolated limb perfusion in extremity soft tissue sarcomas: Evaluation of the EORTC-STBSG response score.

INTRODUCTION: This study aims to evaluate the applicability and prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) histopathological response score in extremity soft tissue sarcoma (ESTS) patients treated with neoadjuvant hyperthermic isolated limb perfusion (HILP) and delayed surgical resection. METHODS: Patients treated between 1991 and 2016 were included. The histopathological tumor response was established in accordance with the EORTC-STBSG response score. The distribution of patients was assorted according to the 5-tier histopathological response score for tumor grade, histological subtype and HILP regimen. Predictors for local recurrence free survival (LRFS) and overall survival (OS) were identified through Kaplan-Meier and Cox regression analyses. RESULTS: Ninety-one patients were included and their resection specimens were reanalyzed. Which resulted in 11 Grade A (12.1%), ten Grade B (11.0%), 15 Grade C (16.5%), 22 Grade D (24.2%) and 33 Grade E (36.3%) responses found among the series. The histopathological response was significantly influenced by the HILP regimen used, p = 0.033. Median follow-up was 65.0 (18.0-157.0) months. The histopathological response was not associated with LRFS nor OS. Resection margins, HILP regimen and adjuvant radiotherapy were associated with LRFS. Patients' age, tumor grade, tumor size and histological subtype were predictors for OS. CONCLUSIONS: The EORTC-STBSG response score is applicable for determining the histopathological response to neoadjuvant ESTS treatment. However, this response does not seem to predict LRFS nor OS in locally advanced ESTS.

Flap choice does not affect complication rates or functional outcomes following extremity soft tissue sarcoma reconstruction.

BACKGROUND: Flap reconstruction plays an essential role in facilitating limb preservation in patients with extremity soft tissue sarcoma (ESTS). However, the effect of flap choice on the rates of postoperative complications and functional outcomes has not been clearly established. This study directly compares the outcomes of free and pedicled flap reconstructions in patients with ESTS. METHODS: Two hundred sixty-six patients who underwent flap reconstruction following ESTS resection were included. Associations between flap type and complications were determined using logistic regression analyses. Functional outcome was evaluated using the Toronto Extremity Salvage Score (TESS) and the Musculoskeletal Tumor Society Scales (MSTS). RESULTS: There was no significant difference between complication rates in the pedicled and free flap groups (32% vs. 38%, p = 0.38). In the lower limb, pedicled flaps had complication rates similar to those of free flaps on univariate analysis (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 0.56-2.26, p = 0.75). Conversely, in the upper limb, pedicled flaps were associated with fewer complications on univariate analysis (OR = 0.31, 95% CI = 0.11-0.86, p = 0.03), but this was not significant on multivariate analysis (OR = 0.45, 95% CI = 0.13-1.59, p = 0.22). Obesity was a strong predictor of complications in the upper limb group on multivariate analysis (body mass index [BMI] ≥ 30 kg/m2, OR = 7.01, 95% CI = 1.28-38.51, p = 0.03). There was no significant difference in functional outcomes between both flap groups in either upper or lower limbs. CONCLUSIONS: Postoperative complications and functional outcomes for patients undergoing free and pedicled flaps are similar in ESTS reconstruction. Selecting the most suitable reconstructive option in each individual case is paramount to preserving function while minimizing postoperative morbidity.