The long-term results and prognostic significance of cutaneous melanoma surgery using sentinel node biopsy with triple technique.

BACKGROUND: The sentinel lymph node biopsy (SLN) is a basic staging method in all primary cutaneous melanomas ≥pT1b. The standard technique is a triple technique consisting of preoperative lymphoscintigraphy, intraoperative blue-dye lymphography, and gamma-probe assessment. We performed the analysis of long-term results in a very large one-institution series of cutaneous melanoma patients. METHODS: We have analyzed treatment results of a group of 1764 consecutive patients with cutaneous melanoma, who underwent SLN biopsy between 1997 and 2008 in one tertiary center. Additionally, we have analyzed the outcomes of a group of 473 patients with positive SLN biopsy undergoing completion lymph node dissection (CLND). Median follow-up time was 5.3 years. RESULTS: Metastases to SLN (SLN+) were found in 19.9%. Eight-year overall survival (OS) rate in the entire group was 73.5%, 80% without SLN metastases (SLN-) and 50% in group with SLN+ (p < 0.001). Independent prognostic factors for OS were as follows: presence of metastases to SLN, primary tumor ulceration, and higher mitotic index (>5/mm(2)) of primary tumor. The nodal recurrences in the biopsied lymphatic basin were 5.4%. The metastases to non-sentinel lymph nodes (NSLN found in 27% of patients with SLN+) correlated (on multivariable logistic regression analysis) with primary tumor thickness >4 mm, SLN metastatic deposit size >1 mm, and extracapsular involvement of SLN. In an additionally analyzed SLN+ group, the NSLN involvement was related to poorer prognosis (8-year OS rate NSLN- vs NSLN+: 59.6 vs. 34.7%, respectively). The independent prognostic factors for OS in the SLN+ group were a higher Breslow thickness and ulceration of primary tumor, metastases to more than 1 lymph nodes. CONCLUSIONS: The long-term results confirm crucial prognostic significance of SLN biopsy in cutaneous melanoma. We identified factors related to NSLN involvement, which in the future may limit indications for CLND.

Preoperative-postoperative immunotherapy as treatment of borderline resectable and oligoprogressive stage III B-D and IV melanoma.

INTRODUCTION: Perioperative therapy has gained significant importance in patients with advanced melanoma. Currently, there is little data on the routine use of preoperative immunotherapy in metastatic melanoma outside clinical trials. This study aimed to evaluate the effectiveness of preoperative treatment in patients with borderline resectable stage III or IV melanoma as well as in oligoprogressing stage IV cases; the secondary aim is to describe the safety of surgery after immunotherapy. MATERIALS AND METHODS: Since 1/Jan/2016 seventeen patients were treated with curative intent neoadjuvant immunotherapy, surgery, and adjuvant immunotherapy, while nineteen patients were operated due to oligoprogression while treted with immunotherapy. Survival was analyzed using the Kaplan-Meier method and association between variables was tested using the chi-squared test. RESULTS: R0 resection was achieved in 76.5 % of cases after neoadjuvant immunotherapy. 24 % of patients achieved objective RECIST response and 35 % complete or major pathological response. At the median follow-up time of 51.4 months, 64.7 % of patients were free of PD after perioperative treatment, while 3-year RFS and OS rates were 68 % and 80.9 %, respectively. R0 resection was achieved in 73.7 % of oligo-progressing nodules. The median time to PD on immunotherapy after the first oligoprogression was 10.3 months. Immunotherapy did not result in any unexpected surgical complications. No patient died during preoperative treatment due to immunotherapy toxicity or disease progression. CONCLUSIONS: We confirmed treatment safety and long-term disease control after perioperative immunotherapy. Patients with borderline resectable melanoma should be referred to reference centers using neoadjuvant immunotherapy.

Melanoma without a detectable primary site with metastases to lymph nodes.

OBJECTIVE: To compare outcomes of patients with clinical nodal melanoma metastases that occurred without a detectable primary tumor (melanoma of unknown primary site; MUP) with those with a known primary site (KPM). METHODS: We included data from 459 consecutive patients treated from 1994 to 2007 with radical therapeutic lymph node dissection (LND; stage IIIB, C) due to clinically palpable and pathologically confirmed lymph node metastases (229 axillary; 230 ilioinguinal). The median follow-up was 49 months. RESULTS: LND was performed in 59 cases (12.9%; 29 men, 30 women) due to MUP nodal metastases, including 33 axillary (14.4%) and 26 ilioinguinal (11.3%). In the MUP group, the 3- and 5-year survival rates were 48% and 41%, respectively. Similar rates were observed in patients with KPM, even with matched-pair analyses. Established prognostic factors (number of metastatic nodes, p=.005; extracapsular extension of metastases, p=.002) influenced survival in the MUP group. Relapses occurred in 31 (53%) and 299 (74.7%) cases in the MUP and KPM groups, respectively. CONCLUSIONS: Survival rates in the MUP and KPM groups were similar, and the same prognostic factors affected both. Thus, all MUP cases should be treated as standard stage III melanomas.

Surgery combined with brachytherapy in patients with retroperitoneal sarcomas.

PURPOSE: The primary aim of this work was to analyze feasibility of combined treatment of retroperitoneal sarcomas (RS): surgery (S) and intraoperative brachytherapy (IOBRT). The secondary aim was to analyze results and complications after this treatment. MATERIAL AND METHODS: 84 patients with retroperitoneal sarcomas were qualified for combined treatment (S and IOBRT) between June 1998 and September 2006. 65 of the patients (77.4%) had local recurrences. Sarcomas with intermediate and high grade of histological malignancy (G2, G3 - 76.2%) were the most frequent within the all surgically treated patients. Resection ability (R0/R1) in analyzed group of patients was estimated as 85% (74 cases). After intraoperative evaluation, 57 (67.8%) patients were qualified for IOBRT. Since 2000, in 34 patients (60%) an adjuvant postoperative external beam radiation therapy (EBRT) in dose of 50 Gy was applied. Median follow-up of the surviving patients was 40 months. RESULTS: On the basis of the univariate analysis, relevant aspects negatively influencing overall survival rate within the RS group treated with IOBRT were as follows: surgery of sarcoma recurrence (p = 0.002), higher grade of histological malignancy (p = 0.05), histological type different than liposarcoma (p = 0.05) as well as no adjuvant EBRT (p = 0.05). On the basis of multivariate analysis one can ascertain that relevant factors negatively influencing LRFS in RS patients treated with IOBRT were: surgery due to recurrence of sarcoma (p = 0.008) and lack of EBRT (p = 0.01). CONCLUSIONS: Combined treatment (surgery and brachytherapy) was possible to be carried out on 68% of RS patients. The overall number of complications was quite high, however acceptable, taking into consideration the application of extensive, multi-organ treatments in case of sarcoma recurrences in this localization. The results suggest that the method of treatment will improve the final outcome when most of patients will be qualified for treatment of primary sarcomas in experienced centre.

Surgery combined with intraoperative brachytherapy in the treatment of retroperitoneal sarcomas.

BACKGROUND: The purpose of this study was to analyze the results of treatment of retroperitoneal soft tissue sarcomas (RSTS) by surgery combined with intraoperative brachytherapy (IOBRT). METHODS: Seventy adult patients with RSTS were considered for combined treatment (surgery plus IOBRT) between June 1998 and February 2004. There were 64 (91%) recurrent tumors, and 93% of tumors exceeded 5 cm. IOBRT was performed with high-dose-rate Gammamed 12 with iridium 192 (IOBRT time range, 20-87 minutes; median, 56 minutes). RESULTS: After intraoperative re-evaluation, 24 patients (34%) were found to be ineligible for IOBRT because of multiple intraperitoneal recurrences, macroscopically nonradical resection, poor general condition, and technical aspects. Thirty-seven patients underwent IOBRT immediately after surgery during the same general anesthesia procedure. Nine patients underwent delayed IOBRT within 1 to 3 days after the primary operation. Ten (21.5%) of 46 patients underwent reoperation because of surgical complications. One patient died in the postoperative period. After IOBRT, 24 patients (52%) underwent adjuvant external beam radiotherapy (EBRT) to a total dose of 50 Gy. Over a median follow-up time of 20 months, the estimated 5-year overall survival and local recurrence-free survival rates in IOBRT patients were 55% and 51%, respectively. Application of adjuvant EBRT showed a favorable local control rate. CONCLUSIONS: The scheduled combined treatment (surgery plus IOBRT) was possible to perform in 66% of RSTS cases that received surgical treatment. The complication rate was high, but we consider it acceptable because of the necessity for extensive aggressive surgical treatment in regionally advanced RSTS. EBRT seems to be an indispensable part of treatment that provides better local control.