Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally advanced myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The use of preoperative hypofractionated radiotherapy 5 × 5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced STS showed a good local control rate. The main objective of our work was to assess the efficacy of hypofractionated radiotherapy in preoperative setting in patients with locally advanced primary MLPS. METHODS: From February 1999 to March 2014, 32 patients with primary MLPS were treated with preoperative hypofractionated radiotherapy for 5 consecutive days followed by immediate surgery (median dose 5 × 5 Gy). Median size of the tumor 10.5 cm. In one patient the tumor was located on the upper extremity, the other (31 patients) had their tumors located on the lower extremity. RESULTS: In 90% patients histologically negative surgical margins (R0) were obtained. 34% patients had distant recurrence of the disease, local recurrence was found in 9.3% of the patients. 5-year local relapse-free survival rate was 90% and overall survival was 68%. In all analyzed surgical specimens the radiotherapy response features (hyalinization, fibrosis, paucicelularity, hemorrhages, dilatation of vessels) were detected. We have not found statistically significant differences in terms of OS and LRFS for RCC component, tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy specimens significantly higher positivity of TP53 expression was detected as compared to primary biopsies. CONCLUSION: Combined therapy with hypofractionated radiotherapy followed by immediate surgery seems to be effective therapy in MLPS demonstrating good local control and pathological response to therapy.

Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas.

BACKGROUND: The primary treatment of soft tissue sarcomas (STS) is a radical resection of the tumor with adjuvant radiotherapy. Conventional fractionation of preoperative radiotherapy is 50 Gy in fraction of 2 Gy a day. The purpose of the conducted study was to assess the efficacy and safety of hypofractionated radiotherapy in preoperative setting in STS patients. METHODS: 272 patients participated in this prospective study conducted from 2006 till 2011. Tumors were localized on the extremities or trunk wall. Median tumor size was 8.5 cm, 42% of the patients had tumor larger than 10 cm, whereas 170 patients (64.6%) had high grade (G3) tumors. 167 patients (61.4%) had primary tumors. Patients were treated with preoperative radiotherapy for five consecutive days in 5 Gy per fraction, with an immediate surgery. Median follow up is 35 months. RESULTS: 79 patients died at the time of the analysis, the 3-year overall survival was 72%. Local recurrences were observed in 19.1 % of the patients. Factors that had a significant adverse impact on local recurrence were tumor size of 10 cm or more and G3 grade. 114 patients (42%) had any kind of treatment toxicity, vast majority with tumors located on lower limbs. 7% (21) of the patients required surgery for treatment of the complications. CONCLUSION: In this non-selected group of locally advanced STS use of hypofractionated preoperative radiotherapy was associated with similar local control (81%) when compared to previously published studies. The early toxicity is tolerable, with small rate of late complications. Presented results warrant further evaluation.

The analysis of the outcomes and factors related to iliac-obturator involvement in cutaneous melanoma patients after lymph node dissection due to positive sentinel lymph node biopsy or clinically detected inguinal metastases.

BACKGROUND: We assessed clinical-pathological features and outcomes of cutaneous melanoma patients after ilio-inguinal lymph node dissection (LND) in relation to the presence of metastases in iliac-obturator nodes. METHODS: We analyzed 390 consecutive patients who underwent ilio-inguinal therapeutic LND [TLND] (237) due to clinical/cytologically detected metastases or after completion LND [CLND] (153) due to positive SLN biopsy (in one cancer centre 1994-2009). Median follow-up time was 60 months. RESULTS: The 5-year overall survival (OS) rate was 49% and median OS - 52 months in the entire group of patients. According to univariate analysis following factors had significant negative influence on OS: presence of metastases to iliac-obturator nodes (5-year OS for positive versus negative: 54.5% and 32%, respectively), macrometastases, higher Breslow thickness, ulceration, higher Clark level, male gender, number of metastatic lymph nodes, extracapsular extension, and, additionally in the CLND group - micrometastases size ≥ 0.1 mm according to the Rotterdam criteria and non-subcapsular location of micrometastases. Iliac-obturator involvement was also negative factor for OS in multivariate analysis. The presence of iliac-obturator nodal metastases correlated with the following factors: type of LND-CLND versus TLND (15% versus 27.5%) of iliac-obturator involvement, respectively), higher Breslow thickness, extracapsular extension of nodal metastases, male gender. We have not identified any metastases in iliac-obturator nodes in group of patients with micrometastases size ≤1.0 mm and primary tumour Breslow thickness <4.0 mm or no ulcerated primary tumours. CONCLUSIONS: Metastases to iliac-obturator nodes have additional negative prognostic value for melanoma patients with inguinal basin involvement. We are able to identify the subgroup of patients after positive SLN biopsy without metastases to iliac-obturator nodes, probably requiring only inguinal LND.

Surgical resection of residual disease in initially inoperable imatinib-resistant/intolerant gastrointestinal stromal tumor treated with sunitinib.

AIM: Sunitinib malate therapy in inoperable and/or metastatic gastrointestinal stromal tumor (GIST) resistant to imatinib mesylate may facilitate surgical removal of residual disease. We explored this possibility in the course of treating patients as part of a treatment-use trial, the objective of which was to provide access to sunitinib treatment. METHODS: Four patients with inoperable and/or metastatic GIST resistant to imatinib who had responded to sunitinib therapy administered at a starting dose of 50 mg daily in 6-week cycles of 4 weeks on treatment followed by 2 weeks off underwent surgical removal of residual disease. Disease progression on or clinical response to treatment was defined based on Response Evaluation Criteria in Solid Tumors. RESULTS: In three of four cases it was possible to perform macroscopically complete resection of residual disease, resulting in surgical complete clinical responses, two with durations of 13 months. The fourth patient achieved a dramatic partial response to sunitinib that required emergency surgical resection of the necrotic tumor mass, with the partial response having been maintained for 15 months. In all cases, viable GIST cells were detected histologically in the resection specimens, and sunitinib treatment was resumed post-surgery. None of the patients experienced any postoperative complications during 13-16 months of follow-up. CONCLUSIONS: Combining sunitinib treatment with surgical removal of residual disease may allow selected imatinib-resistant GIST patients who have shown a favorable response to sunitinib to achieve complete and sustained remission or durable control of previously progressive disease beyond that expected for sunitinib treatment alone.

In transit/local recurrences in melanoma patients after sentinel node biopsy and therapeutic lymph node dissection.

This study has analyzed the incidence of in transit/local recurrences (IT/LR) in melanoma patients after sentinel node (SLN) biopsy; completion lymph node dissection (CLND) that was performed due to positive node; and therapeutic LND (TLND) due to clinically detected node metastases and factors influencing IT/LR. Between May 1995 and May 2004, 1187 consecutive patients underwent SLN biopsy (median Breslow thickness 2.5 mm) and 224 of them had subsequent CLND. During the same time period, 306 patients had TLND (median Breslow 3.9 mm). The excision margin of primaries was > or =1cm. At median follow-up time of 37.5 months, we analyzed the incidence of IT/LR as the first site of relapse and clinicopathological parameters affecting these recurrences. In SLN-negative cases, IT/LR as the site of the first recurrence were rare (46/963; 4.8%) and; in SLN+/-CLND IT/LR were detected in 45/224 cases (20.1%). IT/LR in SLNB group correlated with presence of SLN metastases (P<0.0001), higher Breslow thickness (P<0.001) and lower extremity localization (P=0.03). In TLND group, IT/LR were observed in 52/306 patients (17%), which is similar to all CLND patients (P=0.3), but less common when analyzing only patients who relapsed (TLND: 52/209 (24.9%) vs. CLND: 45/121 (37.2%); P=0.02). Estimated 3-year overall survival (from the date of relapse) in IT/LR only patients was better than in other types of relapses after LND (29% vs. 8%; P<0.0001). IT/LR incidence in the entire group of SLN+/-CLND patients was similar to that observed in TLND patients and it was affected by presence of nodal metastases, Breslow thickness and lower extremity location.