Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison.

PURPOSE: Localized adult high-grade soft tissue sarcomas (STS) usually require multimodality treatment including surgery, radiotherapy, chemotherapy and hyperthermia. If maximal preoperative tumor-shrinkage is envisaged, neoadjuvant chemotherapy + radiation (CRT) is often applied, however at the expense of relatively high toxicities and increased postoperative complication rates. This study aims to compare preoperative CRT with neoadjuvant chemotherapy + regional hyperthermia (HCT) regarding histopathological response, toxicity and outcome. METHODS: In this retrospective analysis, 61 consecutive high-grade STS patients treated between 2009 and 2016 were included. All patients were treated within a prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of 4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered bi-weekly during each cycle. Association of treatment modality with overall survival (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated by Kaplan-Meier and log-rank analyses. RESULTS: The overall patient characteristics were well balanced. Histopathological tumor response did not differ significantly between both groups (p = .67), neither did higher-grade toxicities during neoadjuvant treatment. Wound dehiscence (p = .018) and surgical hospital re-admissions (p < .001) were both significantly more frequent in the CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71% with no significant differences between CRT and HCT. CONCLUSION: Compared to CRT, HCT seems equally efficient and appears to bear less surgical complications. Interpretation should be cautious due to the low number of patients and the retrospective nature of this study.

Acute effects of N-acetylcysteine on skeletal muscle microcirculation following closed soft tissue trauma in rats.

Trauma-induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of N-acetylcysteine (NAC) known to scavenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC on skeletal muscle microcirculation and leukocyte-endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague-Dawley rats using the controlled impact injury technique. Rats were randomly assigned (n = 7) to high-dose intravenous infusion of NAC (400 mg/kg body weight) or isovolemic normal saline (NS). Non-injured, sham-operated animals (n = 7) were subjected to the same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline, 1 h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser-Doppler flowmetry (LDF). Edema index (EI) was calculated by measuring the EDL wet-to-dry weight ratio (EI=injured/contralateral limb). EDL-muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS-infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham-operated animals and leukocyte adherence was significantly (p < 0.05) reduced compared to the NS group. NAC significantly (p < 0.05) increased erythrocyte flux determined by Laser-Doppler flowmetry. Posttraumatic serum CK levels and EI were significantly (p < 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction, attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI-induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin immunoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long-term analysis and investigation of injury severity--or dosage dependency are needed.