Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

Purpose: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials.

Methods: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT.

Results: We have identified seven controversies and five consensus points.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma.

Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m on day 1, 15 and cisplatin 25 mg/m with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m on day 1,8,15), four-weekly over six cycles.

A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers.

Purpose: The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT.

Expanding Valve Repair in Rheumatic Heart Disease.

Rheumatic heart disease is a serious ailment with significant morbidity and mortality in endemic areas; yet, there is no agreement on indication, timing, and surgical modality for treating rheumatic valve affection. There is mounting evidence that rheumatic mitral valve repair is possible with good long-term results, less is the case with rheumatic aortic valve disease. We discuss the surgical approach for both valves emphasizing the role of multimodality imaging.

Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial.

Background: The EORTC 62961-ESHO 95 randomised trial showed improved long-term survival of patients with high-risk soft-tissue sarcoma by adding regional hyperthermia to neoadjuvant chemotherapy. We hypothesised that immune infiltrate of patients treated with neoadjuvant therapy associate with clinical outcome.

Methods: Tumour infiltrating lymphocytes (TILs) and CD8, FOXP3, PD-1, and PD-L1 were evaluated in sequential biopsies of patients after four cycles of therapy.

Post-Neoadjuvant Gemcitabine and Cisplatin with Regional Hyperthermia for Patients with Triple-Negative Breast Cancer and Non-pCR after Neoadjuvant Chemotherapy: A Single-Institute Experience.

Background: Patients with triple-negative primary breast cancer (TNBC) who have residual invasive carcinoma after neoadjuvant chemotherapy have poor prognosis. Proven adjuvant approaches to reduce the risk of recurrence and improve outcome in patients with non-pathological complete response (non-pCR) are limited.

Methods: From our institutional registry, a consecutive case series of patients with operable, unilateral, primary invasive noninflammatory early TNBC of stage I-IIIB and pathologically verified residual cancer cells (no pathological complete response) after neoadjuvant chemotherapy underwent adjuvant treatment with gemcitabine plus cisplatin combined with regional hyperthermia.

Neoadjuvant Chemoradiation Combined with Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer.

Background: To prospectively analyze feasibility and pathological complete response (pCR) rates of neoadjuvant chemoradiotherapy combined with regional hyperthermia (RHT) in patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer.

Methods: between 2012 and 2018, 111 patients with UICC stage IIB-IV or any locally recurrent rectal cancer were included (HyRec-Trial, ClinicalTrials.gov Identifier: NCT01716949).

Ifosfamide, Carboplatin, and Etoposide (ICE) in Combination with Regional Hyperthermia as Salvage Therapy in Patients with Locally Advanced Nonmetastatic and Metastatic Soft-Tissue Sarcoma.

Patients with localized relapse of soft-tissue sarcoma (STS) after anthracycline-based chemotherapy have a dismal prognosis, particularly when surgery is not possible. To facilitate resection and improve long-term tumor control, we applied an intensified perioperative treatment consisting of ICE (ifosfamide 6 g/m, carboplatin 400 mg/m, and etoposide 600 mg/m) in combination with regional hyperthermia (RHT) to maximize local control. Here, we retrospectively evaluate the safety and efficacy of this strategy.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques.

A biological timer in the fat body comprising Blimp-1, βFtz-f1 and Shade regulates pupation timing in Drosophila melanogaster.

During the development of multicellular organisms, many events occur with precise timing. In Drosophila melanogaster, pupation occurs about 12 h after puparium formation and its timing is believed to be determined by the release of a steroid hormone, ecdysone (E), from the prothoracic gland. Here, we demonstrate that the ecdysone-20-monooxygenase Shade determines pupation timing by converting E to 20-hydroxyecdysone (20E) in the fat body, which is the organ that senses nutritional status.

CT fluoroscopy-guided closed-tip catheter placement before regional hyperthermia treatment of soft tissue sarcomas: 5-Year experience in 35 consecutive patients.

Purpose: This study was designed to assess technical success and complications in patients with high-risk soft tissue sarcomas undergoing CT fluoroscopy-guided closed-tip catheter placement before treatment with combined chemotherapy and regional hyperthermia.

Materials And Methods: This retrospective study comprised all patients referred for insertion of closed-tip catheters for the introduction of thermometry probes before regional hyperthermia treatment at a single university centre from 2010 to 2015. Catheter placements were performed under local anaesthesia and intermittent CT fluoroscopy guidance.

Concomitant trimodality therapy of re-irradiation, chemotherapy and regional hyperthermia for a pretreated inoperable sarcoma recurrence.

We hereby present a case of pre-treated unresectable sarcoma recurrence of the trunk which showed an excellent response to concomitant tri-modal therapy, consisting of re-irradiation, chemotherapy and regional hyperthermia even with a strong compromised re-irradiation dose. No significant toxicity of the combined therapy and fast achievement of the pain and neurological symptoms relief are reported. The case shows that concurrent tri-modality treatment can be considered as a therapeutic option for the management of pre-treated unresectable recurrence even in there-irradiation setting.

Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study.

Objective: To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas.

Background: Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections.

Function of the nuclear receptor FTZ-F1 during the pupal stage in Drosophila melanogaster.

The nuclear receptor βFTZ-F1 is expressed in most cells in a temporally specific manner, and its expression is induced immediately after decline in ecdysteroid levels. This factor plays important roles during embryogenesis, larval ecdysis, and early metamorphic stages. However, little is known about the expression pattern, regulation and function of this receptor during the pupal stage.

Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer.

Purpose: There is no standard second-line therapy for patients with advanced pancreatic cancer (APC) after gemcitabine (G) failure. Cisplatin (Cis)-based chemotherapy has shown activity in APC. It is proven that cytotoxicity of G and Cis is enhanced by heat exposure at 40° to 42°C.

Quality assurance for clinical studies in regional deep hyperthermia.

Background: A guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients.

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study.

Background: The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone.

Comparison of radiological and pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia (RHT) and study of response dependence on the applied thermal parameters in patients with soft tissue sarcomas (STS).

Purpose: To compare the radiological criteria RECIST, WHO, and tumor volume for evaluation of tumor response in patients with soft tissue sarcomas (STS) showing either good or poor pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia, and to examine the dependence of the findings on the applied thermal dose.

Materials And Methods: 19 patients with pathohistological complete response (no vital tumor cells, group 1) and 27 with pathohistological no response (<25% necrosis, group 2) were selected from our previous clinical trials. The change in tumor size before and after therapy was determined.

Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas.

Background: Prognosis of patients with metastatic soft tissue sarcomas (MSTS) is poor even after response to doxorubicin-based chemotherapy. We report phase II data of high-dose chemotherapy and peripheral blood stem cell (PBSC) rescue in patients with MSTS responding to AI-G chemotherapy.

Patients And Methods: From 1997 to 2002, 55 patients with MSTS were prospectively treated with 4 cycles of AI-G (doxorubicin 75 mg/m(2), ifosfamide 6 g/m(2) with G-CSF support).

Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas.

Purpose: To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS).

Patients And Methods: From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation.

Results: Objective response rate assessable in 40 patients was 13% (five partial responses).