Radiotherapy With Hyperthermia in Recurrent and Radiation-Induced Sarcomas (HOT)

Hyperthermia and Radiotherapy in the Treatment for In-field Recurrent and Radiation-induced Soft Tissue and Bone Sarcomas

After a screening, which consists of biopsy, physical examination, initial diffusion-weighted magnetic resonance imaging (DWI-MRI) or body computed tomography (CT) scan, blood tests and case analysis on Multidisciplinary Team (MDT) meeting, a patient with radiation-induced or in-field recurrent sarcoma will receive the hypofractionated radiotherapy with deep hyperthermia (twice a week) within three weeks. The response analysis in CT or DWI-MRI and toxicity assessment will be performed after 6 weeks. In resectable tumors, a patient will be referred to surgery. In the case of unresectability, the patient will followed-up.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Soft Tissue Sarcoma; Recurrent Sarcoma; Radiation Induced Neoplasms; Radiation-Induced Cancer
• Intervention / Treatment: Other: Hyperthermia; Radiation: Hypofractionated radiotherapy; Radiation: Hypofractionated radiotherapy with boost

Detailed Description

Due to the rarity of radiation-induced (RIS) or previously irradiated recurrent (PIRS) sarcomas, no guidelines nor randomized prospective clinical trials on this topic exist. Thus the management of RIS and PIR is challenging. The only curable modality in non-metastatic RIS/PIRS is radical resection with wide negative margins. The role of secondary radiotherapy in locally advanced RIS/PIRS is unclear, mostly due to the concerns about possible severe side effects after re-irradiation.

The addition of deep hyperthermia to irradiation and in the prolonged gap between the end of moderately hypofractionated radiotherapy (with or without integrated boost) and surgery may allow obtaining the long-term local control with the maintenance of a good treatment tolerance Hyperthermia is a method of increasing the temperature in the tumor to damage cancer cells with minimum injury to the normal cells. It should be combined with another treatment modality (radio- or chemotherapy) rather than used alone. Its efficacy was proven in clinical trials. Treatment tolerance is usually very good.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mateusz J Spałek, MD PhD; Phone Number: +48225462455; Email: mateusz.spalek@pib-nio.pl
• Study Contact Backup: Name: Aneta Borkowska, MD; Phone Number: +48225462455; Email: aneta.borkowska@pib-nio.pl

Study Locations

• Poland
  • Mazovian
    • Warsaw, Mazovian, Poland, 02-781
      • Recruiting
      • The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw
      • Contact: Mateusz J Spałek, MD PhD; Phone Number: +48225462455; Email: mateusz.spalek@pib-nio.pl
      • Sub-Investigator: Aneta Borkowska, MD
      • Principal Investigator: Mateusz J Spałek, MD PhD
      • Sub-Investigator: Piotr Ł Rutkowski, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to provide informed consent
• Eastern Cooperative Oncology Group performance status 0 - 2
• Age ≥18 years old
• Histologically-proven diagnosis of radiation-induced or recurrent soft tissue sarcoma
• Previous radiotherapy within the planned target volume

Exclusion Criteria:

• Histologic diagnosis of rhabdomyosarcoma (except spindle cell and pleomorphic subtype), osteogenic sarcoma, Ewing's sarcoma/PNET, aggressive fibromatosis
• Contraindications to radiotherapy or hyperthermia
• Predicted unacceptable high risk of reirradiation-related toxicity, in the Investigator's judgment
• Unresectable metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Radiotherapy with hyperthermia in resectable sarcomas; 12x 3 Gy (4 fractions per week) + hyperthermia (6x) + surgery	Other: Hyperthermia; Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.; Radiation: Hypofractionated radiotherapy; Resectable or marginally resectable tumors: preoperative hypofractionated 12x 3 Gy radiotherapy (4 days in a week, three weeks) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with daily image guidance with cone beam-CT or kV-portal position verification.
EXPERIMENTAL: Radiotherapy with hyperthermia in non-resectable sarcomas; 12x 3 Gy with simultaneous integrated boost 3.5 Gy (4 fractions per week) + hyperthermia (6x)	Other: Hyperthermia; Deep hyperthermia (Celsius TCS or BSD-2000) according to local protocol combined with radiotherapy, twice a week.; Radiation: Hypofractionated radiotherapy with boost; Non-resectable/inoperable tumors: definitive hypofractionated 12x 3 Gy radiotherapy prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with simultaneous integrated boost 3.5 Gy per fraction prescribed on boost planned target volume (tumor volume + setup/error margin), 4 days in a week, three weeks. Radiotherapy with daily image guidance with cone beam-CT or kV-portal position verification.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of late adverse events	Ratio of grade 3 or higher late adverse events related to reirradiation, according to CTCAE 5.0	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	18 months
Local control rate	18 months
Cancer-specific survival	18 months

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Investigators: Principal Investigator: Mateusz J Spałek, MD PhD, The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw

Publications and helpful links

General Publications

• de Jong MA, Oldenborg S, Bing Oei S, Griesdoorn V, Kolff MW, Koning CC, van Tienhoven G. Reirradiation and hyperthermia for radiation-associated sarcoma. Cancer. 2012 Jan 1;118(1):180-7. doi: 10.1002/cncr.26252. Epub 2011 Jun 28.
• Haas RL, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K, O'Sullivan B. Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies. Radiother Oncol. 2016 Apr;119(1):14-21. doi: 10.1016/j.radonc.2015.12.002. Epub 2015 Dec 21.
• Kosela-Paterczyk H, Szacht M, Morysinski T, Lugowska I, Dziewirski W, Falkowski S, Zdzienicki M, Pienkowski A, Szamotulska K, Switaj T, Rutkowski P. Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas. Eur J Surg Oncol. 2014 Dec;40(12):1641-7. doi: 10.1016/j.ejso.2014.05.016. Epub 2014 Sep 20.
• Lindner LH, Issels RD. Hyperthermia in soft tissue sarcoma. Curr Treat Options Oncol. 2011 Mar;12(1):12-20. doi: 10.1007/s11864-011-0144-6.
• Borghede G, Hedelin H. Radiotherapy of localised prostate cancer. Analysis of late treatment complications. A prospective study. Radiother Oncol. 1997 May;43(2):139-46. doi: 10.1016/s0167-8140(96)01871-3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 23, 2019
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 25, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Wounds and Injuries; Disease Attributes; Body Temperature Changes; Heat Stress Disorders; Radiation Injuries; Sarcoma; Recurrence; Hyperthermia; Neoplasms, Radiation-Induced
• Other Study ID Numbers: HOT1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No