Clinical trial NCT05978024: Predicting Radiotherapy Response and Toxicities in Soft Tissue Sarcoma of the Extremities - Cohort B
Official title: Predicting Radiotherapy Response, Toxicities and Quality of Life Related Functional Outcome in Soft Tissue Sarcoma of the Extremities: a Prospective Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Soft Tissue Sarcoma of the Extremities
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
First posted: 2023-08-07
Enrollment: 150
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population to be enrolled in this observational study will have had been diagnosed with STSE and referred to receive a course of radiotherapy either in the primary, palliative, pre-operative or post-operative settings.

Brief summary: This is a multicentre prospective cohort study, primarily aimed at reporting the frequency and intensity of radiotherapy side-effects of patients with soft tissues sarcoma of the extremities (STSE).

Two sub-studies are proposed within this study:

* MRI radiation response assessment Aimed at establishing whether changes in median apparent diffusion coefficients (ADC) are predictive of pre-operative STSE response measured using histopathology.
* Biomarker development and Immune mediators associated with radiotherapy Aimed at establishing prognostic markers which may refine selection of cases for pre-operative, palliative or no radiotherapy.

Also, aimed at determining if radiotherapy stimulates the tumour microenvironment, resulting in measurable change in anti-tumour immunity and if certain subtypes could potentially benefit from the addition of immunotherapy with radiation.

Patients participation in the sub-studies is optional.

Detailed description: This is a multicentre prospective cohort study, primarily aimed at validating the dose-volume parameters identified in the analyses of the VorteX and IMRiS trials datasets.

• Delineation of healthy tissues

Pre-defined outlining guidelines of normal tissues as bones, muscle compartments, joints, lymph drainage basins and subcutaneous tissue from Predict A will be delineated in radiotherapy planning computed tomography (CT) images. All cases will be delineated by a single observer (Rita Simoes). Verification of all outlines will be carried out by Dr Aisha Miah (clinical supervisor).

• Dose-volume constraints validity testing

Patients will be treated as per local protocol treatment technique.

Radiotherapy, clinical and toxicities data will be collected, with no new intervention on the treatment. Patients enrolled will receive standard radiation prescription doses as described below:

* Pre-operative radiotherapy- 50 Gy in 25 fractions equivalent (pre-operative radiotherapy). Where appropriate hypo-fractionated schedules as per institutional guidelines can considered: eg. 25 Gy/ 5 daily fractions. In myxoid liposarcomas, 36 Gy in 18 fractions can be considered where suitable;
* Post-operative radiotherapy- 60 Gy in 30 fractions or 66 Gy in 33 fractions (positive resection margins); alternative hypo-fractionated schedules as per institutional guidelines can be considered;
* Palliative radiotherapy- 30-36 Gy in 10-12 daily fractions, 40-45 Gy in 15 fractions, 30-36 Gy in 5-6 once weekly fractions or 25 Gy in 5 daily fractions.

Toxicity will be assessed with the TESS and RTOG scoring instruments and Stern score for lymphoedema. Patients enrolled in the study will fill in a specific quality-of-life questionnaire to assess quality of life related functional outcomes following treatment for STSE. This questionnaire is based on validated questions for assessing quality-of-life. Patients will be followed up at 3, 6, 12, 18, and 24 months post-radiotherapy.

Eligibility criteria: Inclusion Criteria:

* Histopathological diagnosis of soft tissue sarcoma of the upper or lower limb or limb girdle;
* Patients receiving pre-operative (neo-adjuvant), post-operative (adjuvant) or palliative radiotherapy;
* Patients receiving radiotherapy planned as per local protocols (neoadjuvant chemotherapy will be allowed). Neoadjuvant chemotherapy patients may be approached as they commence chemotherapy;
* WHO performance status 0-2;
* Aged ≥16 years;
* Patients fit enough to undergo radiotherapy treatment and willing to attend follow up visits, during two years;
* Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment;
* Capable of giving written informed consent.

Exclusion Criteria:

* Previous radiotherapy to the same site;
* Pregnancy;
* Patients with concurrent or previous malignancy that could compromise assessment of primary and secondary endpoints of the trial.

Primary outcomes:
measure: The incidence of any RTOG grade ≥ 2 toxicities following treatment for STSE at 24 months
timeFrame: 24 Months
Secondary outcomes:
measure: The ability of the fitted model from dose-volume constraints from PredicT A (IMRiS and Vortex analysis) to correctly predict the incidence of grade 2+ among PredicT B patients.
timeFrame: 24 Months
measure: To report frequencies and proportions of radiotherapy-induced late toxicities
timeFrame: 24 Months
measure: To determine the time to developing early and late side-effects.
timeFrame: 24 Months
measure: To determine radiological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
timeFrame: 24 Months
measure: To determine histological response rates to radiotherapy and where applicable chemo-radiotherapy for STSE of different histological subtypes.
timeFrame: 24 Months
measure: To determine quality of life-related functional outcomes and explore correlations with dose-volume parameters for patients who have received pre, post-operative or palliative radiotherapy for STSE.
timeFrame: 24 Months
measure: To determine predictive and prognostic factors for local and distant recurrence and overall survival for patients receiving pre-operative and palliative RT.
timeFrame: 24 Months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: The Royal Marsden Hospital
name: Aisha Miah
role: PRINCIPAL_INVESTIGATOR
References: