Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Hypofractionated stereotactic radiotherapy to the resection cavity, dose prescription: 6-7 x 5 Gy

Single fraction stereotactic radiotherapy to the resection cavity, dose prescription: 1 x 12-20 Gy

Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiotherapy radiosurgery (SRS)

Maria Waltenberger

Stephanie E Combs, Prof. Dr.

Stephanie E. Combs, Prof. Dr.

This prospective, randomized, controlled, monocentric clinical phase III study focuses on stereotactic irradiation of resection cavities of brain metastases after surgical resection and seeks to demonstrate the superiority of fractionated irradiation schemes in terms of local control.

There is a growing scientific focus on single fraction stereotactic (SRS) and hypofractionated stereotactic irradiation (HFSRT) after surgical resection of brain metastasis and its use is more frequently recommended in international guidelines. Despite intensive research, the optimal fractionation scheme and dose prescription for adjuvant irradiation of the resection cavity remains unclear.

Based on our own institutional data \[Cit.1\] and a recently published metaanalysis \[Cit.2\], we hypothesize that local control (LC) after HFSRT is superior compared to SRS in terms of LC. To evaluate the hypothesis in a prospective, randomized, controlled setting we designed the SATURNUS study.

A total of 126 patients will be randomized 1:1 to either HFSRT (dose 6-7 x 5 Gy) or SRS (dose 1 x 12-20 Gy). If further unresected brain metastases are present, they will be treated with SRS (1 x 14 - 22 Gy). Irradiation is carried out with a Gamma Knife or a Linear Accelerator. In line with current clinical practice, the choice of positioning method for SRS with the Gamma Knife (mask or stereotactic frame) is left to the patient. In the case of SRS with the Linear Accelerator or HFSRT, fixation is done with a mask as technically not otherwise feasible. Follow-up-MRI will be at least carried out 6 weeks and 3, 6, 9 and 12 months after treatment. Primary endpoint of the study is local control (LC) at the irradiated resection cavity after 12 months. Locoregional control (LRC) and overall survival (OS) as well as salvage-treatments, irradiation-associated toxicities (especially rate of radionecrosis) and quality-of-life parameters are investigated as secondary endpoints.

To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different techniques of postoperative stereotactic radiotherapy after resection of brain metastases adequately powered to detect a superiority of HSFRT regarding LC.

The affiliation to the treatment arm will not be blinded to anyone except the study neuroradiologist.

Hypofractionated Versus Single Fraction Stereotactic Adjuvant Radiotherapy to the Resection Cavity of Brain Metastases

Hypofractionated Stereotactic Radiotherapy Versus Single Fraction Stereotactic Radiosurgery to the Resection Cavity of Brain Metastases After Surgical Resection - A Prospective, Randomized, Controlled, Monocentric Phase III Trial

Locoregional control=CNS progression free survival

Number and kind of intracranial salvage treatments

according to CTCAE v4.03, especially rate of radionecrosis

Quality of life according to EORTC QLQ-C30 and EORTC QLQ-B20

defined as decrease in Barthel index by \> 20 points

Technical University of Munich

Univ.-Prof. Dr. med. Stephanie E. Combs

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Hyaluronic Acid

Moderate hypofractionated radiotherapy of 62Gy in 20 fraction of 3.1Gy.

Moderate hypofractionated radiotherapy

Stereotactic radiotherapy of 37.5Gy in 5 fraction of 7.5Gy.

Stereotactic radiotherapy

The present randomized, open, multicentric Phase II trial, in parallel groups with two arms of treatment, compares the treatment A, moderate hypofractionated radiotherapy of 62Gy, to treatment B, stereotactic irradiation of 37.5 Gy with hyaluronic acid injection in the space between the prostate and the rectum to preserve the rectal-wall from high doses of irradiation. The study aims to assess the rates of late urinary toxicities of grade ≥ 2 induced by a moderate hypofractionated radiotherapy (62Gy in 20 fractions of 3.1Gy) and by a stereotactic radiotherapy (37.5Gy in 5 fractions of 7.5Gy), and the rectal toxicities after an injection of hyaluronic acid between the rectal wall and the prostate.

Ninety-six patients and 9 centers are included in the protocol.

Hypofractionated Radiotherapy Versus Stereotactic Irradiation With Hyaluronic Acid

Moderate Hypofractionated Radiotherapy (62 Gy in 20 Fractions of 3.1 Gy) Versus Stereotactic Radiotherapy (37.5 Gy in 5 Fractions of 7.5 Gy) With Hyaluronic Acid Injection Between the Prostate and the Rectum for Prostate Cancer of Low- to Intermediate Risk; RPAH2

Late urinary toxicities of grade ≥ 2 assessed using the Common Toxicity Criteria for Adverse Effects ( CTCAE) v 4.0 classification from 3 months to 3 years.

Survival rates without biological relapse (increase of the PSA (prostate-specific antigen) beyond nadir + 2 ng/ml, using Phoenix definition).

all toxicities will be listed using Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.

evaluation and comparison of the sexual preservation rates in both arms using International Index of Erectile Function (IIEF).

Late rectal toxicities in both arms, for the evaluation of the hyaluronic acid efficacy to preserve the rectal wall in both approaches, using Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0.

Hospices Civils de Lyon

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Antineoplastic Agents

Carboplatin

Cetuximab

Fluorouracil

Cisplatin

Chemotherapy is based on patient Performance Status (PS) and comorbidities:

* PS 0-1: standard treatment: 6 cycles, every 3 weeks cisplatin (100 mg/m² iv on D1), 5FU (4000 mg/m² total dose starting on Day 1 to Day 4 and during 96h in continuous infusion)
* PS 2/cardiac contra-indication to 5 Fluorouracil (5FU): 6 cycles, every 3-4 weeks cisplatin (100 mg/m² iv on Day 1) or carboplatin Area Under Curve (AUC) 4 or 5 on Day 1 In both case: Cetuximab (loading dose 400 mg/m² iv on Day1, then 250 mg/m² weekly or 500mg/m² every 2 weeks).

Cycle 1 of systemic treatment will be administered before the start of the stereotactic RT. Then, following cycles will be performed after the end of stereotactic irradiation.

Cetuximab maintenance: 250 mg/m² iv weekly. It will be given only if at least disease stabilization is observed at the end of chemotherapy, and will be continued until progression or unacceptable toxicity.

Splitting will be based on the tumor diameter, and proximity of organs at risk which constitutes any limiting toxicities. It will be 3 or 5 fractions based on the recommendations (CARO-Stereotactic Body Radiation Therapy (SBRT) 2012) and for the purpose of harmonization practices. The prescription dose is 3 x 10 = 30 Gy 3 x 11 = 33 Gy or 3 x 15 = 45 Gy (if 3 fractions) with the possibility of 3 x 20 Gy to the peripheral lung nodules with tracking in Cyberknife or 5 x 7 = 35 Gy or 5 Gy x 10 = 50 (if 5 fractions). Beyond 3 cm of tumor diameter and / or to a distance of less than 1 cm from the GTV in an organ critical risk (eg spinal cord), a splitting up into 5 sessions must be privileged.

* cisplatin
* 5FU
* carboplatin
* cetuximab

Chemotherapy

The aim of this study is to evaluate the rate of living patients at 1 year with a quality of life criteria (no decrease) and reduced toxicities. This criteria will be compared in both groups., A cost effectiveness study is scheduled also.

Patients with cancers of aerodigestive tract have metastases limited in their evolution and a pauci-metastatic disease. In these cases, systemic therapy is the standard attitude. However, patients often received chemotherapy in their history and response rates are relatively low. The median survival is between 7 and 11 months with secondary effects and degradation of quality of life. It is a palliative treatment. Data on systemic treatment in the context of a micro-metastatic disease are limited. In contrast, stereotactic irradiation in pauci-metastatic context leads to better local control rates and may sustainedly reduce the progression of metastatic disease.

Stereotactic radiotherapy is increasing use in clinical practice for limited metastatic stages (oligo metastatic with 1-3 synchronized metastases). Radiotherapy in this indication has major advantages and a similar efficacy compared with other ablative treatments.

Stereotactic Radiotherapy Combined With Chemotherapy or Not for Treatment of Oligometastases in HNSCC

Randomized Phase II Trial Comparing Chemotherapy Combined With Stereotactic Radiotherapy and Stereotactic Radiotherapy Alone, for Treatment of Oligometastases in Squamous Cell Cancers of the Upper Aerodigestive Tract

The Data Monitoring Committee will meet every year either by a physical meeting or by conference call. Data on the recruitment, toxicity and autonomy are submitted every year.

Overall Survival rate without definitive deterioration of quality of life (by QLQC30) measured at 1 year post treatment

Toxicity of grade \> or equal to 3, occurring within the first 6 months of treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypofractionated Versus Single Fraction Stereotactic Adjuvant Radiotherapy to the Resection Cavity of Brain Metastases	NCT05160818	Brain Metastase... Resection Cavit...	Hypofractionate...	18 Years -	Technical University of Munich
Hypofractionated Radiotherapy Versus Stereotactic Irradiation With Hyaluronic Acid	NCT02361515	Prostatic Adeno...	Moderate hypofr... Stereotactic ra...	18 Years - 80 Years	Hospices Civils de Lyon
Stereotactic Radiotherapy Combined With Chemotherapy or Not for Treatment of Oligometastases in HNSCC	NCT03070366	Head and Neck S...	Chemotherapy Stereotactic ra...	18 Years - 77 Years	Groupe Oncologie Radiotherapie Tete et Cou

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