Three clinical trials on breast cancer stereotactic radiotherapy: presentation and analysis of the results obtained throughout the months by Dr. Marco Trovò – Director of Radiation Oncology Department at University Hospital in Udine.
Breast cancer represents 25% – or more – of the cases treated in radiotherapy centres. For this reason, reducing the number of fractions and increasing the efficiency of radiation treatment for early-stage breast cancers, could have a significant impact: improve patient satisfaction, and reduce waiting times and operational costs.
In relation to the outcomes presented during the Xcision clinical education webcast on May 2nd, 2023, Dr. Marco Trovò, Director of Radiation Oncology Department at University Hospital in Udine, will be providing us with new data from the clinical trial that examined the application of GammaPod™, a stereotactic radiotherapy system specifically designed to treat breast cancer.
Keep reading to discover the results that could lead to the revolution in breast cancer treatment. The trials discussed by Dr. Trovò are the following: post-operative stereotactic radiotherapy in a single fraction, preoperative stereotactic radiotherapy in a single fraction, and single fraction as a boost.
Post-operative stereotactic radiotherapy in a single fraction
The study regarding post-operative breast irradiation wants to demonstrate the safety of a high-dose stereotactic radiotherapy (18Gy) in a single fraction, delivered by the GammaPod™ system in less than an hour session. The treatment includes stereotactic breast immobilization, CT scan, planning and delivery.
The Planning Target Volume (PTV) is obtained by increasing the Clinical Target Volume (CTV) margin by only 3 mm, thanks to the high localization accuracy offered by the GammaPod™.
The purpose is to obtain less than 7 patients to experience grade 2 toxicity (or more) out of the first 40 patients. If this goal is reached, the second phase will involve 148 patients.
The study population includes two groups, each defined by specific criteria. The first one, according to the GEC-ESTRO guidelines, includes women aged 50 years or older, diagnosed with an unifocal invasive ductal carcinoma of any grade (1-3) and in an early pathological stage (pT1 pT2 e pN0). The second group consists of women aged 70 years or more, who may be affected by lobular or multifocal carcinoma, or exhibit 1-3 positive lymph nodes (pN1a).
The treatment is made of two phases: a simulation of the procedure without the delivery of the dose (referred to as a “dry-run test”) followed by the actual radiation treatment.
The primary endpoint of this clinical trial is acute and late toxicity, mainly subcutaneous (fibrosis). The researchers aim to achieve similar levels of toxicity compared to a standard treatment, but with the advantage of the radiotherapy being delivered in a single fraction.
The treatments begun in January 2022 and the first phase ended in May 2023, involving a total of 77 treated patients. Most of them were affected by a pT1 and pN0 invasive ductal carcinoma, all falling under the category of luminal cancer.
Finally, regarding the treatment specifics, it is worth mentioning that the median target volume corresponded to 48 CC, with an average dose of 18.6 Gy and a median delivery time of 36 minutes.
As of September 2023, 99 patients have been treated.
Preoperative radiosurgery for early-stage breast cancer
Procediamo con il secondo protocollo dello studio, ovvero la radiochirurgia pre-operatoria per il cancro alla mammella in stadio iniziale.
Let’s move on to the second protocol: preoperative radiosurgery for early-stage breast cancer.
During this phase, the GammaPod™ system delivers a high dose of 30-36 Gy in a single fraction. The targeted area is identified by a fiducial marker positioned by ultrasound guidanced. The PTV is defined by adding a 3 mm margin to the target. Surgery is performed from 3 to 4 months after radiotherapy.
The major endpoint is to obtain a rate of acute and late toxicity lower than 14%. Just like the previous protocol, among the first 40 patients, in order to pass on to the next accrual of 148 patients, only less than 7 patients have to develop a grade 2 (or more) toxicity.
In this specific protocol, the selection is stricter: patients are required to be 50 years old or more and to be affected with a clinical stage tumor (cT1-cT2, cN0). Furthermore, the neoplasia must be ER-positive and HER2-negative (luminal tumors included). Finally, the tumor must be detectable on ultrasound in order for the fiducial marker to be placed.
4 months after radiotherapy, after carrying out a clinical evaluation and a restaging to assess the radiological response, surgery is performed. The primary endpoint corresponds to the one from the first protocol.
The trial went on from January 2022 to July 2023, with a total of 50 patients (40 of whom underwent surgery). The treatment has an average target volume of 5,5 cc, an average dose of 33 Gy and a median delivery administration time of 16 minutes.
The results of the study will be presented at the American Congress of Radiation Therapy Oncology (ASTRO) in San Diego this October 2023, and subsequently at the Italian Association for Radiotherapy and Clinical Oncology (AIRO).
Single fraction as a boost
Let’s continue with the third and last protocol: single fraction as boost. Only patients with stage pT1-2 and pN0-1a tumors, that do not require irradiation of supraclavicular lymph node stations and have a high risk of local recurrence were included.
The boost, delivered by the GammaPod™ in a single fraction (7,5 Gy), is followed by 15 fractions delivered through the conventional LINAC for a total dose of 40 Gy.
The main purpose is to reduce the toxicity effects caused by the treatment to below 25%. Moreover, the study aims to demonstrate that the GammaPod™ system does not cause additional side effects compared with the standard breast cancer treatment.
The criteria include: women aged less than 50 years old, with either a triple-negative molecular phenotype, a grade 3 tumor, or the presence of positive or close margins not amenable to further surgery. Between June 2022 and July 2023, 36 patients who met those characteristics were selected. The majority of these patients manifested only one risk factor.
After one year using the GammaPod™ stereotactic radiotherapy system to treat breast cancer in a single fraction, this approach has proven to be extremely reliable, with a clear minimal toxicity profile. Overall, the patients demonstrated high satisfaction towards the treatment, suggesting a promising contribution in breast cancer therapy.