Donato Pezzulla

Stereotactic Ablative Radiation Therapy for Oligometastatic Ovarian Cancer Lymph Node Disease: The MITO-RT3/RAD Phase II Trial

MITO-RT3/RAD (NCT04593381) is a prospective multicenter phase 2 trial designed to assess the effectiveness and safety of stereotactic body radiation therapy (SBRT) in patients who received diagnoses of oligometastatic ovarian cancer. In this report, we provide the results of the trial in the setting of lymph node disease. The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival, treatment-free interval, and toxicity rates. The sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a β error of 0.1. The study met its primary endpoint of a statistically significant improvement in CR. One hundred thirty-five patients with 249 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 194 lesions (77.9%), partial responses in 40 (16.1%), stable disease in 14 (5.6%), and progressive disease in 1 lesion (0.4%). The objective response rate was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs 63.1%, P < .001). The 12-month actuarial rates for PFS and for overall survival were 36.6% (CR, 38.3% vs not-CR, 18.8%; P, .022) and 97.2% (CR, 97.8% vs not-CR, 93.8%; P, .067), respectively. The 12-month actuarial rate for treatment-free interval was 52.7% (CR, 58.4% vs not-CR, 24.4%; P, .004). CR was substantially associated with higher PFS (P, .036) and treatment-free interval (P, .006) rates in the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly grade 1. This trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes, and a significant systemic therapy-free survival period for complete responders.

Treatment of Oligometastatic Parenchymal Lesions in Ovarian Cancer With Stereotactic Ablative Radiation Therapy: A Multicenter Prospective Phase 2 Trial (MITO RT3/RAD)

The results of stereotactic body radiation therapy (SBRT) for parenchymal lesions in the setting of oligometastatic ovarian cancer are reported in the context of the prospective multicenter phase 2 MITO-RT3/RAD trial (NCT04593381). The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival, overall survival, treatment-free interval, and toxicity rates. Sample size was based on a previous study reporting an average 40.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 40.0% to 55.0%, with an α error of 0.05 (one-side) and a β error of 0.1. The study met its primary endpoint of a statistically significant improvement of CR. A total of 88 patients with 127 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 71 lesions (55.9%), partial response in 37 (29.1%), stable disease in 14 (11.0%), and progressive disease in 5 lesions (4.0%). The objective response rate was 85.0%, with an overall clinical benefit rate of 96.0%. The overall 12-month LC was 81.6%, with CR lesions exhibiting a significantly higher rate than partial or not responding lesions (12-month LC: 96.3% vs 61.4%, P < .001). The 12-month actuarial rates for progression-free survival and for overall survival were 34.9% and 91.5%, respectively. The median actuarial treatment-free interval was 9 months (range, 2.5-15.4 months), whereas the 12-month actuarial rate was 44.1%. No grade 3 or higher toxicity was reported. In particular, 15 (20.5%) patients experienced mild acute toxicity (≤grade 2). There were 12 grade 1 events and 6 grade 2 events, the latter mostly represented by pain flare (N = 2). Late toxicity was reported in 4 patients (4.5%) accounting for 4 events, mostly grade 1, except for one case of moderate asthenia (grade 2). Parenchymal oligometastatic lesions showed a high rate of CR and encouraging long-term outcomes for patients achieving CR, including a substantial period of systemic therapy-free survival after radiation therapy. The observed toxicity was minimal, strengthening the safety of ablative SBRT as a noninvasive alternative to surgical resection for parenchymal metastases in high-risk areas.

Efficacy and Safety of Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer (MITO-RT2/RAD): A Large, Real-World Study in Collaboration With Italian Association of Radiation Oncology, Multicenter Italian Trials in Ovarian Cancer, and Mario Negri Gynecologic Oncology Group Groups

This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiation therapy in a large cohort of patients with oligometastatic/persistent/recurrent uterine cancer. Clinical and radiation therapy data from several radiation therapy centers treating patients by stereotactic body radiation therapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, and clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiation therapy, and the 2-year actuarial local control rate "per-lesion" basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. In the study, 157 patients with oligometastatic/persistent/recurrent uterine cancer bearing 272 lesions treated by stereotactic body radiation therapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in 5 fractions (range, 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), and 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤13.7 cc) and total dose (BED The efficacy of stereotactic body radiation therapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/β10, to the high risk clinical target volume, and 60 Gy EQD2α/β10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Efficacy and Safety of SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer

This is a prospective, multicenter, Phase II study aimed at defining the activity and safety of SBRT in MPR-OC. Clinical and imaging data as well as SBRT parameters would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome.