Investigating the Local Effectiveness of Carbon Ion Radiotherapy for Unresectable Female Genital Tract Melanomas: A Preliminary Real-World Study
by
, , , , , , ,
Amelia Barcellini
1,2,*
,
Giulia Fontana
3,
Alessandro Vai
4,
Giovanni Damiano Aletti
5,6,
Alexandra Charalampopoulou
7,8,
Silvia Chiellino
9,
Antonino Ditto
10,11,
Fabio Landoni
12,13,
Laura Deborah Locati
1,14
,
Giorgia Mangili
15
,
Fabio Martinelli
16,17
,
Federica Piccolo
18,
Jessica Franzetti
2,
Sara Imparato
19,
Francesco Raspagliesi
10 and
Ester Orlandi
2,20 1
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
2
Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
3
Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
4
Medical Physics Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
5
Department of Gynecologic Surgery, IRCCS European Institute of Oncology, 20141 Milan, Italy
6
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
7
Hadron Academy PhD Course, University School for Advanced Studies (IUSS), 27100 Pavia, Italy
8
Radiobiology Unit, Development and Research Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
9
Department of Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
10
Department of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
11
Department of Gynecologic Oncology, Centro di Riferimento Oncologico, National Cancer Institute, 33081 Aviano, Italy
12
Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy
13
Division of Gynecologic Surgery, IRCCS Fondazione San Gerardo dei Tintori, 20900 Monza, Italy
14
Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
15
Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
16
Department of Gynecologic Oncology, Humanitas San Pio X, 20159 Milan, Italy
17
Department of Biomedical Science, Humanitas University, 20072 Milan, Italy
18
Radiotherapy Unit, Ospedale di Circolo Fondazione Macchi, 21100 Varese, Italy
19
Radiology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
20
Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(24), 4147; https://doi.org/10.3390/cancers16244147
Submission received: 4 October 2024
/
Revised: 30 October 2024
/
Accepted: 24 November 2024
/
Published: 12 December 2024
(This article belongs to the Special Issue Vaginal Cancer: From Pathology to Treatment)
Simple Summary
Gynecological mucosal melanomas are rare, aggressive, and radioresistant neoplasms for which no standardized treatment protocols currently exist. When surgery, which appears to be the gold standard, is not feasible, radiation therapy can be considered. However, mucosal melanomas exhibit specific biological hallmarks of radioresistance, and, indeed, the outcomes reported in the literature on the use of photons in this context are not encouraging. Currently, there are limited data on the use of carbon ion radiotherapy (CIRT) in this setting. The aim of this study is to evaluate, in a real-world cohort, the efficacy and tolerance of CIRT for gynecological melanomas, with the goal of expanding knowledge on the use of this radiotherapy technique in such a radioresistant and difficult-to-treat malignancy.
Abstract
Background/Objectives: Primary gynecological melanomas are rare malignancies with lower survival rates compared to cutaneous melanomas. Both preclinical and clinical data support the evidence that mucosal melanomas are photon-radioresistant but responsive to carbon ion radiotherapy (CIRT). The aim of this study is to assess, in a real-world cohort, the effectiveness and tolerability of radical CIRT in patients with inoperable gynecological mucosal melanoma. Methods: This is a real-world study aimed to assess the effectiveness and the safety of CIRT in this setting. We defined as the primary endpoints the objective response rate (ORR) and the clinical benefit (CB). The secondary endpoints included the actuarial local control rate (LC) assessed after 1 year and 2 years and the toxicity scored according to CTCAE v.5. Actuarial outcomes were analyzed using the Kaplan–Meier method, while potential predictors were investigated through the Log-rank test. Results: Between 2017 and 2023, eleven Caucasian patients underwent pelvic CIRT (total dose 68.8 GyRBE) for mucosal malignant melanoma of the vulva or the vagina. With a median follow-up of 18 months, we observed an ORR of 82% and a CB of 100%. LC at 1 and 2 years was 100% and 86%, respectively, and among the factors analyzed for their potential impact on LC, age < 60 years seems to be a potential predictor (p = 0.014). The treatment was well tolerated, with only one case of acute grade 3 erythema and, in the late phase, one case of grade 3 erythema and grade 3 urethral toxicity. Conclusions: CIRT was effective and safe for gynecological melanomas. Larger collaborative cohort studies and longer follow-ups are needed to take a step forward in comprehending the correct management of this disease.
