Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in the Postoperative Treatment of High-Risk to Intermediate-Risk Endometrial Cancer: Results of ADA II Phase 1-2 Trial.
A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes.



Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions).



Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age-Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade ≥3 GI or grade ≥2 GU toxicity. The 3-year late grade ≥2 GI and GU toxicity-free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0).



This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients.
Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy. Electronic address: gmacchia@rm.unicatt.it.
Gabriella
G
Macchia
Medical Physics Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Savino
S
Cilla
Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Francesco
F
Deodato
Medical Physics Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Anna
A
Ianiro
Gynecologic Oncology Unit, F. Miulli General Regional Hospital, Acquaviva delle Fonti, Bari, Italy.
Francesco
F
Legge
Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Martina
M
Marucci
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna, Italy.
Silvia
S
Cammelli
Gynecologic Oncology Unit, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna, Italy.
Anna Myriam
AM
Perrone
Gynecologic Oncology Unit, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna, Italy.
Pierandrea
P
De Iaco
Department of Radiotherapy, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
Maria Antonietta
MA
Gambacorta
Department of Radiotherapy, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
Rosa
R
Autorino
Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy; Department of Radiotherapy, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
Vincenzo
V
Valentini
Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, Azienda Ospedaliera Universitaria, Policlinico S. Orsola-Malpighi, Bologna, Italy.
Alessio G
AG
Morganti
Department of Medicine and health sciences, Università del Molise, Campobasso/Ginecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy.
Gabriella
G
Ferrandina
D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy / Q000401:mortality / Q000706:statistics & numerical data; D055356:Endometrial Ablation Techniques / Q000401:mortality / Q000706:statistics & numerical data; D016889:Endometrial Neoplasms / Q000401:mortality* / Q000532:radiotherapy* / Q000601:surgery; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000517:prevention & control; D011182:Postoperative Care; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000453:epidemiology* / Q000517:prevention & control; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000401:mortality / Q000706:statistics & numerical data; D050397:Radiotherapy, Intensity-Modulated / Q000401:mortality* / Q000706:statistics & numerical data; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome