Francesco Deodato1, Gabriella Macchia1, Savino Cilla2, Anna Ianiro2, Giuseppina Sallustio3, Silvia Cammelli4, Milly Buwenge4, Gian Carlo Mattiucci5, Vincenzo Valentini5, Alessio G Morganti4. 1. 1 Radiotherapy Unit, "Giovanni Paolo II" Foundation, Catholic University of Sacred Heart , Campobasso , Italy. 2. 2 Medical Physics Unit, "Giovanni Paolo II" Foundation, Catholic University of Sacred Heart , Campobasso , Italy. 3. 3 Radiology Unit, "Giovanni Paolo II" Foundation, Catholic University of Sacred Heart , Campobasso , Italy. 4. 4 Department of Experimental, Diagnostic and Specialty Medicine -DIMES, Radiation Oncology Unit, University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy. 5. 5 Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Gemelli ART (Advanced Radiation Therapy) - Interventional Oncology Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore , Rome , Italy.
Abstract
OBJECTIVE: : A multiarm Phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or volumetric modulated arc therapy technique in seven predefined clinical settings. METHODS: : The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field reirradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the retreatment (<4 vs >4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged from 4 to 10 Gy in 5 days. RESULTS: : A total of 281 patients (M/F: 167/114; median age: 69 years) with 376 lesions underwent SBRT. No acute toxicity was reported in 175 patients (62.3%) while 106 (37.7%) experienced only low-grade (G < 2) acute toxicity. Four patients (all previously irradiated in the same site) showed >Grade 2 toxicity within 6 months from SBRT. With a median follow-up of 19 months, 204 patients (72.6%) did not experience late toxicity, and 77 (27.4%) experienced low grade late toxicity. On per-lesion basis, the 12-and 24 months actuarial local control inside the SBRT field were 84.3 and 73.7 %, respectively. CONCLUSIONS: : SBRT delivered in five consecutive fractions up to the doses evaluated is well tolerated. The MTD was reached in four (a, b, c and f) of the seven study arms. Recruitment for (d), (e) and (g) arms is still ongoing. ADVANCES IN KNOWLEDGE:: In a prospective dose-escalation trial, the MTD of 50 Gy/10 Gy fraction and 35 Gy/7 Gy fraction were defined for primary and metastatic lesions and as boost after prior RT dose ≤50 Gy, respectively.
OBJECTIVE: : A multiarm Phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or volumetric modulated arc therapy technique in seven predefined clinical settings. METHODS: : The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field reirradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the retreatment (<4 vs >4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged from 4 to 10 Gy in 5 days. RESULTS: : A total of 281 patients (M/F: 167/114; median age: 69 years) with 376 lesions underwent SBRT. No acute toxicity was reported in 175 patients (62.3%) while 106 (37.7%) experienced only low-grade (G < 2) acute toxicity. Four patients (all previously irradiated in the same site) showed >Grade 2 toxicity within 6 months from SBRT. With a median follow-up of 19 months, 204 patients (72.6%) did not experience late toxicity, and 77 (27.4%) experienced low grade late toxicity. On per-lesion basis, the 12-and 24 months actuarial local control inside the SBRT field were 84.3 and 73.7 %, respectively. CONCLUSIONS: : SBRT delivered in five consecutive fractions up to the doses evaluated is well tolerated. The MTD was reached in four (a, b, c and f) of the seven study arms. Recruitment for (d), (e) and (g) arms is still ongoing. ADVANCES IN KNOWLEDGE:: In a prospective dose-escalation trial, the MTD of 50 Gy/10 Gy fraction and 35 Gy/7 Gy fraction were defined for primary and metastatic lesions and as boost after prior RT dose ≤50 Gy, respectively.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
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Authors: Gabriella Macchia; Roberta Lazzari; Nicoletta Colombo; Concetta Laliscia; Giovanni Capelli; Giuseppe Roberto D'Agostino; Francesco Deodato; Ernesto Maranzano; Edy Ippolito; Sara Ronchi; Fabiola Paiar; Marta Scorsetti; Savino Cilla; Rossana Ingargiola; Alessandra Huscher; Anna Maria Cerrotta; Andrei Fodor; Lisa Vicenzi; Donatella Russo; Simona Borghesi; Elisabetta Perrucci; Sandro Pignata; Cynthia Aristei; Alessio Giuseppe Morganti; Giovanni Scambia; Vincenzo Valentini; Barbara Alicja Jereczek-Fossa; Gabriella Ferrandina Journal: Oncologist Date: 2019-10-10