Gabriella Macchia1, Savino Cilla2, Francesco Deodato1, Francesco Legge3, Aida Di Stefano3, Vito Chiantera3, Giovanni Scambia4, Vincenzo Valentini5, Alessio G Morganti6, Gabriella Ferrandina4. 1. 1 Radiotherapy Unit, Department of Oncology, "John Paul II" Foundation, Catholic University, Campobasso, Italy. 2. 2 Medical Physics Unit, "John Paul II" Foundation, Catholic University, Campobasso, Italy. 3. 3 Gynecologic Oncology Unit, Department of Oncology, "John Paul II" Foundation, Catholic University, Campobasso, Italy. 4. 4 Department of Obstetrics and Gynecology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. 5. 5 Department of Radiotherapy, "A. Gemelli" Hospital, Catholic University, Rome, Italy. 6. 6 Radiation Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, DIMES University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Abstract
OBJECTIVE: To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation. METHODS: A radiation dose of 40 Gy over 4 weeks, 2 Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2 Gy; PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), Level 2 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and Level 3 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3 months from treatment. RESULTS: 19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA-IIIB: 6] were enrolled. Median follow-up was 24 months (9-60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded. CONCLUSION: The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2 and 40 Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity. ADVANCES IN KNOWLEDGE: A Phase I radiotherapy dose-escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.
OBJECTIVE: To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation. METHODS: A radiation dose of 40 Gy over 4 weeks, 2 Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2 Gy; PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), Level 2 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and Level 3 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3 months from treatment. RESULTS: 19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA-IIIB: 6] were enrolled. Median follow-up was 24 months (9-60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded. CONCLUSION: The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2 and 40 Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity. ADVANCES IN KNOWLEDGE: A Phase I radiotherapy dose-escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.
Authors: Gabriella Ferrandina; Alfredo Ercoli; Anna Fagotti; Francesco Fanfani; Valerio Gallotta; Alessandro P Margariti; Maria Giovanna Salerno; Vito Chiantera; Francesco Legge; Gabriella Macchia; Alessio G Morganti; Vincenzo Valentini; Giovanni Scambia Journal: Ann Surg Oncol Date: 2014-01-10 Impact factor: 5.344
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