Abstract

Erica Scirocco^1,2,3, Francesco Cellini^4,5, Alice Zamagni², Alice Zamagni³, Federica Medici^2,3, Chiara Bellarosa^6,3, Gabriella Macchia⁷, Francesco Deodato^5,7, Savino Cilla⁸, Vincenzo Picardi⁷, Lidia Strigari⁹, Milly Buwenge^2,3, Stefania Rizzo^3,10, Silvia Cammelli^2,3, Alessio Giuseppe Morganti^2,3

¹Radiation Oncology, IRCCS - Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ²Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ³Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy; ⁴Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Rome, Italy; ⁵Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy; ⁶Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bolog, Bologna, Italy; ⁷Radiation Oncology Unit, Gemelli Molise Hospital – Università Cattolica del Sacro Cuore, Campobasso, Italy; ⁸Medical Physics Unit, Gemelli Molise Hospital – Università Cattolica del Sacro Cuore, Campobasso, Italy; ⁹Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ¹⁰Clinica di Radiologia EOC, Istituto Imaging della Svizzera Italiana (IIMSI), Lugano, Switzerland

The efficacy of low-dose fractionated radiotherapy (dose/fraction < 1 Gy; LDFRT) and chemotherapy (CHT) combination has several preclinical evidences. However, only a few clinical trials were performed on this topic. Therefore, the aim of this review was to collect and analyze the clinical results of this combined modality treatment.

A systematic literature search was conducted on PubMed using the PRISMA methodology. Only studies based on the combination of LDFRT (< 1 Gy/fraction) and CHT were included. Endpoints of the analysis were tumor response, toxicity, and overall survival, with a particular focus on any differences between LDFRT-CHT and CHT alone. 

Twelve studies (307 patients) fulfilled the selection criteria and were included in this review. Two studies were retrospective, one was a prospective pilot study, six were phase II studies, two were phase I studies, and one was a phase I/II open label study. No randomized controlled trials were found. Seven out of eight studies comparing clinical response showed higher rates after LDFRT-CHT compared to CHT alone. Three out four studies comparing survival reported improved results after combined treatment. Three studies compared toxicity among the two treatments and all of them reported similar adverse events rates. In most cases toxicity was manageable with only three likely treatment-unrelated fatal events (1.0%) [Table 1].