Split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck cancer patients—final results of a randomized clinical trial

Abstract

Objective: Evaluation of the efficacy and toxicity of splitcourse accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck (H&N) cancer patients. Methods: We enrolled 101 patients (39 in CHA-CHA and 37 in conventional (Conv.) arm completed the treatment). The CHA-CHA arm patients were irradiated twice a day, 7 days a week, using a fraction dose (fd) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm. Patients in the control (Conv.) arm group were irradiated with a fd of 2 Gy, five times a week to a total dose of 72-74 Gy in the overall treatment time of 50-53 days. Quality of life (QOL) and acute mucosal reaction were evaluated during radiotherapy (RT). After RT, we followed the effect of treatment, QOL, performance status and adverse effects of radiation. For statistical analysis mainly a hierarchical multilevel modelling was used.Results: QOL was most deteriorated in the CHA-CHA arm; the CHA-CHA scheme also caused a relatively stronger acute injury. There were no significant differences in late adverse effects. In the CHA-CHA arm in 35% and in Conv. arm in 30% of patients, disease was controlled during follow-up. Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm. However, the overall survival rate analysis did not show significant difference between both arms. Conclusion: Despite differences in treatment results, we cannot conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients. Advances in knowledge: Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients.There are, and have been, many attempts to create a clear and effective treatment modality for advanced inoperable head and neck (H&N) cancers. The most common are different combinations of chemoradiotherapy, or different schedules of altered and usually intensive radiation treatment. It is clear that intense dose delivery combined with a high total dose (TD) and short treatment time gives a higher probability of tumour destruction; unfortunately, it is also connected with a higher, usually unacceptable, risk of normal tissue damage. One of the causes of radiation toxicity in such cases is the inability of sufficient repair of healthy tissue damage.The reason for this is the intensity of dose delivery and the lack of time for repopulation of normal cells and proper repair. On the other hand, the accelerated repopulation of squamous cancer cells starts 4 weeks after radiotherapy (RT); therefore, radiation treatment should be completed in that time. Considering the aforementioned facts, we tried to construct a very intense and short RT schedule allowing for normal tissue (mainly mucosa) repair. We went back to the old concept of split-course RT and combined it with accelerated, continuous, intense hyperfractionation.Finally, we proposed twice-a-day irradiation, usi...

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer

“…There are several examples in other cancer types, associated with reduced toxicity while maintaining efficacy ( Pradier et al , 2004 ; Metcalfe et al , 2010 ; Fukuda et al , 2012 ; Gogna et al , 2012 ). The high metabolic response rates of the primary rectal cancer reported here support that this strategy warrants further study, but it should also be noted that split-course radiation was reported to have a negative impact in head and neck ( Daoud et al , 2007 ; Miszczyk et al , 2014 ), gynaecological ( Pedersen et al , 1994 ), and anal cancers ( John et al , 1996 ).…”

Accelerated Hyperfractionated Radiotherapy versus Conventional Fractionation Radiotherapy for Head and Neck Cancer: A Meta-Analysis of Randomized Controlled Trials

“…After screening the title and abstract and reading full texts, 55 of the 67 articles were subsequently excluded from the meta-analysis: 44 studies were related to other comparisons, 5 studies lacked usable data, 2 studies did not report relevant outcome, and 4 studies were not RCT. Finally, a total of 12 articles were included [7, 9–12, 15–21]. The PRISMA research flowchart is shown in Figure 1.…”

Adaptive Split Course Radiotherapy for Skin Cancers Decreases Toxicity and Improves Compliance

“…Split Course Radiation Therapy (SCRT) refers to a regime of RT that is broken into at least two phases, with each phase being separated by a rest interval, usually four weeks, to allow for the healing of acute toxicities such as mucositis and desquamation. This method has been used in the treatment of head, neck [8] and anal cancers [9] but abandoned due to decreased local control thought to be due to accelerated repopulation [10]. However, SCRT could be coming back into vogue in scenarios similar to ours [11].…”