Abstract
Background: Squamous-cell carcinoma of the head and neck is predominantly a locoregional disease, and the primary treatment methods are surgery and radiotherapy. A cause of treatment resistance could be radiation induced accelerated proliferation of clonogenic tumour cells. Reduced overall treatment time is expected to counteract the accelerated growth and thereby improve loco-regional control. Such shorter overall treatment time without a dose reduction can be achieved either by applying a higher dose per fraction or by applying more fractions per week. The aim of the study was to compare acute toxicities between the patients treated with 5 day vs 6 day a week radiotherapy.
Material and Methods: This was a prospective randomized controlled study performed at Regional Cancer Centre (RCC) Bikaner, Rajasthan, in which total 50 cases of LAHNC with no prior treatment were included. These cases were randomly divided into two arms: in Arm A patients received 2Gy/fraction(#) for 5 days in a week for a total of 33#, while cases in Arm B patients received 2Gy/# for 6 days in a week for 33#. Patients were assessed during treatment, at the end of treatment, 3 and 6 months after completion of treatment for acute toxicities according to the RTOG guidelines.
Results: Median overall treatment time in Arm A was 46 days and for Arm B was 39 days. Grade I and II skin reactions were seen in 19 cases of Arm A and 14 cases of Arm B (p value = .998). Grade III skin reactions were significantly high in Arm B patients (11 patients in Arm B vs 6 in Arm A, p value = .034) at treatment completion. Though skin reactions were disappeared at 3 months follow up, patients in Arm B required more time to heal then Arm A. In both arms patients had most commonly grade I, II mucositis (21 patients in Arm A and 16 in Arm B, p value = 0.902). Grade III mucositis was present in 4 patients of Arm A and 9 patients of Arm B (p value = .031) at treatment completion. All patients recovered at 3 months follow up. No grade IV toxicity seen in any of the arm. Local tumor control was significantly higher in Arm B compared to Arm B (p value = 0.03)
Conclusion: This study concluded that reduction in overall treatment time resulted in improved local tumor control at the cost of increased acute toxicities.
References
- Siddiqui MS, Chandra R, et al. Epidemiology and Histopathological Spectrum of Head and Neck Cancers in Bihar, a State of Eastern India. Asian Pacific Journal of Cancer Prevention, Vol 13, 2012 3949-53
- GLOBOCAN 2012 (IARC) Section of Cancer Surveillance. [Last accessed on 2016 Jun 23]. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx .
- Majumder D, Choudhury K, Das P, Kundu S, Mitra D. Different fractionation schedules of radiotherapy in locally advanced head and neck malignancy: A prospective randomized study to compare the results of treatment and toxicities of different protocols. South Asian J Cancer 2013;2:31-5
- Vigneswaran N, Williams MD, et al. Epidemiological Trends in Head and Neck Cancer and Aids in Diagnosis. Oral Maxillofac Surg Clin North Am. 2014 May; 26(2): 123–141.
- Fan S, Tang QL, Lin YJ, et al. A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma. Int J Oral Sci 3: 180–191, 2011
- Cummings B, Keane T, Pintilie M, Warde P, Waldron J, Payne D, et al. Five-year results of a randomized trial comparing hyperfractionated to conventional radiotherapy over four weeks in locally advanced head and neck cancer. Radiother Oncol. 2007;85:7–16.
- Koulis TA, Dang A, et al. Factors affecting radiotherapy prescribing patterns in the post-mastectomy setting. Curr Oncol. 2018 Apr; 25(2): e146–e151.
- Orton CG, Hendee WR, et al. Controversies in Medical Physics: a Compendium of Point/Counterpoint Debates. American Association of Physicists in Medicine One Physics Ellipse. 2008 Feb;
- Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 1988; 27: 131–46.
- Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 2008; 8: 545–54.
- Hansen O, Overgaard J, Sand Hansen H, et al. The importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma. Dependency on tumour diff erentiation. Radiother Oncol 1997; 43: 47–51.
- Overgaard J, Vendelbo Johansen L, Hjelm-Hansen M, An dersen AP. Comparison of conventional and split-course radiotherapy as primary treatment in carcinoma of the larynx. Acta Oncol 1988; 27: 147–52.
- Overgaard J, Hansen HS, Specht L, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 2003; 362: 933–40.
- Fu KK, Pajak TF, Trotti A, et al. Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000; 48: 7–16.
- Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006; 368: 843–54.
- Peters LJ, Ang KK, Thames HD. Accelerated fractionation in the radiation treatment of head and neck cancer. A critical comparison of diff erent strategies. Acta Oncol 1988; 27: 185–94.
- Bernier J, Bentzen SM. Altered fractionation and combined radio-chemotherapy approaches: pioneering new opportunities in head and neck oncology. Eur J Cancer 2003; 39: 560–71.
- Overgaard J, Sand Hansen H, Jørgensen K, et al. Primary radiotherapy of larynx and pharynx carcinoma: an analysis of facors influencing local control and survival. Int J Radiat Oncol Phys Biol 1986; 12: 515–21.
- Overgaard J, Horsman MR. Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol 1996; 6: 10–21.
- Peters LJ, Ang KK. The role of altered fractionation in head and neck cancers. Semin Radiat Oncol 1992; 2: 180–94.
- Withers HR, Taylor JM, et al. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27(2):131-46.
- Hansen O, Overgaard J, Hansen HS, Overgaard M, Hoyer M, Jorgensen KE, et al. Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 1997;43:47–51.
- Nguyen LN, Ang KK. Radiotherapy for cancer of the head and neck: altered fractionation regimens. Lancet Oncol 2002; 3: 693–701.
- Bernier J, Bentzen SM. Altered fractionation and combined radiochemo-therapy approaches: pioneering new opportunities in head and neck oncology. Eur J Cancer 2003; 39: 560–71.
- Overgaard J, Hansen HS, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet. 2003 Sep 20;362(9388):933-40.
Corresponding Author
H. S. Kumar
Senior Professor and Head, Department of Radiation Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, S.P. Medical Collage, Bikaner, India
DOI: https://dx.doi.org/10.18535/jmscr/v6i12.128
