Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic.

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.

Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer.

Acute mucositis is dose-limiting in many accelerated radiotherapy schedules for head and neck cancer. Cytokines may be one means of reducing the severity of mucositis. A study was designed to assess the effect of subcutaneous molgramostin (granulocyte-macrophage colony stimulating factor; GM-CSF) injections on acute radiation morbidity in patients undergoing accelerated radiotherapy for laryngeal cancer. A prospective, randomized, observer-blind, controlled trial was conducted in 29 patients who were to receive radical radiotherapy over 3 weeks for early stage laryngeal cancer. Patients were randomized to receive 150 microg (approximately 2 microg kg(-1)) GM-CSF subcutaneously once daily for 14 days after the second week of radiotherapy, or no GM-CSF. Patients were assessed weekly for grade of mucositis, skin reactions and related parameters. The severity of mucositis was reduced in the GM-CSF arm (p<0.05). No other end-points reached statistical significance. Two patients failed to complete their courses of GM-CSF. Three developed influenza type symptoms and in one an allergic reaction was noted. There was no difference in tumour control rates. Subcutaneous GM-CSF reduced the severity of mucositis in patients undergoing accelerated radiotherapy. Injections were well tolerated. Further studies of cytokines are warranted, to assess the feasibility of increasing the total doses of accelerated radiotherapy given, with the aim of improving tumour cure rates.

Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls.

PURPOSE: To assess the survival benefit of palliative hypofractionated radiotherapy in patients with poor prognosis high grade glioma by a matched comparison to conventionally treated controls. METHOD: Ninety-two elderly and/or disabled patients with high grade glioma with poor prognostic features received palliative partial brain radiotherapy to a dose of 30Gy in six fractions over 2 weeks. Patients were matched for WHO histological grade, performance status and age from a cohort of patients treated with conventionally fractionated radiotherapy to a dose of 60Gy in 30 fractions in an Medical Research Council (MRC) BR05 trial. RESULTS: Patients treated with hypofractionated radiotherapy had a median survival of 5 months with a 1-year survival rate of 12% from diagnosis. The median survival of case-matched controls was estimated to be 2.5-4.5 months longer. Following hypofractionated radiotherapy, Barthel score was improved or remained stable in 68% of patients. CONCLUSION: Hypofractionated partial brain radiotherapy is a well-tolerated regimen with palliative benefit. Comparison with matched controls suggests lesser survival benefit than would be obtained with radical radiotherapy. However, this is compensated by lower intensity and duration of irradiation induced side effects. It is postulated that there may not be a significant difference in good quality survival or 'quality adjusted survival' between the two regimens and this requires testing in prospective trials.