High tech hypofractionation to optimise treatment: Patient selection and radiation-delivery set of problems

Hypofractionation has lately been implemented as standard treatment in the adjuvant setting as well as in radical radiotherapy for various solid tumors such as in breast and lung carcinomas. Also for metastatic disease in the liver or brain, hypofractionated stereotactic radiotherapy has proven effective for both palliative purposes and sometimes cure. Palliative schedules have conventionally been designed to deliver sufficient radiation dose within a short period of time to achieve optimal palliation with particular consideration to life expectancy. Such treatment strategies may be assigned to frail and elderly patients at the expense of curative fractionation schedules, particularly for logistic reasons in those with impaired functional conditions, that the patient may better comply to treatment. However, data from DAHANCA showed no impact of age, comorbidity, or WHO performance status on delay of treatment in patients undergoing a fast-track work-up for head and neck cancer (H&N), and elderly patients (above 70) demonstrated equivalent compliance to prescribed radical radiation treatment compared to younger patients which was further translated into similar cancer-specific survival figures between the age-groups. However, if for a particular clinical reason a reduced treatment time is opted for in an the elderly H&N patient, several considerations should be made. Whether the intention of treatment is palliative or curative, treatment volume and fractionation schedules are obviously related to toxicity. Elderly H&N patients with a low propensity for HPV-derived carcinomas have generally lower rates of neck metastases than younger patients (N0-1 below 20% vs 35%) which defines a smaller target area. With modern diagnostic procedures and cone-beam based adaptive IMRT techniques, both dose-planning and execution of radiation treatment have become more precise which elderly patients may profit from, particularly if elective radiation is omitted, similar to stereotactic strategies. Delivery of 30 Gy in 10 fraction over 2 weeks, or 20 Gy in 5 fx, confer a doseintensity much higher than conventional or accelerated regimens and, consequently, increases the risk of severe mucositis. We have adopted a hypofractionated schedule from the DAHANCA 2 trial consisting of 52 Gy in 13 fractions with two weekly fractions (8 Gy per week). This has secured a tolerable treatment schedule with a considerably high radiobiological dose for potential cure. Toxicity has been mild in comparison to standard fractionation, and the schedule has been employed for patients considered unsuitable for standard treatment. IMRT and VMAT are easily applied in hypofractionated regimens for elderly patients since these techniques have become standard of care, and acceptable toxicity and cure rates are expected.