Optimizing radiation dose and fractionation for the definitive treatment of locally advanced non-small cell lung cancer

Abstract

Radiation therapy is the foundation for treatment of locally advanced non-small cell lung cancer (NSCLC), a disease that is often inoperable and has limited long term survival. Local control of disease is strongly linked to patient survival and continues to be problematic despite continued attempts at changing the dose and fractionation of radiation delivered. Technological advancements such as 4-dimensional computed tomography (CT) based planning, positron emission tomography (PET) based target delineation, and daily image guidance have allowed for ever more accurate and conformal treatments. A limit to dose escalation with conventional fractions of 2 Gy once per day appears to have been reached at 60 Gy in the randomized trial Radiation Therapy Oncology Group (RTOG) 0617. Higher doses were surprisingly associated with worse overall survival. Approaches other than conventional dose escalation have been explored to better control disease including accelerating treatment to limit tumor repopulation both with hyperfractionation and its multiple small (<2 Gy) fractions each day and with hypofractionation and its single larger (>2 Gy) fraction each day. These accelerated regimens are increasingly being used with concurrent chemotherapy, and multiple institutions have reported it as tolerable. Tailoring treatment to individual patient disease and normal anatomic characteristics has been explored with isotoxic dose escalation up to the tolerance of organs at risk, with both hyperfractionation and hypofractionation. Metabolic imaging during and after treatment is increasingly being used to boost doses to residual disease. Boost doses have included moderate hypofractionation of 2-4 Gy, and more recently extreme hypofractionation with stereotactic body radiation therapy (SBRT). In spite of all these changes in dose and fractionation, lung and cardiovascular toxicity remain obstacles that limit disease control and patient survival.

How to integrate stereotactic body radiation therapy and hypofractionation in the management of stage III lung cancer in the age of immunotherapy

“…In this study, the median dose administered over the tumor was 83 Gy x 30 fractions and most patients received CT concurrently. Local control at two years was 82% and OS 25 months 30 .…”

Alternative Multidisciplinary Management Options for Locally Advanced Non-Small Cell Lung Cancer During the COVID-19 Global Pandemic

“…Multiple studies have demonstrated such an approach to be safe and effective. [38][39][40] Shorter courses have been associated with decreased immunosuppression in other cancers such as leukemia and pancreatic cancer. [41][42][43] This may offer advantages for LA-NSCLC, although minimizing the number of visits may provide the most risk reduction.…”

Radiation dose escalation with modified fractionation schedules for locally advanced NSCLC: A systematic review

“…Nevertheless, a further improvement of survival by both better local and systemic control remains challenging . Better LC and OS by cCRT go hand in hand with potentially higher toxicity, which is one of the reasons why not all patients may be regarded as fit enough for the concurrent approach by the treating physician . The second reason are comorbid conditions, which allow for the inclusion of only 30% of the patient population with stage III NSCLC in concomitant treatment regimens .…”

“…The second reason are comorbid conditions, which allow for the inclusion of only 30% of the patient population with stage III NSCLC in concomitant treatment regimens . While guidelines generally propose concurrent treatment some of them, such as The National Institute for Health and Care Excellence (NICE), recommend alternative fractionation schedules (eg, CHART) for patients who are not eligible for the concurrent approach …”

“…In 2015 the RTOG 0617 trial, which applied conventional dose escalation, was negative for the experimental arm in terms of LC and OS . The increase of the number of fractions entails prolonged OTT, which leads to accelerated repopulation and may therefore not yield the best possible results . A meta‐analysis by Mauguen et al .…”