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D. De Ruysscher



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    MS18 - Optimizing Control of Local and Medastatic NSCLC with Radiotherapy (ID 35)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MS18.3 - Re-Irradiation Following Radical Radiotherapy (ID 543)

      14:45 - 15:05  |  Author(s): D. De Ruysscher

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      Abstract
      As the prognosis of cancer patients gets better, more individuals are at risk to develop a local recurrence or a new primary tumour in previously irradiated organs. New radiation techniques, better imaging and more knowledge of dose volume relationships have fuelled re-irradiation to high doses. The aim of high-dose re-irradiation is to give the patient a chance for long-term disease-free survival and even cure. Re-irradiation is only expected to be beneficial when a high-dose can be delivered. In order to do this safely, knowledge about the dose-response relation for the organs at risk (OAR) is needed. Here, the first problem starts. Even in patients that have never been irradiated, in-depth individual knowledge about dose-response relations for all AORs is lacking. As is clear from e.g. the QUANTEC reviews, even for widely used parameters such as the mean lung dose (MLD) or the V20, the accuracy of the model to predict subsequent development of radiation pneumonitis is very moderate, with AUC values under the ROC curve of 0.60-0.65. For other organs like the heart, current models score even worse. Functional, imaging and genetic parameters are an area of intensive research, but not usable in standard practice yet. In case of re-irradiation, only limited data coming from retrospective studies with small numbers at risk for late complications are available. Keeping all caveats in mind, it seems that the aorta can tolerate cumulative physical doses of up to 120 Gy (given in 2 Gy fractions), above which dose level lethal bleeding may occur (Evans et al. Radiother Oncol 2013). In other retrospective series, grade 4-5 stenosis, fistula and bleeding occurred only when re-irradiation included central structures (Peulen et al. Radiother Oncol 2011). Even when stereotactic body radiotherapy (SBRT) is used for re-irradiation, the risk for radiation pneumonitis seems to be more than 20 % with cumulative V20 values over 30 % (Liu et al. Int J Radiat Oncol Biol Phys 2012). This points to the importance to obtain composite plans, which should include non-rigid deformation. Whether alpha/beta values that are used for primary irradiation are safe in the re-irradiation setting is not investigated thoroughly, as is the repair of OARs over time, the influence of co-morbidities, medication and anti-cancer drugs. Nevertheless, one prospective ( Wu et al. Int J Radiat Oncol Biol Phys 2003) and several retrospective studies (Okamoto et al. Int J Radiat Oncol Biol Phys 2002; Kruser et al. Am J Clin Oncol 2013; Tada et al. Int J Clin Oncol 2005; Ebara et al. Anticancer Res 2007; Peulen et al. Radiother Oncol 2011; Meijneke et al. Radiother Oncol 2013) have been published. In most series, the median radiation dose of the first treatment was about 60 Gy and that of the second 40-50 Gy in 4-5 fractions in case of re-treatment with SBRT or 60 Gy in 2 Gy daily fractions. The median interval between the first treatment and the second was in most studies between 12 and 24 months. All series indicate that re-irradiation is “feasible”, with after a median follow-up of about one year approximately 25 % of the patients having grade 3 or more toxicities. It comes as no surprise that the median overall survival after re-irradiation is low, ranging from 6-15 months. Because apart from one prospective trial with 23 patients only small, retrospective studies have been presented, it is not clear what the prognostic factors for survival are. Thorough staging, a good performance status, a small GTV and the possibility to give a high dose of radiotherapy seem obvious. In view of all uncertainties and the observation a significant proportion of patients with important toxicity, the time is right to launch prospective studies, randomised or not. These studies should focus on prognostic factors both for survival and toxicity, in order to ultimately be able to identify a subgroup of patients with truly curable disease or in which systemic treatment can be delayed significantly without undue toxicity. In the meantime, an individual patient should clearly understand the limitations and doubts of re-irradiation with regard to survival and toxicity. In case of a limited recurrence in an otherwise good performance patient, SBRT is reasonable if central structures can be avoided and 2 Gy per day, 5 days per week in other cases. A biological dose of at least 60 Gy should be given, taking into account the OARs. Probably the most suited patients are those with a long delay, possibly of more than one year, between the first irradiation and the recurrence.

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