High-Dose Thoracic Re-irradiation of Lung Cancer Using Highly Conformal Radiotherapy Is Effective with Acceptable Toxicity / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Thoracic re-irradiation (re-RT) of lung cancer has been challenged by the tolerance doses of normal tissues. We retrospectively analyzed local control, overall survival (OS) and toxicity after thoracic re-RT using highly conformal radiotherapy, such as intensity modulated radiotherapy and stereotactic body radiotherapy. MATERIALS AND METHODS: Thirty-one patients who received high-dose thoracic re-RT were analyzed. Doses were recalculated to determine biologically equivalent doses. The median interval to re-RT was 15.1 months (range, 4.4 to 56.3 months), the median initial dose was 79.2 Gy₁₀ (range, 51.75 to 150 Gy₁₀), and the median re-RT dose was 68.8 Gy₁₀ (range, 43.2 to 132 Gy₁₀). RESULTS: Eighteen (58.1%) and eleven (35.5%) patients showed loco-regional recurrence and distant metastasis, respectively, after 17.4 months of median follow-up. The 1-year and 2-year local control rates were 60.2% and 43.7%, respectively. The median loco-regional recurrence-free-survival (LRFS) was 15.4 months, and the median OS was 20.4 months. The cumulative and re-RT biologically equivalent dose for α/β=10 (BED₁₀) doses were the most significant prognostic factors. Cumulative BED₁₀ ≥145 Gy₁₀ and re-RT BED₁₀≥68.7 Gy₁₀ were significantly associated with longer OS (p=0.029 and p=0.012, respectively) and LRFS (p=0.003 and p=0.000, respectively). The most frequent acute toxicity was grade 1-2 pulmonary toxicity (41.9%). No acute grade 3 or higher toxicities occurred. CONCLUSION: Our results show that high-dose thoracic re-RT of lung cancer can be safely delivered using highly conformal radiotherapy with favorable survival and acceptable toxicity. An optimal strategy to select patients who would benefit from re-RT is crucial in extending the indications and improving the efficacy with a sufficiently high dose.

Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation

Despite recent innovation in treatment techniques and subsequently improved outcomes, the majority of glioblastoma (GBL) have relapses, especially in locoregional areas. Local re-irradiation (re-RT) has been established as a feasible option for recurrent GBL of all ages with safety, tolerability, and effectiveness both in survival and quality of life regardless of fractionation schedule. To keep adverse effects under acceptable range, cumulative dose limit in equivalent dose at 2 Gy fractions by the linear-quadratic model at α/β = 2 for normal brain tissue (EQD2) with narrow margin should be observed and single/hypofractionated re-RT should be undertaken very carefully to recurrent tumor with large volume or adjacent to the brainstem. Promising outcome of re-operation (re-Op) plus re-RT (re-Op/RT) need to be validated and result from re-RT with temozolomide/bevacizumab (TMZ/BV) or new strategy is expected. Development of new-concept prognostic scoring or risk group is required to select patients properly and make use of predictive biomarkers such as O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation that influence outcomes of re-RT, re-Op/RT, or re-RT with TMZ/BV.

Hypofractionated Re-irradiation after Maximal Surgical Resection for Recurrent Glioblastoma: Therapeutic Adequacy and Its Prognosticators of Survival

PURPOSE: To evaluate the adequacy of retreatment, including hypofractionated re-irradiation (HFReRT), after surgery for recurrent glioblastoma (GBM) and related prognosticators of outcomes. MATERIALS AND METHODS: From 2011 to 2014, 25 consecutive patients with recurrent (n=17) or secondary (n=7) disease underwent maximal surgery and subsequent HFReRT after meeting the following conditions: 1) confirmation of recurrent or secondary GBM after salvage surgery; 2) Karnofsky performance score (KPS) ≥60; and 3) interval of ≥12 months between initial radiotherapy and HFReRT. HFReRT was delivered using a simultaneous integrated boost technique, with total dose of 45 Gy in 15 fractions to the gross tumor volume (GTV) and 37.5 Gy in 15 fractions to the clinical target volume. RESULTS: During a median follow-up of 13 months, the median progression-free and overall survival (OS) were 13 and 16 months, respectively. A better KPS (p=0.026), no involvement of the eloquent area at recurrence (p=0.030), and a smaller GTV (p=0.005) were associated with better OS. Additionally, OS differed significantly between risk groups stratified by the National Institutes of Health Recurrent GBM Scale (low-risk vs. high-risk, p=0.025). Radiologically suspected radiation necrosis (RN) was observed in 16 patients (64%) at a median of 9 months after HFReRT, and 8 patients developed grade 3 RN requiring hospitalization. CONCLUSION: HFReRT after maximal surgery prolonged survival in selected patients with recurrent GBM, especially those with small-sized recurrences in non-eloquent areas and good performance.

Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence

Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.

Re-Irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors

PURPOSE: The aim of this study was to evaluate the efficacy of re-irradiation in patients with recurrent gliomas and to identify subgroups for whom re-irradiation for recurrent gliomas is most beneficial. MATERIALS AND METHODS: We retrospectively reviewed 36 patients with recurrent or progressive gliomas who received re-irradiation between January 1996 and December 2011. Re-irradiation was offered to recurrent glioma patients with good performance or at least 6 months had passed after initial radiotherapy (RT), with few exceptions. RESULTS: Median doses of re-irradiation and initial RT were 45.0 Gy and 59.4 Gy, respectively. The median time interval between initial RT and re-irradiation was 30.5 months. Median overall survival (OS) and the 12-month OS rate were 11 months and 41.7%, respectively. In univariate analysis, Karnofsky performance status (KPS) ≥70 (p<0.001), re-irradiation dose ≥45 Gy (p=0.040), and longer time interval between initial RT and re-irradiation (p=0.040) were associated with improved OS. In multivariate analysis, KPS (p=0.030) and length of time interval between initial RT and re-irradiation (p=0.048) were important predictors of OS. A radiographically suspected mixture of radiation necrosis and progression after re-irradiation was seen in 5 patients. CONCLUSION: Re-irradiation in conjunction with surgery could be a salvage treatment for selected recurrent glioma patients with good performance status and recurrence over a long time.

Re-Irradiation of Hepatocellular Carcinoma: Clinical Applicability of Deformable Image Registration

PURPOSE: This study aimed to evaluate whether the deformable image registration (DIR) method is clinically applicable to the safe delivery of re-irradiation in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between August 2010 and March 2012, 12 eligible HCC patients received re-irradiation using helical tomotherapy. The median total prescribed radiation doses at first irradiation and re-irradiation were 50 Gy (range, 36-60 Gy) and 50 Gy (range, 36-58.42 Gy), respectively. Most re-irradiation therapies (11 of 12) were administered to previously irradiated or marginal areas. Dose summation results were reproduced using DIR by rigid and deformable registration methods, and doses of organs-at-risk (OARs) were evaluated. Treatment outcomes were also assessed. RESULTS: Thirty-six dose summation indices were obtained for three OARs (bowel, duodenum, and stomach doses in each patient). There was no statistical difference between the two different types of DIR methods (rigid and deformable) in terms of calculated summation operatorD (0.1 cc, 1 cc, 2 cc, and max) in each OAR. The median total mean remaining liver doses (M(RLD)) in rigid- and deformable-type registration were not statistically different for all cohorts (p=0.248), although a large difference in M(RLD) was observed when there was a significant difference in spatial liver volume change between radiation intervals. One duodenal ulcer perforation developed 20 months after re-irradiation. CONCLUSION: Although current dose summation algorithms and uncertainties do not warrant accurate dosimetric results, OARs-based DIR dose summation can be usefully utilized in the re-irradiation of HCC. Appropriate cohort selection, watchful interpretation, and selective use of DIR methods are crucial to enhance the radio-therapeutic ratio.