Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer

PurposeIntensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), two advanced modes of high-precision radiotherapy (RT), have become standard of care in the treatment of head and neck cancer. The development in RT techniques has markedly increased the complexity of target volume definition and accurate treatment delivery. The aim of this study was to indirectly investigate the quality of current TV delineation and RT delivery by analyzing the patterns of treatment failure for head and neck cancer patients in our high-volume RT center.MethodsBetween 2004 and 2014, 385 patients with pharyngeal, laryngeal, and oral cavity tumors were curatively treated with primary RT (IMRT/VMAT). We retrospectively investigated locoregional recurrences (LRR), distant metastases (DM), and overall survival (OS).ResultsMedian follow-up was 6.4 years (IQR 4.7–8.3 years) during which time 122 patients (31.7%) developed LRR (22.1%) and DM (17.7%). The estimated 2- and 5-year locoregional control was 78.2% (95% CI 73.3, 82.3) and 74.2% (95% CI 69.0, 78.8). One patient developed a local recurrence outside the high-dose volume and five patients developed a regional recurrence outside the high-dose volume. Four patients (1.0%) suffered a recurrence in the electively irradiated neck and two patients had a recurrence outside the electively irradiated neck. No marginal failures were observed. The estimated 2- and 5-year DM-free survival rates were 83.3% (95% CI 78.9, 86.9) and 80.0% (95% CI 75.2, 84.0). The estimated 2- and 5-year OS rates were 73.6% (95% CI 68.9, 77.8) and 52. 6% (95% CI 47.3, 57.6). Median OS was 5.5 years (95% CI 4.5, 6.7).ConclusionTarget volume definition and treatment delivery were performed accurately, as only few recurrences occurred outside the high-dose regions and no marginal failures were observed. Research on dose intensification and identification of high-risk subvolumes might decrease the risk of locoregional relapses. The results of this study may serve as reference data for comparison with future studies, such as dose escalation or proton therapy trials.

Patterns of nodal spread in stage III NSCLC: importance of EBUS-TBNA and 18F-FDG PET/CT for radiotherapy target volume definition

Purpose The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by 18F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC. Methods This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011–06/2018). Inclusion criteria were curative treatment intent, 18F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings. Results In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p < 0.0001, exact symmetry test). In a multivariable logistic model for EBUS-positivity at echelon-3, prognostic factors were PET-positivity at echelon-3 (Hazard ratio (HR) = 12.1; 95%-CI: 3.2–46.5), EBUS-TBNA positivity at echelon-2 (HR = 6.7; 95%-CI: 1.31–31.2) and left-sided tumor location (HR = 4.0; 95%-CI: 1.24–13.2). There were significantly less combined ipsilateral upper (LN-stations 2 and 4) and lower (LN-station 7) mediastinal involvements (16.8% of patients) with EBUS-TBNA than with PET (38.9%, p < 0.0001, exact symmetry test). EBUS-TBNA detected a lobe specific heterogeneity between the odds ratios of LN-positivity in the upper versus lower mediastinum (p = 0.0021, Breslow-Day test), while PET did not (p = 0.19). Conclusion Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET.