Automatic segmentation for adaptive planning in nasopharyngeal carcinoma IMRT: Time, geometrical, and dosimetric analysis.

The aim of this study was to quantify the geometrical differences between manual contours and autocontours, the dosimetric impacts, and the time gain of using autosegmentation in adaptive nasopharyngeal carcinoma (NPC) intensity-modulated radiotherapy (IMRT) for a commercial system. A total of 20 consecutive Stages I to III NPC patients who had undergone adaptive radiation therapy (ART) re planning for IMRT treatment were retrospectively studied. Manually delineated organs at risks (OARs) on the replanning computed tomography (CT) were compared with the autocontours generated by VelocityAI using deformable registration from the original planning CT. Dice similarity coefficients and distance-to-agreements (DTAs) were used to quantify their geometric differences. IMRT test plans were generated with the assistance of RapidPlan based on the autocontours of OARs and manually segmented target volumes. The dose distributions were applied on the manually delineated OARs, their dose volume histograms and dose constraints compliances were analyzed. Times spent on target, OAR contouring, and IMRT replanning were recorded, and the total time of replanning using manual contouring and autocontouring were compared. The averaged mean DTA of all structures included in the study were less than 2 mm, and 90% of the patients fulfilled the mean distance agreement tolerance recommended by AAPM 132.1 The averaged maximum DTA for brainstem, cord, optic chiasm, and optic nerves were all less than 4 mm, whereas temporal lobes and parotids have larger average maximum DTA of 4.7 mm and 6.8 mm, respectively. It was found that large contour discrepancies in temporal lobes and parotids were often associated with large magnitude of deformation (warp distance) in image registrations. The resultant maximum dose of manually segmented brainstem, cord, and temporal lobe and the median dose of manually segmented parotids were found to be statistically higher than those to their autocontoured counter parts in test plans. Dose constraints of the manually segmented OARs in test plans were only met in 15% of the cases. The average time of manual contouring and autocontouring were 108 and 10 minutes, respectively (p < 0.001). More than 30% of the total replanning time would be spent in manual OAR contouring. Manual OAR delineation takes up a significant portion of time spent in ART replanning and OAR autocontouring could considerably enhance ART workflow efficiency. Geometrical discrepancies between auto- and manual contours in head and neck OARs were comparable to typical interobserver variation suggested in various literatures; however, some of the corresponding dosimetric differences were substantial, making it essential to carefully review the autocontours.

Hyperfractionation compared to standard fractionation in intensity-modulated radiation therapy for patients with locally advanced recurrent nasopharyngeal carcinoma.

We prospectively studied the efficacy and safety of hyperfractionated intensity-modulated radiation therapy (HF-IMRT) and compared to a historical cohort treated with standard fractionation (SF-IMRT) in patients with locally advanced recurrent (rT3-T4, rN0-N1, M0) nasopharyngeal carcinoma (NPC). Ten patients were treated with induction chemotherapy followed by HF-IMRT (64.8 Gy/54 fr/5.5 weeks) concurrent with weekly cisplatin. They were compared to another ten patients treated with induction chemotherapy followed by SF-IMRT (60 Gy/30 fr/6 weeks) concurrent with weekly cisplatin. After a median follow-up duration of 44.6 months, we demonstrated that the median local failure-free survival (LFFS) showed a trend in favor of HF-IMRT (28.2 vs. 16.6 months, p = 0.164). Overall survival (OS) (34.8 vs. 35.5 months, p = 0.603) was not different between the two groups. Treatment-related hemorrhage was slightly less with HF-IMRT (30.0 vs. 0 %), reaching marginal significance (p = 0.060). Judging from our study results, HF-IMRT offered a marginally better LFFS and an apparently more favorable toxicity profile compared to SF-IMRT in locally advanced recurrent NPC.

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma.

Plasma Epstein-Barr virus (EBV) DNA titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (NPC). However, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. We recruited 260 evaluable patients with non-metastatic NPC treated with radical intensity-modulated radiation therapy (IMRT) with or without adjunct chemotherapy. Plasma EBV DNA titers at baseline and then 8 weeks and 6 months after IMRT were measured. Cox regression models were employed to identify interaction between post-IMRT 8th week and 6th month undetectable titers and 3-year survival endpoints. Concordance indices (Ct) from time-dependent receiver-operating characteristics (TDROC) were compared between patients with post-IMRT undetectable and those with detectable titers. After a median follow-up duration of 3.4 years (range 1.4-4.6 years), patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 3-year survival endpoints than those who had detectable titers at the same time points. Post-IMRT 8th week, and more significantly, post-IMRT 6th month undetectable plasma EBV DNA were the only significant prognostic factors of 3-year survival endpoints. Ct values for all 3-year survival endpoints for both post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significantly higher in those with stage IVA-IVB diseases compared to stage I-III counterparts. Early post-IMRT undetectable plasma EBV DNA titers were prognostic of 3-year survival endpoints in patients with non-metastatic NPC. Intensified treatment should be further explored for patients with persistently detectable titers after IMRT.

Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma.

PURPOSE: We investigated if programmed death-ligand 1 (PD-L1) expression levels were prognostic of survival outcomes after intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: 104 patients with non-metastatic NPC treated with radical IMRT were investigated for their PD-L1 expression by immunohistochemistry (IHC) which were correlated with survival endpoints including locoregional failure-free survival (LRFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: After a median follow-up of 7.6 years, 21 (20.2%), 19 (18.3%) and 31 (29.8%) patients suffered from locoregional failure, distant metastases and overall disease progression, respectively, and 31 (29.8%) patients died. Patients whose tumors had PD-L1 IHC 2+ (moderate to strong membrane staining in ≥ 25% of tumor cells) enjoyed longer LRFFS (5-year 100% vs. 74.4%, Hazard ratio [HR], 0.159, 95% confidence interval [CI], 0.021-0.988; P = 0.042) and marginally longer PFS (5-year 95.0% vs. 65.2%, HR, 0.351, 95% CI, 0.08-0.999, P = 0.067) compared to those whose tumors had PD-L1 IHC 0 (minimal membrane staining with PD-L1 in < 5% tumor cells or no staining with PD-L1) or 1+ (minimal to moderate membrane staining with PD-L1 in between 5-24% tumor cells). PD-L1 IHC 2+ was independently prognostic of both LRFFS (P = 0.014) and PFS (P = 0.045) in multivariable analyses. Only induction chemotherapy followed by concurrent chemoradiation was prognostic of DMFS (P = 0.003) and no prognostic factor for OS was identified. CONCLUSION: PD-L1 expression levels correlated with LRRFS and PFS in non-metastatic NPC treated with radical IMRT. It may play a role in radiosensitivity for NPC, which should be further confirmed in prospective studies using immunotherapy together with IMRT.

Dosimetric Predictors of Hypothyroidism After Radical Intensity-modulated Radiation Therapy for Non-metastatic Nasopharyngeal Carcinoma.

AIMS: To investigate dosimetric predictors of hypothyroidism after radical intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Patients with non-metastatic NPC treated with radical IMRT from 2008 to 2013 were reviewed. Serum thyroid function tests before and after IMRT were regularly monitored. Univariable and multivariable analyses were carried out for predictors of biochemical and clinical hypothyroidism. RESULTS: In total, 149 patients were recruited. After a median follow-up duration of 3.1 years, 33 (22.1%) and 21 (14.1%) patients developed biochemical and clinical hypothyroidism, respectively. Eight (24.2%) patients who had biochemical hypothyroidism developed clinical hypothyroidism later. Univariable and multivariable analyses revealed that the volume of the thyroid (P=0.002, multivariable), VS60 (the absolute thyroid volume spared from 60 Gy or less) (P<0.001, multivariable) and VS45 (P<0.001, multivariable) of the thyroid were significant predictors of biochemical hypothyroidism. The freedom from biochemical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (mean 90.9 versus 62.6 months; P<0.001) and VS45 ≥ 5 cm(3) (mean 91.9 versus 65.2 months; P=0.001). Similarly multivariable analyses revealed that VS60 (P=0.001) and VS45 (P=0.003) were significant predictors of clinical hypothyroidism. The freedom from clinical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (91.5 versus 73.3 months; P=0.002) and VS45 ≥ 5 cm(3) (91.5 versus 75.9 months; P=0.007). CONCLUSIONS: VS60 and VS45 of the thyroid should be considered important dose constraints against hypothyroidism without compromising target coverage during IMRT optimisation for NPC.