br NTCP calculation br NTCP
NTCP values were determined for each patient at all end-points in both PBT and photon plans using the NTCP formulae23: NTCPZ1þ1e S with the linear predictor (S ) for complications defined as: SZb0 þ bi$xi where b0
(intercept) and bi (variable coefficients) were the model parameters and xi the predictor variables.
Patient and treatment characteristics and the observed rates of toxicities at 6-months with corresponding OAR mean doses for relevant endpoints of the 2 patient cohorts are shown in Table 1. The difference in increased sparing of an organ at risk, such as the oral cavity, is shown in Figure 2. A summary of all model performance results for all endpoints is shown in Table 2, which presents the uncorrected (apparent) modeling results with uncorrected regression coefficients.
The final NTCP models for the endpoints were based on outcomes of each endpoint from all patients; they include the corrected coefficients (after internal validation):
Table 1 Patient and treatment characteristics
Patient/Treatment factor n %
n % P value
Abbreviations: CTCAEv4 Z National Cancer Institute Common Terminology Criteria for Adverse Events version 4; G1 Z grade 1 toxicity;
G2 Z grade 2 toxicity; G3 Z grade 3 toxicity; PCM Z pharyngeal constrictor muscles; PTV Z planning tumor volume; RT Z radiation therapy;
SMD Z standardized mean difference.
* In the photon cohort, 1 patient received open (nonrobotic) surgery to the primary site (without neck surgery), 3 patients received neck surgery without surgery to the primary tumor.
Volume 104 Number 3 2019 Predictive outcomes model for Dexmedetomidine therapy in oropharyngeal cancer 557
Fig. 2. Intensity-modulated radiation therapy (IMRT) versus proton beam therapy (PBT) Comparison: axial (left) and sagittal (right) slices of representative radiation plans for adjuvant radiation therapy in a patient with T1N2aM0 stage IVA (seventh edition) base of tongue carcinoma, showing IMRT and PBT radiation plans (60 Gy in 30 fractions) for the same patient. The PBT plan demonstrates lower dose to oral cavity structures compared with IMRT.
The NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing signifi-cantly higher NTCP values for the IMRT plans for all endpoints (Table 3). PBT was associated with statistically significant reductions in the paired mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of grade 2 dysphagia and xerostomia (Table 3). The absolute reductions in individual patient NTCP by PBT compared with IMRT ranged from
Although IMRT has led to reduction of radiation-induced adverse effects with improved global quality of life from 3-dimensional conformal techniques, efforts are still needed to enhance the therapeutic ratio in oropharyngeal carcinoma after multimodality curative therapy.24-27 It is for this reason that proton therapy, with its ability to improve normal tissue sparing compared with IMRT, might help to improve patient toxicity outcomes and long-term quality of life. However, precise estimates of the clinical impact of PBT are lacking with the current absence of randomized data. The present study evaluates toxicity outcomes between IMRT to PBT using normal tissue complication probability models to estimate potential clinical benefits of PBT and using a large cohort of patients receiving radiation therapy for oropharyngeal carcinoma.
Our study extends the existing literature regarding the comparative effectiveness of PBT for head and neck radi-ation therapy, and it is the first report of such a comparative analysis limited to patients with oropharynx cancer, in whom high rates of long-term survival emphasize a focus