Abstract
e22134 Purpose: To generate quantitative parameters describing the effect of concomitant chemotherapy on incidence of grade 3 dysphagia (CTCAE v3.0, assisted feeding) using dose response curves in patients receiving radical treatment for head and neck cancer. Methods: Patients treated at a single centre in prospective phase I and II trials of concomitant chemo-IMRT (CRT) (n=85) and the phase III trial of IMRT vs. conventional radiotherapy (PARSPORT) (n=82) formed the basis of this non-randomized comparison. Patients in the PARSPORT trial received radiation alone (RT). Radiation dose for all patients was radiobiologically equivalent to at least 70Gy in 35 fractions. Concomitant chemotherapy was cisplatin (100 mg/m2) on days 1 and 29. G3 dysphagia was recorded prospectively. Dose volume histograms (DVH) were generated for the pharyngeal mucosa. The mean dose (converted to equivalent dose in 2Gy/fraction, MD2) was used as a univariate descriptor of the DVH, for the generation of the dose response curves. A logistic function of the form p=1/[1+(MD50/D)k] was fitted where, p is the probability of the incidence of toxicity, D is the mean dose, MD50 is the mean dose at which 50% of patients experience toxicity and k describes the increase in incidence with increasing dose. The dose response curves were fitted using non-linear logistic regression. Results: The mean MD2 to the pharyngeal mucosa were 56Gy and 55.8Gy respectively, in the CRT and RT groups. There was a statistically significant difference of 25% (95% CI: 10–38, p=0.002) in the incidence of G3 dysphagia between the CRT (68%) and RT (43%) groups. Fitting dose response curves to the clinical data yielded parameter values (95% CIs) of MD50=46 Gy (42–49), k=4.8 (2.3–7.2) for the CRT group and MD50= 58 Gy (55–61), k=3 (1.6-.45) for RT group. Dose response gradients for CRT and RT showed approximately 1.95% and 1.3% increase (respectively) in probability of G3 dysphagia resulting from an increase in mean dose of 1Gy between doses of 30Gy to 70Gy. Conclusions: Addition of concomitant chemotherapy increases the incidence of G3 dysphagia by 0.65% for every 1 Gy increase in radiation dose. The observed MD50 for G3 dysphagia is lower for RT alone (46 Gy vs. 58 Gy). No significant financial relationships to disclose.
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