Toxicity Related to Radiotherapy Dose and Targeting Strategy: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer
Menée à partir de données portant sur 3 600 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé et inclus dans des essais évaluant une chimioradiothérapie concomitante, cette étude analyse la survenue d'événements indésirables en fonction de la dose de rayonnements administrée et de la stratégie thérapeutique (irradiation élective des ganglions, radiothérapie des champs impliqués)
Purpose : Concurrent chemoradiotherapy(CRT) is the standard treatment for locally-advanced non–small-cell lung cancer(LA-NSCLC). This study was performed to examine thoracic radiotherapy(TRT) parameters and their impact on adverse events(AE’s). Patients and Materials : We collected Individual patient data(IPD) from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The TRT parameters examined included field design strategy(elective nodal irradiation(ENI) vs. involved field TRT(IF-TRT)) and TRT dose(60Gy vs >60Gy). The primary endpoint of this analysis was the occurrence of AE’s. Odd ratios(ORs) for AE’s were calculated with univariable and multivariable logistic models. Results : TRT doses ranged from 60 to 74Gy. ENI wasn’t associated with more grade 3+(>3)AE’s than IF-TRT(multivariable OR:0.77(95%CI:0.543-1.102,p=0.1545). Doses >60Gy(high dose) were associated with significantly more grade 3+AE’s(multivariable OR:1.82(95%CI1.501-2.203,P<0.0001). In contrast, ENI was associated with significantly more grade 4+(>4)AE’s(multivariable OR:1.33(95%CI:1.035-1.709,P=0.0258). Doses>60Gy were also associated with more grade 4+AE’s(multivariate OR1.42(95%CI:1.191-1.700,P=0.0001). Grade 5 AE’s plus treatment related deaths were more frequent with higher dose TRT(p=0.0012) but not ENI(p=0.099). Conclusions : For LA-NSCLC patients treated with concurrent CRT, IF-TRT wasn’t associated with the overall risk of grade 3+AE’s but was associated with significantly less grade 4+AE’s than ENI-TRT. This is likely the result of irradiating less adjacent critical normal tissue. Higher TRT doses were associated significantly with grade 3+ and 4+AE’s. Based on these findings and our prior report on survival, CRT employing IF-TRT and 60Gy(conventionally fractionated) were associated with more favorable patient survival and less toxicity than the use of ENI or higher RT doses.