Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study

Abstract

Purpose Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification. Methods and Materials Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1). Conclusions Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

Correlations of cofilin1 and phosphorylation at Ser3 site with sensitivity of elderly patients with non-small cell lung cancer to radiotherapy

“…reoxidation are vital factors that determine the efficacy of radiotherapy (6). In this study, the TNM stage was advanced and the lymph node metastasis rate was higher in the radiotherapy-resistant group than those in the radiotherapy-sensitive group, which is consistent with a previous study on the influencing factors for the sensitivity of tumors to radiotherapy (8). The TNM stage of NSCLC patients is primarily associated with tumor diameter, lymph node metastasis and distant metastasis (9).…”

A Comparison of Isotoxic Dose-escalated Radiotherapy in Lung Cancer with Moderate Deep Inspiration Breath Hold, Mid-ventilation and Internal Target Volume Techniques

“…Statistically significant differences in multiple dosevolume metrics were shown when comparing motion-management techniques (Figure 2). For the predefined dose-volume metrics of the heart (mean) and lungs (mean and V 21Gy ), there were significant reductions in mean values for all patients with mDIBH in comparison to both four-dimensional techniques (all P < 0.01): the mean heart dose was reduced to 15 The differences in heart and lung dose-volume produced significant improvements in NTCP for cardiac and pulmonary toxicity using mDIBH compared with either fourdimensional technique (Table 2). Again, examining the three motion-management strategies, there were no significant differences seen in other OAR predefined dosevolume metrics between the techniques other than spinal canal D 1cm3, which had a lower mean dose on MidV compared with ITV plans (40.51 Gy AE 8.95 versus 41.67 Gy AE 9.29, P ¼ 0.007).…”

“…Statistical significance of the differences was evaluated using the Wilcoxon signed-rank test and compared using a significance level of P ¼ 0.01 (accounting for multiple endpoint testing). Further dose-volume metrics (PTV mean dose and maximum doses to 1 cm 3 [D 1cm3 ] to spinal canal, mediastinal envelope [15] and brachial plexus) were compared using an exploratory analysis with significance of P ¼ 0.05.…”

Avoiding Toxicity With Lung Radiation Therapy: An IASLC Perspective

“…75 In a feasibility study of isotoxic intensitymodulated RT (IMRT), which limited dose to the central structures on the basis of strict dose constraints, comparable toxicity rates were reported despite dose escalation and acceleration. 76 Normal Tissue and Target Definition Uncertainties. The accuracy of target volumes and normal tissues is also critical to avoid excessive doses to organs at risk.…”