MTE06.01 Radiotherapy Techniques in Lung Cancer

Abstract

Recent Advances in Radiation Treatment Technique for Lung Cancer Lung cancer is the leading cause of cancer-related death in the United States and throughout the world. Advancement of Radiation Treatment have been parallel to imaging capability to target cancer and avoid surrounding normal tissue structure which associated with volume and dose. We can cure most of early lung cancer if it is well staged early cancer and targeted correctly by stereotactic body radiation therapy (SBRT). Because of high dose per fraction, technical aspects and quality assurance to deliver the radiation to the tumor precisely and avoid high dose of radiation to the critical surrounding normal tissue are critical issues organs in addition to controlling tumor motion. Technologic advancements of imaging and radiotherapy to conform the gross target volume(GTV) with tighter margins but adequate clinical targeted volume (CTV) and planning tumor volume (PTV) considering daily set up variations which are supposed to minimize the dose to nearby normal tissues. We have tried to answer higher radiation dose improve survival by the RTOG 0617 which compared overall survival after standard-dose versus high-dose intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiation therapy (3DCRT) with concurrent chemotherapy +/- cetuximab for patients with inoperable stage III non-small-cell lung cancer. In this open-label randomized, phase 3 study in 185 institutions in the USA and Canada, we enrolled patients (aged ≥18 years) with unresectable stage III non-small-cell lung cancer, a Zubrod performance status of 0–1, adequate pulmonary function, and no evidence of supraclavicular or contralateral hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All received concurrent chemotherapy with 45 mg/m2 paclitaxel and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel (200 mg/m2) and carboplatin (AUC 6). Radiation dose was prescribed to the PTV and was given in 2 Gy daily fractions with either IMRT or 3DCRT. For patients assigned to receive cetuximab, 400 mg/m2 cetuximab was given on day 1 followed by weekly doses of 250 mg/m2, and was continued through consolidation therapy. 166 patients were randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up for the radiotherapy comparison was 22.9 months (IQR 27.5–33.3). Median overall survival was 28.7 months (95% CI 24.1–3.9) for patients who received standard-dose radiotherapy and 20.3 months (17.7–25.0) for those who received high-dose radiotherapy (hazard ratio [HR] 1.38, 95% CI 1.09–1.76; p=0.004). Median overall survival in patients who received cetuximab was 25.0 months (95% CI 20.2–30.5) compared with 24.0 months (19.8–28.6)in those who did not (HR 1.07, 95% CI 0.84–1.35; p=0.29). Both the radiation-dose and cetuximab results crossed protocol specified futility boundaries. We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups. By contrast, the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects (205 [86%] of 237 vs 160 [70%] of 228 patients; p<0.0001). There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups (radiotherapy comparison: eight vs three patients; cetuximab comparison: ten vs five patients). Severe esophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received standard-dose treatment (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p<0.0001). This study did not mandate 4D simulation and possibly GTV was not well covered by the dose prescribed. There was higher local failure in the 74 Gy arm because of tighter margin in this group: We assumed from this study that 74 Gy radiation given in 2 Gy fractions with further improvements are expected from the use of charged particle therapy with protons or other particles; randomized comparisons of proton therapy vs. intensity-modulated photon radiation therapy for lung cancer are underway in the United States. A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617. The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P =.005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distance metastasis were not different between IMRT and 3D-CRT. IMRT was associated with fewer grade 3 or greater pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyzes (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses (P <0 .05), and volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis (P<0.05): Lung V5 was not associated with any toxicity equal or greater than grade 3, whereas lung V20 was associated with increased grade 3 or greater pneumonitis risk on multivariable analysis (P = .026). IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC. We have evidence that severe pneumonitis and esophagitis have been reduced by proton compared to IMRT with concurrent chemotherapy for stage III NSCLC. However it is difficult to do a randomized trials: In conclusion, screening by low dose spiral CT scan for among previous or current smokers to detect early lung cancer. Early lung cancer can be curable by SBRT Lung cancer treatment planning requires 4D simulation. The technical advancement such as IMRT or Proton Treatment compared to 2 or 3 dimensional radiotherapy with concurrent chemotherapy reduced normal tissue toxicity among patients with locally advanced lung cancer which will improve their outcome in future. We are testing this hypothesis by a randomized prospective study. Advances, Technique, Lung, Cancer