Table 2 Summary of lung cancer practice-defining RT clinical trials

From: Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie?

Trial name (first author) Trial methodology Practice-defining trial results and methods Publications of trial results Publications related to trial conduct Evidence of practice change
Early-stage non-small cell lung cancer
 Indiana SBRT (Timmerman) Phase 2 study of stereotactic body RT (SBRT) for T1/2N0M0 NSCLC in patients unfit for lobectomy. 70 patients. Excessive toxicity for central tumours; practice changing in developing the ‘No Fly’ zone avoiding central airways for SBRT. 43, 167 NA International: ESMO.52
 RTOG 0236 (Timmerman) Phase 2 multicentre study of SBRT for T1/2N0M0 medically inoperable lung cancer. 55 patients. High rates of local tumour control (>90% at 3 years). 45 NA International: ESMO.52 NCCN.168
 Dutch population-based SABR paper (Palma) Population-based study investigating the impact of introducing SBRT in 875 patients 75 years of age or older. SBRT introduction was associated with a decline in the proportion of untreated elderly patients, and an improvement in overall survival. 53 NA International: ESMO.52 NCCN.168
 SPACE (Nyman) Phase 2. Randomised 102 patients with stage I medically inoperable NSCLC to receive SBRT to 66 Gy in three fractions (1 week) or 3DCRT to 70 Gy (7 weeks). First randomised study of SBRT compared to conventional dose fractionation. Better local control, similar OS and less toxicity with SBRT. 169 NA International: ESMO.52 NCCN.168
Locally advanced/metastatic non-small cell lung cancer
 RTOG0617 (Bradley) Phase 3, 2 × 2 factorial design. Randomised 544 patients to 60 or 74 Gy concurrently with carboplatin/paclitaxel, with or without additional cetuximab. 74 Gy was no better than 60 Gy and potentially harmful. Secondary analysis provided evidence supporting the use of IMRT in lung cancer. 59, 60 NA International: ESMO.52
 QUARTZ (Mulvenna) Phase 3. Randomised 538 NSCLC patients with brain metastases to dexamethasone and optimal supportive care with or without whole-brain RT. No significant difference in QUALYs (primary endpoint), overall survival, overall quality of life or dexamethasone use between the two groups. 61 NA International: ESMO.52
Limited-stage small cell lung cancer
 Intergroup0096 (Turrisi) Phase 3. Randomised 417 patients with LS-SCLC to 4 cycles of chemotherapy cisplatin-etoposide with either once (OD) or twice-daily (BD) radiotherapy. BD RT showed improved overall survival at 2 and 5 years. 62 NA International: ESMO.66 NCCN.170
 PCI01 -EULINT1 (LePechoux) Phase 3. Randomised 720 patients with LS-SCLC and complete response after chemotherapy and thoracic RT. Randomised dose of prophylactic cranial irradiation (PCI) to standard (25 Gy in 10#) vs. higher dose (36 Gy in 18# or 36 Gy in 24# given BD). No significant reduction in brain metastases at 2 years with higher dose PCI. 25 Gy in ten fractions to remain standard-of-care. Standardisation of PCI dose in limited-stage SCLC internationally. 171 NA International: ESMO.66
 CONVERT (Faivre-Finn) Phase 3. Randomised 547 patients with LS-SCLC to twice-daily (45 Gy in 30 fractions) vs. once-daily (66 Gy in 33 fractions) concurrently with chemotherapy. OD RT did not result in a superior survival compared to BD RT. 63 172,173,– 174 NA
Extensive-stage small cell lung cancer
 EORTC prophylactic cranial irradiation trial (Slotman) Phase 3. Randomised 286 patients to PCI vs. no further treatment in patients with extensive small cell lung cancer who had responded to chemotherapy. Significant improvement in median overall survival with PCI, as well as a lower cumulative risk of brain metastases at 1 year. 64 175 International: ESMO.66 NCCN.170
 CREST (Slotman) Phase 3. Randomised 498 patients to thoracic radiotherapy 30 Gy in ten fractions vs. no thoracic radiotherapy, in patients with extensive-stage small cell lung cancer who had responded to chemotherapy. No significant difference in 1-year survival (primary endpoint). Significant improvement in overall survival at 2 years with thoracic radiotherapy, with no increase in severe (grade 3 or higher) toxicity. 65, 176 177, 178 International: Survey of European centres: 81% now giving thoracic RT in ES-SCLC compared to 25% previously.177 NCCN.170
  1. ESMO European Society for Medical Oncology, NCCN National Comprehensive Cancer Network