Background
Early stage, localized disease: lung SABR
Clinical scenario | Challenges | Potential solutions being explored | |
---|---|---|---|
Pre Treatment | Incorporating patient preferences for treatment | Choice of SABR in operable NSCLC | • Comparative effectiveness research (including patient-reported outcomes, QOL and cost-effectiveness analyses) with “big data” strategies to facilitate data mining • RCTs underway (NCT02629458, NCT01753414, NCT02468024, VALOR study) |
Obtaining a diagnosis | Risks of treating benign disease Risks of biopsy in frail patients | •Use validated models for cancer risk determination in a given population [9] • Explore blood biomarkers [123] | |
Treatment | Central tumors Multiple primary lung cancers | Proximity to OARs Uncertainty in OAR location Uncertainly in OAR dose constraints | • “Big data” strategies to establish more reliable OAR dose constraints • MRI-guided adaptive RT [44] • Protons [41] |
Oligometastases | Higher pneumonitis risk Identify molecular and clinical characteristics of patients likely to benefit from ablative local therapies Optimize sequencing of RT and new systemic treatments | • Phase I-II trials, as well as randomized trials | |
Follow-up | Detection of recurrences | Distinguishing post-RT fibrosis vs recurrent disease | • Radiomic approaches [24] |
Survivorship issues | Loco-regional recurrences and second lung tumors Smoking cessation | • Survivorship clinics [124] • Patient-reported outcomes, including financial impact of treatments |
Recurrences
Central early-stage NSCLC
Multiple primary lung cancers
SABR and stage IV disease
Locally advanced NSCLC
Trial | Inclusion | Staging PET or PET/CT | Study question | RTa
| Chemotherapy | N (randomized) | Answer | Treatment related mortality | 5-year OS |
---|---|---|---|---|---|---|---|---|---|
EORTC 08941 [125] | Unresectable IIIA (N2) | Not mandatory | CT-S vs CT-RT | 60–62.5 Gy to primary and involved mediastinum; 40–46 Gy to uninvolved mediastinum | Platinum-based with at least one other agent | 332 | No significant difference | 4 % within 30 days of surgery 1 patient died of RP, timing NR | 16 % 14 % |
INT 0139b [126] | Potentially resectable IIIA (N2) | Not mandatory | CRT-S vs CRT | 45 Gy in CRT-S arm 61 Gy in CRT arm | Cisplatin-etoposide | 429 (396 eligible) | No significant difference | 8 % 2 % (No deaths during induction) | 27 % 20 % |
ESPATUEc [127] | Resectable IIIA (N2) and selected IIIB | 97 % | CT-CRT-S vs CT-CRT-CRTboost | Both arms: induction 45 Gy delivered as 1.5 Gy BID In definitive CRT arm: risk-adapted CRTboost to 65–71 Gy | Induction: cisplatin-paclitaxel Concurrent: cisplatin-vinorelbine | 161 | No significant difference, but closed early and was under- powered with respect to the primary end-point of OS | 6 % in surgical arm 3 % in definitive CRT arm (2 additional patients died during induction) | 44 % 40 % |
SAKK 16/00 [128] | Resectable IIIA (N2) | Required (rate NR) | CT-RT-S vs CT-S | 44 Gy (in 22 fractions over 3 weeks) | Cisplatin-docetaxel | 232 | No difference | 0 % within 30 days of surgery 3 % within 30 days of surgery | 40 % 34 % |
Trial | Inclusion | Staging PET-CT | Histology | Treatment regimen in standard CRT arma
| RT technique | N | PTV (mean) | Toxicity in standard CRT arm | Outcomes |
---|---|---|---|---|---|---|---|---|---|
RTOG 0617 [58] | Unresectable III | 91 % | 42/47 % squamous in 60/74 Gy arms | 60 Gy Concurrent carboplatin-paclitaxel, followed by 2 cycles consolidation | 46/47 % IMRT in 60/74 Gy arms (Remainder 3DCRT) | 424 analyzable for radiation end-point | 495/510 mL in the 60/74 Gy arm | In 60 Gy arm: Grade ≥ 3 RP 7 % Grade ≥ 3 esophagitis 7 % Grade 5 toxicity 3 % | In 60 Gy arm: Median OS 29 months 2-year OS 58 % 2-year LF 31 % 2-year DF 47 % |
PROCLAIM [78] | Nonsquamous III | 82 % | Non-squamous only | 60–66 Gy Arm A: pemetrexed-cisplatin, pemetrexed consolidation Arm B: etoposide-cisplatin, non-pemetrexed consolidation | 25 % IMRT (Remainder 3DCRT) | 598 | 607/585 mL | Grade ≥ 3 RP 1.8/2.6 % Grade ≥ 3 esophagitis 15.5/20.6 % Grade 5 toxicity 1.7/1 % | Median OS 27/25 months Median PFS 11.4/9.8 months IFF (site of 1st failure) 42 % DF (site of 1st failure) 48 % |
KCSG-LU05-04 [79] | Unresectable III | 92 % | 32 % squamous | 66 Gy Concurrent docetaxel-cisplatin Arm A: CRT-observation Arm B: CRT-docetaxel-cisplatin consolidation | NR | 437 eligible | NR | Grade ≥ 3 RP 1.2 % Grade ≥ 3 esophagitis 9.5 % Grade 5 toxicity 3.6 % during CRT, 2.9 % during consolidation | Median OS 20.6/21.8 months Median PFS 8.1/9.1 months After median follow-up time of 51 months: DF 25 % LRR 25 % DF and LF 3 % |
RTOG 9410 [129] | Inoperable stage II-III | 0 % | 38 % squamous | 63 Gy Cisplatin-Vinblastine | 2DRT | 610 | N/A | For CRT with early RT arm: Grade ≥ 3 esophagitis 22 % Grade ≥ 3 acute RP 4 % Grade 5 toxicity 2 % (as worst overall toxicity) | For CRT with early RT arm: 5-year OS 16 % Median OS 17 months IFF only 25 % Out of field only 37 % Both IFF and out of field 10 % |
Meta-analysis of 6 trials comparing CRT vs sequential CT/RT [130] | Unresected stage III | 0 % | 46 % | 60 Gy (2 trials), 66 Gy, (1 trial), 66 Gy in 24 fractions (1 trial), 56 Gy split course (1 trial), 48.5 Gy (split course of 36 Gy in 12 fractions, 7 days rest, 12.5 Gy in 5 fractions) Single agent low-dose cisplatin (2 trials), cisplatin-based doublet (3 trials), carboplatin (1 trials) | 3DCRT in 1 trial Remainder 2DRT | 603/602 in concurrent/sequential groups | N/A | Grade ≥ 3 esophagitis 18 % (concurrent CRT) Rates of acute RP and Grade 5 toxicity NR | For concurrent CRT patients: 3-year OS 24 % 5-year OS 15 % 3-year LRF 28 % 5-year LRF 29 % 3-year DF 40 % 5-year DF 41 % |