Important Studies Flashcards
Dose escalation?
RTOG 0617 (Bradley et al, Lancet, 2015
Bradley et al, JCO, 2019): →60 Gy vs. →74 Gy→cetuximab (concurrent and consolidation) vs. →no cetuximab. Carbo/taxol concurrent weekly and adjuvant x2 in all.
Dose escalation to 74 Gy led to worse OS. Cetuximab provides no benefit in OS.
MSKCC (Rosenweig et al, Cancer, 2005): Phase I: Dose escalated from 70.2→75.6→81→84→90 Gy. Induction chemo in 16%. No concurrent chemo. Protocol later amended to omit ENI. The MTD dose was 84 Gy.
Elective nodal irradiation?
PET-PLAN (Nestle et al, Lancet Oncol, 2020): “→RT to PET FDG avid sites and 50 Gy ENI vs. →RT to PET FDG avid sites only. 60-74 Gy as high as feasible, concurrent chemo. ENI was delivered to stations at ≥10% risk based on an algorithm. Targeting FDG avid sites only, compared to doing so with ENI, reduces LRR.
Shandong Cancer Hospital & Institute, Jinan, China (Yuan et al, Am J Clin Oncol, 2007): Induction chemo x1 -> concurrent chemoRT -> adjuvant chemo →ENI 60-64 Gy vs. →IFRT 68-74 Gy. Omission of ENI leads to improved OS and LC and seems to allow dose escalation.
Hypofractionation?
SOCCAR (Maguire et al, Eur J Cancer, 2014): Phase II randomized →55 Gy RT with sequential cis/vinorelbine vs. →concurrent cis/vinorelbine. Hypofractionated radiation therapy of 55 Gy in Stage III NSCLC is safe and results in favorable outcomes.
Benefit of induction chemo?
CALGB 8433 (Dillman et al, JNCI, 1996): →60 Gy RT alone vs. →induction cis/vinblastine then RT. Median OS 9.7 mos vs. 13.8 mos 5-yr OS 6% vs. 17%. Trial showed the benefit of chemotherapy. Later trials showed concurrenct chemo to be superior over induction
Concurrent vs. sequential CRT?
RTOG 9410 (Curran et al, JNCI, 2011): →seq cis/vinbl then 60 Gy RT vs.→concurrent cis/vinbl and RT vs.→concurrent cis/etoposide RT BID. Median OS 14.6 mos vs. 17 mos vs. 15.6. 5-yr OS 10% vs. 16% vs. 13%. Concurrent chemoRT with QD RT results in improved OS over induction chemo or chemoRT with BID fx.
Goustave-Roussy (Auperin et al, JCO, 2010): Meta-analysis of 6 trials evaluating concurrent vs. sequential chemoRT. 5-yr OS increased, 15.1% vs. 10.6%. Concurrent chemoradiation improves OS compared to sequencial chemoRT, with increased esophageal toxicity.
cis/ etoposide vs. carbo/taxol?
Peking Union Medical College, Beijing, China (Liang et al, Ann Oncol, 2017): →concurrent cis/etoposide x2 q4 wks
vs. →concurrent carbo/paclitaxel weekly with 60-66 Gy RT. Cis/etoposide might be superior to weekly carbo/taxol concurrent with RT for Stage III NSCLC.
Lobectomy vs wedge?
Lung Cancer Study Group 821 (Ginsberg et al, Ann Thorac Surg, 1995): →lobectomy vs. →wedge resection, 2 cm margins. Wedge resection does not improve OS or reduce toxicity. Improved LC with lobectomy 6% vs. 18%. Lobectomy is surgical procedure of choice.
Adjuvant RT N2?
ANITA (Douillard et al, IJROBP, 2008): Adj chemo vs. →obs; 45-60 Gy RT was recommended for N+ but not required. Subanalysis of those treated with RT. PORT improves OS in N1 patients who had no chemotherapy (If chemo given, RT worsened OS) and in all N2 patients
University of Leuven, Belgium (Billett et al, Radiother Oncol, 2014): Meta-analysis of phase III trials evaluating LR and OS with adjuvant RT in Stage IIIA N2. Adjuvant RT for N2 is associated with improved OS and LC in this meta-analysis.
Adjuvant RT N2 (ongoing)?
LUNG-ART (EORTC 22055) (ongoing): Post-op N2. 54 Gy/ 27-30 fx vs. no RT
neoadj CRT + Surgery vs. definitive RT?
INT 0139/RTOG 9309 (Albain et al, Lancet, 2009): 45 Gy with concurrent cis/etoposide –> if no PD –>→surgery
vs. →RT to 61 Gy total, then adjuvant x2 cis/etoposide in both arms. The addition of surgery to chemoRT in Stage IIIA NSCLC did not result in OS benefit unless lobectomy was performed
CT-Surgery vs. chemoRT?
EORTC 08941 (van Meerbeeck et al, JNCI, 2007): Induction platinum-based chemo x3, then if response: →radical resection ± PORT vs. →60 Gy definitive RT. After response to induction chemo then surgery, surgery doesn’t improve OS or PFS compared to chemoRT alone in Stage IIIA N2 NSCLC.
Superior sulcus tumors?
SWOG 9416/INT 0160 (Rusch et al, J Thorac Cardiovasc Surg, 2001): 2 cycles of cis/etoposide + 45 Gy → If no progression then surgery in 3-5 weeks → cis/etoposide x2. Patients had lobectomy/pneumonectomy if no progression. Direct tumor extension to chest wall or spine was resected en bloc. Muscle flap not required. Incomplete surgery was allowed. For superior sulcus tumors, chemoRT followed by surgery then adjuvant chemo is feasable and with favorable response, LC, and OS.
superior sulcus T3-4N0-1
1) apical tumor with Pancoast syndrome with or without inv chest wall or spine
2) superior or sulcus tumors with inv of chest wall, spine, or subclavian vessels”
[chemo –> RT –> surgery] vs. [chemo –> surgery]?
Kantonsspital Winterthur, Switzerland (Pless et al, Lancet, 2015): “→cis/docetaxel x3 followed by RT 44 Gy then surgery vs. same without RT. The addition of RT to induction chemotherapy prior to surgery did not improve EFS.
[chemo –> neoadj CRT –> Surgery] vs. [definitive RT]?
ESPATUE (Eberhardt et al, JCO, 2015): Induction cisplatin/paclitaxel → 45 Gy RT (1.5 Gy BID) conc cisplatin/vinorelbine → if resectable → chemoRT 65-71 Gy vs. surgery. The trial was terminated early due to slow accrual and thus was not powered to meet its endpoints. Both approaches resulted in excellent outcomes.
Adjuvant durvalumab (anti-PDL-1)?
PACIFIC (Antonia et al, NEJM, 2017,Antonia et al, NEJM, 2018): NSCLC stage III with no PD after at least 2 cycles platinum chemo, →consolidation durvalumab vs. placebo
Improved OS, PFS, RR, and time to death or DM
2-yr OS 66% vs. 56%
Median OS not reached vs. 29 mos
Median PFS 17.2 mos vs. 5.6 mos
1-yr PFS 56% vs. 35%
18-mo PFS 44% vs. 27%
Median time to death or DM 28.3 mos vs. 16.2 mos
Grade 3-4 toxicity 30% vs. 26%
Improved OS when started <14 days after RT
