Treatment/Prognosis Flashcards
Generally, what is a Tx paradigm for a stage I–II medically operable NSCLC pt?
Stages I–II medically operable NSCLC Tx paradigm: surgical resection (lobectomy) + mediastinal LND → adj chemo for everybody except stage IA, margin-negative resection. Stage IB and IIA with negative margins warrant chemo depending on other high-risk factors (grade, LVSI, >4 cm size, visceral pleural involvement, incomplete LN staging). (NCCN 2018)
What should be the 1st step for a stage I–II medically operable NSCLC pt with a +margin resection?
Re-resection, if possible +/– chemo depending on other clinical factors. (NCCN 2018)
If re-resection is not possible, what RT dose is used for a +margin after Sg?
Microscopic +margin: 54–60 Gy
Gross +margin: 60–70 Gy
Generally, what is the Tx paradigm for a stage I–II medically inoperable NSCLC pt?
Stages I–II medically inoperable NSCLC Tx paradigm: if T1–2N0, consider definitive hypofractionated SBRT or SABR. If T1–T2N1 or T3N0, use definitive CRT. (NCCN 2018)
Name 3 surgical options to resect a T1–T2 tumor.
Surgical options to resect a T1–T2 tumor:
- Wedge or segmental resection
- Lobectomy
- Pneumonectomy
For a T1N0 NSCLC, what is the estimated LC for wedge/segmental resection vs. lobectomy?
Wedge/segmental LC is 82% vs. lobectomy LC is 94% (LF 18% vs. 6%) based on RCT LCSG 821 (Ginsberg RJ et al., NEJM 1995). Lobectomy is preferred when feasible. However, CALGB 140503 is a currently ongoing phase III trial of lobectomy vs. sublobar resection for ≤2 cm peripheral NSCLC (smaller tumors than those treated in LCSG 821).
What % of stage I NSCLC pts will develop a 2nd primary after definitive surgical resection?
Up to 30% of pts develop a 2nd primary.
What is the estimated 5-yr OS of completely resected T1–2N0 NSCLC with no adj chemo?
T1N0 ∼80%; T2N0 ∼68% (Martini N et al., J Thorac Cardiovasc Surg 1999)
What is the 5-yr OS, CSS, and MS for pts who refuse any Tx for T1–2N0 NSCLC?
5-yr OS is 6%, CSS is 22%, and MS is 13 mos (Raz DJ et al., Chest 2007). Tumor size is a prognostic factor, independent of T stage.
What are the indications for adj chemo after definitive resection for stages I–II NSCLC?
Indications for adj chemo after definitive resection for stages I–II NSCLC:
- High-risk stages IB–IIB
- N1 Dz (category 1)
- T2N0 (stage IB), if the tumor is >4 cm as per unplanned analysis of CALGB 9633 (Sg +/– carboplatin/paclitaxel). (Strauss GM et al., JCO 2008)
Other risk factors include poorly differentiated tumor, LVSI, wedge resection, visceral pleural involvement, and incomplete nodal sampling.
What is the estimated 5-yr OS benefit with adj chemo for pts with completely resected stage I or II NSCLC?
∼5% at 5 yrs for adj cisplatin-based chemo based on LACE meta-analysis of recent trials (Pignon JP et al., JCO 2008). However, HR for stages IA and IB were not significant. Adj chemo for stage IA may even be detrimental.
What are possible chemo regimens in the adj or neoadj setting per NCCN 2018?
Cisplatin 50 mg/m2 days 1 and 8; vinorelbine 25 mg/m2 days 1, 8, 15, 22, q28 days for 4 cycles
Cisplatin 100 mg/m2 day 1; vinorelbine 30 mg/m2 days 1, 8, 15, 22, q28 days for 4 cycles
Cisplatin 75–80 mg/m2 day 1; vinorelbine 25–30 mg/m2 days 1 + 8, q21 days for 4 cycles
Cisplatin 100 mg/m2 day 1; etoposide 100 mg/m2 days 1–3, q28 days for 4 cycles
Cisplatin 75 mg/m2 day 1; gemcitabine 1250 mg/m2 days 1, 8, q21 days for 4 cycles
Cisplatin 75 mg/m2 day 1; docetaxel 75 mg/m2 day 1 q21 days for 4 cycles
Cisplatin 75 mg/m2 day 1, pemetrexed 500 mg/m2 day 1 for nonsquamous q21 days for 4 cycles
Is there a role for preop chemo in early-stage lung cancer pts?
No. Based on a meta-analysis, the survival gain is the same as for adj chemo (5%). The largest randomized trial (MRC LU22/EORTC 08012) for 519 pts randomized to preop chemo vs. Sg alone found good RR (49%) and downstaging (31%) but no survival benefit to preop chemo (Gilligan D et al., Lancet 2007). The CHEST Trial tested preop gemcitabine + cisplatin and found no significant benefit for stages IB/IIA but improved OS for stages IIB and IIIA (Scagliotti DV et al., JCO 2012). The NATCH Spanish Trial tested Sg vs. preop chemo + Sg vs. Sg + adj chemo and found no significant differences. However, more pts were able to rcv chemo in the neoadj setting. (Felip E et al., JCO 2010)
Is there a benefit of full mediastinal dissection vs. nodal sampling in early-stage pts undergoing surgical resection?
Possibly. A recent pooled analysis of 3 trials demonstrated a 4-yr OS benefit in stages I–IIIA NSCLC pts (HR 0.78). Mediastinal dissection involves removal of the right 2R, 4R, 7, 8R, and 9R and the left 5, 6, 7, 8L, and 9L. (Manser R et al., Cochrane Database Syst Rev 2005)
What are the indications for PORT after definitive resection for stages I–II NSCLC?
+Margins, +ECE, and unexpected N2 Dz. Per NCCN 2014, give concurrent CRT for an R2+ margin and sequential for R1 Dz (chemo → RT). Although not specified in NCCN, chemo → RT may also be considered for ECE.
Which randomized study demonstrated improved LC and survival with PORT after surgical resection for early-stage (stages IA and IB) NSCLC?
Italian study: 104 pts, stage I, resected with LND (pN0), randomized to PORT vs. observation; PORT encompassed the bronchial stump + ipsi hilum (mean area, 50 cm2) to 50.4 Gy. There were better LF rates (2% vs. 23%) with a trend to improved 5-yr survival (67% vs. 58%, p = 0.048). There was min toxicity and no worsened pulmonary function. (Trodella L et al., Radiother Oncol 2002)
What is the max RT dose that has been used for definitive RT alone in stages I–II NSCLC?
Up to 84 Gy in standard fractionation if lung dose–volume constraints are respected. RTOG 9311 dose-escalation study found that 90.3 Gy dose level was too toxic. (Bradley J et al., IJROBP 2005)
What is the 2-yr LR rate for RT alone using standard fractionation?
50%–78% 2-yr LR is based on RTOG 9311, but this study included stage III pts as well.
In stages I–II NSCLC pts being treated with definitive RT alone, should elective nodal regions be treated? What is the estimated elective nodal failure rate if untreated?
No. Elective nodal failure rate was <10% in RTOG 9311. In most series with stage I lung cancer treated with hypofractionated SBRT, the regional nodal failure rate ranged from 5%–10%. From the Indiana University dose-escalation study using SBRT for stage I lung cancer, regional nodal failure as the site of 1st failure was 10%. (Hoopes DJ et al., Lung Cancer 2007) Multiple retrospective reviews have also shown low elective nodal failure rates.
What are the estimated 3- to 5-yr LC and OS for medically inoperable stage I pts treated with definitive hypofractionated SBRT?
In most series using hypofractionated SBRT for stage I lung cancer pts, the 3-yr LC ranged from 85%–95% and the 3-yr OS was 55%–91%.
How does SBRT compare to lobectomy for operable stage I NSCLC?
In the Chang et al. pooled analysis of the STARS and ROSEL trials (Lancet Onc 2015), OS at 3 yrs was 95% in the SBRT group compared to 79% for the Sg group (HR 0.14; log rank p = 0.037). This remains controversial. In a recent SEER analysis (Shirvani S et al., JAMA Surg 2014), a propensity score matched analysis showed no difference b/t SBRT and Sg.
However, recent NCDB analysis of early stage NSCLC, in a propensity matched cohort of surgery vs. SBRT in 27,200 pts, surgery had significantly higher 30 and 90 days mortality, and highest in those >70 years old and with more extensive surgery. (Stokes WA et al., J Clin Oncol 2018)
What BED should be achieved to attain max LC and survival in pts with stage I lung cancer treated with SBRT?
According to Japanese data, if the BED is ≥100 Gy, then the 5-yr LC rate is 92% and the 5-yr OS is 71%. However, if the BED is <100 Gy, then the 5-yr LC rate is 57% and the 5-yr OS is 30%. (Onishi H et al., JTO 2007)
What is the estimated 5-yr rate of nodal failure, LF, and DM in early-stage NSCLC after definitive SBRT?
LRR (nodal) tends to be higher in SBRT pts than surgical pts and appears to increase with time. In RTOG 0236, 5-yr LR was 7%, involved lobar recurrence was 20% and regional recurrence was 38%. Distant recurrence rate was 31% (RTOG 0236; ASTRO 2014)
What is the SBRT technique that was evaluated in RTOG 0236? What is the 2-yr LC and OS rate for this group of inoperable pts?
SBRT using 20 Gy × 3 (without heterogeneity correction [HC]), or 18 Gy × 3 with HC) given in 1.5–2 wks. 3-yr primary tumor control is 97.6%, but the 3-yr primary tumor and involved lobe control is 90.6%, DFS was 48.3%, and OS was 55.8%. (Timmerman R et al., JAMA 2010)
