Resection Versus SBRT for Stage I Non-small Cell Lung Cancer in Patients with Good Pulmonary Function


Study

N

Treatment

Results

Median F/U

Quality of evidence

Ginsberg et al. [1]

Stage I = 247 (tumors ≤3 cm)

Lobectomy = 125vs

LR = 6.5 % lobe

NR

High

Randomized controlled trial

Limited resection = 122 Segment = 82

LR = 17.5 % sublobar

Wedge = 40

5-year OS and CSS no difference between lobar vs sublobar

Fernando et al. [12]

Stage IA = 291

Lobectomy = 167

LR Sublobar = 17.2 %

34.5 months

Low

Retrospective multicenter

Sublobar = 124

LR Sublobar + Brachy = 3.3 %

(60 + Brachytherapy)

Okada et al. [4]

Stage IA = 567

Lobectomy = 262

5-years DFS Lobe 83 %

>60 months

Moderate

Prospective multicenter

vs

5-years DFS Sublob 86 %

Sublobar= 305

5-years OS Lobe 89 %

Segment = 230

5-years OS Sublob 90 %

Wedge = 30

Schuchert et al. [9]

Stage IA = 325

Lobectomy = 235

LRR Lobe = 5.3 %

31.8 months

Low

Retrospective

Segmentectomy = 178

LRR Segment = 5.2 %

RFS Lobe = 79 %

RFS Segment = 77 %

Fan et al. [10]

Stage I = 11,360

Lobectomy versus Sublobar (wedge or segmentectomy)

All tumors: improved OS/CSS with lobectomy HR 1.4 (p = 0.0006)

NR

Moderate

Meta analysis 24 studies

Tumors2 cm OS/CSS no difference

Lobe vs segment OS/CSS no difference

Tsutani et al. [11]

Stage IA = 481

Lobectomy = 383

3-years RFS 87 %

43.2 months

Moderate

Retrospective

Segmentectomy = 98

3-years RFS 91 %

p = 0.14


NR not reported, OS overall survival, CSS cancer specific survival, RFS recurrence free survival, LRR locoregional recurrence



The potential pitfalls associated with wedge resections have prompted many thoracic surgeons to either limit their use to small tumors (in the range of 1 cm) where an adequate margin of normal tissue is easier to obtain or add brachytherapy with iodine-125 (125I) seeds to the wedge margin, a technique in which reported local recurrence rates are in the single digits (about 3.3 %) [12].



Stereotactic Body Radiation Therapy for Stage I NSCLC


SBRT has emerged as the preferred treatment approach for stage I NSCLC in patients with peripheral tumors who refuse surgery or are deemed medically inoperable. Evidence of efficacy in lung cancer has been accumulating since 1995 and mostly comes from retrospective observational series (single and multi-institution) and some prospective phase I/II clinical trials. Many of the trials are populated with patients who refuse surgery and patients who are deemed too high risk for surgery. One of the largest contributions to the SBRT literature (with >5-year follow-up) comes from Japan where investigators reported on 257 patients from 14 different hospitals and showed the importance of dose response. The local recurrence rate was significantly lower for a BED (biologic effective dose) of ≥100 Gy compared with a BED <100 Gy (8.4 versus 42.9 %, p = 0.01). Disease specific 5-year survival was 73.2 % in the total cohort where 99 patients were considered operable. The overall 5-year survival rates of medically operable and inoperable patients were 64.8 and 35.0 %, respectively [5]. The improved survival in operable patients treated with SBRT has been corroborated in other prospective series [13, 14] and likely speaks to the negative influence of medical comorbidities in high risk patients. Data supporting the use of standardized SBRT dosing in stage I NSCLC in North America was examined in strictly medically inoperable patients in a phase II multi-institution study (RTOG 0236) [7]. Fifty-five patients with T1/T2 NSCLC were treated with 54 Gy (three fractions × 18 Gy) and followed for recurrence and survival over 2 years. Four patients failed at the primary site or within the same lobe rendering a 3-year local control rate = 91 %. Combining local and regional failures, the 3-year local-regional control rate was 87 %. Disease-free survival and overall survival at 3 years were 48.3 and 55.8 %, respectively.

The lack of dose uniformity and optimal fractionation of SBRT for stage I NSCLC can be seen in Table 15.2. Many of these studies are also limited by a median follow up ≤36 months. Results from both retrospective and prospective series (Table 15.2) show 3-year OS and DFS approaching 57 and 81 %, respectively [13, 1517]. Five year overall and cancer specific survival after SBRT treatment are mostly absent in the literature thus making comparisons to surgical series of stage I NSCLC rather limited. Although some of the series have operable patients that refuse surgery [5, 13, 17, 18], there are few data to render conclusions regarding the role of SBRT in patients with preserved lung function. One of the more compelling retrospective series reported on 87 medically operable patients with stage IA (n = 65) or stage IB (n = 22) NSCLC treated with SBRT where 5-year OS = 72 % for stage IA and 62 % for stage IB [19]. These results are very similar to surgical series for stage I NSCLC and have spawned the development of clinical trials to compare SBRT to surgery.


Table 15.2
Stereotactic body radiation therapy


























































































































































Study

N

Treatment

Results

Median F/U

Quality of evidence

Timmerman et al. [21]

Stage IA = 35

SBRT

Local failure 4.3 %

17.5 months

Low

Stage IB = 35

Distant failure 10 %

Prospective
 
Total dose 60 – 66 Gy (3 fractions)

2-years OS 54.7 %

Onishi et al. [5]

Stage IA = 164

SBRT (variable dose and schedule)

Local failure 14 %

38 months

Low

Regional failure 11 %

Distant failure 20 %

Retrospective multicenter

Stage IB = 93

Median tumor = 2.8 cm

Local failure 8.4 % when BED > 100

99 medically operable

5-years DFS 73.2 %

5-years OS 47.2 %

Lagerwaard et al. [18]

Stage IA = 129

SBRT

Local failure 3 %

12 months

Low

Stage IB = 90

Regional failure 4 %
 
Distant failure 15 %

Retrospective

39 medically operable

Total dose 60 Gy (3–8 fractions)

2-years DFS (T1) 81 %

2-years DFS (T1) 54 %

2-years OS 64 %

Fakris et al. [15]

Stage IA = 34

SBRT

Local failure 5.7 %

50.2 months

Moderate

Stage IB = 36

Regional failure 8.6 %
 
Distant failure 12.9 %

Prospective single center observation
 
Total dose 60 – 66 Gy (3 fractions)

3-years DFS 81.7 %
 
3-years OS 42.7 %

Timmerman et al. [7]

Stage IA = 44

SBRT

Local failure 10 %

34.4 months

Moderate

Stage IB = 11

Regional failure 13 %
 
Distant failure 22 %

Prospective multicenter phase II trial
 
Total dose 54 Gy (3 × 18 Gy)

3-years DFS 48.3 %
 
Tumor <5 cm

3-years OS 55.8 %

Haasbeek et al. [17]

Stage IA = 118

SBRT

Local failure 11 %

12.6 months

Low

Stage IB = 85

Regional failure 8.4 %
 
Distant failure 21 %

Retrospective

41 medically operable

Total dose 60 Gy (3–8 fractions)

3-years DFS 72.6 %

3-years OS 45.1 %

Ricardi et al. [16]

Stage IA = 43

SBRT

Local failure 3.2 %

28 months

Low

Stage IB = 19

Regional failure 6.4 %
 
Distant failure 24 %

Prospective single center phase II trial

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Dec 30, 2016 | Posted by in CARDIOLOGY | Comments Off on Resection Versus SBRT for Stage I Non-small Cell Lung Cancer in Patients with Good Pulmonary Function
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