Page 372 - Read Online

Reverberi et al. Mini-invasive Surg 2020;4:43 I http://dx.doi.org/10.20517/2574-1225.2020.33 Page 3 of 10

Table 1. Peripheral lesion
Study Fractionation Toxicity (incidence of adverse events) Survival rates
Timmerman et al. [10] (RTOG 0236) 60-66 Gy/3 fr Grade 3-5: 20% 2-year LC: 95%
2-year OS: 54.7%
Timmerman et al. [11] (RTOG 0618) 54 Gy/3 fr Grade 3: 12.7% 3-year LC: 97.6%
Grade 4: 3.6% 3-year OS: 55.8%
No Grade 5 toxicity
Guckenberger et al. [14] 45 Gy/3 fr LC around 90%
48 Gy/4 fr LC around 90%
54 Gy/3 fr
Videtic et al. [15] (RTOG 0915) 34 Gy/1 fr Toxicity: 16% 2-year OS: 61.3%
48 Gy/4 fr Toxicity: 12% 2-year OS: 77.7%
Singh et al. [16] 30 Gy/1 fr Thoracic Grade 3: 16% 2-year LC: 94.9%
No Grade 4-5 2-year OS: 73%
60 Gy/3 fr Thoracic Grade 3: 12% 2-year LC: 97.1%
No Grade 4-5 2-year OS: 62%
Cummings et al. [18] 30 Gy/1 fr Grade 3 (lung toxicity): 4.6% 1 and 2-year LC: 95%-88%
1 and 2-year OS: 84%-61%
5-year OS: 17%
50 Gy/5 fr Grade 3 (lung toxicity): 7.1% 1 and 2-year LC: 93% -90%
1 and 2-year OS: 85% -70%
5-year OS: 39%
Stephans et al. [19] 54 Gy/3 fr Lung toxicity: 5.1% 2-year LF: 13.1%
Chest wall toxicity: 23.7%
30-34 Gy/1 fr Lung toxicity: 3.2% 2-year LF: 21%
Chest wall toxicity: 8.6%
48-50 Gy/4-5fr Lung toxicity: 3.8% 2-year LF: 15.5%
Chest wall toxicity: 7.7%
Fr: fraction; LC: local control; OS: overall survival; LF: local failure

lesions who were not candidates for surgery (unsatisfactory lung function tests: forced expiratory volume
in 1 sec -FEV1- < 40%), and received 54 Gy/3 fractions of SBRT over 1.5-2 weeks. After a median follow-up
[11]
of 34.4 months, the estimated 3-year LC and OS were 97.6% and 55.8%, respectively .
Patient selection can make the difference in toxicity and survival data: healthier patients reported less
toxicity, better local control and were able to tolerate treatment (total dose delivered and dose per fraction).
The RTOG 0618 trial enrolled patients with T1-2 (< 5 cm) tumors that were potentially operable (the
median FEV1 72.5%, range: 38%-136%) to receive 54 Gy/3 fractions (18 Gy each fraction) of SBRT over
1.5-2 weeks. After a median follow-up of 48.1 months, 2-year LC was 96% and 4-year OS was 56%, no Grade
[12]
4-5 toxicity was registered, and the incidence of Grade 3 toxicity was 15% . LC was excellent: the 3- and
5-year LC rates were 96% and 93%, respectively, for fit patients who refused surgery. The SBRT dose was 60
Gy/5 fractions (12 Gy per fraction) for peripheral lesions not adjacent to the chest wall, and 50 Gy/5 fractions
[13]
(10 Gy per fraction) for peripheral lesions or close to the chest wall . The Advisory Committee on
[14]
Radiation Oncology Practice (ACROP) consensus conference suggested that patients who are not
candidates for surgery might benefit from PTV minimum doses ranging from 105 Gy to 113 Gy.
Consequently, the recommended fractionations were 45 Gy/3 fractions (15 Gy per fraction) for peripherally
located lesions (> 1 cm from chest wall) and 48 Gy/4 fractions (12 Gy per fraction) for lesions having
broad chest wall contact. This regimen can achieve a 90% local control rate and has an acceptable toxicity
profile. The consensus conference also suggested considering 54 Gy/3 fractions (18 Gy per fraction) as the
maximum tolerable dose for patients who refused surgery, without severe comorbidities and have favorable
long-term life expectancies.

The RTOG 0915/North Central Cancer Treatment Group N0927 was a randomized phase II trial designed
to evaluate toxicity related to two regimens for peripheral lesions: 34 Gy in a single fraction and 48 Gy in
four consecutive daily fractions. Grade 3 toxicity rates at 1 year after treatment was similar among groups.