Individual isotoxic radiation dose escalation based on V20 and advanced technologies benefits unresectable stage III non-small cell lung cancer patients treated with concurrent chemoradiotherapy: long term follow-up

Abstract

Under the assumption that the highest therapeutic ratio could be achieved by increasing the total tumor dose (TTD) to the limits of normal tissues, the phase I trial was conducted in patients with unresectable stage III non-small cell lung cancer treated with concurrent chemoradiotherapy, to determine the feasibility and effects of individual isotoxic radiation dose escalation based on bilateral lung V20 and advanced technologies. Consecutive eligible patients were assigned to cohorts of eight. V20 of each cohort was increased from 27% to 30%, 33%, 35%, 37%, and so on. The criterion for cessation of dose escalation was defined as ≥ 2 patients in each cohort experienced dose limiting toxicity. Isotoxic dose escalation was based on V20, functional imaging was used to improve the accuracy of radiotherapy. To test the power of escalation dose, patients with TTD over 66 Gy were assigned to the higher dose group (HD), while the others to the standard dose one (SD). In result, the recommended value of V20 was 35%. For all patients, follow-up ranged from 1 to 112 months, median overall and progression free survivals were 25.0 and 13.0 months, respectively. The 1-, 3-, 5- and 8-year overall survival (OS) rates were 72.5%, 22.5%, 17.5%, and 10.0%, respectively. Especially, the OS and local recurrence-free survival of patients in HD group were significantly longer than those in SD one (P=0.035, P=0.007, respectively) without increasing severe toxicity. Thus, individual isotoxic dose escalation based on V20 with advanced technologies was feasible and effective.

Radiotherapy Dose and Induction Chemotherapy Cycles Are Associated With Prognosis and Toxicity Risk: A Retrospective Study of 227 Patients With Unresectable Stage III Non-Small-Cell Lung Cancer

“… 17 The present study recommends 60-66 Gy as the optimal dose. 11 , 17 , 18 In summary, not all patients diagnosed with unresectable stage III NSCLC are suitable for concurrent chemoradiotherapy. All patient factors must be taken into account before decisions are made.…”

“…We did not record parameters such as V20 that may be related to radiation pneumonitis. 18 These factors may have had an impact on the results. Third, different chemotherapy regimens may have different effects on the hemograms, 24 - 26 but more cycles of induction chemotherapy resulted in more hematological toxicities.…”

Simultaneous integrated boost of intensity‐modulated radiation therapy to Stage II‐III non‐small cell lung cancer with metastatic lymph nodes

“…8 Many studies still supported the idea that high dose of radiotherapy was necessary. [17][18][19][20] After the report of RTOG0617 study in 2012, Machtay et al conducted a meta-analysis, which included seven prospective randomized concurrent chemoradiotherapy studies about locally advanced NSCLC. The study 21 showed that BED ≥74.67 Gy (conventional fractionated dose 62-64 Gy) was more beneficial to improve the local control and survival, increasing the time-adjusted BED (tBED) of 1 Gy can increase the local control by 3%, and the BED of 1 Gy can increase OS by 4%.…”

“…A phase II clinical study by KongFM et al showed that the local control rate was 82% at 2 years and 30% at 5 years because of the high radiotherapy dose (86 Gy/30 day) with adaptive radiotherapy guided by PET/CT 8 . Many studies still supported the idea that high dose of radiotherapy was necessary 17‐20 . After the report of RTOG0617 study in 2012, Machtay et al conducted a meta‐analysis, which included seven prospective randomized concurrent chemoradiotherapy studies about locally advanced NSCLC.…”

Simultaneous Integrated Boost of intensity modulated radiation therapy to Stage II-III Non-Small Cell Lung Cancer with metastatic lymph nodes

“…28.9 [10] .Uncontrolled local tumors may be a potential source of distant metastasis [13] .Although the RTOG0617 study showed that 60 Gy may be more reasonable than other radiation dose [3] , further analysis of the study showed that the result was affected by many other factors [12] .There is still debate about that increasing the dose of radiation therapy can reduce recurrence and prolong survival. A phase II clinical study by KongFM et al showed that the local control rate was 82% at 2 years and 30% at 5 years because of the high radiation therapy (86Gy/30day) with adaptive radiotherapy guided by PET/CT [4] .Many studies still supported the idea that high dose of radiation therapy was necessary [14][15][16][17] .After the report of RTOG0617 study in 2012, MachtayM et al conducted a meta-analysis, which included 7 prospective randomized concurrent chemoradiotherapy studies about locally advanced NSCLC. The study [18] showed that BED ≥ 74.67 Gy (conventional fractionated dose 62-64Gy) was more beneficial to improve the local control and survival, increasing the tBED of 1 Gy can increase the local control by 3%, and the BED of 1 Gy can increase OS by 4%.After conventional fractionated radiotherapy, dose escalation for local tumor may improve local control and survival [19] .…”