Locoregional tumor failure after definitive radiation for patients with stage III non-small cell lung cancer

Abstract

BackgroundLocoregional tumor failure (LRF) after definitive chemoradiation for patients with stage III NSCLC remains unacceptably high. This analysis sought to further define where LRF occurs relative to radiation dose received and pre-treatment PET scan-defined maximum standard uptake value (SUVmax).MethodsThis was a retrospective study analyzing patients with stage III NSCLC treated with definitive radiation between 2006 and 2011. LRF was defined as failure within the ipsilateral lung, hilum or mediastinum. The CT simulation scan with the radiation dose distribution was registered to the CT or PET/CT documenting LRF. The region of LRF was contoured, and the dose to 95% of the volume (D95) of LRF was extracted. The pre-treatment SUVmax was also extracted for the anatomic region of LRF.ResultsSixty-one patients were identified. Median follow-up time was 19.1 months (range 2.37-76.33). Seventy four percent of patients were treated with 3-D conformal technique (3DCRT), 15% were treated with Intensity Modulated Radiotherapy (IMRT), and 11% were treated with a combination of 3DCRT and IMRT. Median prescribed radiation dose for all patients was 66 Gy (39.6-74). Concurrent chemotherapy was delivered in 90% of patients. Twenty-two patients (36%) developed a LRF, with a total of 39 anatomic regions of LRF identified. Median time to LRF was 11.4 months (3.5-44.6). Failures were distributed as follows: 36% were in-field failures, 27% were out-of-field failures, 18% were in-field and out-of-field failures, and 18% were in-field and marginal (recurrences within the field edge) failures. There were no isolated marginal failures. Of the patients that developed a LRF, 73% developed a LRF with an in-field component. Sixty-two percent of LRFs were nodal. The median pre-treatment SUVmax for the anatomic region of LRF for patients with an in-field failure was 13. The median D95 of in-field LRF was 63 Gy.ConclusionsLRF after definitive chemoradiation are comprised primarily of in-field failures, though out-of field failures are not insignificant. Marginal failures are rare, indicating field margins are appropriate. Although radiation dose escalation to standard radiation fields has not yielded success, using PET parameters to define high-risk regions remains worthy of further investigation.

Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase I Study

“…We adopted this SBRT boost strategy because approximately 60% of local regional recurrences after conventional chemoradiation involve the mediastinum. 16 In our study, the MTD of a SBRT boost after 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy was 6 Gy  5, with SBRT delivered to residual nodal and primary disease. Additionally, a SBRT boost dose of 10 Gy  2 was well tolerated, with no grade 3 or higher treatment-related AEs.…”

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease

“…The latter showed that biologically equivalent dose (BED) and local control were associated with overall survival. It is known that local control after chemoradiation (60 Gy) is not optimal [44][45][46][47][48], but dose escalation to 74 Gy did not show the anticipated improvements [28] and was primarily associated with increased cardiopulmonary mortality due to higher doses delivered to these organs at risk. On the basis of these considerations, a reirradiation dose of 60-66 Gy can be prescribed if sufficient sparing of organs at risk can be achieved.…”

Dose distribution and tumor control probability in out-of-field lymph node stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy (3D-CRT) of non-small-cell lung cancer: an in silico analysis

“…Several planning studies examined the potential benefits of incidental nodal irradiation of uninvolved lymph node regions when using 3D-CRT [ 7 , 8 , 20 , 21 ]. Even with PET-based IF-RT of stage III NSCLC, rates of out-of-field nodal recurrences can be as high as 10 % and therefore cannot be considered as insignificant [ 22 ]. It is controversial if these recurrences can be attributed either to the small a priori risk of microscopic involvement in elective nodal regions or the benefits of incidental nodal irradiation.…”