Low Incidence of Isolated Nodal Failures After Involved-Field Radiation Therapy for Non–Small-Cell Lung Cancer: Blinded by the Light?
Authors: Branislav Jeremić
Journal: Journal of Clinical Oncology (2007)

More than 15 years ago, National Cancer Institute contracted with several institutions to introduce three-dimensional (3D) treatment planning in radiotherapy (RT) of various tumors. Four institutions embarked on this project in lung cancer; Memorial Sloan-Kettering Cancer Center (New York, NY) was one of these. In this issue of the Journal of Clinical Oncology, Rosenzweig et al present the data that can be seen as one of the final stages of that endeavor in lung cancer, with the largest number of patients with stages I-III non–small-cell lung cancer (NSCLC) presented to date, addressing the issue of involved-field RT (IFRT) in this disease. They have shown that using IFRT led to only an 8% rate of isolated nodal failures, similar to observations by other investigators in a similar setting. These data fit perfectly with other threedimensional conformal radiotherapy (3D-CRT) data and more conventional data obtained before 3D-CRT, which are all uniform, regardless of the total RT dose, fractionation regimen, or geography. As previously summarized, uniformity of the data (a range of 0% to 7% of isolated nodal recurrences was observed) clearly indicate IFRT as the preferred treatment option. In addition, some (stage III) patients do not live long enough for their nodal failures after IFRT to become evident. Finally, nodal recurrences are few in RT series and we do not have clear indication about salvage therapy, although postsurgical nodal recurrences treated with RT have poor prognosis. Overshadowing RT data are legitimate fears that none of these studies actually looked at nodal recurrences prospectively, especially once distant failures occurred. In addition, none of these studies provided pathologic confirmation of the status of nodal disease, nor data from autopsy findings. Interestingly, the best overall results were achieved when elective nodal irradiation (ENI) was used. Then come cold-blooded surgical data were obtained. When the initial clinical staging based on computed tomography scanning was ultimately verified during surgery, the incidence of nodal metastases in stage I NSCLC was as high as 25% to 35%. Even in the smallest tumors, unsuspected lymph node metastasis was observed to be 18% in T1a ( 2 cm) and 23% in T1b (2 to 3 cm) tumors. With increasing tumor size ( 1.0, 1.1 to 2.0, and 2.0 cm) the incidence of lymphatic invasion/metastasis increases (0%, 17%, and 38%, respectively). When immunohistochemistry was used in patients with peripheral adenocarcinomas of 2.0 cm, occult nodal metastases were detected in 20% of patients (immunohistochemistry is an independent prognosticator of survival), which is in agreement with other studies. In addition, occult nodal metastases were significantly more frequent in poorly differentiated tumors. Finally, the preferred or mandatory surgical approach suggested as treatment for even T1N0 patients (ie, lobectomy) would include systematic removal of all hilar and mediastinal lymph nodes. Extrapolating these principles to RT would include the use of larger RT fields to treat some, if not all, lymph node regions. Thus, we have a large discrepancy among RT data, suggesting no ENI on one end of the spectrum, and at the opposite pole, interpretation of the surgical data (by a radiation oncologist) leading to a suggestion that larger RT field, using ENI (corresponding to a surgical field), should be used. There may be intrinsic differences between the biologic characteristics of tumors of surgical patients and those of RT patients, but to date there is no clear answer to that provocative question. Assuming no such differences between the biologic characteristics of tumors, what should one then do? Discard RT data as low-quality data and reinstitute ENI based on surgery-only data? This approach does not seem either reasonable or realistic. Radiation oncologists would continue using IFRT based on the data available and the low incidence of nodal failures without ENI. Furthermore, there is not much opportunity to escalate the 3DCRT dose meaningfully without IFRT, which remains the most compelling reason for insisting on IFRT. If this is going to happen, what is the future in this field— indiscriminate use of IFRT? In addition, this approach is neither reasonable nor realistic, given that radiation oncologists dealing with lung cancer cannot simply leave their heads in the sand, saying they have never heard of surgical data; it would be similar to claiming Editors are not the biggest band in the United Kingdom nowadays. Ultimately, the question is not whether we should use ENI, but that if we should, how then would we identify the target population? One possible scenario would be to include more translational research in this field by gathering more information on the biologic properties and differences between various subgroups of patients/tumors (eg, stage I v stage II v stage III; histology, tumor grade, and so on) before one can advocate IFRT, ENI, or, likely, selective ENI, in various patient populations. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 35 DECEMBER 1