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Is There a Definitive Answer to the Question of Involved-Field Radiotherapy for Inoperable Non–Small-Cell Lung Cancer?

Department of Radiation Oncology, Oncoville Clinic, Curitiba, Brazil, and Department of Radiotherapy, Catarinense League Combatting Cancer, Florianopolis, Brazil

To the Editor:

We congratulate Rosenzweig et al¹ on their initiative for trying to elucidate a question of paramount importance to radiation oncology. Given the wealth of data corroborating the practice,^2-5 we, like others, have adopted the policy of involved-field radiotherapy in our institutions. The article published in the December 10, 2007, issue of the Journal of Clinical Oncology, however, raises some concerns that should be addressed.

The main limitation of the article by Rosenzweig et al is the heterogeneity of patients studied. First, the criteria used to diagnose tumors as lymph node positive was not uniform: 60% of patients had an [¹⁸F]fluorodeoxyglucose positron emission tomography scan (FDG-PET) for staging, whereas 11% were given intensity-modulated radiation therapy. Second, there was a wide range of delivered doses (50 to 90 Gy). Third, the combination of radiotherapy and chemotherapy ranged from exclusive radiation in 42% of patients, to sequential chemoradiotherapy (41%), to concurrent chemoradiotherapy (15%). Given that it was not possible to stratify the patients according to all these variables (which would have diminished the statistical differences among the groups), it is difficult to draw definitive conclusions from the study. The range of doses used is particularly concerning because it would be almost mandatory to correlate the results with the prescribed doses.

The authors were surprised that the use of FDG-PET did not influence the elective nodal failure rates. However, this seems typical in cases where the possibility of a type II (β) error cannot be ruled out because the sample size is too small.⁶

Concerning FDG-PET technique, we would appreciate a detailed description of the methods used in obtaining gross tumor volumes. (Do the authors use, for example, "visual interpretation, applying an isocontour of a standardized uptake value of 2.5, using a fixed threshold of 40% and 50% of the maximum signal intensity, and applying an adaptive threshold based on the signal-to-background ratio" to obtain gross tumor volume?)⁷

We agree with Dr Jeremic,⁸ who recognizes the necessity for more extensive translational research with the aim of providing more information on the biologic properties among the several subgroups of patients. In the interim, two articles^9,10 apply an intermediate policy pertaining to elective nodal irradiation and involved-field radiotherapy. These articles build an elegant stratification of patients based on risk factors, thus drawing limited elective radiation fields including some at-risk lymph nodes.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Rosenzweig KE, Sura S, Jackson A, et al: Involved-field radiation therapy for inoperable non–small-cell lung cancer. J Clin Oncol 25:5557-5561, 2007[Abstract/Free Full Text]

2. Rosenzweig KE, Sim SE, Mychalczak B, et al: Elective nodal irradiation in the treatment of non–small-cell lung cancer with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 50:681-685, 2001[CrossRef][Medline]

3. MacManus MP, Hicks RJ, Matthews JP, et al: High rate of detection of unsuspected distant metastases by PET in apparent Stage III non–small-cell lung cancer: Implications for radical radiation therapy. Int J Radiat Oncol Biol Phys 50:287-293, 2001[CrossRef][Medline]

4. Emami B, Mirkovic N, Scott C, et al: The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non–small-cell lung cancer: An analysis of RTOG data. Lung Cancer 41:207-214, 2003[CrossRef][Medline]

5. Le Chevalier T, Arriagada R, Tarayre M, et al: Significant effect of adjuvant chemotherapy on survival in locally advanced non–small-cell lung carcinoma. J Natl Cancer Inst 84:58, 1992[Free Full Text]

6. Riffenburgh RH: Statistics in Medicine (ed 2). Amsterdam, the Netherlands, Elsevier, 2006, pp 397-417

7. Schinagl DAX, Vogel WV, Hoffmann AL, et al: Comparison of five segmentation tools for [¹⁸F]fluorodeoxyglucose positron emission tomography-based target volume definition in head and neck cancer. Int J Radiat Oncol Biol Phys 69:1282-1289, 2007[Medline]

8. Jeremic B: Low incidence of isolated nodal failures after involved-field radiation therapy for non–small-cell lung cancer: Blinded by the light? J Clin Oncol 25:5543-5545, 2007[Free Full Text]

9. Giraud P, Rycke YD, Lavole A, et al: Probability of mediastinal involvement in non–small-cell lung cancer: A statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy? Int J Radiat Oncol Biol Phys 64:127-135, 2006[Medline]

10. Jeremic B: Incidental irradiation of nodal regions at risk during limited-field radiotherapy (RT) in dose-escalation studies in non–small-cell (NSCLC). Enough to convert no-elective into elective nodal irradiation (ENI)? Radiother Oncol 71:123-125, 2004[CrossRef][Medline]

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