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Stereotactic Radiotherapy for Centrally Located Early-Stage Lung Tumors

Departments of Radiation Oncology and Pulmonology, VU University Medical Center, Amsterdam, the Netherlands

To the Editor:

Timmerman et al¹ reported that stereotactic radiotherapy (SRT) to a dose of between 60 and 66 Gy delivered in three fractions, is inappropriate for centrally located primary lung tumors as the 2-year freedom from severe toxicity rate is 54%. However, the conclusions of their data safety monitoring committee regarding toxicity should be viewed with caution. Labeling toxicity as SRT related when coexisting bacterial pneumonia is present in patients with severe chronic obstructive pulmonary disease and in part oxygen dependent, or when hemoptysis occurs in the presence of central tumor progression, appears questionable, to say the least. In addition, these results have to be viewed in the light of the alternative scenarios, namely a surgical mortality for treatment of centrally located lung cancer which can be up to 10% for pneumonectomies² and/or the unacceptable local control rates after conventional radiotherapy.³ Therefore, we suggest that only the incidence of grade 4 to 5 nonreversible toxicity is of clinical relevance in such patients.

The Timmerman et al phase II study commenced in 2002 and some aspects of SRT delivery would not be considered optimal at the present time. A single treatment planning computed tomography (CT) scan was used, with standard margins of 10 mm added to the gross tumor volume in order to derive a planning target volume. Recent work has shown that a single four-dimensional (or respiration-correlated) CT is preferred for SRT planning as it allows for use of individual margins for tumor mobility, and results in planning target volumes that are, on average, 50% smaller than the approach described in their study.⁴ The irradiation of excessive amounts of healthy tissue is linked to excessive toxicity when central tumors are treated.⁵ Furthermore, the SRT doses used in their study delivered biologic effective doses (BED) far in excess of the estimated BED of 100 Gy required for optimal local control in stage I non–small-cell lung cancer. ^6-8 Patients treated in their phase II trial received doses of 60 Gy (BED, 180 Gy) and 66 Gy (BED, 211 Gy), respectively.⁶

Dose-dependent late bronchial, cardiac, and esophageal toxicity has been reported after conventionally fractionated high-dose radiotherapy or chemoradiotherapy for lung tumors.⁹ As such, we have treated tumors in the proximity of the hilus, main bronchus, or pericardium with eight fractions of 7.5 Gy (BED, 105 Gy) since 2003, in order to reduce the toxicity risk.¹⁰ An SRT scheme of five fractions of 12 Gy (BED, 132 Gy) was used for T2 lesions and for T1 tumors in close proximity to the chest wall. A total of 20 patients in the first group and 78 in the second group have been prospectively followed up with serial CT scans and patient-scored quality of life assessment. Early results indicate no excessive acute toxicity and no deterioration in quality of life.¹⁰ Our results indicate that SRT should continue to also be evaluated for centrally located tumors, using optimal four-dimensional CT-based treatment planning and delivery, and in conjunction with schemes with a BED of approximately 100 to 110 Gy.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Timmerman R, McGarry R, Yiannoutsos C, et al: Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 24:4833-4839, 2006[Abstract/Free Full Text]

2. Damhuis R, Coonar R, Plaisier P, et al: A case-mix model for monitoring of postoperative mortality after surgery for lung cancer. Lung Cancer 51:123-129, 2006[CrossRef][Medline]

3. Arriagada R, Le Chevalier T, Quoix E, et al: Effect of chemotherapy on locally advanced non-small cell lung carcinoma: A randomized study of 353 patients. Int J Radiat Oncol Biol Phys 20:1183-1190, 1991[Medline]

4. Underberg RWM, Lagerwaard FJ, Cuijpers JP, et al: 4-dimensional CT scans for treatment planning in stereotactic radiotherapy for stage I lung cancer. Int J Radiat Oncol Biol Phys 60:1283-1290, 2004[CrossRef][Medline]

5. Onimaru R, Shirato H, Shimizu S, et al: Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers. Int J Radiat Oncol Biol Phys 56:126-135, 2003[CrossRef][Medline]

6. Fowler JF, Tome WA, Fenwick JD, et al: A challenge to traditional radiation oncology. Int J Radiat Oncol Biol Phys 60:1241-1256, 2004[CrossRef][Medline]

7. Onishi H, Araki T, Shirato H, et al: Stereotactic hypofractionated high-dose irradiation for stage I non-small cell lung carcinoma: Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer 101:1623-1631, 2004[CrossRef][Medline]

8. Wulf J, Baier K, Mueller G, et al: Dose-response in stereotactic irradiation of lung tumors. Radiother Oncol 77:83-87, 2005[CrossRef][Medline]

9. Miller KL, Shafman TD, Anscher MS, et al: Bronchial stenosis: An underreported complication of high-dose external beam radiotherapy for lung cancer? Int J Radiat Oncol Biol Phys 61:64-69, 2005[CrossRef][Medline]

10. Lagerwaard FJ, van der Geld Y, Slotman BJ, et al: Quality of life after stereotactic radiotherapy for medically inoperable stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 66: S133-S134, 2006 (suppl 1; abstr 1009)

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