A phase I radiation dose escalation of stereotactic body radiotherapy for malignant lung tumors

Abstract

Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.

Share and Cite:

Cohen, R. , Sharma, N. , Yu, J. , Wang, L. , Buyyounouski, M. , Unger, M. , Borghaei, H. , King, E. , Scott, W. , Callahan, E. , Movsas, B. and Feigenberg, S. (2010) A phase I radiation dose escalation of stereotactic body radiotherapy for malignant lung tumors. Journal of Biomedical Science and Engineering, 3, 351-358. doi: 10.4236/jbise.2010.34048.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Mountain, C.F. (1997) Revisions in the international system for staging lung cancer. Chest, 111, 1710-1717.
[2] LeChevalier, T. et al. (1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: First analysis of a randomized trial in 353 Patients. Journal of the National Cancer Institute, 83, 417-423.
[3] Bradley, J., Graham, M.V., Winter, K., Purdy, J.A., Komaki, R., Roa, W.H., Ryu, J.K., Bosch, W. and Emami, B. (2005) Toxicity and outcome results of RTOG 9311: A phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non- small-cell lung carcinoma. International Journal of Radiation Oncology Biology Physics, 61, 318-328.
[4] Narayan, S., Henning, G.T., Ten Haken, R.K., Sullivan, M.A., Martel, M.K. and Hayman, J.A. (2004) Results following treatment to doses of 92.4 or 102.9 Gy on a phase I dose escalation study for non-small cell lung cancer. Lung Cancer, 44, 79-88.
[5] Rosenzweig, K.E., Fox, J.L., Yorke, E., Amols, H., Jackson, A., Rusch, V., Kris, M.G., Ling, C.C. and Leibel, S.A. (2005) Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma. Cancer, 103, 2118-2127.
[6] Martel, M.K., Ten Haken, R.K., Hazuka, M.B., Kessler, M.L., Strawderman, M., Turrisi, A.T., Lawrence, T.S., Fraass, B.A. and Lichter, A.S. (1999) Estimation of tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients. Lung Cancer, 24, 31-37.
[7] Mehta, M., Scrimger, R., Mackie, R., Paliwal, B., Chappell, R. and Fowler, J. (2001) A new approach to dose escalation in non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 49, 23- 33.
[8] Andrews, D.W., Scott, C.B., Sperduto, P.W., Flanders, A.E., Gaspar, L.E., Schell, M.C., Werner-Wasik, M., Demas, W., Ryu, J., Bahary, J.P., Souhami, L., Rotman, M., Mehta, M.P. and Curran, W.J.Jr. (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet, 363, 1665-1672.
[9] Blomgren, H., Lax, I., Naslund, I. and Svanstrom, R. (1995) Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncologica, 34, 861-870.
[10] Fukumoto, S., Shirato, H., Shimzu, S., Ogura, S., Onimaru, R., Kitamura, K., Yamazaki, K., Miyasaka, K., Nishimura, M. and Dosaka-Akita, H. (2002) Small-vol- ume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell lung carcinomas. Cancer, 95, 1546-1553.
[11] Hara, R., Itami, J., Kondo, T., Aruga, T., Abe, Y., Ito, M., Fuse, M., Shinohara, D., Nagaoka, T. and Kobiki, T. (2002) Stereotactic single high dose irradiation of lung tumors under respiratory gating. Radiotherapy and Oncology, 63, 159-163.
[12] Harada, T., Shirato, H., Ogura, S., Oizumi, S., Yamazaki, K., Shimizu, S., Onimaru, R., Miyasaka, K., Nishimura, M. and Dosaka-Akita, H. (2002) Real-time tumor- tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy. Cancer, 95, 1720-1727.
[13] Herfarth, K.K., Debus, J., Lohr, F., Bahner, M.L., Fritz, P., Hoss, A., Schlegel, W. and Wannenmacher, M.F. (2000) Extracranial stereotactic radiation therapy: Set-up accuracy of patients treated for liver metastases. International Journal of Radiation Oncology Biology Physics, 46, 329- 335.
[14] Nagata, Y., Takayama, K., Matsuo, Y., Norihisa, Y., Mizowaki, T., Sakamoto, T., Sakamoto, M., Mitsumori, M., Shibuya, K., Araki, N., Yano, S. and Hiraoka, M. (2005) Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. International Journal of Radiation Oncology Biology Physics, 63, 1427-1431.
[15] Negoro, Y., Nagata, Y., Aoki, T., Mizowaki, T., Araki, N., Takayama, K., Kokubo, M., Yano, S., Koga, S., Sasai, K., Shibamoto, Y. and Hiraoka, M. (2001) The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy. International Journal of Radiation Oncology Biology Physics, 50, 889-898.
[16] Timmerman, R., Papiez, L., McGarry, R., Likes, L., DesRosiers, C., Frost, S. and Williams, M. (2003) Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer. Chest, 124, 1946-1955.
[17] Uematsu, M., Shioda, A., Tahara, K., Fukui, T., Yamamoto, F., Tsumatori, G., Ozeki, Y., Aoki, T., Watanabe, M. and Kusano, S. (1998) Focal, high dose, and fractionated modified stereotactic radiation therapy for lung carcinoma patients: A preliminary experience. Cancer, 82, 1062- 1070.
[18] Wulf, J., Hadinger, U., Oppitz, U., Olshausen, B. and Flentje, M. (2000) Stereotactic radiotherapy of extracranial targets: CT-simulation and accuracy of treatment in the stereotactic body frame. Radiotherapy and Oncology, 57, 225- 236.
[19] Herfarth, K.K., Debus, J., Lohr, F., Bahner, M.L., Rhein, B., Fritz, P., Hoss, A., Schlegel, W. and Wannenmacher, M.F. (2001) Stereotactic single-dose radiation therapy of liver tumors: Results of a phase I/II trial. Journal of Clinical Oncology, 19, 164-170.
[20] Wang, L., Feigenberg, S., Chen, L., Pasklev, K. and Ma, C.C. (2006) Benefit of three-dimensional image-guided stereotactic localization in the hypofractionated treatment of lung cancer. International Journal of Radiation Oncology Biology Physics, 66, 738-747.
[21] Wang, L., Hayes, S., Paskalev, K., Jin, L., Buyyounouski, M.K., Ma, C.C. and Feigenberg, S. (2008) Dosimetric comparison of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: Evaluation of the impact on daily dose coverage. Radiotherapy and Oncology, 91, 314-324.
[22] Jin, L., Wang, L., Li, J., Luo, W., Feigenberg, S.J. and Ma, C.M. (2007) Investigation of optimal beam margins for stereotactic radiotherapy of lung-cancer using Monte Carlo dose calculations. Physics in Medicine and Biology, 52, 3549-3561.
[23] Babb, J., Rogatko, A. and Zacks, S. (1998) Cancer phase I clinical trials: Efficient dose escalation with overdose control. Statistics in Medicine, 17, 1103-1120.
[24] Zacks, S., Rogatko, A. and Babb, J. (1998) Optimal bay- esian-feasible dose escalation for cancer phase I trials. Statistics & probability letters, 38, 215-220.
[25] Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A.T., Christian, M.C. and Gwyther, S.G. (2000) New guidelines to evaluate the response to treatment in solid tumors. Journal of the National Cancer Institute, 92, 205-216.
[26] Baumann, P., Nyman, J., Hoyer, M., Gagliardi, G., Lax, I., Wennberg, B., Drugge, N., Ekberg, L., Friesland, S., Johansson, K.A., Lund, J.S., Morhed, E., Nilsson, K., Levin, N., Paludan, M., Sederholm, C., Traberg, A., Wittgren, L. and Lewensohn, R. (2008) Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study. Radiotherapy and Oncology, 88, 359-367.
[27] Baumann, P., Nyman, J., Hoyer, M., Wennberg, B., Gagliardi, G., Lax, I., Drugge, N., Ekberg, L., Friesland, S., Johansson, K.A., Lund, J.A., Morhed, E., Nilsson, K., Levin, N., Paludan, M., Sederholm, C., Traberg, A., Witt- gren, L. and Lewensohn, R. (2009) Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. Journal of Clinical Oncology, 27, 3290-3296.
[28] Fakiris, A.J., McGarry, R.C., Yiannoutsos, C.T., Papiez, L., Williams, M., Henderson, M.A. and Timmerman, R. (2009) Stereotactic body radiation therapy for early- stage non-small-cell lung carcinoma: Four-year results of a prospective phase II study. International Journal of Radiation Oncology Bilolgy Physics, 75, 677-682.
[29] Onishi, H., Araki, T., Shirato, H., Nagata, Y., Hiraoka, M., Gomi, K., Yamashita, T., Niibe, Y., Karasawa, K., Hayakawa, K., Takai, Y., Kimura, T., Hirokawa, Y., Takeda, A., Ouchi, A., Hareyama, M., Kokubo, M., Hara, R., Itami, J. and Yamada, K. (2004) Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer, 101, 1623-1631.
[30] Onishi, H., Shirato, H., Nagata, Y., Hiraoka, M., Fujino, M., Gomi, K., Niibe, Y., Karasawa, K., Hayakawa, K., Takai, Y., Kimura, T., Takeda, A., Ouchi, A., Hareyama, M., Kokubo, M., Hara, R., Itami, J., Yamada, K. and Araki, T. (2007) Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: Updated results of 257 patients in a Japanese multi-institutional study. Journal of Thoracic Oncology, 2, S94- 100.
[31] Voroney, J.P.J. et al. (2008) Pain and rib fracture after stereotactic radiotherapy for peripheral non-small cell lung cancer. International Journal of Radiation Oncology Biology Physics, 72, S35-36.
[32] Dunlap, N.E. et al. (2008) Chest wall volume receiving more than 30 Gy predicts risk of severe pain and/or rib fracture following lung SBRT. International Journal of Radiation Oncology Biology Physics, 72, S36.
[33] Stephens, K.L. et al. (2008) A comparison of Stereotactic Body Radiation (SBRT) fractionation schedules for stage I non-small cell lung cancer (NSCLC): The cleveland clinic experience. International Journal of Radiation Oncology Biology Physics, 72, S38-39.
[34] Forquer, J.A. et al. (2008) Brachial Plexopathy (BP) from Stereotactic Body Radiotherapy (SBRT) in early- stage NSCLC: Dose-limiting toxicity in apical tumor sites. International Journal of Radiation Oncology Biology Physics, 72, S36.
[35] Timmerman, R., Paulus, R., Galvin, J.M., Michalski, J., Straube, W.L., Bradley, J., Fakiris, A., Bezjak, A., Videtic, G. and Choy, H. (2007) Toxicity analysis of RTOG 0236 using stereotactic body radiation therapy to treat medically inoperable early stage lung cancer patients. International Journal of Radiation Oncology Bilolgy Physics, 69, S86.
[36] Guerrero, M. and Li, X.A. (2004) Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Physics in Medicine and Biology, 49, 4825-4835.
[37] Nataf, F., Schlienger, M., Liu, Z., Foulquier, J.N., Gres, B., Orthuon, A., Vannetzel, J.M., Escudier, B., Meder, J.F., Roux, F.X. and Touboul, E. (2008) Radiosurgery with or without A 2-mm margin for 93 single brain metastases. International Journal of Radiation Oncology Bilolgy Physics, 70, 766-772.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.