Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):414-9.

Dose escalation for locally advanced lung cancer using adaptive radiation therapy with simultaneous integrated volume-adapted boost.

Weiss E, Fatyga M, Wu Y, Dogan N, Balik S, Sleeman W 4th, Hugo G.

Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298, USA.



PURPOSE: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer.

METHODS AND MATERIALS: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2).

RESULTS: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase.

CONCLUSIONS: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Copyright © 2013 Elsevier Inc.

PMID: 23523321



Lung cancer is the most frequent cause of cancer death in both men and women with 85% of patients being diagnosed at an advanced stage. While therapy has improved, 5-year lung cancer survival is only 18%. Radiotherapy combined with chemotherapy is the standard therapy for inoperable locally advanced non-small cell lung cancer resulting in large loco-regional failure rates of nearly 50%, with many patients also developing distant metastases.

Higher radiotherapy dose has been shown in several studies to increase both loco-regional tumor control and overall survival in lung cancer. However, lung tumors are often adjacent to critical organs such as the heart and esophagus. Also, the lungs themselves are sensitive to radiation treatment.  The radiation toxicity of these normal tissues is radiation dose dependent, which limits the increase of radiation dose and necessitates new approaches to safely increase tumor dose. The ability to more precisely target lung cancer, avoid normal tissue toxicities, improve the therapeutic ratio and thereby patient survival is hindered by geometrical variation. These include respiratory motion of tumor and involved lymph nodes, tumor regression during therapy and changes in the tumor position relative to visible anatomical landmarks and normal tissue.

Image-guided adaptive radiotherapy (IGART) has emerged as a new treatment paradigm for individualized management of geometric variation by iteratively updating, or adapting, the radiotherapy treatment plan in a feedback loop. Several recent technical developments have made the development of IGART possible. These include management of respiratory motion, e.g., using controlled breath holds, repeated assessment of the tumor position and volume changes through adequate imaging during treatment, and validated methods to accurately accumulate the observed geometrical and dosimetrical variations during treatment. Applying these techniques to radiotherapy enables better tumor targeting, improved sparing of normal tissue structures and is expected to allow safe increase of treatment dose with the hope that this technology will improve tumor control.

The figure below exemplifies the method used in the published study. Treatment planning was adapted twice during therapy to account for position and volume changes of tumor and lymph nodes. In addition, a boost dose was delivered to the shrunken lung tumor simultaneously with the larger treatment volumes, thereby avoiding prolonged treatment times.

Elisabeth Weiss-PIC

Acknowledgements: This work has been supported by grants P01CA116602 and P30CA016059 of the National Institute of Health, USA.

Contact: Elisabeth Weiss, MD, Department of Radiation Oncology, Virginia Commonwealth University, 401 College Street, PO Box 980058, Richmond, VA 23298, phone: 804-828-9463, fax: 804-828-6042, e-mail:


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