High-Dose Radiotherapy in Patients With Stage III Non-Small Cell Lung Cancer in Practical Experience

I. J. Radiation Oncology d Biology d Physics

S522

Volume 69, Number 3, Supplement, 2007

Conclusions: With proper planning, IMRT with gating can reduce both the normal lung dose and the esophageal dose compared to 3D CRT in most patients. Constraining esophageal dose can be performed without sacrificing PTV coverage and quality of the plan. Table 1: Mean Change in Dosimetric Parameters from 3D to IMRT Mean Lung Mean Change Range

1.9 Gy (11%) 3.4 to 0.8 Gy

V20 Lung 5.8% 10% to 5.9%

V5 Lung Mean Esophagus V50Esophagus V60Esophagus D30Esophagus 3.4% 11% to 19.2%

4.9 Gy (14%) 9.9 Gy to 1.4 Gy

9.5% 21.7% to 3.2%

8.4% 30.4% to 7.2%

D50Esophagus

5.1 Gy (29%) 12.2 Gy to 11.3 Gy

9.5 Gy (21%) 23.2 Gy to 0.2 Gy

Author Disclosure: M.K. Garg, Varian TPS, F. Consultant/Advisory Board; M. Castillo, None; P. Scripes, None; J. Shen, None; E. Milan, None; W. Skinner, None; S. Kalnicki, None; D. Mah, None.

2574

Clinical Outcomes and Treatment Planning Strategies for Advanced-Stage Non-Small Cell Lung Cancer (NSCLC) Treated With Intensity Modulated Radiation Therapy (IMRT) and Concurrent Chemotherapy (CCT)

K. Ohnishi, H. Liu, Z. Liao, S. S. Yom, H. Jin, X. Wei, P. K. Allen, S. L. Tucker, R. Mohan, R. Komaki The University of Texas M. D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): IMRT has been used in our institution to treat locally advanced NSCLC patients for whom normal tissue constraints could not be met using 3D conformal radiotherapy (3DCRT). The purposes of this study are 1) to review the clinical outcomes of this patient cohort; and 2) to establish corresponding clinical guidelines for IMRT treatment planning. Materials/Methods: Clinical data were reviewed for lung cancer patients treated with IMRT at our institution from 2002 to 2005. The patient cohort included those who had Stage III-IV NSCLC, and who had definitive concurrent chemoradiation. Patients were excluded if they had a history of major lung surgery, prior chest radiotherapy, or mixed 3DCRT and IMRT plans. Clinical outcomes and major toxicities including pneumonitis and esophagitis were analyzed based on medical records and clinical follow-up. IMRT treatment plans and dosimetric parameters were reviewed. Guidelines for IMRT treatment planning were developed based on the existing clinical outcome and dosimetry data. Results: In total, 83 patients were included in this study, 93% of whom were Stage III NSCLC. The histology types were adenocarcinoma (36%), squamous cell (35%), and unspecified non-small cell (29%). 59% of patients were treated to a dose range of 63–66 Gy, with the rest treated above 66 Gy (23%), or within 60–63 Gy (18%). The median follow-up time was 10 months (range, 1.1–43.8 months). The 18 month locoregional control, disease free survival, and overall survival were 63%, 38%, and 62%, respectively. The rate of grade 3 and higher treatment-related pneumonitis at 12 months was 11%. The rate of grade 3 and higher acute esophagitis was 35%. In achieving effective IMRT treatment plans, mean lung dose and the volume of normal lung receiving low-dose radiation were used as important constraints to minimize pulmonary toxicity. The number of IMRT beams was limited within the range of 5–7, with the beam angles being carefully selected to spare healthy lung. The other physical parameters that affected low-dose radiation and were thus considered during IMRT treatment planning included the number of MLC segments and monitor units used. Conclusions: IMRT may be effective in treating advanced NSCLC with concurrent chemotherapy. Dose distributions for IMRT treatments need careful planning considering normal tissue toxicity and minimization of exposure to healthy lung. Author Disclosure: K. Ohnishi, None; H. Liu, None; Z. Liao, None; S.S. Yom, None; H. Jin, None; X. Wei, None; P.K. Allen, None; S.L. Tucker, None; R. Mohan, None; R. Komaki, None.

2575

High-Dose Radiotherapy in Patients With Stage III Non-Small Cell Lung Cancer in Practical Experience

H. Nakayama1,2, K. Tokuuye1,2, H. Ishikawa3, K. Kurishima3, K. Kanamoto3, S. Kikuchi4, H. Ichimura4 1 Tsukuba University, Proton Medical Research Center, Tsukuba, Japan, 2Tsukuba Medical Center, Division of Radiationoncology, Tsukuba, Japan, 3Tsukuba Medical Center, Division of Respiratory Medicine, Tsukuba, Japan, 4 Tsukuba Medical Center, Division of Thoracic Surgery, Tsukuba, Japan

Purpose/Objective(s): To retrospectively evaluate the efficacy of high-dose radiotherapy in patients with stage III non-small cell lung cancer. Materials/Methods: Between May 1999 and April 2006, 100 patients with inoperable non-small cell lung cancer stage IIIA and IIIB with a performance score of 0–2 were treated by radical radiotherapy and chemotherapy. Thirty-three patients, grouped into a low-dose group, underwent radiotherapy of 56 Gy to under 66 Gy by Aug. 2002; and the remaining 67 patients, grouped into a high-dose group, underwent radiotherapy of 66 Gy up to 84 Gy using three-dimensional conformal radiotherapy after Sep. 2002. All target contouring was performed by the same radiation oncologist during the entire period. Survival rates were compared between the two groups. Results: The median survival duration was 22.3 months for the high-dose group and 13.3 months for the low-dose group, demonstrating a significant difference between the two groups (log-rank test, p = 0.015). The median survival duration was 22.7 months for patients receiving concurrent chemotherapy and 15.2 months for those receiving a sequential chemotherapy, demonstrating a significant difference between the two groups (p = 0.042). Performance score (hazard ratio 0.30, p = 0.001), radiotherapy dose (hazard ratio 0.32, p = 0.002) and weight loss (hazard ratio 2.03, p = 0.011) were shown to be statistically significant independent prognostic factors through multivariate analysis.

Proceedings of the 49th Annual ASTRO Meeting

S523

Conclusions: High-dose radiotherapy using three-dimensional radiotherapy improved the survival of patients with stage III non-small cell lung cancer in practical experience. Author Disclosure: H. Nakayama, None; K. Tokuuye, None; H. Ishikawa, None; K. Kurishima, None; K. Kanamoto, None; S. Kikuchi, None; H. Ichimura, None.

2576

IMRT Treatment for Locally Advanced Non-Small Cell Lung Cancer Achieves Low Levels of Pulmonary Irradiation Including the Low-Dose Volume, V 5 Gy, Along With Low Levels of Esophageal and Cardiac Irradiation

A. Chandra, J. D. Mitchell, A. McCarthy, A. Chachoua, G. Jozsef, K. DeWyngaert, H. I. Pass, S. Formenti NYU Medical Center, New York, NY Purpose/Objective(s): To study if low levels of normal tissue irradiation can be achieved with Intensity Modulated Radiotherapy (IMRT) in treatment planning of locally advanced non-small cell lung cancer (NSCLC). Materials/Methods: 26 patients with locally advanced (stage III) NSCLC were planned with IMRT. The prescribed dose was standard 63 Gy to cover $95% PTV. IMRT planning was performed with intent to minimize the volumes of normal lungs, heart, and esophagus irradiated. Commonly utilized dosimetric indices for the GTV, PTV, total lung, esophagus, heart, and the spinal cord were computed and compared to prominent publications for similar studies by Yoma et al and Murshedb et al. These authors have shown that IMRT reduces normal tissue doses compared to 3DCRT. Results: Target coverage of the GTV and PTV was considered adequate and the minimum mean dose of the GTV and PTV was 64.8 Gy and 63.6 Gy, respectively. Median (range) dose covering $95% of the PTV was 62.9 Gy (57.3–63.9). Median (range) volume of the PTV receiving 63 Gy was 95% (82.2–98.8). The associated Table shows low levels of pulmonary irradiation along with other indices. Low levels of esophageal and cardiac irradiation were achieved at volumes receiving $30 Gy (V30), $40 Gy (V40), $50 Gy (V50), and $60 Gy (V60). For esophagus, the median (ranges) is as follows: (V40) 39% (0–61); (V50) 32% (0–60); (V60) 22% (0–58); mean dose 28.5 Gy (3.4–42.2). For heart, the median (ranges) is as follows: (V30) 14% (0–47); (V40) 11% (0–38); (V50) 8% (0–31). The median (range) spinal cord maximum dose was 43 Gy (14.6–47.1). Although, 3DCRT is not performed as control for each patient, it can be noted that our IMRT results generally parallel the IMRT data of Yoma and Murshedb et al. In distinction, this IMRT study shows a low volume of total lung receiving the low-dose of $5 Gy (V5) with a median of 50%, whereas studies by Yoma and Murshedb et al show median V5 of 63% and 59%, respectively. Conclusions: It is possible for IMRT to achieve low levels of pulmonary irradiation including the V5 by focusing on the low-dose lung volume as a constraint, using fewer beams, and carefully selecting beam angles. This is important as previous studiesa,b had noted an increase in V5 with IMRT for lung tumors. Low levels of esophageal and cardiac irradiation were also noted. Whether the dosimetric advantages of IMRT will translate into clinical reduction of normal tissue toxicity needs to be evaluated in clinical trials. a b

Yom et al. Initial evaluation of... Int J Radiat Oncol Biol Phys. 2007 Feb 21. Murshed et al. Dose and volume... Int J Radiat Oncol Biol Phys. 2004 Mar 15;58(4):1258–67.

Median (ranges) of our IMRT dosimetric indices in comparison to those by Murshed and Yom et al Parameters GTV Volume (cc) PTV Volume (cc) # of beams Total Lung: V5 Gy (%) Total Lung: V10 Gy (%) Total Lung: V20 Gy (%) Total Lung: Mean Dose (Gy) Esophagus: V55 Gy (%) Heart: V40 Gy (%)

Present Study: IMRT 253 (15–870) 626 (103–1322) 5 (3–8) coplanar & non-coplanar 50 (10–68) 40 (9–54) 27 (8–34) 17 (5–23) 27 (0–59) 11 (0–38)

Murshed et al: 3DCRT

Murshed et al: IMRT

Yom et al: 3DCRT

Yom et al: IMRT

121 (4–535) 623 (75–1645) 3–6 coplanar

121 (4–535) 623 (75–1645) 9 equidistant coplanar 59 (25–78) 38 (18–59) 25 (13–43) 17 (9–27) 29 (0–71) 11 (0–59)

142 (1.5–1186) N/A 3–6 coplanar

194 (21–911) N/A 5–6 generally coplanar 63 (5–98) 48 (4–89) 35 (3–48) 21 (2–36) N/A N/A

52 (28–86) 45 (22–64) 35 (17–55) 19 (10–29) 35 (0–72) 13 (0–58)

57 (12–98) 49 (10–92) 38 (8–78) 22 (5–44) N/A N/A

Author Disclosure: A. Chandra, None; J.D. Mitchell, None; A. McCarthy, None; A. Chachoua, None; G. Jozsef, None; K. DeWyngaert, None; H.I. Pass, None; S. Formenti, None.

2577

Consolidation Therapy Using Cyberknife Radiosurgery in Non-Small Cell Lung Cancer Patients With Low-Volume Residual Disease After Completion of Systemic Therapy

M. P. McLaughlin Wellstar Kennestone Hospital, Marietta, GA Background: Pts with unresectable IIIB and IV NSCLC with PS 0–1 are usually treated with chemotherapy (CH) ± targeted therapy (TT) with overall survival (OS) improvement. Upon completion, standard of care is observation. Pts eventually progress within 9 to 12 months. If still in good PS, they are treated with salvage CH or TT; otherwise, they receive palliative care. We evaluated 36 patients with PR to initial therapy, found to have small volume residual disease (SVRD) defined as one or two sites to receive ‘‘consolidation’’ local therapy with Cyberknife Radisurgery (CRS). Methods: Since September 2006, 36 pts with NSCLC, stage IIIB unresectable (9) or IV (27), median age 64 (range 61–78), adenocarcinoma (21), squamous cell carcinoma (15), 27 males, all ECOG PS 0–1, were treated with induction CH (carboplatin/