Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients.

PURPOSE: To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. METHODS AND MATERIALS: Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. RESULTS: The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. CONCLUSIONS: Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.

Phase I trial of radiation with concurrent and consolidation pemetrexed and cisplatin in patients with unresectable stage IIIA/B non-small-cell lung cancer.

PURPOSE: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy. RESULTS: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. CONCLUSIONS: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

Chest wall pain and rib fracture after stereotactic radiotherapy for peripheral non-small cell lung cancer.

Stereotactic body radiotherapy is an emerging treatment option for peripheral non-small cell lung cancer in medically inoperable patients. With high dose per fraction radiotherapy, late side effects are of possible concern. In our initial cohort of 42 patients treated with 54 to 60 Gy in three fractions, nine patients have rib fracture. The median dose to rib fracture sites was 46 to 50 Gy, depending on the method of dose calculation. We describe a typical case of poststereotactic radiotherapy rib fracture and present dosimetric analysis of patients with rib fracture.

Practical considerations arising from the implementation of lung stereotactic body radiation therapy (SBRT) at a comprehensive cancer center.

INTRODUCTION: With the anticipation of improved outcomes, especially for patients with early-stage non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has been rapidly introduced into the thoracic radiation oncology community. Although at first glance lung SBRT might seem methodologically similar to conventional radiotherapy, there are important differences in its execution that require particular consideration. The objective of this paper is to highlight these and other issues to contribute to the safe and effective diffusion of lung SBRT. We discuss practical challenges that have been encountered in the implementation of lung SBRT at a single, large institution and emphasize the importance of a systematic approach to the design of lung SBRT services. METHODS: Specific technical and clinical components that were identified as being important during the development of lung SBRT at Princess Margaret Hospital are described. The clinical system that evolved from these is outlined. RESULTS: Using this clinical framework the practical topics addressed include: patient assessment, simulation and treatment planning, tumor and organ at risk delineation, trial set up before treatment, on-line image-guidance, and patient follow-up. CONCLUSIONS: The potential gain in therapeutic ratio that is theoretically possible with lung SBRT can only be realized if the tumor is adequately irradiated and normal tissue spared. A discussion of the component parts of lung SBRT is presented. It is a complex process and specific challenges need to be overcome to effect the satisfactory transition of lung SBRT into routine practice.

Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy.

PURPOSE: Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. METHODS AND MATERIALS: Twenty patients received permanent seed 125I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. RESULTS: The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). CONCLUSION: Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.

Sequential evaluation of prostate edema after permanent seed prostate brachytherapy using CT-MRI fusion.

PURPOSE: To analyze the extent and time course of prostate edema and its effect on dosimetry after permanent seed prostate brachytherapy. METHODS AND MATERIALS: Twenty patients scheduled for permanent seed (125)I prostate brachytherapy agreed to a prospective study on postimplant edema. Implants were preplanned using transrectal ultrasonography. Postimplant dosimetry was calculated using computed tomography-magnetic resonance imaging (CT-MRI) fusion on the day of the implant (Day 1) and Days 8 and 30. The prostate was contoured on MRI, and the seeds were located on CT. Factors investigated for an influence on edema were the number of seeds and needles, preimplant prostate volume, transitional zone index (transition zone volume divided by prostate volume), age, and prostate-specific antigen level. Prostate dosimetry was evaluated by the percentage of the prostate volume receiving 100% of the prescribed dose (V(100)) and percentage of prescribed dose received by 90% of the prostate volume (D(90)). RESULTS: Prostate edema was maximal on Day 1, with the median prostate volume 31% greater than preimplant transrectal ultrasound volume (range, 0.93-1.72; p < 0.001) and decreased with time. It was 21% greater than baseline at Day 8 (p = 0.013) and 5% greater on Day 30 (p < 0.001). Three patients still had a prostate volume greater than baseline by Day 30. The extent of edema depended on the transition zone volume (p = 0.016) and the preplan prostate volume (p = 0.003). The median V(100) on Day 1 was 93.6% (range, 86.0-98.2%) and was 96.3% (range, 85.7-99.5%) on Day 30 (p = 0.079). Patients with a Day 1 V(100) >93% were less affected by edema resolution, showing a median increase in V(100) of 0.67% on Day 30 compared with 2.77% for patients with a V(100) <93 % on Day 1. CONCLUSION: Despite the extreme range of postimplant edema, the effect on dosimetry was less than expected. Dose coverage of the prostate was good for all patients during Days 1-30. Our data indicate that postimplant dosimetry on the day of implant is sufficient for patients with good dose coverage (Day 1 V(100) >93%).

Factors predicting an increased dose to the penile bulb in permanent seed prostate brachytherapy.

PURPOSE: Erectile dysfunction following permanent seed brachytherapy for prostate cancer may be related to the dose to the penile bulb. We investigated anatomic and dosimetric factors that might contribute to an increased dose to the penile bulb. METHODS AND MATERIALS: One-month CT and MR images were examined for 50 consecutive patients treated with exclusive (125)I permanent seed prostate brachytherapy to a prescribed dose of 145 Gy. Implants were preplanned by transrectal ultrasound (TRUS). Postimplant dosimetry was performed at 1 month using an MRI-CT fusion. Spearman's correlation was used to establish a correlation between dosimetric parameters, anatomical factors, and the dose to the penile bulb. RESULTS: Penile bulb volumes ranged from 1.2-8.5 cc (median, 3.9 cc). The distance from the penile bulb to the prostate apex ranged from 5-33 mm (median, 15.5 mm). D50 of the penile bulb ranged from 13-121 Gy. The range for the V45 (65 Gy) was 0-87%; only 3% of patients had >2 cc covered by this isodose and in 16% of patients the V45 covered more than 50% of the penile bulb. About one-third of the patients received a dose to the bulb that would put them at a high risk of erectile dysfunction after external beam radiation, if the dose were radiobiologically equivalent. There was a significant inverse correlation between the distance between the prostate apex and the penile bulb, and the dosimetric parameters of the bulb: r = -0.548, -0.656, p = < 0.01. The further caudal the apex was from the symphysis, the closer it was to the penile bulb (r = -0.564, p = <0.01). We could not find a correlation between the dose to the prostate or its apex and the dose to the penile bulb. CONCLUSION: When the prostate apex is close to the penile bulb, care should be taken to limit the dose to the penile bulb, if possible. This may reduce the incidence of erectile dysfunction and urinary toxicity after permanent seed prostate brachytherapy.