Anthony Brade

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.

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.

Treatment of the Elderly When Cure is the Goal: The Influence of Age on Treatment Selection and Efficacy for Stage III Non-small Cell Lung Cancer

Background: Treatment of elderly patients with stage III NSCLC is controversial. Limited data exist, as the elderly are underrepresented in clinical trials. Methods: After ethics approval, we performed a retrospective review of 1372 stage III NSCLC patients treated at our institution during the period 1997–2007. Patients with malignant effusions and microscopic N2 discovered only postoperatively were excluded, leaving 740 who were classified by treatment plan: palliative (palliative chemotherapy or radiation [≤40 Gy]); nonsurgical multimodality (>40 Gy radiation ± chemotherapy); or surgical multimodality (chemotherapy, radiation, and surgery). Demographics, treatment, toxicity, and survival were analyzed by age, 0 to 65 years, n = 384; 66 to 75 years, n = 256; 76+ years, n = 100, and compared using log-rank, univariate, and multivariate statistical tests. Results: Patients older than 65 years were more likely to have poor performance status (p < 0.0001), multiple comorbidities (p < 0.0001), and to receive palliative therapy only (p < 0.0001). Older and younger patients treated with curative intent with nonsurgical bimodality therapy or trimodality therapy including surgery had similar rates of grade 3/4 toxicity (0–65 years, 39%; 66–75 years, 43%; 76+ years, 5%; p = 0.18) and toxic death (0–65 years, 4%; 66–75 years, 4%; 76+ years, 0%; p = 0.76). Survival was worse with increasing age (p < 0.0001), likely due to greater use of palliative treatment in the elderly. When survival was analyzed for patients treated with curative intent, there was no difference between age groups for nonsurgical (p = 0.32) or surgical (p = 0.53) therapy. Conclusion: In select fit elderly patients, combined modality therapy is tolerable and is associated with survival similar to that of younger patients.

Effect of Image-Guidance Frequency on Geometric Accuracy and Setup Margins in Radiotherapy for Locally Advanced Lung Cancer

PURPOSE To assess the relative effectiveness of five image-guidance (IG) frequencies on reducing patient positioning inaccuracies and setup margins for locally advanced lung cancer patients. METHODS AND MATERIALS Daily cone-beam computed tomography data for 100 patients (4,237 scans) were analyzed. Subsequently, four less-than-daily IG protocols were simulated using these data (no IG, first 5-day IG, weekly IG, and alternate-day IG). The frequency and magnitude of residual setup error were determined. The less-than-daily IG protocols were compared against the daily IG, the assumed reference standard. Finally, the population-based setup margins were calculated. RESULTS With the less-than-daily IG protocols, 20-43% of fractions incurred residual setup errors ≥ 5 mm; daily IG reduced this to 6%. With the exception of the first 5-day IG, reductions in systematic error (∑) occurred as the imaging frequency increased and only daily IG provided notable random error (σ) reductions (∑ = 1.5-2.2 mm, σ = 2.5-3.7 mm; ∑ = 1.8-2.6 mm, σ = 2.5-3.7 mm; and ∑ = 0.7-1.0 mm, σ = 1.7-2.0 mm for no IG, first 5-day IG, and daily IG, respectively. An overall significant difference in the mean setup error was present between the first 5-day IG and daily IG (p < .0001). The derived setup margins were 5-9 mm for less-than-daily IG and were 3-4 mm with daily IG. CONCLUSION Daily cone-beam computed tomography substantially reduced the setup error and could permit setup margin reduction and lead to a reduction in normal tissue toxicity for patients undergoing conventionally fractionated lung radiotherapy. Using first 5-day cone-beam computed tomography was suboptimal for lung patients, given the inability to reduce the random error and the potential for the systematic error to increase throughout the treatment course.

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.

Tumor Regression and Positional Changes in Non-small Cell Lung Cancer During Radical Radiotherapy

Introduction: We have used respiratory-correlated cone beam computed tomography (rcCBCT) imaging to study the volumetric and positional changes that occur throughout the course of radical radiotherapy in non-small cell lung cancer (NSCLC). Methods: Tumor volumes and centers of mass were recorded and analyzed on weekly serial rcCBCT images of NSCLC patients treated with radical radiotherapy to a dose ≥45 Gy with concurrent chemotherapy. Results: Sixty patients with locally advanced NSCLC were included; in 31 patients, the primary tumor was peripheral and thus suitable for contouring. There was a mean percent decrease of 40.2% by fraction 15 and 51.1% by treatment completion. Among all 60 patients, 19 patients (32%) had more than 30% regression by fraction 15 and 25 patients (81%) by treatment completion. Statistically significant tumor migration in at least one direction between the first and the last 2 weeks was demonstrated in 14 of 27 patients. Clinically relevant changes (atelectasis and effusions) were noted in 11 of 29 visually assessed patients. Conclusions: Current rcCBCT image quality allows assessment of tumors located more peripherally. Significant tumor regression was documented in the majority of patients. In view of these observations, the suitability of adaptive radiotherapy in radical lung cancer treatment should be further investigated.

Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma

This study reports the adoption of prophylactic cranial irradiation (PCI) in patients with limited stage small cell lung carcinoma (LS‐SCLC) at Princess Margaret Hospital (PMH) and the factors that impact PCI utilization.

Early Metabolic Response Evaluation After Stereotactic Radiotherapy for Lung Cancer: Pilot Experience with 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography

The early response of lung tumours to stereotactic radiotherapy was prospectively evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography. Three months after treatment, the maximum standardised uptake value and the tumour diameter fell by 64 and 30%, respectively. This imaging strategy therefore remains under ongoing evaluation with the aim of identifying predictive and prognostic factors.