Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non-small-cell Lung Cancer: Analysis by Operability, Fractionation Regimen, Tumor Size, and Tumor Location.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. PATIENTS AND METHODS: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. RESULTS: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. CONCLUSIONS: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.

First Clinical Report of Proton Beam Therapy for Postoperative Radiotherapy for Non-Small-Cell Lung Cancer.

BACKGROUND AND PURPOSE: The characteristic Bragg peak of proton beam therapy (PBT) allows for sparing normal tissues beyond the tumor volume that may allow for decreased toxicities associated with postoperative radiation therapy (PORT). Here we report the first institutional experience with proton therapy for PORT in patients with non-small-cell lung cancer (NSCLC) and assess early toxicities and outcomes. MATERIALS AND METHODS: We identified 61 consecutive patients treated from 2011 to 2014 who underwent PORT for locally advanced NSCLC for positive microscopic margins and/or positive N2 lymph nodes (stage III), with 27 patients receiving PBT and 34 receiving intensity-modulated radiation therapy (IMRT). RESULTS: Median follow-up time was 23.1 months for PBT (2.3-42.0 months) and 27.9 months for IMRT (0.5-87.4 months). The median radiation dose was 50.4 Gy for PBT (50.4-66.6 Gy) and 54 Gy for IMRT (50.0-72.0 Gy). Grade 3 radiation esophagitis was observed in 1 and 4 patients in the PBT and IMRT groups, respectively. Grade 3 radiation pneumonitis was observed in 1 patient in each cohort. Dosimetric analysis revealed a significant decrease in the V5 and mean lung dose (P = .001 and P = .045, respectively). One-year median overall survival and local recurrence-free survival were 85.2% and 82.4% (95% confidence interval, 72.8%-99.7% and 70.5%-96.2%, P = .648) and 92.3% and 93.3% (82.5%-100%, 84.8%-100%, P = .816) for PBT and IMRT cohorts, respectively. CONCLUSIONS: Postoperative PBT in NSCLC is well-tolerated and has similar excellent short-term outcomes when compared with IMRT. Longer follow-up is necessary to determine if PBT has a meaningful improvement over IMRT for PORT.

Prospective study of proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma: Early response and toxicity assessment.

BACKGROUND AND PURPOSE: Radiation is an important modality in treatment of thymic tumors. However, toxicity may reduce its overall benefit. We hypothesized that double-scattering proton beam therapy (DS-PT) can achieve excellent local control with limited toxicity in patients with thymic malignancies. METHODS AND MATERIALS: Patients with thymoma or thymic carcinoma treated with DS-PT between 2011 and 2015 were prospectively analyzed for toxicity and patterns of failure on an IRB-approved study. RESULTS: Twenty-seven consecutive patients were evaluated. Patients were a median of 56 years and had thymoma (85%). They were treated with definitive (22%), salvage (15%) or adjuvant (63%) DS-PT to a median of 61.2/1.8 Gy [CGE]. No patient experienced grade ⩾3 toxicity. Acute grade 2 toxicities included dermatitis (37%), fatigue (11%), esophagitis (7%), and pneumonitis (4%). Late grade 2 toxicity was limited to a single patient with chronic dyspnea. At a median follow-up of 2 years, 100% local control was achieved. Three-year regional control, distant control, and overall survival rates were 96% (95% CI 76-99%), 74% (95% CI 41-90%), and 94% (95% CI 63-99%), respectively. CONCLUSIONS: This is the first cohort and prospective series of proton therapy to treat thymic tumors, demonstrating low rates of early toxicity and excellent initial outcomes.

Cost-effectiveness of stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer.

BACKGROUND: The traditional treatment for clearly operable (CO) patients with stage I non-small cell lung cancer (NSCLC) is lobectomy, with wedge resection (WR) and stereotactic body radiation therapy (SBRT) serving as alternatives in marginally operable (MO) patients. Given an aging population with an increasing prevalence of screening, it is likely that progressively more people will be diagnosed with stage I NSCLC, and thus it is critical to compare the cost-effectiveness of these treatments. METHODS: A Markov model was created to compare the cost-effectiveness of SBRT with WR and lobectomy for MO and CO patients, respectively. Disease, treatment, and toxicity data were extracted from the literature and varied in sensitivity analyses. A payer (Medicare) perspective was used. RESULTS: In the base case, SBRT (MO cohort), SBRT (CO cohort), WR, and lobectomy were associated with mean cost and quality-adjusted life expectancies of $42,094/8.03, $40,107/8.21, $51,487/7.93, and $49,093/8.89, respectively. In MO patients, SBRT was the dominant and thus cost-effective strategy. This result was confirmed in most deterministic sensitivity analyses as well as probabilistic sensitivity analysis, in which SBRT was most likely cost-effective up to a willingness-to-pay of more than $500,000/quality-adjusted life year. For CO patients, lobectomy was the cost-effective treatment option in the base case (incremental cost-effectiveness ratio of $13,216/quality-adjusted life year) and in nearly every sensitivity analysis. CONCLUSIONS: SBRT was nearly always the most cost-effective treatment strategy for MO patients with stage I NSCLC. In contrast, for patients with CO disease, lobectomy was the most cost-effective option.

Management of an anterior mediastinal pheochromocytoma causing tracheomalacia.

Thoracic paragangliomas are rare tumors that arise from extra-adrenal chromaffin cells and have the capacity to secrete catecholamines. Surgical excision is the optimal treatment of these tumors as they are resistant to chemotherapy and radiation therapy. Although these tumors are most commonly found in the abdomen, 10% of paraganagliomas are located in the thorax, usually in the posterior mediastinum. Occasionally these tumors present in the anterior mediastinum, which can pose a significant surgical challenge due to the proximity of the great vessels and airway. In this report we describe the treatment of an anterior mediastinal pheochromocytoma that presented with tracheal obstruction and required pulmonary artery reconstruction and airway stenting.

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Pleurectomy and decortication for malignant mesothelioma.

P/D in combination with other therapies remains an effective weapon in the thoracic surgeon's armamentarium for treating patients with MPM, particularly patients with limited lung function. A clear benefit has been demonstrated in terms of symptom relief. Further strategies aimed at eliminating residual disease in an effort to prevent locoregional recurrence and as potential curative therapies currently are being investigated.

Arterial invasion predicts early mortality in stage I non-small cell lung cancer.

BACKGROUND: A retrospective study was performed to evaluate the association between arterial invasion and survival in patients with stage I non-small cell lung cancer. METHODS: One hundred patients were identified who had undergone complete anatomic resection as definitive treatment for stage I non-small cell lung cancer. The tumors were reviewed for the presence or absence of arterial invasion. Five-year survival data were obtained for all patients. RESULTS: The 100 patients had an overall 5-year survival of 61%. There were 64 stage IA patients with a 62% 5-year survival and 36 stage IB patients with a 58% 5-year survival. The 39 patients identified with arterial invasion had a 38% 5-year survival compared with a 73% 5-year survival in the 61 patients without arterial invasion (p < 0.001), with an unadjusted hazard ratio of 3.5 (p < 0.001). Multivariate analysis by stage IA versus IB and by size greater or less than 2 cm demonstrated hazard ratios of 3.5 and 4.0, respectively (p < 0.001). This difference was independent of demographic characteristics, tumor type, or grade. Subgroup analysis revealed a hazard ratio of 5.8 in patients with stage IA non-small cell lung cancer (p < 0.001) and 19.8 in patients with tumors < or = 2 cm (p = 0.006). CONCLUSIONS: Arterial invasion is present in a substantial percentage of patients with stage I non-small cell lung cancer and is adversely associated with survival.

Lung transplantation for lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis is a rare disease in women leading to respiratory failure. We describe a single-institution experience with lung transplantation for end-stage lymphangioleiomyomatosis. METHODS: We retrospectively reviewed records of patients transplanted for lymphangioleiomyomatosis between 1989 and 2001. Follow-up was complete on all patients (median 3.5 years). RESULTS: Seven single and 7 bilateral transplants were performed on 14 recipients (mean age 41.8 years). Eleven patients suffered the following intra-operative complications: dysrhythmia (1); blood loss > 1,000 ml (7); extensive pleural adhesions (10); hypothermia (1); phrenic nerve injury (1); and graft dysfunction (2). The following post-operative complications occurred in 11 recipients: dysrhythmia (7); respiratory failure (5); sepsis (3); airway dehiscence (2); vocal cord dysfunction (1); cholecystitis (1); deep vein thrombosis (1); acute renal failure (1); and pericarditis (1). Post-operative chylous fistulas necessitated thoracic duct ligation (1); sclerosis (6); and drainage of ascites (1). There were no peri-operative deaths. Late deaths occurred due to sepsis in 2 patients and obliterative bronchiolitis in 1 patient. Survival rates were 100%, 90% and 69% at (1, 2 and 5 years, respectively.) Mean FEV1 (1.77 +/- 1.06 vs 0.60 +/- 0.91) and 6-minute walk (1,519 +/- 379 vs 826 +/- 293 feet) improved at 1 year as compared with pre-transplant evaluation. Five patients reached criteria for bronchiolitis obliterans syndrome. One recipient has had a documented recurrence of lymphangioleiomyomatosis in the transplanted lung. CONCLUSIONS: Early and late survival after lung transplant are comparable in lymphangioleiomyomatosis patients versus patients with other diseases. Morbidity is common after transplant for lymphangioleiomyomatosis and is usually due to lymphangioleiomyomatosis-related complications. Lymphangioleiomyomatosis recurrence in the allograft does not pose a substantial clinical problem.