A dose-volume analysis of radiation pneumonitis in non-small cell lung cancer patients treated with stereotactic body radiation therapy.

PURPOSE: To examine the rates and risk factors of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Dosimetry records for 251 patients with lymph node-negative Stage I-IIB NSCLC and no prior chest radiation therapy (RT) treated with SBRT were reviewed. Patients were coded on the basis of the presence of at least Grade (G) 2 RP using the Common Toxicity Criteria version 2 criteria. Radiation doses, V5, V10, V20, and mean lung dose (MLD) data points were extracted from the dose-volume histogram (DVH). RESULTS: Median PTV volume was 48 cc. Median prescribed radiation dose was 60 Gy delivered in three fractions to the 80% isodose line. Median age at treatment was 74 years. Median follow-up was 17 months. RP was reported after treatment of 42 lesions: G1 in 19 (8%), G2 in 17 (7%), G3 in 5 (2%), and G4 in 1 (0.4%). Total lung DVHs were available for 143 patients. For evaluable patients, median MLD, V5, V10, and V20 were 4.1 Gy, 20%, 12%, and 4%, respectively. Median MLDs were 4 Gy and 5 Gy for G0-1 and G2-4 groups, respectively (p = 0.14); median V5 was 20% for G0-1 and 24% for G2-4 (p = 0.70); median V10 was 12% in G0-1 and 16% in G2-4 (p = 0.08), and median V20 was 4% in G0-1 and 6.6% in G2-4 (p = 0.05). G2-4 RP was noted in 4.3% of patients with MLD ≤4 Gy compared with 17.6% of patients with MLD >4 Gy (p = 0.02), and in 4.3% of patients with V20 ≤4% compared with 16.4% of patients with V20 >4% (p = 0.03). CONCLUSION: Overall rate of G2-4 RP in our population treated with SBRT was 9.4%. Development of symptomatic RP in this series correlated with MLD and V20.

Chest wall toxicity after stereotactic body radiotherapy for malignant lesions of the lung and liver.

PURPOSE: To quantify the frequency of rib fracture and chest wall (CW) pain and identify the dose-volume parameters that predict CW toxicity after stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: The records of patients treated with SBRT between 2000 and 2008 were reviewed, and toxicity was scored according to Common Terminology Criteria for Adverse Events v3.0 for pain and rib fracture. Dosimetric data for CW and rib were analyzed and related to the frequency of toxicity. The risks of CW toxicity were then further characterized according to the median effective concentration (EC(50)) dose-response model. RESULTS: A total of 347 lesions were treated with a median follow-up of 19 months. Frequency of Grade I and higher CW pain and/or fracture for CW vs. non-CW lesions was 21% vs. 4%, respectively (p < 0.0001). A dose of 50 Gy was the cutoff for maximum dose (Dmax) to CW and rib above which there was a significant increase in the frequency of any grade pain and fracture (p = 0.03 and p = 0.025, respectively). Volume of CW receiving 15 Gy - 40 Gy was highly predictive of toxicity (R(2) > 0.9). According to the EC(50) model, 5 cc and 15 cc of CW receiving 40 Gy predict a 10% and 30% risk of CW toxicity, respectively. CONCLUSION: Adequate tumor coverage remains the primary objective when treating lung or liver lesions with SBRT. To minimize toxicity when treating lesions in close proximity to the CW, Dmax of the CW and/or ribs should remain <50 Gy, and <5 cc of CW should receive ≥ 40 Gy.

Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease.

PURPOSE: To analyze the Surveillance, Epidemiology and End Results (SEER) registry data to determine the impact of postoperative radiotherapy (PORT) for thymoma and thymic carcinoma (T/TC). METHODS AND MATERIALS: Patients with surgically resected localized (LOC) or regional (REG) malignant T/TC with or without PORT were analyzed for overall survival (OS) and cause-specific survival (CSS) by querying the SEER database from 1973-2005. Patients dying within the first 3 months after surgery were excluded. Kaplan-Meier and multivariate analyses with Cox proportional hazards were performed. RESULTS: A total of 901 T/TC patients were identified (275 with LOC disease and 626 with REG disease). For all patients with LOC disease, PORT had no benefit and may adversely impact the 5-year CSS rate (91% vs. 98%, p = 0.03). For patients with REG disease, the 5-year OS rate was significantly improved by adding PORT (76% vs. 66% for surgery alone, p = 0.01), but the 5-year CSS rate was no better (91% vs. 86%, p = 0.12). No benefit was noted for PORT in REG disease after extirpative surgery (defined as radical or total thymectomy). On multivariate OS and CSS analysis, stage and age were independently correlated with survival. For multivariate CSS analysis, the outcome of PORT is significantly better for REG disease than for LOC disease (hazard ratio, 0.167; p = 0.001). CONCLUSIONS: Our results from SEER show that PORT for T/TC had no advantage in patients with LOC disease (Masaoka Stage I), but a possible OS benefit of PORT in patients with REG disease (Masaoka Stage II-III) was found, especially after non-extirpative surgery. The role of PORT in T/TC needs further evaluation.

Treatment options for stage I non-small-cell lung carcinoma patients not suitable for lobectomy.

The standard of care for stage I non-small-cell lung carcinoma is generally accepted to be lobectomy. In patients who are deemed not to be candidates for lobectomy, various treatment strategies are available, including observation, sublobar resection, conventional fractionated radiotherapy, stereotactic body radiotherapy and radiofrequency ablation. However, there is no standardized, clearly established therapy to offer patients in this situation. While ongoing prospective trials will allow refinement of these techniques, the role of these treatment modalities warrants further investigation for this setting.

Brachial plexopathy from stereotactic body radiotherapy in early-stage NSCLC: dose-limiting toxicity in apical tumor sites.

BACKGROUND AND PURPOSE: We report frequency of brachial plexopathy in early-stage non-small cell lung cancer treated with stereotactic body radiotherapy. MATERIALS AND METHODS: 276 T1-T2, N0 or peripheral T3, N0 lesions were treated in 253 patients with stereotactic radiotherapy at Indiana University and Richard L. Roudebush VAMC from 1998 to 2007. Thirty-seven lesions in 36 patients were identified as apical lesions, defined as epicenter of lesion superior to aortic arch. Brachial plexus toxicity was scored for these apical lesions according to CTCAE v. 3.0 for ipsilateral shoulder/arm neuropathic pain, motor weakness, or sensory alteration. RESULTS: The 37 apical lesions (19 Stage IA, 16 IB, and 2 IIB) were treated with stereotactic body radiotherapy to a median total dose of 57 Gy (30-72). The associated brachial plexus of 7/37 apical lesions developed grade 2-4 plexopathy (4 pts--grade 2, 2 pts--grade 3, 1 pt--grade 4). Five patients had ipsilateral shoulder/arm neuropathic pain alone, one had pain and upper extremity weakness, and one had pain progressing to numbness of the upper extremity and paralysis of hand and wrist. The median of the maximum brachial plexus doses of patients developing brachial plexopathy was 30 Gy (18-82). Two-year Kaplan-Meier risk of brachial plexopathy for maximum brachial plexus dose >26 Gy was 46% vs 8% for doses 26 Gy (p=0.04 for likelihood ratio test). CONCLUSIONS: Stereotactic body radiotherapy for apical lesions carries a risk of brachial plexopathy. Brachial plexus maximum dose should be kept <26 Gy in 3 or 4 fractions.

Stereotactic body radiation therapy for oligometastases.

The standard treatment for metastatic cancer is systemic therapy. However, in a subset of patients with limited extracranial metastases or oligometastases, local ablative therapy in combination with systemic therapy may improve treatment outcomes. Stereotactic body radiation therapy (SBRT) has emerged as a novel approach for local ablation of extracranial oligometastases. There is a good body of experience in the use of SBRT for the treatment of oligometastases in various sites including the lung, the liver and the spine with promising results. This article provides an overview of the use of SBRT in the management of extracranial oligometastases.

Stereotactic body radiation therapy for early-stage non-small-cell lung cancer.

Stereotactic body radiation therapy has emerged as a novel oncologic therapy and experience with the use of stereotactic body radiation therapy for the treatment of early-stage non-small-cell lung cancer has grown over the last 10 years. This article reviews the radiobiologic, physical/technical and clinical aspects of stereotactic body radiation therapy for early-stage non-small-cell lung cancer. The literature is also reviewed.

Brain metastasis from non-seminomatous germ cell tumor of the testis.

Brain metastasis occurs rarely in patients with testicular cancer in the modern era where cisplatin-based chemotherapy regimens are used. The occurrence of brain metastasis can be synchronous or metachronous (with or without concurrent systemic disease). Long-term survival can be achieved in some patients. The vast majority of testicular cancer cases with brain metastasis reported in the literature involve nonseminomatous germ cell tumor and this subtype will be the focus of this review. This article reviews the literature of the diagnosis and management of brain metastasis from nonseminomatous germ cell tumor of the testis.

FDG-PET and stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer.

PURPOSE: To investigate the utility of positron emission tomography (PET) in patients treated with stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) on prospective institutional trials. PATIENTS AND METHODS: Fifty-eight patients with medically inoperable stage I NSCLC who participated in prospective phase I and II trials of SBRT, had >or=2 years of follow-up, and received FDG-PET imaging are the focus of this evaluation. Fifty-seven of 58 patients received pre-SBRT FDG-PET to confirm stage I status. All patients received stereotactic body frame immobilization and treatment with 7-10 photon beams. SBRT total doses ranged from 24 to 72Gy in three fractions. No elective nodal irradiation was undertaken. Regular follow-up with planned CT imaging was performed on all patients. Post-SBRT FDG-PET was not mandated by protocol and was typically ordered upon concern for disease recurrence. Thirty-eight post-SBRT PET studies were performed in 28 patients at a median 17.3 months following SBRT. RESULTS: With a median follow-up of 42.5 months, the 3-year actuarial overall survival and local control for this select subset of our SBRT experience were 48.9% and 74.8%, respectively. Pre-SBRT FDG-PET SUV did not predict 3-year overall survival or local control. Fourteen of 57 patients eventually failed in nodal stations by CT and/or PET. Isolated first site of failure was nodal in 6 patients (10%). Out of 28 patients with post-SBRT PET, 4 (14%) had delayed PET imaging (22-26 months after SBRT) showing moderate hypermetabolic activity (SUV 2.5-5.07), but no evidence of local, nodal, or distant recurrence by clinical examination and conventional imaging performed 20-26 months following these concerning PET findings. CONCLUSIONS: Isolated nodal recurrence following PET-staged I NSCLC treated with SBRT is uncommon. Moderate post-SBRT PET hypermetabolic activity may persist 2 years following treatment without definite evidence of recurrence. Further study is needed to confirm these results in larger populations with longer follow-up.