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.

Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy.

PURPOSE: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. METHODS AND MATERIALS: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm(2) wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. RESULTS: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. CONCLUSIONS: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Permanent interstitial reirradiation with 198Au as salvage therapy for low volume recurrent gynecologic malignancies: a single institution experience.

OBJECTIVE: To examine the Indiana University experience using 198Au permanent interstitial reirradiation (198Au-IRI) in the treatment of selected patients with recurrent gynecologic malignancies. METHODS: A retrospective review of 19 patients with recurrent gynecologic malignancies treated with 198Au-IRI between 1994 and 2006 was performed to evaluate disease response, local control, disease-free survival, overall survival, and toxicity. RESULTS: All patients had no evidence of regional or distant metastatic disease at the time of treatment. Median age at treatment was 76 years (range, 38-87). Median tumor volume was 3.3 cm3 (range, 0.8-21.3). Median previous radiation dose from all radiation modalities was 67 Gy (range, 38.7-91.6). Median prescribed dose was 50 Gy (range, 25-55). With a median follow-up of 21 months, complete responses were obtained in 94.7% of patients, with local control being achieved after 198Au-IRI in 63.1% of patients. Including further salvage therapy, local control was ultimately achieved in 78.9% of patients. At the time of the analysis, 52.6% of patients were alive with no evidence of disease. Treatment-related toxicity was limited, with only 1 grade III toxicity (5.3%). CONCLUSIONS: 198Au-IRI is a safe, cost-effective, and reasonably efficacious method for controlling locally recurrent, low-volume, well-selected gynecologic malignancies, and treated with previous full-dose radiotherapy. It represents a reasonable potential therapeutic option in the salvage setting in patients who meet these criteria, particularly in women who are not candidates for or are unwilling to undergo radical salvage surgery.

Chinese herbal formula, Bing De Ling, enhances antitumor effects and ameliorates weight loss induced by 5-fluorouracil in the mouse CT26 tumor model.

The use of complementary and alternative medicines-including a variety of herbal therapies-by patients undergoing cancer chemotherapy has been well documented. Despite such widespread use, however, the benefits and potential mechanisms of such herbal medicines remain largely anecdotal. In this study we examined the effects of a Chinese herbal formula, Bing De Ling, when administered as an adjunct to chemotherapeutic agent 5-fluorouracil (5-FU) in the CT26 mouse colon cancer model. 5-FU and Bing De Ling were administered to both nave and CT26 mouse colon cancer-bearing BALB/c mice. Our results indicate that although the herbal formula alone did not result in antitumor effects under experimental conditions, it significantly enhanced 5-FU-induced tumor growth inhibition. Oral administration of Bing De Ling also increased survival rates of both tumor-bearing and tumor-free mice treated with 5-FU. Furthermore, oral administration of Bing De Ling reduced weight loss in tumor-free mice receiving 5-FU when compared to tumor-free mice that received 5-FU alone. Our data further show that 5-FU upregulates serum levels of IL-6, known to contribute to weight loss, in tumor-free mice, and that this increase in IL-6 is significantly less in mice that received Bing De Ling in addition to 5-FU. These data show Bing De Ling both enhances the antitumor responses of 5-FU and ameliorates side effects.