Proposed prognostic scoring system evaluating risk factors for biochemical recurrence of prostate cancer after salvage radiation therapy.

OBJECTIVE: To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/mL and rising as the definition of BCR. PATIENTS AND METHODS: We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks (RRs) from multivariable Cox regression models. RESULTS: With a median follow-up of 5.5 years after SRT, 354 patients (61%) experienced BCR. At 5 years after SRT, 40% of patients were free of BCR. Independent associations with BCR were identified for the PSA level before SRT (RR [doubling]: 1.25, P < 0.001), pathological tumour stage (RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score (RR [7 vs <7] 1.63, P < 0.001; RR [8-10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status (RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c-index of 0.66. Scores ranged from 0 to 7, and 5-year freedom from BCR for different levels of the score was as follows: Score = 0-1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5-7: 15%. CONCLUSION: We developed a scoring system that provides an estimation of the risk of BCR after SRT. These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.

Stereotactic Body Radiotherapy for Medically Inoperable Stage I-II Non-Small Cell Lung Cancer: The Mayo Clinic Experience.

OBJECTIVE: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models. RESULTS: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P=.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P=.01). The SUVmax was not significantly associated with other outcomes (P≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively (P=.02); this difference was independent of lesion size (P=.02). CONCLUSION: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.

The incidence of fat necrosis in balloon-based breast brachytherapy.

PURPOSE: To investigate the incidence of and potential risk factors for fat necrosis in high dose-rate (HDR) balloon-based breast brachytherapy (BBB). MATERIAL AND METHODS: Fifty-four patients were treated postoperatively with HDR-BBB between May 2007 and December 2010. Median age was 71 years (range: 50-88 years). Median tumor size was 1 cm (range: 0.1-2.7 cm). Forty-four had invasive histology; 43% were grade 1, 24% grade 2, and 15% grade 3. The median margin size was 0.7 cm (range: 0.1-1.5 cm). RESULTS: With a median follow-up of 2.9 years (range: 0.5-5.2 years), local control was 98% with one in-breast failure, and overall survival was 89%. Fifty percent of patients experienced fat necrosis. Seven patients were symptomatic, with the remainder detected by mammography alone. Two patients required surgical resection with pathology confirming fat necrosis; 1 required i.v. steroids. At 1, 3, and 5 years following treatment, estimated cumulative incidences of fat necrosis were 7.5%, 52.7%, and 60.6%. Breast laterality, location, tumor size, histology, margin size, balloon volume, skin distance, skin dose, and number of dwell positions were not significantly associated with fat necrosis on univariate analysis. CONCLUSIONS: In this retrospective review of HDR-BBB, we found a 50% incidence of both asymptomatic and symptomatic fat necrosis. Only three patients, however, required intervention. None of the risk factors considered were significantly associated with fat necrosis. Further studies evaluating factors associated with fat necrosis for patients undergoing HDR-BBB are necessary to appropriately assess the risks associated with treatment.

Extranodal rosai-dorfman disease of the bone treated with surgery and radiotherapy.

Rosai-Dorfman disease (RDD) is a rare, benign histiocyte disorder originally described by Rosai and Dorfman in 1969 as sinus histiocytosis with massive lymphadenopathy. It most typically presents as massive, painless cervical lymphadenopathy, and it is most often found in adolescents and young adults. Extranodal involvement is a common feature of RDD and may occur in more than 40% of patients. Less commonly, the disease can be seen in the bone. There are scattered case reports discussing the use of radiotherapy in the treatment of RDD. Here, we present a case of extranodal RDD of the femur in a 49-year-old African American female. The patient underwent three surgical procedures prior to undergoing radiotherapy. Pathology was consistent with extranodal RDD. The cells stained positive for CD68 and S-100. Pathognomonic features such as emperipolesis and replacement of the bone marrow by diffuse infiltrating of histiocytes and intervening bands of plasma cells proliferation were noted. Prior to radiotherapy, the patient required a walker to assist with ambulation and was utilizing a wheelchair while in the clinic. The decision was made to proceed with 30 Gy of external beam radiotherapy in 15 fractions. After five fractions, the patient's pain resolved entirely. She no longer required pain medication and was ambulating without assistance. She experienced no adverse events from the radiation. Extranodal RDD is a rare disorder, and evidence for treatment is derived from scattered case reports. Previous reports have indicated a dose response to radiotherapy in the 20-30 Gy range for RDD; however, our patient developed complete resolution of her symptoms after 10 Gy. While the optimal dose regimen has not yet been established, symptomatic patients appear to benefit from external beam radiotherapy for extranodal RDD.

Evaluation of Serum Calcium as a Predictor of Biochemical Recurrence following Salvage Radiation Therapy for Prostate Cancer.

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0-72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P = 0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P = 0.79) or high (RR: 1.08, P = 0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT.

Multimodality local therapy for retroperitoneal sarcoma.

PURPOSE: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. METHODS AND MATERIALS: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at the University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. RESULTS: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). CONCLUSION: For retroperitoneal sarcoma, local control remains a challenge and combined-modality therapy may be associated with significant acute and late morbidity. Our patterns of failure data suggest that improvements in local control may translate into a survival benefit.