Men with large prostates are at high risk of genitourinary (GU) and gastrointestinal (GI) toxicities after definitive radiotherapy for prostate cancer. Therefore, they may undergo cytoreduction with androgen deprivation therapy (ADT) before treatment, which negatively impacts their quality of life. Proton therapy (PT) can reduce the radiation dose to the nontargeted rectum and bladder and may obviate the need for cytoreduction. This is a retrospective study of the toxicity profile of men with large prostates (≥ 60 g) following definitive PT for prostate cancer. From 2006 to 2010, 190 men with prostates ≥ 60 g were treated with definitive PT (median dose, 78 CGE) for low- (46%), intermediate- (37%), and high-risk (17%) prostate cancer at our institution. The median age of patients was 70 years, the median prostate size was 76 g (range, 60 – 143g), and pretreatment International Prostate Symptom Score (IPSS) was > 15 in 27%. Before PT, 51% were treated for obstructive symptoms with ≥ 1 of the following: transurethral resection of the prostate (TURP; 9.5%) or medical management (MM) with α blockers (32%), 5 α-reductase inhibitors (15%), and/or saw palmetto (12%). Also, 33 men received ADT (14 for cytoreduction). Toxicity was assessed per CTCAE v3.0 weekly during PT and then every 6 months. Prostate-specific antigen (PSA) was evaluated every 3 months. The median follow-up was 21 months and 2-year Phoenix-defined biochemical failure-free survival was 99%. Grade (GR) 3 GU toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). The 6-, 12-, and 24-month cumulative incidence of GR 3 GU toxicity was 0.5%, 4.1%, and 7.2%. The median change in IPSS at 6, 12, and 24 months was 8, 11, and 7.5. On univariate analysis, prostate size > 76 g, pretreatment TURP, and pretreatment MM with α blockers or 5 α-reductase inhibitors were all associated with an increased risk of GR 3 GU toxicities. On multivariate analysis (MVA) of prostate size, dose, ADT, and pretreatment IPSS, MM, and TURP, only pretreatment MM (p = 0.0061) and pretreatment TURP (p = 0.0002) were significantly predictive of GR 3 GU toxicity during or after PT. In the cohort who did not receive neoadjuvant ADT or TURP, GR 3 late GU toxicity was 4%. One man experienced GR 3 GI toxicity and 12 men had GR 2 GI toxicities. The 6-, 12-, and 24-month incidence of GR 2+ GI toxicity was 0.5%, 6.2%, and 10.3%. On MVA, an association between dose > 78 CGE and an increased risk of Grade 2+ GI toxicities approached significance (p = 0.058). Cytoreduction with ADT in men with large prostates may not be necessary before PT treatment considering the acceptably low rates of GU and GI toxicities in this study. Longer follow-up is needed to confirm these results.

Compared with IMRT, proton therapy (PT) for prostate cancer reduces the dose to the rectum and bladder at the expense of higher doses to the femoral neck. There is concern that this could lead to higher hip-fracture rates. In the present study, we assessed the risk of hip fracture and hip pain in men treated with PT for prostate cancer. The medical records of 400 men treated with PT for prostate cancer on an IRB-approved protocol (UFJ 2006-153) between September 2006 and April 2008 were retrospectively reviewed. At 6-month intervals after PT, patients were evaluated by a nurse and physician who assessed CTCAE v3.0 toxicities, including genitourinary (GU), gastrointestinal (GI), erectile, and pain symptoms, and recorded interim events and interventions. Factors potentially associated with hip fracture or pain were recorded, including androgen deprivation (AD), steroid use, testosterone level, body mass index (BMI), previous fracture, smoking, excessive alcohol consumption, arthritis, osteoporosis, renal/liver disease, hyperparathyroidism, diabetes, and dosimetry factors. The observed median follow-up was 2.2 years (range, 0.1 to 3.6 years). The World Health Organization (WHO) Fracture Risk Assessment Tool was applied to each patient to generate an individual annual hip-fracture risk, with a mean of 0.2% (range, 0 to 1.5%) and an expected 1.5 patient fractures in the study population based on individual follow-up. National Health and Nutrition Examination Survey (NHANES) III was reviewed to generate an expected 12.4% rate of hip pain in an untreated population of similarly aged men. Two patients developed fractures after PT for an observed-expected ratio (OER) of 1.31 (confidence interval, 0.2 to 4.7; p = 0.9043). One patient (79 years old), with a fracture (mean femoral neck dose, 33 CGE) at 10 months had a history of osteoporosis, AD use, arthritis, steroid use, and had the highest WHO annual fracture risk of 1.5%. A second patient (77 years old), developed bilateral femoral neck fractures (mean doses, 32 CGE and 33.5 CGE) at 19 and 29 months, had a history of prior bone fracture (jaw), AD for 6 months, and a WHO annual fracture risk of 0.6%. Nine (2.2%) patients reported pain at day 0 of PT and an additional 44 (11%) reported hip pain during or after PT at a median time of 13.3 months (range, 1 to 39 months), including 28 (7%) with Grade 1, 12 (3%) with Grade 2, and 4 (1%) with Grade 3 hip pain. Only arthritis was found to be associated with Grade 1+ hip pain (p = 0.0049). Proton therapy does not appear to increase either the risk of hip fracture or hip pain in the first 2 years of follow-up compared to expected rates in an untreated, similarly aged population of men. Longer follow-up is needed to confirm these findings.

Purpose/Objective(s)There are little data on optimal management of patients with prostate cancer progression after high-intensity focused ultrasound (HIFU) or cryosurgery (CRYO), two clinical situations likely to increase with the growing use of these treatment methods. To date, there are no published reports of outcomes with proton therapy (PT) for prostate cancer progression after HIFU or CRYO, which may offer a less toxic treatment option for these patients than prostatectomy or other forms of radiation therapy. This study reports early disease control and toxicity in a small cohort of patients treated with PT for disease progression after HIFU or CRYO.Materials/MethodsOne post-HIFU and 5 post-CRYO patients were treated with PT for disease progression on UFPTI OTP (UFJ-2006-153). An IRB-approved (UFJ-2009-111) retrospective review of medical records was used to study disease control and toxicity outcomes. Follow-up ranged from 12 months to 30 months. PSA response was used as a surrogate for treatment efficacy. Gastrointestinal (GI) and genitourinary (GU) toxicities were assessed through self-reported International Prostate Symptom Scores (IPSS) and through provider assessment using the CTCAE v3.0 scoring system.ResultsAt last follow-up, all patients had experienced a prostate-specific antigen (PSA) response to PT. Pre- and post treatment PSAs for the HIFU patient were 6.1 ng/mL and 0.4 ng/mL (at 12 months). For the CRYO group, mean pre- and post treatment PSAs were 10.1 ng/mL (range, 5 to 15 ng/mL) and 0.2 ng/mL (range, 0.1 to 0.3 ng/mL) at 15 to 30 months. At 1 year, the HIFU patient reported an improvement in IPSS from pretreatment (Δ -2). Similarly, among the CRYO patients, only 1 patient reported a worsening IPSS (Δ +2) with a mean IPSS change for the 5 CRYO patients of -1 (range, -4 to +2). No Grade 3 GU or GI toxicity was observed.ConclusionsProton therapy appears to be an effective and well-tolerated treatment option for patients whose prostate cancer progresses after CRYO or HIFU. A larger study with long-term follow-up is needed to confirm these findings. Purpose/Objective(s)There are little data on optimal management of patients with prostate cancer progression after high-intensity focused ultrasound (HIFU) or cryosurgery (CRYO), two clinical situations likely to increase with the growing use of these treatment methods. To date, there are no published reports of outcomes with proton therapy (PT) for prostate cancer progression after HIFU or CRYO, which may offer a less toxic treatment option for these patients than prostatectomy or other forms of radiation therapy. This study reports early disease control and toxicity in a small cohort of patients treated with PT for disease progression after HIFU or CRYO. There are little data on optimal management of patients with prostate cancer progression after high-intensity focused ultrasound (HIFU) or cryosurgery (CRYO), two clinical situations likely to increase with the growing use of these treatment methods. To date, there are no published reports of outcomes with proton therapy (PT) for prostate cancer progression after HIFU or CRYO, which may offer a less toxic treatment option for these patients than prostatectomy or other forms of radiation therapy. This study reports early disease control and toxicity in a small cohort of patients treated with PT for disease progression after HIFU or CRYO. Materials/MethodsOne post-HIFU and 5 post-CRYO patients were treated with PT for disease progression on UFPTI OTP (UFJ-2006-153). An IRB-approved (UFJ-2009-111) retrospective review of medical records was used to study disease control and toxicity outcomes. Follow-up ranged from 12 months to 30 months. PSA response was used as a surrogate for treatment efficacy. Gastrointestinal (GI) and genitourinary (GU) toxicities were assessed through self-reported International Prostate Symptom Scores (IPSS) and through provider assessment using the CTCAE v3.0 scoring system. One post-HIFU and 5 post-CRYO patients were treated with PT for disease progression on UFPTI OTP (UFJ-2006-153). An IRB-approved (UFJ-2009-111) retrospective review of medical records was used to study disease control and toxicity outcomes. Follow-up ranged from 12 months to 30 months. PSA response was used as a surrogate for treatment efficacy. Gastrointestinal (GI) and genitourinary (GU) toxicities were assessed through self-reported International Prostate Symptom Scores (IPSS) and through provider assessment using the CTCAE v3.0 scoring system. ResultsAt last follow-up, all patients had experienced a prostate-specific antigen (PSA) response to PT. Pre- and post treatment PSAs for the HIFU patient were 6.1 ng/mL and 0.4 ng/mL (at 12 months). For the CRYO group, mean pre- and post treatment PSAs were 10.1 ng/mL (range, 5 to 15 ng/mL) and 0.2 ng/mL (range, 0.1 to 0.3 ng/mL) at 15 to 30 months. At 1 year, the HIFU patient reported an improvement in IPSS from pretreatment (Δ -2). Similarly, among the CRYO patients, only 1 patient reported a worsening IPSS (Δ +2) with a mean IPSS change for the 5 CRYO patients of -1 (range, -4 to +2). No Grade 3 GU or GI toxicity was observed. At last follow-up, all patients had experienced a prostate-specific antigen (PSA) response to PT. Pre- and post treatment PSAs for the HIFU patient were 6.1 ng/mL and 0.4 ng/mL (at 12 months). For the CRYO group, mean pre- and post treatment PSAs were 10.1 ng/mL (range, 5 to 15 ng/mL) and 0.2 ng/mL (range, 0.1 to 0.3 ng/mL) at 15 to 30 months. At 1 year, the HIFU patient reported an improvement in IPSS from pretreatment (Δ -2). Similarly, among the CRYO patients, only 1 patient reported a worsening IPSS (Δ +2) with a mean IPSS change for the 5 CRYO patients of -1 (range, -4 to +2). No Grade 3 GU or GI toxicity was observed. ConclusionsProton therapy appears to be an effective and well-tolerated treatment option for patients whose prostate cancer progresses after CRYO or HIFU. A larger study with long-term follow-up is needed to confirm these findings. Proton therapy appears to be an effective and well-tolerated treatment option for patients whose prostate cancer progresses after CRYO or HIFU. A larger study with long-term follow-up is needed to confirm these findings.

This analysis queried the relationship between the radiation (RT) dose delivered to the initial planning target volume (PTV) and local tumor control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) results for patients with Ewing's sarcoma family of tumors (ESFT). Between 1990 and 2009, 61 patients with non-metastatic ESFT underwent local treatment with RT (n = 22), surgery (S) + RT (n = 13), or S (n = 26). Median patient age was 13 years. The most common sites of primary tumor were in the extremities (n = 29) or pelvis (n = 11). All patients received chemotherapy according to cooperative group protocols or guidelines. The initial RT PTV included the pre-treatment bony and soft tissue extent of disease. The boost PTV included the pre-treatment bony abnormality and post-chemotherapy soft tissue residual tumor with reduced margins. Ten patients treated off protocol received low dose RT (30-36 Gy) to the initial PTV, while the remainder received a standard median dose of 45 Gy. The median cumulative dose of RT was 55.2 Gy. Median follow-up time was 5.4 years. The five-year actuarial LC rates were 94 (RT), 90 (S + RT), and 100% (S), p = 0.39. Local tumor recurrence developed in 1 patient treated with RT alone and 1 patient treated with S + RT. Both patients with local failure had pelvic tumors measuring over 8 cm and received standard dose to the initial PTV with a final total dose of 55.8 Gy. Five-year actuarial DMFS rates were 71 (RT), 89 (S + RT), and 87% (S), p = 0.38. Both patients with local failure developed distant metastasis. Five-year actuarial OS rates were 78 (RT), 91 (S + RT), and 95% (S), p = 0.08. On multivariate analysis, RT dose to the initial PTV was not a significant predictor of LC (p = 0.37), DMFS (p = 0.36), or OS (p = 0.82). Two children developed secondary leukemia. One child developed a meningioma adjacent to the prior treatment field following RT for a spinal ESFT. The above patients received standard dose RT to the initial PTV. The initial delivery of 30-36 Gy to the pre-chemotherapy tumor volume followed by a cone-down boost to the post-chemotherapy volume to standard cumulative doses provides excellent LC and does not appear to adversely impact DMFS or OS. Local control was 100% in patients treated with this approach. Dose de-escalation to the initial PTV will enable significant sparing of normal tissues and has the potential to diminish late toxicity. Further investigation is warranted to validate these results.

Response of craniopharyngiomas to radiation as measured by MRI has not been extensively described. Clinical experience suggests that these tumors may temporarily increase in size after radiation therapy. The goal of this study is to determine the incidence and natural history of this response in a cohort of patients treated at Children's Healthcare of Atlanta/Emory University. Between 08/1998 and 06/2009, 41 children and young adults were diagnosed with crainopharyngioma at Children's Healthcare of Atlanta and/or Emory University. Of these, 21 received external beam radiation treatments either at initial diagnosis after a subtotal resection (STR) (47.6%) or at recurrence (52.4%) and were included in our analysis. Median age at diagnosis was 8.2 years (range: 3.2-23.5 years). 30% of these patients were male while 70% were female. The median radiation dose used was 54.0 Gy (range: 50.4-59.4 Gy) with standard fractionation. Serial MRIs were evaluated to assess volumetric response to radiation therapy. With a median follow-up of 32.4 months (range: 1.3 - 121.8 months), the overall survival rate is 100%. Crude local control rate following radiation therapy is 90.5% with failures occurring at 14.0 and 52.8 months after treatment. A total of 52.4% of subjects (11 of 21) are noted on serial MRI evaluation to have tumor enlargement (mostly cystic component) after radiation treatment before eventual shrinkage without further intervention. For tumors that expanded, the median volume increase is 32.4% (range: 15.6%-224.4%). Median time to maximal tumor/cyst expansion was 1.5 months (range: 1.0-5.0 months). Finally, the majority of patients (19 of 21) show a measurable objective response to therapy by MRI imaging regardless of ultimate disease control status. Median time to maximal response post-radiation, as defined by MRI, is 9.9 months (range: 3.5-39.9 months). Radiation therapy is an effective management of craniopharyngioma either at initial diagnosis after STR or at recurrence. Approximately half of the patients will show tumor/cyst expansion on early post-radiation MRIs. This initial enlargement may be seen for up to 5-6 months after completion of radiation before eventual shrinkage. Caution should be taken not to subject patients to "salvage surgery" during this early time period unless there are other overriding reasons (e.g., increasing hydrocephalus due to new obstruction from tumor/cyst enlargement) for surgical intervention. Understanding the natural history of this phenomenon could potentially help guide the management of craniopharyngioma patients who have MRI evidence of tumor/cyst enlargement in the first few months following completion of radiation therapy.

Purpose/Objective(s)Controversy exists over the optimal management of young men with prostate cancer. We report early outcomes in men ≤ 55 years old treated with proton therapy.Materials/MethodsFrom August 15, 2006, to September 1, 2009, 98 men ≤ 55 years old with low- (N = 57), intermediate- (N = 29), and high- (N = 12) risk prostate cancer were enrolled on University of Florida IRB-approved protocols and received proton therapy to between 78 and 82 CGE at 2 CGE per fraction or 70 to 72.5 CGE at 2.5 CGE per fraction. Androgen deprivation (AD) was given to 14 patients. Before treatment and every 6 months after, patients had a PSA evaluation and completed international index of erectile function (IIEF) and international prostate symptom score (IPSS) questionnaires. Physician toxicity assessments (CTCAE, v3.0) were performed at the same intervals and weekly during treatment. The median follow-up was 18 months.ResultsThe median pretreatment, 6-month, 12-month, and 18-month PSAs were 5.0 (range, 0.7 to 124), 1.5 (range, 0 to 10), 1.3 (range, 0 to 7.6), and 1.2 (range, 0 to 4.2). One biochemical failure occurred at 18 months in a patient with Gleason 8 T2c disease with pretreatment PSA of 124. One patient on an alpha blocker prior to proton therapy required a transurethral resection of the prostate (TURP) 3 months after treatment. No other patient required a catheter or developed other Grade 3 side effects. Genitourinary (GU) symptoms requiring prescription medications (Grade 2) occurred in 14% of men before treatment, an additional 25% during treatment, and 16%, 14%, and 21% at 6, 12, and 18 months after proton therapy. Temporary urinary urge incontinence requiring a pad (Grade 2) occurred in 3 patients during follow-up but resolved with antibiotics (N=2) or anti-cholinergics (N=1). Gastrointestinal (GI) symptoms requiring prescription medications occurred in 10% of patients during treatment and 5%, 10%, and 3% at 6, 12, and 18 months. No Grade 2 or higher rectal incontinence occurred. The median IIEF score in non-AD men was 24 (range, 12 to 25) before treatment and then 22 (range, 9 to 25), 21 (range, 5 to 25), and 18 (range, 5 to 25) at 6, 12, and 18 months after proton therapy. At 6, 12, and 18 months, 90%, 95%, and 94% of men remained sexually active. Patient dissatisfaction rates at 6, 12, and 18 months were 1%, 0%, and 5%, respectively.ConclusionsYoung men treated with proton therapy for prostate cancer have few significant side effects in the first 18 months after treatment. Although erectile dysfunction after treatment can occur, complete impotence was rare and few were dissatisfied with their treatment choice. More follow-up is needed to confirm these findings. Purpose/Objective(s)Controversy exists over the optimal management of young men with prostate cancer. We report early outcomes in men ≤ 55 years old treated with proton therapy. Controversy exists over the optimal management of young men with prostate cancer. We report early outcomes in men ≤ 55 years old treated with proton therapy. Materials/MethodsFrom August 15, 2006, to September 1, 2009, 98 men ≤ 55 years old with low- (N = 57), intermediate- (N = 29), and high- (N = 12) risk prostate cancer were enrolled on University of Florida IRB-approved protocols and received proton therapy to between 78 and 82 CGE at 2 CGE per fraction or 70 to 72.5 CGE at 2.5 CGE per fraction. Androgen deprivation (AD) was given to 14 patients. Before treatment and every 6 months after, patients had a PSA evaluation and completed international index of erectile function (IIEF) and international prostate symptom score (IPSS) questionnaires. Physician toxicity assessments (CTCAE, v3.0) were performed at the same intervals and weekly during treatment. The median follow-up was 18 months. From August 15, 2006, to September 1, 2009, 98 men ≤ 55 years old with low- (N = 57), intermediate- (N = 29), and high- (N = 12) risk prostate cancer were enrolled on University of Florida IRB-approved protocols and received proton therapy to between 78 and 82 CGE at 2 CGE per fraction or 70 to 72.5 CGE at 2.5 CGE per fraction. Androgen deprivation (AD) was given to 14 patients. Before treatment and every 6 months after, patients had a PSA evaluation and completed international index of erectile function (IIEF) and international prostate symptom score (IPSS) questionnaires. Physician toxicity assessments (CTCAE, v3.0) were performed at the same intervals and weekly during treatment. The median follow-up was 18 months. ResultsThe median pretreatment, 6-month, 12-month, and 18-month PSAs were 5.0 (range, 0.7 to 124), 1.5 (range, 0 to 10), 1.3 (range, 0 to 7.6), and 1.2 (range, 0 to 4.2). One biochemical failure occurred at 18 months in a patient with Gleason 8 T2c disease with pretreatment PSA of 124. One patient on an alpha blocker prior to proton therapy required a transurethral resection of the prostate (TURP) 3 months after treatment. No other patient required a catheter or developed other Grade 3 side effects. Genitourinary (GU) symptoms requiring prescription medications (Grade 2) occurred in 14% of men before treatment, an additional 25% during treatment, and 16%, 14%, and 21% at 6, 12, and 18 months after proton therapy. Temporary urinary urge incontinence requiring a pad (Grade 2) occurred in 3 patients during follow-up but resolved with antibiotics (N=2) or anti-cholinergics (N=1). Gastrointestinal (GI) symptoms requiring prescription medications occurred in 10% of patients during treatment and 5%, 10%, and 3% at 6, 12, and 18 months. No Grade 2 or higher rectal incontinence occurred. The median IIEF score in non-AD men was 24 (range, 12 to 25) before treatment and then 22 (range, 9 to 25), 21 (range, 5 to 25), and 18 (range, 5 to 25) at 6, 12, and 18 months after proton therapy. At 6, 12, and 18 months, 90%, 95%, and 94% of men remained sexually active. Patient dissatisfaction rates at 6, 12, and 18 months were 1%, 0%, and 5%, respectively. The median pretreatment, 6-month, 12-month, and 18-month PSAs were 5.0 (range, 0.7 to 124), 1.5 (range, 0 to 10), 1.3 (range, 0 to 7.6), and 1.2 (range, 0 to 4.2). One biochemical failure occurred at 18 months in a patient with Gleason 8 T2c disease with pretreatment PSA of 124. One patient on an alpha blocker prior to proton therapy required a transurethral resection of the prostate (TURP) 3 months after treatment. No other patient required a catheter or developed other Grade 3 side effects. Genitourinary (GU) symptoms requiring prescription medications (Grade 2) occurred in 14% of men before treatment, an additional 25% during treatment, and 16%, 14%, and 21% at 6, 12, and 18 months after proton therapy. Temporary urinary urge incontinence requiring a pad (Grade 2) occurred in 3 patients during follow-up but resolved with antibiotics (N=2) or anti-cholinergics (N=1). Gastrointestinal (GI) symptoms requiring prescription medications occurred in 10% of patients during treatment and 5%, 10%, and 3% at 6, 12, and 18 months. No Grade 2 or higher rectal incontinence occurred. The median IIEF score in non-AD men was 24 (range, 12 to 25) before treatment and then 22 (range, 9 to 25), 21 (range, 5 to 25), and 18 (range, 5 to 25) at 6, 12, and 18 months after proton therapy. At 6, 12, and 18 months, 90%, 95%, and 94% of men remained sexually active. Patient dissatisfaction rates at 6, 12, and 18 months were 1%, 0%, and 5%, respectively. ConclusionsYoung men treated with proton therapy for prostate cancer have few significant side effects in the first 18 months after treatment. Although erectile dysfunction after treatment can occur, complete impotence was rare and few were dissatisfied with their treatment choice. More follow-up is needed to confirm these findings. Young men treated with proton therapy for prostate cancer have few significant side effects in the first 18 months after treatment. Although erectile dysfunction after treatment can occur, complete impotence was rare and few were dissatisfied with their treatment choice. More follow-up is needed to confirm these findings.

Purpose/Objective(s)Angiosarcoma is a rare but aggressive malignant vascular tumor often associated with prior radiotherapy. This study aimed to define prognostic factors and to identify successful therapeutic approaches in the treatment of angiosarcoma with radiation therapy (RT).Materials/MethodsBetween 1964 and 2009, 41 patients with nonmetastatic, histologically proven angiosarcoma were treated with RT at the University of Florida. The median age of the patients was 67 years (range, 21 to 87 years). Sixteen of the 41 angiosarcomas were considered radiation-induced. Twenty-two patients had angiosarcomas of the head and neck, including 9 of the scalp. Fourteen angiosarcomas were located on the breast or chest wall while 5 were located on the extremities, retroperitoneum, or deep soft tissues. Thirty-one patients were treated with both surgery and RT (12 with preoperative RT and 19 with postoperative RT), whereas 10 patients were treated with RT alone. The median RT dose was 60 Gy (range, 37.5 to 76 Gy). Sixteen patients were treated with RT once daily, 7 patients were treated twice daily, and 18 patients were treated three times daily. Two patients received adjuvant chemotherapy. The median follow-up was 44 months (range, 2 to 343 months).ResultsThe 5-year local control and overall survival rates were 64% and 54%, respectively. Of 23 patients who relapsed, 15 had a component of local failure: 11 had an isolated local recurrence and 4 occurred in conjunction with metastatic disease. The median time to a local failure was 1.5 years from RT and the longest time interval to a local failure was 10.2 years. Predictors of 5-year local control were non-scalp primary location (92% breast vs. 80% other vs. 60% non-scalp head and neck vs. 18% scalp; p< 0.05), tumor size ≤ 5 cm (76% vs. 26%; p <0.01), radiation-induced tumors versus de novo angiosarcoma (92% vs. 47%; p < 0.01), and combined-modality local therapy (78% surgery + RT vs. 30% RT alone; p<0.01). Predictors of 5-year overall survival were non-scalp primary location (79% breast vs. 69% non-scalp head and neck vs. 20% other vs. 9% scalp; p < 0.05) and tumor size ≤ 5 cm (69% vs. 17%; p < 0.05). With regard to both local control and overall survival, the most favorable cohort was comprised of patients who were treated with radiotherapy three times daily combined with surgery for angiosarcoma of the breast.ConclusionsFor angiosarcomas treated with radiotherapy, outcome varies widely and is most impacted by site, size, and resectability. In amenable sites, aggressive treatment with surgical resection and hyperfractionated radiation therapy may offer the best prognosis. Purpose/Objective(s)Angiosarcoma is a rare but aggressive malignant vascular tumor often associated with prior radiotherapy. This study aimed to define prognostic factors and to identify successful therapeutic approaches in the treatment of angiosarcoma with radiation therapy (RT). Angiosarcoma is a rare but aggressive malignant vascular tumor often associated with prior radiotherapy. This study aimed to define prognostic factors and to identify successful therapeutic approaches in the treatment of angiosarcoma with radiation therapy (RT). Materials/MethodsBetween 1964 and 2009, 41 patients with nonmetastatic, histologically proven angiosarcoma were treated with RT at the University of Florida. The median age of the patients was 67 years (range, 21 to 87 years). Sixteen of the 41 angiosarcomas were considered radiation-induced. Twenty-two patients had angiosarcomas of the head and neck, including 9 of the scalp. Fourteen angiosarcomas were located on the breast or chest wall while 5 were located on the extremities, retroperitoneum, or deep soft tissues. Thirty-one patients were treated with both surgery and RT (12 with preoperative RT and 19 with postoperative RT), whereas 10 patients were treated with RT alone. The median RT dose was 60 Gy (range, 37.5 to 76 Gy). Sixteen patients were treated with RT once daily, 7 patients were treated twice daily, and 18 patients were treated three times daily. Two patients received adjuvant chemotherapy. The median follow-up was 44 months (range, 2 to 343 months). Between 1964 and 2009, 41 patients with nonmetastatic, histologically proven angiosarcoma were treated with RT at the University of Florida. The median age of the patients was 67 years (range, 21 to 87 years). Sixteen of the 41 angiosarcomas were considered radiation-induced. Twenty-two patients had angiosarcomas of the head and neck, including 9 of the scalp. Fourteen angiosarcomas were located on the breast or chest wall while 5 were located on the extremities, retroperitoneum, or deep soft tissues. Thirty-one patients were treated with both surgery and RT (12 with preoperative RT and 19 with postoperative RT), whereas 10 patients were treated with RT alone. The median RT dose was 60 Gy (range, 37.5 to 76 Gy). Sixteen patients were treated with RT once daily, 7 patients were treated twice daily, and 18 patients were treated three times daily. Two patients received adjuvant chemotherapy. The median follow-up was 44 months (range, 2 to 343 months). ResultsThe 5-year local control and overall survival rates were 64% and 54%, respectively. Of 23 patients who relapsed, 15 had a component of local failure: 11 had an isolated local recurrence and 4 occurred in conjunction with metastatic disease. The median time to a local failure was 1.5 years from RT and the longest time interval to a local failure was 10.2 years. Predictors of 5-year local control were non-scalp primary location (92% breast vs. 80% other vs. 60% non-scalp head and neck vs. 18% scalp; p< 0.05), tumor size ≤ 5 cm (76% vs. 26%; p <0.01), radiation-induced tumors versus de novo angiosarcoma (92% vs. 47%; p < 0.01), and combined-modality local therapy (78% surgery + RT vs. 30% RT alone; p<0.01). Predictors of 5-year overall survival were non-scalp primary location (79% breast vs. 69% non-scalp head and neck vs. 20% other vs. 9% scalp; p < 0.05) and tumor size ≤ 5 cm (69% vs. 17%; p < 0.05). With regard to both local control and overall survival, the most favorable cohort was comprised of patients who were treated with radiotherapy three times daily combined with surgery for angiosarcoma of the breast. The 5-year local control and overall survival rates were 64% and 54%, respectively. Of 23 patients who relapsed, 15 had a component of local failure: 11 had an isolated local recurrence and 4 occurred in conjunction with metastatic disease. The median time to a local failure was 1.5 years from RT and the longest time interval to a local failure was 10.2 years. Predictors of 5-year local control were non-scalp primary location (92% breast vs. 80% other vs. 60% non-scalp head and neck vs. 18% scalp; p< 0.05), tumor size ≤ 5 cm (76% vs. 26%; p <0.01), radiation-induced tumors versus de novo angiosarcoma (92% vs. 47%; p < 0.01), and combined-modality local therapy (78% surgery + RT vs. 30% RT alone; p<0.01). Predictors of 5-year overall survival were non-scalp primary location (79% breast vs. 69% non-scalp head and neck vs. 20% other vs. 9% scalp; p < 0.05) and tumor size ≤ 5 cm (69% vs. 17%; p < 0.05). With regard to both local control and overall survival, the most favorable cohort was comprised of patients who were treated with radiotherapy three times daily combined with surgery for angiosarcoma of the breast. ConclusionsFor angiosarcomas treated with radiotherapy, outcome varies widely and is most impacted by site, size, and resectability. In amenable sites, aggressive treatment with surgical resection and hyperfractionated radiation therapy may offer the best prognosis. For angiosarcomas treated with radiotherapy, outcome varies widely and is most impacted by site, size, and resectability. In amenable sites, aggressive treatment with surgical resection and hyperfractionated radiation therapy may offer the best prognosis.

To report long-term outcomes following radiotherapy for cranial and spinal ependymomas. This is a retrospective review of all patients treated with radiotherapy for intracranial and spinal ependymomas at the University of Florida between 1964 and 2006. Patients with grade I spinal tumors with gross total resection, subependymomas, ependymoblastomas, and patients undergoing re-irradiation were excluded from this analysis. Fifty-seven patients met inclusion criteria for outcome analysis. Most patients received local radiotherapy alone to a median tumor dose of 54 Gy. One-quarter of the patients received craniospinal irradiation to a median dose of 35 Gy. The 5- and 10-year local control rates for the entire population were 67% and 57%, respectively, with 23% of local recurrences occurring after 5 years. The great majority (92%) of patients recurred at the primary site while only 8% had spinal seeding with no evidence of disease at the primary site. No patient who received craniospinal irradiation recurred in the spine. The 5- and 10-year disease-free survival and overall survival rates for the entire cohort were 65% and 53% and 62% and 51%, respectively. On multivariate analysis, age ≥ 18 years, gross total resection, and spinal cord site were associated with improved local control. Tumor grade and treatment year or treatment era (early, 1964-1985, versus more recent, 1986-2006) did not influence outcome. There were no grade 4 or 5 toxicities in patients with continuous local control. Twenty-four percent of patients had Grade 2 or 3 toxicities. Two patients developed radiation-induced tumors (meningioma and glioblastoma multiforme) greater than 20 years after radiotherapy. The rate of cure of a cranial or spinal ependymoma is almost 50% and this has not improved over the past 40 years. Maximum safe resection followed by radiotherapy to a dose of 54 to 59 Gy, usually limited to the primary site, remains the treatment of choice. Changes in surgery or radiotherapy are unlikely to improve the outcome of these patients as we are pushing the limit of normal-tissue tolerance at the primary site with current approaches. These findings have implications for future studies on ependymoma.

Published data from adult patients at the University of Florida demonstrates that local control of desmoid tumors following external-beam radiotherapy (RT) exceeds 80%. According to the literature, pediatric patients treated in a similar manner have a much lower rate of local control. The purpose of this retrospective review is to report our comparable long-term outcomes treating pediatric and young adult patients with desmoid tumors, and identify variables impacting local control and treatment complications. Between 1978 and 2008, 30 patients under the age of 30-years-old (5 patients <18-years-old) were treated with RT for pathologically confirmed desmoid tumor/aggressive fibromatosis. The median age at RT was 23.7-years-old (range, 10.3–29.9-years-old). Fifteen patients underwent definitive RT (median, 54 Gy); 14 received EBRT after gross total resection (median, 54 Gy); and 1 received preoperative treatment (50.4 Gy). Treatment included standard 1.8 Gy once-daily fractions in 16 cases and 1.2 Gy twice-daily fractions in 14 cases. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at RT, tumor site, tumor size, extent of resection, and RT dose. Median follow-up was 13.3 years. The actuarial 15-year overall survival and local control rates were 96% and 55%, respectively. Sixty-nine percent of relapses were observed within 5 years of treatment. Local control in patients <18 years old at the time of RT was 20% compared to 63% in those 18 to 30-years-old (p = 0.08). Local control rates for ≥55 Gy and <55 Gy were 79% and 30%, respectively (p = 0.02). No other factors were statistically associated with local control on univariate analysis. Twelve of 30 patients had NCI Common Toxicity Criteria (CTCAE v3) Grade 3–4 treatment complications. These included pathologic fractures, impaired range of motion, pain, and 2 in-field skin cancers. There were no Grade 5 complications. Fifty percent of patients receiving ≥55 Gy had Grade 3–4 complications, compared to 31% receiving <55 Gy (p = 0.46). Otherwise, no single factor correlated with treatment complications. The role of RT in the management of young patients with desmoid tumors is not clearly established. Our institutional experience adds to the data suggesting that patient age is proportional to local control following RT and late failures are not uncommon. In the pediatric and young adult population, doses ≥55 Gy were associated with improved local control, but may also lead to increased long-term complications.

Functional imaging modalities are gaining increased application in radiotherapy planning. Many centers utilize F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in involved-field radiotherapy planning for lymphomas, although clinical data is lacking, particularly in children. We report the impact of FDG- PET findings on radiotherapy field design in pediatric Hodgkin's Lymphoma. We performed a retrospective review of records of 30 pediatric patients (ages 5-18) with histologically confirmed Hodgkin's disease treated with combined chemotherapy and involved-field radiation therapy (IFRT) at our institution from June 2003 to February 2008. All of the patients underwent initial diagnostic contrast CT scan of the neck, chest, abdomen, and pelvis and whole-body combined FDG-PET/CT scans for staging as well as therapy response evaluation. The FDG-PET/CT and post-contrast CT scans were co-registered using our in-house fusion software. The CT scans were reviewed for all potential sites of involvement and correlated with FDG-PET/CT corresponding sites for determining concordance and discordance of radiographic findings. These data were then correlated with IFRT fields as designed by the treating radiation oncologist in order to determine the influence of FDG-PET/CT findings in outlining target volumes (regions). All patients were treated with conventional AP-PA fields. The median dose delivered was 2100 cGy. Of the 600 regions analyzed for each modality, FDG-PET and CT were concordant in a total of 525 regions (positive 97, negative 428) and discordant in 78 regions. The most common sites of disease upstaging were contralateral neck (8), hilum (8), para-aortic nodes (5), and bone marrow (5). The common sites for disease downstaging were lung nodules (6), pleural effusions (7), and contralateral neck (4). Radiotherapy fields in all patients were delineated based on pre-chemotherapy disease coverage with adjustment made for tumor bulk reduction horizontally after chemotherapy response. The IFRT volumes were adjusted based on initial FDG-PET finding in 21 (70%) patients with 34 regions added and 14 regions excluded from fields. The most common field adjustments were made by extending the fields for contralateral neck (8) and paraaortic/spleen (5) regions. The most common sites excluded from IFRT were pleural (4) and pericardial (2) cavities, and lung nodules (3). The incorporation of FDG-PET findings into CT-based treatment planning for pediatric patients with Hodgkin's disease resulted in considerable changes in treatment target definition. Because of the novelty of this method, clinical correlation of patient outcome is warranted, which is the goal of our future research.

Bee colonies were treated with 1.2 g lincomycin hydrochloride per hive (single treatment in sucrose solution) and samples of honey were then collected at intervals over a 41-week period. The samples were analysed for lincomycin using Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC–MS/MS). The highest mean concentration of lincomycin (pooled analytical results for brood and super honey) was 24 μg g−1 3 days after treatment, a mean of 3.5 μg g−1 after 129 days. The shook swarm procedure was investigated and resulted in a lincomycin concentration of 34 μg g−1 in honey (pooled results for brood and super honey) 3 days after treatment, declining to 0.38 μg g−1 129 days after treatment. Lincomycin was persistent in the hive and detected in all over winter (290 days after dosing) samples of honey collected from both non-shook swarmed and shook swarmed colonies. The results overall indicate that lincomycin parent is a suitable marker compound to detect lincomycin misuse in apiculture.

For giant cell tumors of bone, does radiotherapy provide a safe and effective treatment? This retrospective review includes 24 patients with 26 histologically diagnosed tumors treated with megavoltage radiotherapy between March 1972 and July 1996. Of the 10 recurrent tumors, five had an intralesional resection, two had a biopsy, and three had no biopsy before radiotherapy. Of the 16 previously untreated tumors, one was irradiated after a marginal resection, five after an intracapsular resection, and 10 after biopsy alone. The total doses ranged from 35 to 55 Gy (median, 43 Gy) in fractions of 1.67 to 2.33 Gy per day. Twenty of 26 tumors (77%) were controlled locally. All of the local recurrences occurred within the irradiated field. Five of six patients with local recurrence were treated successfully with additional surgery. Salvage surgery after local recurrence required amputation of an extremity in three patients and a total knee replacement in one patient. The ultimate local control rate was 96% with one patient alive with progressive disease. Lung metastases in one patient were treated successfully with surgery, chemotherapy, and radiotherapy. In one patient a radiation-induced sarcoma developed 22 years after treatment. The authors conclude that radiation therapy is a safe and effective treatment option for benign giant cell tumors of bone. A total dose greater than 40 Gy is the only variable found to significantly influence local control.

Since 1969, 144 patients with previously untreated Ewing's sarcoma of bone were entered in prospective protocols at the University of Florida. From 1969 through 1981, three institutional protocols were used, and some patients were entered into the First Intergroup Ewing's Sarcoma Study. Starting in 1982, an attempt was made to intensify treatment, with patients divided according to their primary tumor size into standard-risk (< or = 8 cm in maximum diameter) and high-risk groups. Patients with metastases at diagnosis also were considered high risk. The standard-risk protocols (Number 1 and Number 2 specified treatment with chemotherapy considered to be standard for the era; the patients who were high risk had standard chemotherapy followed by end-intensification. Treatment for patients with metastases at diagnosis was intensified additionally in 1993 with a protocol (high-risk protocol Number 5) specifically designed just for these patients. The absolute survival rate of all patients treated before 1982 was 50% at 5 years for patients without metastases at diagnosis and 18% for patients with metastases. Patients with small primary lesions had a better survival rate than patients with large primary lesions. After 1982, the 5-year survival rate for patients treated on the standard-risk protocols was 53% (1985-1998), whereas for high-risk protocols the 5-year survival rate was 63%. Survival rates were better for younger patients at diagnosis and for patients who responded well to induction chemotherapy, indicating that future trials may need to tailor therapy based on the response to induction chemotherapy.

Purpose: To review a large single-institution experience in the management of aggressive fibromatosis to determine the effectiveness of external beam radiotherapy (EBRT) and identify the presentation and treatment variables predictive of locoregional control.Methods and Materials: Between 1975 and 2000, 72 patients were treated with EBRT for a pathologically confirmed diagnosis of aggressive fibromatosis. Thirty patients were treated at the primary presentation and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data were available for 65 patients (median 6 years). Megavoltage irradiation with Co-60 to 20 MV photons or electron therapy was used for all patients. Most patients were treated after attempted complete surgical resection; 16 patients underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8 Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The median prescribed dose was 54 Gy. The prognostic variables and treatment results were evaluated by Kaplan-Meier actuarial analysis.Results: Locoregional control was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was 83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent tumors). Only two failures occurred within the irradiation fields; nine failures occurred at the field margins. Eleven patients were salvaged by surgery: wide excision in nine and amputation in two. The only prognostic factor significant for locoregional control was primary vs. recurrent presentation (p=0.0193). The 5-year locoregional control rates for irradiation at initial presentation and at recurrence were 96% and 75%, respectively. The variables without significance for locoregional control included primary tumor location, surgical procedures performed, resection margins, and gross vs. microscopic residual tumor at irradiation. Lymphedema was the most common late effect, occurring in 7 patients, 5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had fibromatosis involving the bone at presentation but without recurrence at the time of fracture.Conclusion: EBRT is effective treatment for aggressive fibromatosis. The probability of locoregional control decreases with multiple prior recurrences. (C) 2002 Elsevier Science Inc.

The purpose of this study was to review treatment results, sites of failure, and complications in relation to the irradiation volume for carcinoma of the vagina treated with radiotherapy alone. A retrospective review of 65 patients with histologically confirmed squamous cell carcinoma of the vagina who received definitive radiotherapy was undertaken. The 5-year cause-specific survival rates were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB, 55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5 years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III, 89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients. Eighty-five percent of pelvis recurrences were in the primary treatment field. Although pelvic control rates were not increased by use of larger treatment fields (>2,700 cm(3)), moderate acute and late effects were increased with these fields. Carcinoma of the vagina appears to have a different failure pattern than carcinoma of the cervix. The primary failure sites are the vagina and the paracolpal tissues and the inguinal nodes. Because of this, the superior edge of the pelvic fields does not have to extend above the bottom of the sacroiliac joints except with advanced lesions. (C) 2002 Wiley-Liss, Inc.

for different coronary vessels.The measured data (average, standard deviation, and range) are tabulated for different coronary vessels for radiation delivery catheters. Conclusions:The contribution of source motion should be included into the treatment volume to avoid "geographic miss" and the subsequent marginal failure.

Purpose/Objective: To assess local (in-field) disease control, identify potential prognostic factors, and elucidate the optimal radiotherapy dose in various clinical settings of Stage I and II nonHodgkin's lymphoma (non-CNS).Materials & Methods: A total of 285 consecutive patients with Stage I and II non-Hodgkin's lymphoma were treated with curative intent, including 159 with radiotherapy (RT) alone and 126 with combined-modality therapy (CMT). Of these, 72 patients had low-grade lymphomas (LGL), 92 had intermediate or high-grade lymphomas (I/HGL), and 21 had unclassified lymphomas. Clinical and treatment variables with potential prognostic significance for in-field disease control, freedom from relapse (FFR), and absolute survival (AS) were evaluated by univariate and multivariate analyses.Results: The 5-, 10-, and 20-year actuarial AS rates were 73%, 46%, and 33% for patients with LGL and 64%, 44%, and 18% for patients with I/HGL, respectively, The 5-, 10-, and 20-year actuarial FFR rates were 62%, 59%, and 49% for patients with LGL and 66%, 57%, and 57% for patients with I/HGL, respectively. Significant prognostic factors identified by the multivariate analysis were age, tumor size, and histology for AS; tumor size and treatment for FFR; and only tumor size for in-field disease control. There were 95 total failures, with only 12 occurring infield. Most failures (65%) were in contiguous unirradiated sites. All 4 in-field failures in patients with LGL occurred after RT doses < 30 Gy, although none occurred in 10 patients with small-volume LGL of the orbit treated with doses < 30 Gy. The 8 in-field failures in patients with I/HGL were distributed evenly throughout the RT dose range; 5 occurred in patients treated with CMT, all with tumors > 6 cm, and 4 with less than a complete response (CR) to chemotherapy.Conclusion: Our analysis suggests that the overwhelming problem in the treatment of non-Hodgkin's lymphoma is not in-field failure but, rather, failure in contiguous unirradiated sites. A dose of 20-25 Gy may be sufficient for small-volume LGL of the orbit. A dose of 30 Gy is sufficient for LGL in general, as well as for patients with nonbulky (less than or equal to 6 cm) I/HGL treated with CMT who have a CR. However, patients with I/HGL treated with CMT for tumors > 6 cm and/or without a CR may benefit from doses greater than or equal to 40 Gy. (C) 1999 Elsevier Science Inc.

Purpose: The purpose of this study is to analyze the effect of radiation dose, as well as other clinical and therapeutic factors, on in-field disease control.Patients and Materials: The study population comprised 232 patients with Stage I and II Hodgkin's disease (HD) treated with curative intent at the University of Florida with radiotherapy (RT) alone (169 patients) or chemotherapy and radiotherapy (CMT) (63 patients). Sites of involvement and radiation doses were prospectively recorded and correlated with sites of disease recurrence.Results: Freedom from relapse and absolute survival rates at 10 years were as follows: 76% and 77%, entire group; 76% and 80%, RT group; 79% and 70%, CMT group; 85% and 78%, Stage I; and 71% and 77%, Stage II. Treatment failure occurred in 50 patients (22%) including in-field failure in 22 patients (9%). In-field failure was rare in electively treated sites. Multivariate analysis of clinical factors (tumor size, number of sites involved, B-symptoms, gender, histology, age, and site of involvement) and treatment factors (use of chemotherapy, number of cycles of chemotherapy, radiation dose, radiation treatment volume, and radiation treatment time) showed only tumor size (p = 0.0001) to be significantly correlated with in-field disease control. In RT patients, the in-field failure rate according to tumor size was as follows: 0% for less than or equal to 3 cm; 4% for > 3 cm and less than or equal to 6 cm; 23% for > 6 cm and less than or equal to 9 cm; and 36% for > 9 cm. In CMT patients, the in-field failure rate was as follows: 0% for less than or equal to 3 cm; 0% for > 3 and less than or equal to 6 cm; 5% for > 6 cm and less than or equal to 9 cm; and 26% for > 9 cm. In-field recurrence was not a predominant pattern of failure in RT patients,vith small tumors (less than or equal to 6 cm); thus, the difference in in-field control in tumors less than or equal to 6 cm between doses less than or equal to 35 Gy (6%) and doses greater than or equal to 36 Gy (0%) was not statistically significant. In larger tumors (> 6 cm), in-field recurrence was a predominant pattern of failure; the in-held failure rate in RT patients with tumors > 6 cm of 30% for doses less than or equal to 35 Gy was not significantly different from 25% for doses > 35 Gy. In moderately bulky tumors (> 6 cm and less than or equal to 9 cm), the addition of chemotherapy did appear to increase in-field disease control; the in-field failure rate was 23% with RT and 5% with CMT (p = 0.07).Conclusion: Our data do not demonstrate statistically significant evidence of increasing tumor control in HD with doses > 30 Gy. The data do show that increasing tumor size is associated with increased rates of in-field failure, and the addition of chemotherapy may improve in-field disease control in tumors > 6 cm. In-held recurrence in large tumors remains a predominant pattern of failure, however, and the role of radiation doses higher than 30-35 Gy in this high-risk subset warrants further study. (C) 1999 Elsevier Science Inc.