Late isolated central nervous system relapse in childhood B-cell acute lymphoblastic leukemia treated with intensified systemic therapy and delayed reduced dose cranial radiation: A report from the Children's Oncology Group study AALL02P2.

BACKGROUND: Patients with late, ≥18 months postdiagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-year overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy. PROCEDURES: COG AALL02P2 enrolled 118 eligible patients with B-cell ALL (B-ALL) and late iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy, and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until 104 weeks postdiagnosis. RESULTS: The 3-year event-free survival (EFS) and OS were 64.3% ± 4.5% and 79.6% ± 3.8%, with 46.1% (18/39) of second relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard-risk classification fared better than high-risk patients. CONCLUSIONS: COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.

Late toxicity following craniospinal radiation for early-stage medulloblastoma.

BACKGROUND: The purpose of this study is to review late toxicity following craniospinal radiation for early-stage medulloblastoma. MATERIAL AND METHODS: Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3) medulloblastoma were treated at our institution. The median age at diagnosis was 7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was 28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and the high-risk boost volume reduced. Twenty-one patients (40%) received chemotherapy in their initial management, including 12 who received concurrent chemotherapy. Late sequelae were evaluated by analyzing medical records and conducting phone interviews with surviving patients and/or care-takers. Complications were graded using the NCI Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up for all patients was 15.4 years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4). The overall survival, cause-specific survival, and progression-free survival rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of patients who survived five years or more) developed grade 3 + toxicity; 15 of these 16 patients received a CSI dose > 23.4 Gy. The most common grade 3 + toxicities for long-term survivors are hearing impairment requiring intervention (20.5%) and cognitive impairment (18%) prohibiting independent living. Four patients developed secondary (non-skin) malignancies, including three meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three patients (5.6%) died from treatment complications, including radionecrosis, severe cerebral edema, and fatal secondary malignancy. CONCLUSION: Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood.

Local control in non-metastatic medulloblastoma.

BACKGROUND: A single-institution review of long-term outcomes and factors affecting local control (LC) following radiotherapy for non-metastatic medulloblastoma. MATERIAL AND METHODS: From 1963 to 2008, 50 children (median age, 7.3 years; range 1.2-18.5) with stage M0 medulloblastoma were treated with radiotherapy; half underwent a gross total resection (no visible residual tumor) or near-total resection (< 1.5 cm(3) of gross disease remaining after resection). Median craniospinal dose was 28.8 Gy (range 21.8-38.4 Gy). Median total dose to the posterior fossa was 54.3 Gy (range 42.4-64.8 Gy). Eighteen patients (36%) received chemotherapy as part of multimodality management, including 11 who received concurrent chemotherapy. RESULTS: Median follow-up was 15.7 years (range 0.3-44.4 years) for all patients and 26.6 years (range 7.3-44.4 years) for living patients. The 10-year overall survival, cancer-specific survival, and progression-free survival rates were 65%, 65%, and 69%. The 10-year LC rate was 84% and did not significantly change across eras. Four percent of patients experienced local progression five years after treatment. On univariate analysis, chemotherapy and overall duration of radiotherapy ≤ 45 days were associated with improved LC. Patients receiving chemotherapy had a 10-year 100% LC rate versus 76% in patients not receiving chemotherapy (p = 0.0454). When overall radiotherapy treatment lasted ≤ 45 days, patients experienced a superior 95% 10-year LC rate (vs. 73% in patients treated > 45 days; p = 0.0419). Three patients (6%) died from treatment complications, including radionecrosis/cerebellar degeneration, severe cerebral edema leading to herniation, and secondary malignancy. CONCLUSIONS: While we cannot draw definitive conclusions given the retrospective nature of our study, our long-term data suggest that reductions in craniospinal dose and boost target volume to reduce toxicity have not compromised disease control in the modern era. Our data also support analyses that implicate duration of radiotherapy, rather than interval between surgery and radiotherapy, as a factor in LC. Chemotherapy in multimodality management of medulloblastoma may have an underappreciated role in improving LC rates.

Radiation therapy target volume reduction in pediatric rhabdomyosarcoma: implications for patterns of disease recurrence and overall survival.

BACKGROUND: The use of radiation therapy (RT) "cone-down" boost to reduce high-dose treatment volumes according to tumor response to induction chemotherapy in patients with pediatric rhabdomyosarcoma (RMS) may reduce treatment morbidity, yet the impact on tumor control is unknown. METHODS: Fifty-five children, including 18 (33%) with parameningeal (PM) RMS and 37 (67%) with non-PM RMS, who received definitive treatment with chemotherapy and RT from April 2000 through January 2010 were retrospectively reviewed. RESULTS: In total, 28 patients (51%) received a cone-down boost. The high-dose boost volume was reduced by a median of 56% of the initial target volume (range, 5%-91%). The median time to initiating RT was 3 weeks for patients with PM RMS and 16 weeks for patients with non-PM RMS (P < .001). After a median follow-up of 41 months, local failure occurred in 5 patients (9%), including 2 patients who received a cone-down boost, and there were no marginal failures. Twelve patients (67%) with PM RMS had intracranial tumor extension. In this subgroup, 4 patients (30%) who received a cone-down boost and had ≥ 3 weeks between chemotherapy and RT initiation experienced leptomeningeal failure as their first site of disease progression, and a delayed time to RT initiation was associated with decreased survival (P = .055) CONCLUSIONS: A cone-down boost allowed for significant reductions in high-dose RT treatment volume while maintaining excellent tumor control in most patients. However, in the subset of patients with PM RMS and intracranial tumor extension, early RT initiation and wider margin RT to cover adjacent areas at high risk for meningeal extension may be more important for adequate disease control.

Urinary functional outcomes and toxicity five years after proton therapy for low- and intermediate-risk prostate cancer: results of two prospective trials.

BACKGROUND: To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT. MATERIAL AND METHODS: Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78-82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively. RESULTS: Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15-25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months. CONCLUSION: Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15-25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15-25).

Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression.

BACKGROUND: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. MATERIAL AND METHODS: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. RESULTS: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. CONCLUSION: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.

The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity.

BACKGROUND: Marginal excision of soft tissue sarcoma (STS), defined as resection through the tumor pseudocapsule or surrounding reactive tissue, increases the likelihood of local recurrence and necessitates re-excision or postoperative radiation. However, its impact after preoperative radiation therapy (RT) remains unclear. This study therefore investigated the significance of marginal margins in patients treated with preoperative RT for extremity STS, reporting long-term local control and limb preservation endpoints. METHODS: The records of 317 adults at the University of Florida with nonmetastatic extremity STS treated from 1980 to 2008 with preoperative RT as part of a limb conservation strategy were reviewed. The median follow-up was 4.7 years (8.3 years for living patients). The median tumor size was 10 cm (range, 2-36 cm), and 86% were high grade. The median RT dose was 50.4 Gy (range, 12.5-57.6 Gy). Margins were classified as wide/radical (n = 105), marginal (n = 179), contaminated (n = 15), positive (n = 17), or unknown (n = 1). Endpoints were local control (LC), amputation-free survival (AFS), cause-specific survival (CSS), and overall survival (OS). RESULTS: Five-year CSS and OS rates were 62% and 59%, respectively. Five-year LC and AFS was 93% and 89%, respectively. AFS by margin status was 64%, 83%, 97%, and 92% for positive, contaminated, marginal, and wide/radical margins, respectively (P<.005). Marginal excision following preoperative RT resulted in equivalent LC and AFS compared with wide/radical margins. CONCLUSIONS: Marginal resection after preoperative RT does not compromise LC or AFS in extremity STS. This finding may be related to radiosterilization of tumor cells within the reactive zone following preoperative RT.

Erectile function, incontinence, and other quality of life outcomes following proton therapy for prostate cancer in men 60 years old and younger.

BACKGROUND: This study sought to evaluate patient-reported health-related quality of life following proton therapy for prostate cancer in men ≤ 60 years old. METHODS: Between August 2006 and January 2010, 262 hormone-naive men ≤ 60 years old were treated with definitive proton therapy for prostate cancer. Before treatment and every 6 months after treatment, patients filled out the Expanded Prostate Index Composite (EPIC) and the International Index of Erectile Function (IIEF) questionnaires. Potency was defined as successful sexual intercourse in the prior month or an EPIC sexual summary (SS) score ≥ 60. RESULTS: Median follow-up was 24 months; 90% of men completed follow-up EPIC forms within the last year. For EPIC urinary, bowel, and hormone subscales, the average decline from baseline to 2 years was ≤5 points, except for bowel function (5.2 points). SS scores declined 12.6 points after 2 years. Potency rates declined by 11% from baseline at 2 years, but 94% of men were potent with a baseline IIEF > 21, body mass index < 30, and no history of diabetes. At 2 years after treatment, only 1.8% of men required a pad for urge incontinence. On multivariate analysis, factors associated with a significant decline in SS score were mean penile bulb dose ≥40 cobalt Gy equivalents (P = .012) and radiation dose ≥ 80 cobalt Gy equivalents (P = .017); only diabetes was significantly associated with impotence (P = .015). CONCLUSIONS: Young men undergoing proton therapy for treatment of prostate cancer have excellent outcomes with respect to erectile dysfunction, urinary incontinence, and other health-related quality of life parameters during the first 2 years after treatment. Longer follow-up is needed to confirm these findings.

Transient enlargement of craniopharyngioma after radiation therapy: pattern of magnetic resonance imaging response following radiation.

Clinical experience suggests that craniopharyngiomas may temporarily increase in size after radiation therapy (RT). The study goal is to determine the incidence and natural history of this response in a cohort of patients managed at Children's Healthcare of Atlanta (CHOA) or Emory Healthcare (EHC). Between 08/1998 and 06/2009, 41 children and young adults were diagnosed with craniopharyngioma at CHOA and/or EHC. Of these, 21 received external-beam radiation and were included in our analysis. Serial magnetic resonance imaging (MRI) studies were evaluated volumetrically to assess response to RT. Median age at diagnosis was 8.2 years (range 3.2-23.5 years). Median radiation dose was 54.0 Gy using standard fractionation (1.8-2.0 Gy/day). With median follow-up of 41.3 months (range 7.2-121.8 months), actuarial local control and overall survival rates at 5 years were 78.7 % and 100 %, respectively. Of subjects, 52.4 % of subjects (11 of 21) were noted on serial MRI evaluation to have tumor enlargement (mostly cystic component) after radiation before eventual shrinkage without further intervention. For tumors that expanded, the median volume increase was 33.9 % (range 15.6-224.4 %). Median time to maximal tumor/cyst expansion was 1.5 months (range 1.0-5.0 months). Finally, nearly all patients (20 of 21) showed a measurable objective response to therapy by MRI regardless of ultimate disease control. Median time to maximal response post-radiation, as defined by MRI, was 9.5 months (range 3.5-39.9 months). In summary, RT is effective for managing craniopharyngioma. However, despite good ultimate responses, approximately 50 % of the patients show tumor/cyst expansion on MRI over the first few months post-radiation. Caution should be taken not to subject these patients to "salvage surgery" or cyst aspiration during this early time unless there are other overriding surgical indications. Understanding the natural history of this phenomenon could potentially help guide the management of these craniopharyngioma patients.

Intracranial ependymomas treated with radiotherapy: long-term results from a single institution.

The purpose of the study is to report long-term outcomes following surgery and radiotherapy for intracranial ependymoma. We retrospectively reviewed the medical records of patients treated with radiotherapy for localized intracranial ependymomas from 1964 to 2006. Patients with subependymomas and ependymoblastomas, and those undergoing re-irradiation, were excluded. Our study population is 44 patients: 37 infratentorial lesions, 7 supratentorial. All patients had postoperative radiotherapy; most received sub-total resection and one-third received gross total resection. Most patients received local radiotherapy alone (median tumor dose 55 Gy); one-quarter received craniospinal irradiation (median dose 35 Gy). The 5- and 10-year local-control rates for all patients were 60 and 46%, respectively; 23% of local recurrences occurred after 5 years. Ninety-five percent of the patients recurred at the primary site; 5% 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 all patients were 60 and 42% and 57 and 43%, respectively. On multivariate analysis, age ≥18 years, gross total resection and infratentorial site were associated with improved local control. No patient with continuous local control had grade 4 or 5 toxicities; 27% of patients had grade 2 or 3 toxicities. One patient developed a radiation-induced meningioma >20 years after radiotherapy. Maximal safe resection followed by adjuvant radiotherapy provided local control in one-half of patients at 10 years. Age, extent of surgery, and location were identified as major independent prognostic factors in patients with intracranial ependymomas.

External-beam radiotherapy for pediatric and young adult desmoid tumors.

BACKGROUND: To report long-term outcomes following radiotherapy for desmoid tumors in children and young adults and identify variables impacting local-regional control and treatment complications. PROCEDURE: From 1978 to 2008, 30 patients <30 years old were treated with radiotherapy for a pathologically confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14 received radiotherapy after gross total resection, and 1 received preoperative radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy twice daily. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site, tumor size, extent of resection, fractionation schedule, and radiotherapy dose. RESULTS: The actuarial 15-year overall survival and local-regional control rates were 96% and 55%, respectively. Local-regional control in patients <18 years old at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P = 0.08). Local-regional control rates for tumors receiving ≥ 55 Gy and < 55 Gy were 79% and 30%, respectively (P = 0.02). No other factors had a statistically significant association with local-regional control by univariate analysis. Twelve of 30 patients experienced grade 3-4 complications, including pathologic fractures, impaired range of motion, pain, and in-field skin cancers. CONCLUSIONS: The role of radiotherapy in managing young patients with desmoid tumors remains unclear. Younger patient age is associated with inferior local-regional control following RT. In children and young adults, doses ≥55 Gy were associated with improved tumor control, but also lead to increased risk of complications.

Definitive radiotherapy for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma.

BACKGROUND: Few published articles describe outcomes following definitive radiation for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The purpose of this study is to evaluate the prognostic factors, outcomes, and complications in patients age 30 years or younger with NRSTS treated at the University of Florida from 1973 to 2002. PROCEDURE: Nineteen pediatric and young adult patients with NRSTS were treated with radiotherapy after biopsy. Thirteen patients had high-grade tumors. The median age at radiotherapy was 19.6 years; the median dose was 55.2 Gy. Twelve patients received chemotherapy. Prognostic factors for local recurrence, distant metastases, and survival were analyzed. RESULTS: Median follow-up was 2.6 years. The 5-year local-control rate was 40%. Nine out of 13 local failures occurred in the absence of metastatic disease. All patients with local failures died of their cancer, and 8 patients died without evidence of distant metastases. There was a trend toward improved local control with low/intermediate-grade tumors. Freedom from distant metastases at 5 years was 68%. Fourteen patients died of their disease. The 5-year overall survival was 37%. There was one grade 4 complication based on NCI Common Terminology Criteria for Adverse Events version 3. CONCLUSION: Young patients with unresectable NRSTS have a poor outcome thereby justifying current study efforts focused on treatment intensification. By demonstrating that all patients with local recurrence died of disease and more than half of these deaths occurred in the absence of distant spread, these results suggests that improved means of local control may translate into improvement in survival.

Dosimetric characterization of whole brain radiotherapy of pediatric patients using modulated proton beams.

This study was designed to investigate dosimetric variations between proton plans with (PPW) and without (PPWO), a compensator for whole brain radiotherapy (WBRT). The retrospective study on PPW and PPWO in Eclipse and XiO systems and photon plans (XP) using controlled segments in Pinnacle system was performed on nine pediatric patients for craniospinal irradiations. DVHs and derived metrics, such as the homogeneity index (HI), the doses to 2% (D(2%)) and 5% (D(5%)) volumes, and mean dose (D(mean)) of the whole brain (i.e., PTV), and the organs at risk (OARs) such as lens and skull, were obtained. The PPW plans from both Eclipse and XiO systems uncovered the following advantages: (1) encompassing a cribriform plate area with the 100% isodose line was better than either PPWO or XP, according to calculated two-dimensional distributions of one patient; (2) the mean value of D(5%) for lens was reduced to 23.6% of D(P) from 54.1% for PPWO or 41.6% for XP; and (3) the mean value of D(mean) for skull was reduced to 94.8% of D(P) from either 98.4% for PPWO or 98.3% for XP. However, the PPW plans also exposed several disadvantages including: (1) the HI of PTV increased to 7.7 from 4.7 for PPWO or 3.7 for XP; (2) D(2%) to PTV increased to 108.8% of D(P) from 104.8% for PPWO or 105.1% for XP; and (3) D(5%) to the skull increased to 104.9% of D(P) from 101.6% for PPWO or 103.4% of for XP. One-half of the observed variations were caused by different penumbra on lateral profiles and distal fall-off depth doses of protons in Eclipse and XiO. Because the utilization on the sharp proton distal fall-off was limited for WBRT, the difference between PPW and PPWO or XP indicated no distinguishable improvement by using a compensator in proton plans.

Titanium screws as fiducial markers for image-guided stereotactic proton irradiation in pediatric central nervous system tumors: a technical report.

OBJECTIVES: Fiducial markers (FM) have been used to enhance the accuracy of radiation therapy in central nervous system (CNS) tumors. Recently, image-guided radiotherapy utilizing FM has been used in proton therapy of CNS tumors. We describe our surgical technique of placement of titanium screws as cranial FM in children undergoing proton therapy for CNS tumors. METHODS: Records of children undergoing cranial fiducial placement for proton therapy were reviewed. Details of the adjuvant treatment of their CNS tumors were examined. Indications for placement of the FM, the technique of placement as well as the operative data and complications were reviewed. RESULTS: Twelve children, aged 10 months to 16 years (mean: 7.6 years), underwent FM placement. When available, the patients had their proton irradiation as part of or according to Children's Oncology Group protocols. All patients had implantations of FM onto bilateral frontal and parietal bone sites, using commercial titanium screws, in a noncollinear fashion. Ten operations were performed on an outpatient basis. There were no surgery-related complications. FM facilitated the cranial alignment for targeting of proton irradiation in all patients. CONCLUSIONS: Commercially available titanium screws can be used as FM for cranial proton radiotherapy. The procedure can be done quickly and safely on an outpatient basis. Pediatric neurosurgeons can perform this procedure on their patients at their home institutions to facilitate treatment at regional proton therapy centers.

Impact of local management on long-term outcomes in Ewing tumors of the pelvis and sacral bones: the University of Florida experience.

PURPOSE: This retrospective analysis describes our 35-year experience with respect to disease control and functional status. PATIENTS AND METHODS: Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years. RESULTS: The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications. CONCLUSION: Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.

Long-term clinical and functional outcomes after treatment for localized Ewing's tumor of the lower extremity.

PURPOSE: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. PATIENTS AND METHODS: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/- RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). RESULTS: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70-100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. CONCLUSIONS: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.

Role of total skin electron beam therapy for leukemia cutis in pediatric patients.

The role of radiation therapy for those with leukemia cutis, particularly pediatric patients, remains unclear. This report describes the first two cases of disseminated leukemia cutis in adolescents treated with total skin electron beam therapy. Both patients had resolution of their skin disease and significant palliation of symptoms. Total skin electron irradiation is an option for adolescents suffering from significant extramedullary leukemia involving the skin. While it is uncertain if this treatment has any improvement in disease-free survival, the benefits of total skin electron therapy for symptom palliation should be considered.

Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma.

PURPOSE: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. METHODS AND MATERIALS: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. RESULTS: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. CONCLUSIONS: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

External beam radiotherapy for primary and adjuvant management of aggressive fibromatosis.

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 60Co 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.