RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma.

Glioneuronal tumor with neuropil-like islands of the spinal cord with diffuse leptomeningeal neuraxis dissemination.

A 54-year-old Caucasian female presented with a 1 year history of intermittent numbness of the left leg progressing to bilateral, lower extremity sensory loss that advanced to include impaired vibration and proprioception. The subsequent thoracic spine magnetic resonance imaging (MRI) scan revealed a heterogeneous, avidly enhancing, centrally situated spinal cord mass involving T7 through T10 in association with thick linear enhancement of the anterior and posterior cord surfaces extending both superiorly and inferiorly. Both the cervical and lumbar spine MRI demonstrated diffuse leptomeningeal disease as well. A brain MRI revealed focal leptomeningeal enhancement in the left and right sylvian fissures, the suprasellar cistern, and the posterior fossa; a pattern consistent with metastatic disease. The patient underwent a T6-T10 laminectomy for tumor biopsy and debulking. Histology revealed a WHO grade III glioneuronal tumor with rosetted neuropil-like islands. Synaptophysin and neurofilament (NF) positive staining was noted within the neural appearing component, whereas, glial fibrillary acidic protein (GFAP) immunopositivity was evident in the fibrillary astrocytoma component of the tumor. The Ki-67 labeling index was 7%. This tumor pattern, now included in the 2007 World Health Organization (WHO) classification of central nervous system tumours as a pattern variation of anaplastic astrocytoma (Kleihues et al. In: Louis et al. (eds) WHO classification of tumours of the central nervous system, 2007), was first described in a four-case series by Teo et al. in 1999. The majority of subsequently reported cases described them as primary tumors of the cerebrum. Herein, we report a unique example of a spinal glioneuronal tumor with neuropil-like islands with associated leptomeningeal dissemination involving the entire craniospinal axis.

High-dose radiotherapy to 78 Gy with or without temozolomide for high grade gliomas.

OBJECTIVES: To describe outcomes associated with high-dose radiotherapy with and without temozolomide for high grade central nervous system (CNS) neoplasms. METHODS: Retrospective chart review of 60 patients diagnosed with malignant glioma treated with > or =70 Gy radiotherapy. RESULTS: Median age at diagnosis was 52 years, and 52 patients had astrocytomas (38 glioblastomas). Median prescribed radiotherapy dose was 78 Gy (range 70-80), and 29 patients received concurrent temozolomide. Eighty-six percent completed the planned course treatment. Three patients experienced RTOG grade 3 acute CNS toxicity; late brain necrosis was suspected in four patients. Overall median survival was 13 months (range 2-83). Within glioblastoma patients, temozolomide provided a statistically significant survival improvement over no chemotherapy (median survival 12.7 vs. 7.5 months; P = 0.0058). CONCLUSIONS: High dose conformal radiotherapy to > or =70 Gy with chemotherapy for high-grade CNS neoplasms appears safe but survival remains suboptimal. Within glioblastoma patients, temozolomide provided statistically significant survival improvement over no chemotherapy.

Late chest wall toxicity after MammoSite breast brachytherapy.

PURPOSE: Accelerated partial breast irradiation (APBI) with the MammoSite breast brachytherapy (MBB) system is being investigated as an alternative to whole breast radiation in breast conservation therapy (BCT) at multiple centers worldwide. The newness of MBB means a complete understanding of long-term toxicity, particularly involving the chest wall, has yet to be completely articulated. We report the first pathologic rib fractures associated with MBB and dosimetric analysis of the original treatment plans. METHODS AND MATERIALS: As part of ongoing quality assurance, we reviewed the records of 129 sequential patients who underwent MBB for breast cancer and identified those who subsequently had clinically significant and radiographically documented rib fracture(s) involving the ipsilateral chest wall. Equivalent tolerance doses yielding a 5% and 50% risk of rib toxicity within 5 years from treatment with 10 fractions (as with MBB) were previously calculated using the linear quadratic equation based on 2Gy per fraction treatments delivered to one-third of the rib volume (TD5/5=37Gy; TD50/5=44Gy). The original radiation therapy plans were evaluated vis-à-vis the plane films or PET/CT images documenting the osseous abnormalities and presenting complaints to find the specific fractured ribs. The specific effected ribs were contoured on the planning CT in "bone windows" using the Nucletron MicroSelectron-classic V2 (Nucletron B.V., Veenendaal, The Netherlands) for this analysis and the original patient treatments. With these datasets, we determined the dose-volume characteristics of the effected ribs including maximal dose encompassing the entire rib on one CT slice, V(20Gy), V(30Gy), V(37Gy), V(44Gy), D(50), D(25), and D(5) (the mean dose to 50%, 25%, and 5% of the rib). RESULTS: Between May 2002 and August 2007, three of 105 patients with a minimum of 6-months follow-up who underwent adjuvant APBI by MBB were found to have a total of five treatment-related rib fractures. The average dose-volume characteristics from the original plans were as follows: D(50)=22.1Gy, D(25)=32.2Gy, D(5)=41.6Gy, max dose to 1cc=34.8, D(max) (to 0.1cc)=45.6Gy, V(20)Gy=57.4%, V(30)Gy=30.8%, V(37)Gy=15.9%, V(44)Gy=6.6%, and max dose through rib=35.8Gy. Two patients sustained two rib fractures and 1 patient had a single rib fracture. Four of five fractures occurred in postmenopausal patients and two of five fractures occurred in a patient with a history of osteoporosis and exposure to adjuvant chemotherapy. CONCLUSIONS: Fractures occurred in ribs with V(37)Gy and V(44)Gy each well below 33%. As long-term toxicity data accrue from APBI series, the traditional models for estimating the biologic equivalent dose may benefit from refinements that specifically address the unique radiobiologic and physical properties intrinsic to high-dose-rate brachytherapy for breast conservation therapy.

Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.

PURPOSE: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use of multiple dwell positions reduced the risk of severe hyperpigmentation (p = 0.0278). Infection was associated with an increased risk of fair or poor overall cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS seems to have acceptable toxicity rates and cosmetic outcomes, comparable to those with whole-breast radiotherapy. On the basis of these data, the closed-cavity placement technique, use of prophylactic antibiotics, use of multiple dwell positions, and a minimum skin spacing of 6 mm seem to improve patient outcome.

A case of orbital Rosai-Dorfman disease responding to radiotherapy.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder most often characterized by painless cervical lymphadenopathy, but it may also present with orbital disease. The clinical course of RDD is variable; it can be either relapsing-remitting or progressive, and the outcome relates to clinical location and treatment response. Orbital RDD can have an insidious onset and similar presentation to other ophthalmic conditions; this can result in a delayed diagnosis. Nearly all cases of orbital RDD cause visual disturbances and require treatment. Because orbital RDD is an uncommon presentation, a variety of interventions have been employed, including surgery, immunotherapy, chemotherapy, and radiotherapy. We present a case of salvage radiotherapy for progressive orbital RDD refractory to surgery and chemotherapy in a pediatric patient.

Incidence and prognostic factors for seroma development after MammoSite breast brachytherapy.

PURPOSE: Describe the incidence and identify risk factors for seroma development after MammoSite breast brachytherapy (MBT). METHODS AND MATERIALS: MBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors associated with development of any seroma including the subset of clinically significant seroma (CSS). CSS was defined as a symptomatic seroma requiring multiple aspirations, biopsy, and/or excision. Variables analyzed included age, weight, number of excisions, time from resection to catheter placement, placement technique, balloon volume, dosimetric factors, and postbrachytherapy infection. RESULTS: MBT was performed in 109 patients, of whom 97 had minimum 6 months (median, 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1cm depth from balloon surface, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range, 0.1-25) post-MBT. One-third of seromas (13% of all patients) were CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection vs. > or =1 day later (59% vs. 33%; p = 0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs. 7%; p<0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p = 0.011). CONCLUSIONS: The incidence of CSS after MBT is low. Post-MBT infection is statistically significantly associated with CSS development, the incidence of which is reduced with prophylactic antibiotics.

Radiation therapy for palliation of Eisenmenger's syndrome-associated painful splenomegaly.

Painful splenomegaly has a clinical presentation that is often associated with myeloproliferative disorders, such as acute or chronic lymphoblastic or myelogenous leukemia. In these situations low-dose radiotherapy is effective in reducing the splenomegaly and relieving pain. The potential benefit of radiotherapy for cardiogenic splenomegaly is less well established. The present report discusses a case in which radiotherapy was employed to benefit a patient with Eisenmenger's-associated painful splenomegaly. Because of the patient's high anesthesia risk, palliative surgical splenectomy was not feasible. The patient underwent three-dimensional conformal treatment planning, and a total of 42.5 Gy at 2.5 Gy per fraction was prescribed to the spleen. At 4 months following radiotherapy completion, the patient reported durable pain relief and no untoward small bowel effects; moreover, there was a 43% reduction in splenic volume on follow-up CT. Although there have been previous reports of hematological and myeloproliferative-associated splenomegaly that have been treated with a lower dose per fraction and lower total dose radiotherapy, we advocate the use of 2.0-2.5 Gy per fraction to a total dose approaching 40 Gy for adequate duration of response when treating cardiogenic-associated painful splenomegaly in patients for whom surgical splenectomy cannot be performed.

Helical tomotherapy for total lymphoid irradiation.

Total lymphoid irradiation is employed in the preparative regimens for allogeneic bone marrow and solid organ transplantation, solid organ transplant rejection, and chronic graft-versus-host disease. Linear accelerator-based radiotherapy, typically involving opposed anteroposterior and posteroanterior beams, has been commonly used; however, extended source-to-skin patient setup and/or field matching are required, and all organs within the beam coverage receive the entire prescribed dose. Megavoltage helical tomotherapy represents a technological advance in terms of both treatment delivery and patient positioning. The continuously rotating multileaf collimated fan beam allows highly conformal coverage of complex target geometries, in turn allowing avoidance of radiosensitive adjacent organs. In addition, the megavoltage computed tomographic scans allow potentially more accurate, targetbased setup verification. The present case report describes tomotherapy-based total lymphoid irradiation in an adult patient with late-onset cardiac transplant rejection. Treatment planning allowed dose minimization to the spinal cord, kidneys, intestinal compartment, and lungs. The patient tolerated treatment well without acute adverse effects, and he is now in early follow-up.

Radiotherapy-induced reactivation of neurotrophic human herpes viruses: Overview and management.

PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. MATERIALS AND METHODS: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. CONCLUSIONS: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy.

Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539.

OBJECTIVE This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). METHODS NRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I-III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3-year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. RESULTS Fifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09-3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events. CONCLUSIONS This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. Clinical trial registration no.: NCT00895622 (clinicaltrials.gov).

Predictors of cosmetic outcome following MammoSite breast brachytherapy: a single-institution experience of 100 patients with two years of follow-up.

PURPOSE: To identify the factors that predict for excellent cosmesis in patients who receive MammoSite breast brachytherapy (MBT). METHODS AND MATERIALS: One hundred patients with Stage 0, I, or II adenocarcinoma of the breast underwent adjuvant therapy using MBT. A dose of 34 Gy, delivered in 10 fractions twice daily, was prescribed to 1-cm depth using (192)Ir high-dose-rate brachytherapy. Patients were assessed for acute toxicity on the day of therapy completion, 4 weeks after therapy, and at least every 3 months by radiation, surgical, and/or medical oncologists. All available data were reviewed for documentation of cosmesis and rated using the Harvard Scale. All patients had a minimum follow-up of 6 months (median = 24 months). RESULTS: Of 100 patients treated, 90 had adequate data and follow-up. Cosmesis was excellent in 62 (68.9%), good in 19 (21.1%), fair in 8 (8.9%), and poor in 1 (1.1%) patient. Using stepwise logistic regression, the factors that predicted for excellent cosmesis were as follows: the absence vs. presence of infection (p = 0.017), and the absence vs. presence of acute skin toxicity (p = 0.026). There was a statistically significant association between acute skin toxicity (present vs. absent) and balloon-to-skin distance (<8 vs. >8 mm, p = 0.001). Factors that did not predict for cosmesis were age, balloon placement technique, balloon volume, catheter days in situ, subcutaneous toxicity, and chemotherapy or hormonal therapy. CONCLUSIONS: The acute and late-term toxicity profiles of MBT have been acceptable. Cosmetic outcome is improved by proper patient selection and infection prevention.

Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma.

High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%-9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.

Acute complications of MammoSite brachytherapy: a single institution's initial clinical experience.

PURPOSE: To report the acute complications incurred by the initial 37 patients who underwent accelerated partial breast irradiation with the MammoSite balloon breast brachytherapy applicator at the Medical University of South Carolina. METHODS AND MATERIALS: Between May 2002 and March 2003, 37 patients with ductal carcinoma in situ or invasive carcinoma had MammoSite brachytherapy catheters successfully place after lumpectomy by one of four surgeons and were deemed eligible for high-dose-rate brachytherapy. An open technique was used in 32 implants and the scar entry technique was used in 5 implants. Patients had Stage pTis-pT2N1 with negative margins. A dose of 34 Gy was prescribed to 1 cm from the balloon surface using (192)Ir high-dose-rate brachytherapy and was delivered in 10 fractions twice daily. CT was used to confirm that the balloon surface was adherent to the lumpectomy cavity and to measure the balloon surface to skin surface distance. CT images and daily fluoroscopic simulations were used for treatment planning. Patients were assessed for acute toxicity on the day of therapy completion and 4 weeks after therapy by the radiation oncologist. In addition, all available data from radiation, surgical, and medical oncology were retrospectively reviewed for documentation of complications. All patients in this series had a minimal follow-up of 3 months; the mean follow-up for all patients was 7 months. RESULTS: The acute complications were categorized as operative wound complications, infections, skin toxicity, seromas, or catheter failures. Operative wound complications occurred in 3 patients (8%). Radiation Therapy Oncology Group Grade 2 and Grade 3 toxicity occurred in 2 (5.4%) and 1 (2.7%) patient, respectively. Six (16.2%) developed wound infections and 12 (32.4%) seromas. Catheter failures due to leak occurred in 2 patients (5.4%) and rupture in 3 (8%). CONCLUSION: The types of complications in this experience were similar to those in the Phase I trial of the MammoSite brachytherapy applicator. However, catheter failure due to leak occurred in our experience and was not described in the Phase I trial. The incidence of complications was greater in our series than in the Phase I trial; however, differences in toxicity scoring and the length of follow-up between the two series impeded direct comparisons. The incidences of complications over time reflect the steep learning curve for accelerated partial breast irradiation using the MammoSite brachytherapy applicator. Finally, radiation recall dermatitis developed in 1 patient treated after this review was completed.

Outcome of radiation therapy for renal transplant rejection refractory to chemical immunosuppression.

Twenty consecutive patients with kidney graft rejection refractory to chemical immunosuppression were treated with local irradiation to the transplanted renal graft (3 x 1.5 Gy). Ten patients were complete responders (median follow-up: 47 months). Six patients were partial responders and failed after 1-4 months. Four patients did not respond.

Chest wall dose in MammoSite breast brachytherapy: radiobiologic estimations of late complication risk based on dose-volume considerations.

PURPOSE: To estimate the risk of late effects in women treated with MammoSite brachytherapy (MBT), the balloon catheters of which were placed near the ribs. METHODS AND MATERIALS: Upon reviewing 93 plans, 16 patients (17%) treated with MBT were considered to have received a high chest wall dose (>or=120% isodose line in contact with a rib). A dose-volume histogram was generated for this rib, and its distance from the MBT balloon measured. Using the linear quadratic equation, the equivalent dose, delivered in 10 fractions, to the dose that causes a 5% and 50% risk of rib late effects at 5 years using 2Gy per fraction, was calculated to be 37 and 44Gy, respectively. The rib volume receiving greater than or equal to these doses (V37 and V44) was correlated to the balloon-to-rib distance. Chest wall signs, symptoms, and radiologic findings for all 16 patients were recorded. RESULTS: The median balloon-to-rib distance was 4.8mm. The median values of V37 and V44 were 13.5% and 3.3%, respectively. All patients with a V37>or=15% and V44>or=5% had a minimum balloon-to-rib distance of <5mm. Two patients reported treatment-related chest wall tenderness (both had balloons placed <5mm from the chest wall), but neither presented with radiologic complications. CONCLUSIONS: Sixteen patients considered to receive relatively high chest wall doses had less than one-third of their primary rib volume being exposed to the estimated TD 5/5 and TD 50/5 doses. Therefore, we estimate the risk of late effects in women treated with MBT, the balloon catheters of which placed near the ribs were negligible, and believe that MBT remains a safe and effective treatment for selected patients with early stage breast cancer.

Significant fibrosis after radiation therapy in a patient with Marfan syndrome.

Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-ß1) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-ß1 level during and after treatment. Despite maintaining stable levels of plasma TGF-ß1, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.

PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF). RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.

Central nervous system myelomatosis with optic neuropathy and intramedullary spinal cord compression responding to radiation therapy.

Central nervous system (CNS) involvement by multiple myeloma is a rare complication that occurs in less than 1% of cases. The purpose of this report is to highlight the unique presentation and treatment of a patient with CNS myelomatosis. A 58-year-old Caucasian woman with multiple myeloma developed subacute vision loss bilaterally and was found to have plasma cells in her cerebrospinal fluid. Using a helmet field to 25 Gy in 10 fractions, her vision was stabilized with radiotherapy. After developing right upper extremity numbness and weakness, magnetic resonance imaging revealed intramedullary spinal cord lesions from C5 to C7. She received radiotherapy to 25 Gy in 10 fractions from C4 to T1, with improvement in upper extremity strength after 15 Gy. Although CNS involvement by multiple myeloma is a rare complication, increasing awareness is necessary for clinicians to consider meningeal myelomatosis in patients with this neoplasm.