Require Radiation Therapy Research Articles

A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial.

The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

Introduction: Antiretroviral Treatment (ART) has led to an improvement in survival of HIV infected individuals. Some of them will develop cancer during the course of their infection and will require radiation therapy. HIV positive cancer patients have presented with adverse side effects of radiotherapy and elevated chromosomal radiosensitivity. This study investigated if ART has an influence on chromosomal radiosensitivity of HIV positive individuals. Methods and materials: Blood samples from 60 HIV positive individuals were in vitro exposed to doses of X-rays of 0, 2 and 4Gy and chromosomal radiosensitivity was assessed with the micronucleus assay. The micronucleus assay was also performed on lymphocytes of a group of non HIV-infected health care workers taking prophylactic post-exposure ART to measure the effect of these ART drugs on chromosomal radiosensitivity without HIV as a confounding factor. Results: All HIV patients (those on ART and without ART) had significantly higher radiation induced Micronuclei (MN) than healthy controls. The MN yields increased in the HIV patients taking ART compared to HIV patients not on treatment. The evaluation of chromosomal radiosensitivity of health care workers on ART revealed no effects of ART. Conclusions: HIV positive individuals show an increased chromosomal radiosensitivity. Antiretroviral treatment given to HIV positive individuals can lead to enhanced chromosomal radiosensitivity and therefore impose higher risks for radiotherapy side effects in these patients.

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-β1) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-β1 level during and after treatment. Despite maintaining stable levels of plasma TGF-β1, 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.

Radiation Related Inflatable Penile Prosthesis Complex Erosions

Delayed erosion of components of an inflatable penile prosthesis (IPP) is a rare complication after placement. Both erosion of the cylinders into the urethra, and the reservoir into the bladder, as a complication of radiation has not been previously reported. We report the case of a 71 year-old male with post-prostatectomy erectile dysfunction treated with an IPP, with subsequent biochemical recurrence requiring radiation therapy, complicated by erosion of his IPP cylinder into his distal urethra, and reservoir into the bladder.

Bone Marrow Staging For Lymphoma: A Re-Evaluation Of Clinical Utility

Bone marrow examination is an established component of the process used to stage patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical Hodgkin Lymphoma (CHL); and it is a general requirement of clinical trials. The procedure involves significant discomfort and inconvenience to the patient, as well as expense for the NHS, and this study was designed to evaluate the clinical utility of the information derived from staging bone marrow examinations. All patients presenting with DLBCL (n=1908), CHL (n=604) and FL (n=770) between 1st Sept 2004 and 31st August 2011 in the UK's population-based (3.6M) study area (Haematological Malignancy Research Network - www.hmrn.org) were included. Comprehensive clinical data, including diagnostic, prognostic, outcome and socio-demographic information are available for all patients. All diagnostic and staging specimens are reported in a single specialist haematopathology laboratory (the Haematological Malignancy Diagnostic Service – www.hmds.info). HMDS routinely undertake morphology and flow testing on bone marrow aspirate and trephine biopsies; while further molecular and cytogenetic tests are carried out at clinical discretion. This study aimed to assess the impact of bone marrow examination on the calculation of disease specific prognostic indices.Bone marrow examinations were performed in 85% of patients, providing morphological evidence of disease in 10.2% of DLBCL, 7.2% of CHL and 36.5% of FL. In 18 patients with DLBCL and 16 patients with CHL the bone marrow was the presenting site of disease and this was associated with a very poor clinical outcome. In DLBCL knowledge of the bone marrow result increased the IPI by 1 point in 4.0% and by 2 points in 1.1% of cases. Similarly, the Hasenclaver index increased by 1 point in 3.6% of CHLs and the FLIPI increased by 1 point in 9.0% of FLs. In the case of DLBCL, 70% of these patients had an IPI score of >2 before the results of the marrow examination were added. As well as the assessment of prognosis, the results of bone marrow examination are a component of a number of key clinical decisions. Patients with stage 1 FL are routinely treated with radiotherapy with curative intent. In the absence of a bone marrow result, an additional 27 patients would have potentially been treated with radiotherapy. The 5 year relative survival (corrected for underlying population mortality rates) of this group was similar to those with stage 2 disease on watch and wait, and was slightly inferior to that seen in true stage 1 disease. Similarly, patients with stage1A DLBCL may be treated with 3 courses of R-CHOP and radiotherapy in preference to 6 or 8 courses of R-CHOP alone. In our data , lack of knowledge of the bone marrow result would not have affected the classification of this group in. In DLBCL the decision to give prophylaxis to prevent CNS relapse may be based on 2 or more extranodal sites, including bone marrow, involved at presentation. In this group, this decision could have been affected in 51 cases.In the UK the approximate cost of taking and reporting a bone marrow is around $900. When used routinely the cost could approach $25,000 per patient whose IPI score is increased by the results of examination; the figure for CHL is $44,000. It is, therefore, difficult to justify the cost effectiveness of this approach. In newly presenting patients with lymphoma, bone marrow examination should be reserved for those with unexplained cytopenia, and those who may potentially require radiation therapy for early stage FL or CNS prophylaxis in DLBCL. Disclosures:Jack:Roche /Genentech: Research Funding. Off Label Use: Rituximab in Burkitts Lymphoma. Patmore:Roche: Consultancy, Honoraria.

Radiation testing of the AeroForm co2-based breast tissue expander implant

BackgroundTissue expanders are used in breast reconstruction after mastectomy to stretch the remaining tissue to create space for placement of permanent breast implants. The AeroForm™ Tissue Expander, developed by AirXpanders™ Inc., contains electronic components designed to activate the release of carbon dioxide from an internal reservoir to inflate the expander. Breast cancer patients who undergo mastectomy and tissue expander/implant-based breast reconstruction may require radiation therapy at doses up to 50–60 Gy while the expander is in place. The ionizing radiation used in postmastectomy radiation therapy interacts with electronic components in medical implants, which may cause degradation in performance above certain levels. Most commercial electronic components used in medical devices, such as complementary metal-oxide semiconductor or bipolar integrated circuits can withstand radiation levels in the 50 Gy range without any performance degradation. Beyond this level, the performance may still be sufficient to guarantee functionality, but this needs to be confirmed at the system and electronic circuit level. We assessed the impact of radiation levels up to 75 Gy on 32 AeroForm™ Tissue Expanders (AirXpanders, Inc., Palo Alto, CA USA) and on the associated internal printed circuit assemblies.FindingsThe electronics inside the AeroForm™ Tissue Expander implant continued to function properly after exposure to radiation levels up to 75 Gy, which is well above the maximum total dose level typically used in postmastectomy radiation therapy.ConclusionsStandard postmastectomy radiation therapy doses do not damage or affect the functionality of the AeroForm™ Tissue Expander.

Mature Clinical Outcomes of Proton Radiation for Pediatric Low-Grade Gliomas

Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy as definitive treatment. Radiation therapy in the pediatric brain is associated with a variety of late effects. However, increased conformality of radiation therapy to spare as much normal brain tissue from radiation will decrease the incidence and severity of late effects. We report our experience with 36 pediatric patients treated with proton radiation therapy for low-grade gliomas.

Using Chemotherapy Response to Personalize Choices Regarding Locoregional Therapy: A New Era in Breast Cancer Treatment?

The reduction in breast cancer mortality rates in the United States is one of the hallmark successes of modern oncology. This progress is largely the result of a rich tapestry of clinical research that has been conducted over the last three decades and has consistently, yet largely incrementally, improved screening and therapy. However, therapeutic strategies do not necessarily advance in unison, and as a result, evolution of one treatment may prove problematic to appropriate application of another. Such is the case with the growing popularity of neoadjuvant chemotherapy and its impact on decisions regarding locoregional radiation therapy. For decades, radiation therapy indications have been based on initial pathologic analysis of all tumor and nodal tissue that was resected before initiation of systemic therapy. A robust body of both prospective and retrospective literature has emerged to inform radiation treatment decisions on the basis of initial pathologic analysis of the untreated tumor. Such literature is of vital importance, given the recognition that radiation when indicated improves not only locoregional control but also survival. Conversely, radiation does have certain toxicities and may impact reconstructive options; thus, its avoidance when not indicated is also of paramount importance. Unfortunately, this radiation therapy literature does not readily extend to patients who are treated with neoadjuvant chemotherapy. Because neoadjuvant chemotherapy has the potential to sterilize disease in up to 40% of patients (and even a higher percentage of patients with human epidermal growth factor receptor 2/neu positive disease who are receiving trastuzumab), there is often a discordance between what the pathologic stage would have been if the patient had undergone surgery before chemotherapy versus the actual pathologic stage when surgery is performed after chemotherapy. Accordingly, it is likely that the patterns of locoregional failure and the impact of radiation on locoregional control and survival may differ meaningfully for the same nominal pathologic stage, depending on whether the stage is rendered before or after treatment with chemotherapy. Although neoadjuvant chemotherapy results in a loss of information regarding what the pathologic stage would have been before chemotherapy, neoadjuvant chemotherapy results in a gain of information regarding the in vivo chemosensitivity of a patient’s tumor, which can be quantified using the residual cancer burden. Theoretically, this novel information that reflects the biology of the patient’s tumor could be used to personalize subsequent decisions regarding locoregional radiation and/or the addition of further systemic agents. To date, the literature to define radiation indications after neoadjuvant chemotherapy remains limited. A systematic review identified 24 relevant studies, 23 of which were retrospectively conducted at single institutions. The only prospective, multi-institution data that were identified by this review are represented in the article by Mamounas et al that accompanies this editorial. Particular strengths of the study by Mamounas et al include its large sample size, prospective data collection and quality control, and uniform policy prohibiting postmastectomy radiation therapy (PMRT) in patients undergoing mastectomy and prohibiting regional nodal radiation in patients undergoing breast-conserving surgery (BCS). As a result, outcomes reported from this relatively unselected patient group should be more broadly applicable than retrospective, single-institution studies. From a conceptual perspective, the key finding is that response to neoadjuvant chemotherapy can be used to prognosticate risk of locoregional recurrence, implying the hypothesis that chemotherapy response may also predict which patients do and do not require radiation therapy. Specifically, in both the mastectomyand BCStreated cohorts, patients with a pathologic complete response to neoadjuvant chemotherapy in both the primary tumor and the axillary nodes experienced the lowest risk of locoregional recurrence, whereas patients with residual invasive disease in the breast who were pathologically node-negative had an intermediate risk of locoregional recurrence, and patients with residual positive lymph nodes had the highest risk of locoregional recurrence. An important caveat of this finding is that initial clinical nodal assessment was performed using a physical examination without a corroborating ultrasound or needle biopsy. Accuracy of clinical nodal assessment was moderate, given that 86% of patients with clinically node-positive disease who were randomly assigned to initial surgery on the B-18 study were confirmed to have nodal metastasis. The misclassification of clinical nodal status limits somewhat the accuracy of risk estimates that are based on this variable. Furthermore, the current study cannot reliably discriminate whether there may be a difference in locoregional recurrence risk for patients who convert from node-positive to node-negative status with neoadjuvant chemotherapy versus patients who are truly node-negative at initial diagnosis and remain node-negative after chemotherapy. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 32 NOVEMBER 1

Endoscopic Treatment of Olfactory Neuroblastomas

Objective: To illustrate an transnasal approach (endoscopic assisted transnasal-craniectomy) used for olfactory neuroblatoma treatment and to advocate this method of management followed by radiation therapy for selected cases, based on the Stamm-Kennedy (SK) stage system. Method: A retrospective chart review was performed with 16 patients harboring olfactory neuroblastomas. Patients were categorized secondary to SK staging system. Twelve patients underwent the endoscopic assisted transnasal craniectomy (EATNC) approach, and 4 were submitted to hybrid approach (cranio-endoscopic) between 2000 and 2011 at a tertiary referral center. Results: Seven SK-IVa, 5 SK-II, 2 SK-IVb, 1 SK-I, and 1 SK-V patients, aged 10 to 67 years (9 females and 7 males), were identified. In 10 cases the tumor was bilateral, and in six cases the tumor was unilateral. Twelve patients were submitted to EATNC, 4 patients were submitted to hybrid approach (cranio-endoscopic), and 1 was submitted to endonasal approach without craniectomy. Gross total resection was achieved in 12, and near total was achieved in 4 patients. Twelve patients were submitted to radiotherapy (75%). Four cases needed posterior surgery. Fourteen patients were disease free 5 to 72 months postresection, and 2 patients were lost during follow-up. Only 4 patients preserved olfactory function (unilateral cases treated without radiotherapy). Conclusion: The EATNC is a promising approach for olfactory neuroblastoma treatment, even for those tumors with intradural extension. Most patients require radiation therapy, and in these cases there is no olfaction preservation.

Pleuropulmonary Blastoma

Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal malignancy that occurs exclusively in early childhood. Twelve patients were diagnosed with PPB (1 type I, 5 type II, and 6 type III) between 1979 and 2009 at our institution. Upfront complete tumor resection was successful in 5 of 6 patients. Six patients had biopsy followed by neoadjuvant chemotherapy, 2 had complete tumor resection, and 2 had microscopic residual disease after surgery. All patients received vincristine, dactinomycin, and cyclophosphamide chemotherapy. Eight received additional chemotherapy with doxorubicin, cisplatin, etoposide, or ifosfamide. Three patients received local irradiation. The 5-year event-free and overall survivals were 33% ± 14% and 42% ± 14%, respectively. Median time to progression was 8 months. Five of 9 patients with gross total resection survived, whereas all 3 with gross residual disease died. Three of 5 survivors did not receive radiation. A high index of suspicion for PPB must be maintained in all patients diagnosed with intrathoracic sarcoma in early childhood. Gross total resection is necessary for cure, and selected patients do not require radiation therapy.

Taste disorders in myasthenia gravis: a multicenter cooperative study

The purpose of the present study was to investigate the prevalence and clinical characteristics of taste disorders in patients with myasthenia gravis (MG). We studied 371 Japanese patients with MG (127 men and 244 women; mean age, 56.6±16.9years) consecutively evaluated between May and September 2010 in six neurological centers comprising the East Japan MG Study Group. Ninety-three patients (25%) had thymoma. We interviewed all patients to determine whether they had taste disorders during the clinical course of MG and then further evaluated the patients with MG, who reported having taste disorders, using a questionnaire. Taste disorders were observed in 16 (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of patients with MG excluding other factors were associated with MG itself. All patients had thymoma with seropositivity for anti-acetylcholine receptor antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage IVa required radiation therapy or chemotherapy. Five patients noticed taste disorders 2-3 months before the onset of MG. Sweet taste loss was more common than salty, bitter, and sour taste loss. This was the first systematic survey of taste disorders in patients with MG by a multicenter study. Taste disorders were more common in the present sample of patients with MG than in the general population.

The Effect of Neoadjuvant versus Adjuvant Irradiation on Microvascular Free Flap Reconstruction in Sarcoma Patients

Sarcoma patients often require radiation therapy in addition to surgical resection. Although neoadjuvant irradiation possesses advantages over adjuvant irradiation related to smaller doses and field sizes, existing studies suggest adverse effects on wound healing and possibly microvascular free flap success. Conversely, microvascular reconstruction may counteract some of the negative effects of irradiation by replacing irradiated tissue with well-vascularized unirradiated tissue from a distant site. A review of sarcoma patients who underwent resection, microsurgical reconstruction, and either neoadjuvant or adjuvant irradiation was performed. A total of 119 patients met inclusion criteria, of which 73 underwent neoadjuvant irradiation and 46 underwent adjuvant irradiation. Sarcomas were located in the head and neck (n = 47), trunk (n = 7), upper extremity (n = 15), and lower extremity (n = 50). The rate of perioperative (≤ 30 days) complications was 26.9 percent, whereas the rate of late recipient-site complications was 14.3 percent. No significant differences in perioperative recipient-site (p = 0.19), donor-site (p = 1.00), or medical complications (p = 0.30) were observed between patients undergoing neoadjuvant and adjuvant irradiation. Free flap loss rates were lower in patients undergoing neoadjuvant irradiation (0 percent versus 8.7 percent, respectively; p = 0.02). Late recipient-site complications occurred less often in patients undergoing neoadjuvant radiation (6.8 percent versus 26.1 percent, respectively; p = 0.006). Neoadjuvant irradiation does not increase the risk of acute wound or microvascular complications when combined with free flap reconstruction, and is associated with fewer late recipient-site complications than adjuvant irradiation. These factors should be considered when determining the timing of radiation therapy in sarcoma patients undergoing oncologic resections and microsurgical reconstruction. Therapeutic, III.

Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy

Within 10 years of radical prostatectomy (RP), up to 30% of prostate cancer (PCa) patients will have a rise in prostate-specific antigen (PSA), requiring radiation therapy (RT). However, with current technology, distinction between local and distant recurrent PCa is not possible. This lack of an accurate test constrains the decision whether to offer systemic or local treatment. We hypothesise tests for detecting circulating tumour cells (CTCs) within the blood may assist with clinical decision-making and in this pilot study we investigated whether CTCs could be detected in this patient population using the CellSearch® system. Blood samples were collected from PCa patients (n=26) prior to RT and 3 months following completion of RT. Samples were analysed for PSA level via immunoassay and CTC number using the CellSearch® system. CTCs could be detected in this patient population and following RT CTCs appeared to decrease. However, no association was observed between a higher PSA and an increased number of CTCs pre- or post-RT. Interestingly, patients who failed RT trended toward an increased/ unchanged number of CTCs following RT vs. a decreased number in patients with RT response. Our results demonstrate that CTCs can be detected in early-stage PCa and suggest the possibility that post-treatment reduction in CTC levels may be indicative of RT response . We are currently evaluating CTCs in a larger cohort of patients to validate our preliminary findings and further investigate the prognostic value of CTCs in this patient population.

Breast reconstruction and radiation therapy: A Canadian perspective

When and how best to perform breast reconstruction in the setting of radiation therapy is a much debated topic. To investigate the approaches that Canadian plastic surgeons are taking to breast reconstruction in patients who require or may require radiation therapy. In April 2009, a survey invitation was sent to Canadian plastic surgeons via e-mail. Survey responses were collected over a two-month period. Of the 307 invitees, 90 surgeons responded, of whom 76 met the inclusion criteria. Most surgeons (66%) do not perform immediate reconstruction in patients who require postmastectomy radiation. Most respondents (64%) perform immediate reconstructions for patients whose need for radiation is uncertain at the time of mastectomy. Expander and implants is their preferred option, followed by free transverse rectus abdominis myocutaneous (TRAM) flap. Thirty-five per cent use the delayed immediate technique in these cases. Twenty-one per cent are unfamiliar with the delayed-immediate technique. For delayed reconstruction of the irradiated patient, the pedicled TRAM is the most common choice. The reconstructive options are increasing for patients who may need postmastectomy radiation. The use of the delayed immediate technique could increase as physicians gain more knowledge of the technique.

Incidental Gonadal Radiation Exposure In The Prophylactic Treatment Of Heterotopic Ossification

Radiation therapy is commonly used for heterotopic ossification (HO) prophylaxis after the orthopedic repair of fractures involving the hip and femur. Given the young age of many of these patients presenting for treatment and the proximity of the reproductive organs to tissue requiring radiation therapy, incidental radiation exposure to the gonads must be considered for potential fertility issues. The purpose of this study was to report dosimetric gonadal exposure among a large cohort of patients who underwent 3-dimensional simulation and radiation therapy for HO prophylaxis.

Emergencies in Children and Young Adults with Central Nervous System Tumors

Central nervous system (CNS) tumors are the most common solid tumors in childhood and adolescence. Evaluation and management of patients with CNS tumors by emergency medicine practitioners are critically important at the time of initial diagnosis as well as during emergency department visits for treatment-related complications. Increased intracranial pressure, hydrocephalus, spinal cord compression, or seizures may occur as a result of direct tumor disruption of normal CNS structures. For those patients who require radiation therapy and/or chemotherapy, recognition of common adverse events from these treatment modalities is important for accurate diagnoses and management in the emergency department. Emergencies in survivors of childhood CNS tumors are also reviewed.

Palliative Radiotherapy—New Approaches

Most cancer patients will require radiation therapy some time during their disease. Thirty percent to 50% of all radiation treatments are palliative, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life from local progressive disease. Radiotherapy is a locally effective tool. It typically causes no systemic and mostly mild acute side effects. We will provide an overview of principles, decision-making, and new developments in palliative radiation therapy.

Riluzole Enhances Ionizing Radiation–Induced Cytotoxicity in Human Melanoma Cells that Ectopically Express Metabotropic Glutamate Receptor 1 In Vitro and In Vivo

Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G(2)/M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells. Clonogenic assays were performed to evaluate clonogenic survival after treatment in hGRM1 expressing and nonexpressing melanoma cells. Western immunoblots were performed to confirm apoptotic cell death. A xenograft mouse model was used to validate the in vitro experiments. Tumors harvested from the xenografts were fixed and stained for apoptosis and DNA damage markers. In the hGRM1-positive cell lines C8161 and UACC903, riluzole enhanced the lethal effects of ionizing radiation; no difference was seen in the hGRM1-negative UACC930 cell line. C8161 cells treated with riluzole plus irradiation also showed the highest levels of the cleaved forms of PARP and caspase-3; excised C8161 xenografts showed the greatest number of apoptotic cells by immunohistochemistry (P < 0.001). On cell cycle analysis, a sequence-dependent enrichment in the G(2)/M phase was shown with the combination of riluzole and irradiation. Xenografts treated with riluzole and weekly radiation fractions showed significant growth inhibition and revealed markedly increased DNA damage. We have shown, in vitro and in vivo, that the combination of riluzole and ionizing radiation leads to greater cytotoxicity. These results have clinical implications for patients with brain metastases receiving whole brain radiation therapy.

Gamma-ray Irradiation Impairs Dendritic Cell Migration to CCL19 by Down-regulation of CCR7 and Induction of Cell Apoptosis

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role in the regulation of immune response and migration of DCs into secondary lymphoid tissues also play an important role in the initiation of innate and adaptive immunity. Radiation therapy is now a routine treatment for certain types of cancer and over 20 percent of cancer patients will require radiation therapy during the treatment of their disease. However, the influence of ionizing irradiation on the migratory ability of DCs is largely unknown. In this article, we report that γ ray irradiation can significantly inhibit LPS-triggered up regulation of CCR7 expression and PGE2 production by DC, thus impairing DC migration towards CCL19 in vitro and in vivo. Moreover, γ ray exposed DC also displayed an increased apoptosis rate and decreased cell viability. Furthermore, we demonstrate that exogenous PGE2 can partly reduce the gamma-ray induced migratory impairment and restored CCR7 expression of DC. Our work suggests that γ irradiation affects DC function at multiple steps during the immune response including DC migration, and that PGE2, via control of CCR7 expression, is an important regulator of DC migration.

Translocation Procedure of Implanted Devices Due to Radiation Therapy for Malignancy

Case 1: A 73 years-old male had a prior myocardial infarction with ventricular tachycardia (VT). An implantable cardioverter defibrillator (ICD; Medtronic VIRTUOSO) was implanted on his left anterior chest at the age of 71 years. It worked appropriately for VT by anti-tachy programming over 2 years. However, under the diagnosis of malignant lymphoma, he had to be done 60 Gy mediastinal and bilateral axillary radiation therapy. We displaced his device 13 cm lower from the original position, which was enough distance to avoid the radiation-induced trouble. No malfunctions were observed during radiation therapy. Case 2: A 79 years-old male was implanted a pacemaker (Medtronic Adapta) on his right anterior chest 5 years ago due to atrial fibrillation with brady ventricular response. He had to receive 60 Gy radiation therapy on his mediastinum and right upper lung field because of lung and esophageal double cancer. We displaced his device about 10 cm downward and outward to avoid the radiation induced failures. Radiation therapy was successfully performed without any trouble. Conclusion: The number of patients with implanted devices is increasing in aging society. In addition, the incidence of malignancy requiring radiation therapy is also increasing in theses population. When implantable devices are within the field of radiation, to avoid the various malfunctions of the devices, translocation procedure is sometimes required.