International Journal of Radiation OncologyBiologyPhysics (INT J RADIAT ONCOL)

Description

International Journal of Radiation Oncology*Biology*Physics (IJROBP), known in the field as the Red Journal, offers authoritative articles linking new research and technologies to clinical applications. Original contributions by leading scientists and researchers include experimental studies of combined modality treatment, especially chemoradiotherapy approaches, and relevant innovations in hyperthermia, brachytherapy, high LET irradiation, nuclear medicine, radiosensitizers, and radioprotectors. Technical advances related to tumor imaging, dosimetry, and 2-D/3-D conformal radiation treatment planning are also included. Visit the ASTRO web site at http://www.astro.org for information on membership, education, meetings, press releases and more.

Publisher details

Elsevier

Publications in this journal

• Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder: In Regard to Koay et al. (Int J Radiat Oncol Biol Phys 2011 Oct 20).

  Authors: INabil Ismaili

  International Journal of Radiation OncologyBiologyPhysics.

• Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: A Survey in Japan.

  Authors: Naoki Nakamura, Naoto Shikama, Hitoshi Wada, Hideyuki Harada, Miwako Nozaki, Hisayasu Nagakura, Masao Tago, Masahiko Oguchi, Nobue Uchida, Japanese Radiation Oncology Study Group Working Subgroup of Palliative Radiother...

  International Journal of Radiation OncologyBiologyPhysics.

  Purpose To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT). Methods and Materials MembersPurpose To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT). Methods and Materials Members of the Japanese Radiation Oncology Study Group (JROSG) completed an Internet-based survey and described the radiotherapy dose fractionation they would recommend for four hypothetical cases describing patients with painful bone metastasis (BM). Case 1 described a patient with an uncomplicated painful BM in a non-weight-bearing site from non-small-cell lung cancer. Case 2 investigated whether management for a case of uncomplicated spinal BM would be different from that in Case 1. Case 3 was identical with Case 2 except for the presence of neuropathic pain. Case 4 investigated the prescription for an uncomplicated painful BM secondary to oligometastatic breast cancer. Radiation oncologists who recommended multifraction radiotherapy (MF-RT) for Case 2 were asked to explain why they considered MF-RT superior to SF-RT. Results A total of 52 radiation oncologists from 50 institutions (36% of JROSG institutions) responded. In all four cases, the most commonly prescribed regimen was 30 Gy in 10 fractions. SF-RT was recommended by 13% of respondents for Case 1, 6% for Case 2, 0% for Case 3, and 2% for Case 4. For Case 4, 29% of respondents prescribed a high-dose MF-RT regimen (e.g., 50 Gy in 25 fractions). The following factors were most often cited as reasons for preferring MF-RT: “time until first increase in pain” (85%), “incidence of spinal cord compression” (50%), and “incidence of pathologic fractures” (29%). Conclusions Japanese radiation oncologists prefer a schedule of 30 Gy in 10 fractions and are less likely to recommend SF-RT. Most Japanese radiation oncologists regard MF-RT as superior to SF-RT, based primarily on the time until first increase in pain.

• Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: A Survey in Japan.

  Authors: Nakamura N, Shikama N, Wada H, Harada H, Nozaki M, Nagakura H, Tago M, Oguchi M, Uchida N, Japanese Radiation Oncology Study Group Working Subgroup of Palliative Radiother...

  International Journal of Radiation OncologyBiologyPhysics.

  PURPOSE: To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT). METHODS AND MATERIALS:PURPOSE: To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT). METHODS AND MATERIALS: Members of the Japanese Radiation Oncology Study Group (JROSG) completed an Internet-based survey and described the radiotherapy dose fractionation they would recommend for four hypothetical cases describing patients with painful bone metastasis (BM). Case 1 described a patient with an uncomplicated painful BM in a non-weight-bearing site from non-small-cell lung cancer. Case 2 investigated whether management for a case of uncomplicated spinal BM would be different from that in Case 1. Case 3 was identical with Case 2 except for the presence of neuropathic pain. Case 4 investigated the prescription for an uncomplicated painful BM secondary to oligometastatic breast cancer. Radiation oncologists who recommended multifraction radiotherapy (MF-RT) for Case 2 were asked to explain why they considered MF-RT superior to SF-RT. RESULTS: A total of 52 radiation oncologists from 50 institutions (36% of JROSG institutions) responded. In all four cases, the most commonly prescribed regimen was 30 Gy in 10 fractions. SF-RT was recommended by 13% of respondents for Case 1, 6% for Case 2, 0% for Case 3, and 2% for Case 4. For Case 4, 29% of respondents prescribed a high-dose MF-RT regimen (e.g., 50 Gy in 25 fractions). The following factors were most often cited as reasons for preferring MF-RT: "time until first increase in pain" (85%), "incidence of spinal cord compression" (50%), and "incidence of pathologic fractures" (29%). CONCLUSIONS: Japanese radiation oncologists prefer a schedule of 30 Gy in 10 fractions and are less likely to recommend SF-RT. Most Japanese radiation oncologists regard MF-RT as superior to SF-RT, based primarily on the time until first increase in pain.

• Exposure to ionizing radiation causes long-term increase in serum estradiol and activation of PI3K-Akt signaling pathway in mouse mammary gland

  Authors: Shubhankar Suman, Michael D. Johnson, Albert J. Fornace, Kamal Datta

  International Journal of Radiation OncologyBiologyPhysics.

• Elective Nodal Irradiation (ENI) Doesn't Appear to Provide a Clear Benefit for Patients With Unresectable Non-Small-Cell Lung Cancer (NSCLC).

  Authors: Steven E Schild

  International journal of radiation oncology, biology, physics. 72(2):311-2.

• Synopsis of history of american society for therapeutic radiology and oncology 1958-2008.

  Authors: Gustavo S Montana

  International journal of radiation oncology, biology, physics. 72(2):315-22.

  PURPOSE: To provide a synopsis of the history of the association of radiation oncologists in the United States, currently known as the American Society for Therapeutic Radiology and Oncology (ASTRO),PURPOSE: To provide a synopsis of the history of the association of radiation oncologists in the United States, currently known as the American Society for Therapeutic Radiology and Oncology (ASTRO), with the occasion of the 50th anniversary of the organization. METHODS AND MATERIALS: The history of ASTRO, from its beginning as the American Club of Therapeutic Radiologists, is the subject of a book that is to be released with the occasion of the 50th Annual Meeting of the Society in 2008. This book was prepared by members of ASTRO's History Committee and History Working Subcommittee. The source material for the book was the archives of the Society and recorded interviews, conducted by members of the subcommittee, of members of the Society and of the past and present Society staff. The book was also based on previously published material. This article used the source material used for the Society anniversary book. RESULTS: This synopsis of the history of the Society will provide a source of reference for anyone interested in the history of the Society from its foundation in 1958 to the present, 2008.

• Report From the International Atomic Energy Agency (IAEA) Consultants' Meeting on Elective Nodal Irradiation in Lung Cancer: Non-Small-Cell Lung Cancer (NSCLC).

  Authors: José S A Belderbos, Lucyna Kepka, Feng-Ming Spring Kong, Mary K Martel, Gregory M M Videtic, Branislav Jeremic

  International journal of radiation oncology, biology, physics. 72(2):335-42.

  Lymphatic spread is an important pathway of progression in non-small-cell lung cancer (NSCLC), along with local spread and distant metastasis. The probability of lymph node (LN) involvement isLymphatic spread is an important pathway of progression in non-small-cell lung cancer (NSCLC), along with local spread and distant metastasis. The probability of lymph node (LN) involvement is dependent on the site of the primary tumor, stage, and histology. Elective nodal irradiation (ENI) is the irradiation of clinical and radiological uninvolved LN to account for microscopic tumor invasion in these LNs because we have not been able to determine the extent of LN spread accurately. The clinical value of ENI is uncertain. The impact of ENI is dependent on many (staging-, treatment-, and patient-related) factors. The purpose of this report is to analyze the current status of ENI and to provide comprehensive in-depth analysis and guidance on how to generally approach this issue in NSCLC.

• Augmentation of radiation response by panitumumab in models of upper aerodigestive tract cancer.

  Authors: Tim J Kruser, Eric A Armstrong, Amol J Ghia, Shyhmin Huang, Deric L Wheeler, Robert Radinsky, Daniel J Freeman, Paul M Harari

  International journal of radiation oncology, biology, physics. 72(2):534-42.

  PURPOSE: To examine the interaction between panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, and radiation in head-and-neck squamous cell carcinoma andPURPOSE: To examine the interaction between panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, and radiation in head-and-neck squamous cell carcinoma and non-small-cell lung cancer cell lines and xenografts. METHODS AND MATERIALS: The head-and-neck squamous cell carcinoma lines UM-SCC1 and SCC-1483, as well as the non-small-cell lung cancer line H226, were studied. Tumor xenografts in athymic nude mice were used to assess the in vivo activity of panitumumab alone and combined with radiation. In vitro assays were performed to assess the effect of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage. RESULTS: Panitumumab increased the radiosensitivity as measured by the clonogenic survival assay. Radiation-induced epidermal growth factor receptor phosphorylation and downstream signaling through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) was inhibited by panitumumab. Panitumumab augmented radiation-induced DNA damage by 1.2-1.6-fold in each of the cell lines studied as assessed by residual gamma-H(2)AX foci after radiation. Radiation-induced apoptosis was increased 1.4-1.9-fold by panitumumab, as evidenced by Annexin V-fluorescein isothiocyanate staining and flow cytometry. In vivo, the combination therapy of panitumumab and radiation was superior to panitumumab or radiation alone in the H226 xenografts (p = 0.01) and showed a similar trend in the SCC-1483 xenografts (p = 0.08). In vivo, immunohistochemistry demonstrated the ability of panitumumab to augment the antiproliferative and antiangiogenic effects of radiation. CONCLUSION: These studies have identified a favorable interaction in the combination of radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant additional pursuit.

• RLIP76 in Defense of Radiation Poisoning.

  Authors: Jyotsana Singhal, Sharad S Singhal, Sushma Yadav, Sumihiro Suzuki, Molly M Warnke, Adly Yacoub, Paul Dent, Sejong Bae, Rajendra Sharma, Yogesh C Awasthi, Daniel W Armstrong, Sanjay Awasthi

  International journal of radiation oncology, biology, physics. 72(2):553-61.

  PURPOSE: To determine the role of RLIP76 in providing protection from radiation and chemotherapy. In the present report, we used RLIP76 to refer to both the mouse (Ralbp1) and the human (RLIP76)PURPOSE: To determine the role of RLIP76 in providing protection from radiation and chemotherapy. In the present report, we used RLIP76 to refer to both the mouse (Ralbp1) and the human (RLIP76) 76-kDa splice variant proteins (RLIP76) for convenience and to avoid confusion. In other reports, Ralbp1 refers to the mouse enzyme (encoded by the Ralbp1 gene), which is structurally and functionally homologous to RLIP76, the human protein encoded by the human RALBP1 gene. METHODS AND MATERIALS: Median lethal dose studies were performed in RLIP76(-/-) and RLIP76(+/+) C57B mice after treatment with a single dose of RLIP76 liposomes 14 h after whole body radiation. The radiosensitivity of the cultured mouse embryonic fibroblasts and the effects of buthionine sulfoximine (BSO), amifostine, c-jun N-terminal kinase (JNK), protein kinase B (Akt), and MAPK/ERK kinase (MEK) were determined by colony-forming assays. Glutathione-linked enzyme activities were measured by spectrophotometric assays, glutathione by dithiobis-2-nitrobenzoic acid (DTNB), lipid hydroperoxides by iodometric titration, and aldehydes and metabolites by thiobarbitauric acid reactive substances and liquid chromatography-mass spectrometry (LCMS). RESULTS: RLIP76(-/-) mice were significantly more sensitive to radiation than were the wild-type, and RLIP76 liposomes prolonged survival in a dose-dependent manner in both genotypes. The levels of 4-hydroxynonenal and glutathione-conjugate of 4-hydroxynonenal were significantly increased in RLIP76(-/-) tissues compared with RLIP76(+/+). RLIP76(-/-) mouse embryonic fibroblasts were markedly more radiosensitive than RLIP76(+/+) mouse embryonic fibroblasts, despite increased glutathione levels in the former. RLIP76 augmentation had a remarkably greater protective effect compared with amifostine. The magnitude of effects of RLIP76 loss on radiation sensitivity was greater than those caused by perturbations of JNK, MEK, or Akt, and the effects of RLIP76 loss could not be completely compensated for by modulating the levels of these signaling proteins. CONCLUSION: The results of our study have shown that RLIP76 plays a central role in radiation resistance.

• Analysis of radiation pneumonitis risk using a generalized lyman model.

  Authors: Susan L Tucker, H Helen Liu, Zhongxing Liao, Xiong Wei, Shulian Wang, Hekun Jin, Ritsuko Komaki, Mary K Martel, Radhe Mohan

  International journal of radiation oncology, biology, physics. 72(2):568-74.

  PURPOSE: To introduce a version of the Lyman normal-tissue complication probability (NTCP) model adapted to incorporate censored time-to-toxicity data and clinical risk factors and to apply thePURPOSE: To introduce a version of the Lyman normal-tissue complication probability (NTCP) model adapted to incorporate censored time-to-toxicity data and clinical risk factors and to apply the generalized model to analysis of radiation pneumonitis (RP) risk. METHODS AND MATERIALS: Medical records and radiation treatment plans were reviewed retrospectively for 576 patients with non-small cell lung cancer treated with radiotherapy. The time to severe (Grade >/=3) RP was computed, with event times censored at last follow-up for patients not experiencing this endpoint. The censored time-to-toxicity data were analyzed using the standard and generalized Lyman models with patient smoking status taken into account. RESULTS: The generalized Lyman model with patient smoking status taken into account produced NTCP estimates up to 27 percentage points different from the model based on dose-volume factors alone. The generalized model also predicted that 8% of the expected cases of severe RP were unobserved because of censoring. The estimated volume parameter for lung was not significantly different from n = 1, corresponding to mean lung dose. CONCLUSIONS: NTCP models historically have been based solely on dose-volume effects and binary (yes/no) toxicity data. Our results demonstrate that inclusion of nondosimetric risk factors and censored time-to-event data can markedly affect outcome predictions made using NTCP models.

• Treatment planning study to determine potential benefit of intensity-modulated radiotherapy versus conformal radiotherapy for unresectable hepatic malignancies.

  Authors: Cynthia L Eccles, Jean-Pierre Bissonnette, Tim Craig, Mojgan Taremi, Xia Wu, Laura A Dawson

  International journal of radiation oncology, biology, physics. 72(2):582-8.

  PURPOSE: To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal riskPURPOSE: To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal risk of liver toxicity in a treatment planning study. METHODS AND MATERIALS: A total of 26 CRT plans were evaluated. Prescription doses (24-54 Gy within six fractions) were individualized on the basis of the effective liver volume irradiated maintaining </=5% risk of radiation-induced liver disease. The dose constraints included bowel (0.5 cm(3)) and stomach (0.5 cm(3)) to </=30 Gy, spinal cord to </=25 Gy, and planning target volume (PTV) to </=140% of the prescribed dose. Two groups were evaluated: (1) PTV overlapping or directly adjacent to serial functioning normal tissues (n = 14), and (2) the liver as the dose-limiting normal tissue (n = 12). IMRT plans using direct machine parameter optimization maintained the CRT plan beam arrangements, an estimated radiation-induced liver disease risk of 5%, and underwent dose escalation, if all normal tissue constraints were maintained. RESULTS: IMRT improved PTV coverage in 19 of 26 plans (73%). Dose escalation was feasible in 9 cases by an average of 3.8 Gy (range, 0.6-13.2) in six fractions. Three of seven plans without improved PTV coverage had small gross tumor volumes (</=105 cm(3)) already receiving 54 Gy, the maximal prescription dose allowed. In the remaining cases, the PTV range was 9.6-689 cm(3); two had overlapped organs at risk; and one had four targets. IMRT did not improve these plans owing to poor target coverage (n = 2) and nonliver (n = 2) dose limits. CONCLUSION: Direct machine parameter optimization IMRT improved PTV coverage while maintaining normal tissue tolerances in most CRT liver plans. Dose escalation was possible in a minority of patients.

• The observed variance between predicted and measured radiation dose in breast and prostate patients utilizing an in vivo dosimeter.

  Authors: Charles W Scarantino, Bradley R Prestidge, Mitchel S Anscher, Carolyn R Ferree, William T Kearns, Robert D Black, Natasha G Bolick, Gloria P Beyer

  International journal of radiation oncology, biology, physics. 72(2):597-604.

  PURPOSE: Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatmentPURPOSE: Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatment to determine difference between expected and measured dose. METHODS AND MATERIALS: The Dose Verification System is a wireless, permanently implantable metal-oxide semiconductor field-effect transistor dosimeter using a bidirectional antenna for power and data transfer. The study cohort includes 36 breast (33 patients received two devices) and 29 prostate (21 patients received two devices) cancer patients. A total of 1,783 and 1,749 daily dose measurements were obtained on breast and prostate patients, respectively. The measurements were compared with the planned expected dose. Biweekly computed tomography scans were obtained to evaluate migration and the National Cancer Institute's Common Toxicity Criteria, version 3, was used to evaluate adverse events. RESULTS: Only Grade I/II adverse events of pain and bleeding were noted. There were only four instances of dosimeter migration of >5 mm from known factors. A deviation of >/=7% in cumulative dose was noted in 7 of 36 (19%) for breast cancer patients. In prostate cancer patients, a >/=7% deviation was noted in 6 of 29 (21%) and 8 of 19 (42%) during initial and boost irradiation, respectively. The two patterns of dose deviation were random and systematic. Some causes for these differences could involve organ movement, patient movement, or treatment plan considerations. CONCLUSIONS: The Dose Verification System was not associated with significant adverse events or migration. The dosimeter can measure dose in situ on a daily basis. The accuracy and utility of the dose verification system complements current image-guided radiation therapy and intensity-modulated radiation therapy techniques.

• Evaluation of Multiple Breathing States Using a Multiple Instance Geometry Approximation (MIGA) in Inverse-Planned Optimization for Locoregional Breast Treatment.

  Authors: Alexander Lin, Jean M Moran, Robin B Marsh, James M Balter, Benedick A Fraass, Daniel L McShan, Marc L Kessler, Lori J Pierce

  International journal of radiation oncology, biology, physics. 72(2):610-6.

  PURPOSE: Although previous work demonstrated superior dose distributions for left-sided breast cancer patients planned for intensity-modulated radiation therapy (IMRT) at deep inspiration breath holdPURPOSE: Although previous work demonstrated superior dose distributions for left-sided breast cancer patients planned for intensity-modulated radiation therapy (IMRT) at deep inspiration breath hold compared with conventional techniques with free-breathing, such techniques are not always feasible to limit the impact of respiration on treatment delivery. This study assessed whether optimization based on multiple instance geometry approximation (MIGA) could derive an IMRT plan that is less sensitive to known respiratory motions. METHODS AND MATERIALS: CT scans were acquired with an active breathing control device at multiple breath-hold states. Three inverse optimized plans were generated for eight left-sided breast cancer patients: one static IMRT plan optimized at end exhale, two (MIGA) plans based on a MIGA representation of normal breathing, and a MIGA representation of deep breathing, respectively. Breast and nodal targets were prescribed 52.2 Gy, and a simultaneous tumor bed boost was prescribed 60 Gy. RESULTS: With normal breathing, doses to the targets, heart, and left anterior descending (LAD) artery were equivalent whether optimizing with MIGA or on a static data set. When simulating motion due to deep breathing, optimization with MIGA appears to yield superior tumor-bed coverage, decreased LAD mean dose, and maximum heart and LAD dose compared with optimization on a static representation. CONCLUSIONS: For left-sided breast-cancer patients, inverse-based optimization accounting for motion due to normal breathing may be similar to optimization on a static data set. However, some patients may benefit from accounting for deep breathing with MIGA with improvements in tumor-bed coverage and dose to critical structures.

• In reply to dr. Healy.

  Authors: Mike E Robbins

  International journal of radiation oncology, biology, physics. 72(2):628-9.

• In reply to dr. Healy.

  Authors: Marie-Catherine Vozenin-Brotons, Valerie Haydont

  International journal of radiation oncology, biology, physics. 72(2):629.

• Small Molecular Inhibitor of Transforming Growth Factor-beta Protects Against Development of Radiation-Induced Lung Injury. In Regard to Anscher MS et al. (Int J Radiat Oncol Biol Phys 2008;71:1-9).

  Authors: Amit Bahl, Daya N Sharma, Gaura K Rath, Pramod K Julka

  International journal of radiation oncology, biology, physics. 72(2):630.

• Report From the International Atomic Energy Agency (IAEA) Consultants' Meeting on Elective Nodal Irradiation in Lung Cancer: Small-Cell Lung Cancer (SCLC).

  Authors: Gregory M M Videtic, José S A Belderbos, Feng-Ming Spring Kong, Lucyna Kepka, Mary K Martel, Branislav Jeremic

  International journal of radiation oncology, biology, physics. 72(2):327-34.

  Thoracic radiotherapy (RT) is an integral part of the management of small-cell lung cancer (SCLC) because its administration provides a survival benefit in patients with limited-stage disease.Thoracic radiotherapy (RT) is an integral part of the management of small-cell lung cancer (SCLC) because its administration provides a survival benefit in patients with limited-stage disease. However, there are many areas of controversy with respect to the delivery of curative RT, and these include definition of the target to be irradiated. A current area of concern is defining what the RT portal must encompass with respect to the mediastinal lymph nodes; that is, whether one should electively treat all mediastinal nodes, or selectively include those with some clinical risk for harboring disease, or perhaps omit elective nodal irradiation altogether. The purpose of the present report is therefore to address the concepts underlying elective or selective nodal irradiation as it applies to SCLC, looking at clinical, imaging, and RT reports to help define the parameters appropriate to treating individual patients.

• Isn't It Reasonable to Ask for Fraction Numbers?

  Authors: Jack F Fowler

  International journal of radiation oncology, biology, physics. 72(2):313-4.

• Intersociety Radiation Oncology Summit-SCOPE II.

  Authors: Prabhakar Tripuraneni, Robyn L Watson, K Kian Ang, Louis Harrison, Patricia Eifel, Anthony Zietman, Bruce Haffty, Laura I Thevenot, Christopher G Willett, Paula J Schomberg, Tom Pickles, Francine E Halberg, Phillip M Devlin

  International journal of radiation oncology, biology, physics. 72(2):323-6.

• Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma.

  Authors: Ashwatha Narayana, John G Golfinos, Ingeborg Fischer, Shahzad Raza, Patrick Kelly, Erik Parker, Edmond A Knopp, Praveen Medabalmi, David Zagzag, Patricia Eagan, Michael L Gruber

  International journal of radiation oncology, biology, physics. 72(2):383-9.

  INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose ofINTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

• Targeting Pro-Apoptotic TRAIL Receptors Sensitizes HeLa Cervical Cancer Cells to Irradiation-Induced Apoptosis.

  Authors: John H Maduro, Elisabeth G E de Vries, Gert Jan Meersma, Brigitte M T Hougardy, Ate G J van der Zee, Steven de Jong

  International journal of radiation oncology, biology, physics. 72(2):543-52.

  PURPOSE: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and theirPURPOSE: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. METHODS AND MATERIALS: Recombinant human TRAIL (rhTRAIL) and the agonistic antibodies against DR4 and DR5 were added to irradiated HeLa cells. The effect was evaluated with apoptosis and cytotoxicity assays and at the protein level. Membrane receptor expression was measured with flow cytometry. Small-interfering RNA against p53, DR4, and DR5 was used to investigate their function on the combined effect. RESULTS: rhTRAIL and the agonistic DR4 and DR5 antibodies strongly enhanced 10-Gy-induced apoptosis. This extra effect was 22%, 23%, and 29% for rhTRAIL, DR4, and DR5, respectively. Irradiation increased p53 expression and increased the membrane expression of DR5 and DR4. p53 suppression, as well as small-interfering RNA against DR5, resulted in a significant downregulation of DR5 membrane expression but did not affect apoptosis induced by irradiation and rhTRAIL. After small-interfering RNA against DR4, rhTRAIL-induced apoptosis and the additive effect of irradiation on rhTRAIL-induced apoptosis were abrogated, implicating an important role for DR4 in apoptosis induced through irradiation in combination with rhTRAIL. CONCLUSION: Irradiation-induced apoptosis is strongly enhanced by targeting the pro-apoptotic TRAIL receptors DR4 or DR5. Irradiation results in a p53-dependent increase in DR5 membrane expression. The sensitizing effect of rhTRAIL on irradiation in the HeLa cell line is, however especially mediated through the DR4 receptor.

• L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy.

  Authors: Silvia Capuani, Tommaso Gili, Marco Bozzali, Salvatore Russo, Paola Porcari, Cesare Cametti, Emanuela D'Amore, Marco Colasanti, Giorgio Venturini, Bruno Maraviglia, Giuseppe Lazzarino, Francesco S Pastore

  International journal of radiation oncology, biology, physics. 72(2):562-7.

  PURPOSE: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCTPURPOSE: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for (10)B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. METHODS AND MATERIALS: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. RESULTS: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. CONCLUSIONS: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.

• Commissioning and Quality Assurance of RapidArc Radiotherapy Delivery System.

  Authors: C Clifton Ling, Pengpeng Zhang, Yves Archambault, Jiri Bocanek, Grace Tang, Thomas LoSasso

  International journal of radiation oncology, biology, physics. 72(2):575-81.

  PURPOSE: The Varian RapidArc is a system for intensity-modulated radiotherapy (IMRT) treatment planning and delivery. RapidArc incorporates capabilities such as variable dose-rate, variable gantryPURPOSE: The Varian RapidArc is a system for intensity-modulated radiotherapy (IMRT) treatment planning and delivery. RapidArc incorporates capabilities such as variable dose-rate, variable gantry speed, and accurate and fast dynamic multileaf collimators (DMLC), to optimize dose conformality, delivery efficiency, accuracy and reliability. We developed RapidArc system commissioning and quality assurance (QA) procedures. METHODS AND MATERIALS: Tests have been designed that evaluate RapidArc performance in a stepwise manner. First, the accuracy of DMLC position during gantry rotation is examined. Second, the ability to vary and control the dose-rate and gantry speed is evaluated. Third, the combined use of variable DMLC speed and dose-rate is studied. RESULTS: Adapting the picket fence test for RapidArc, we compared the patterns obtained with stationary gantry and in RapidArc mode, and showed that the effect of gantry rotation on leaf accuracy was minimal (</=0.2 mm). We then combine different dose-rates (111-600 MU/min), gantry speeds (5.5-4.3 degrees /s), and gantry range (Deltatheta = 90-12.9 degrees ) to give the same dose to seven parts of a film. When normalized to a corresponding open field (to account for flatness and asymmetry), the dose of the seven portions show good agreement, with a mean deviation of 0.7%. In assessing DMLC speed (0.46, 0.92, 1.84, and 2.76 cm/s) during RapidArc, the analysis of designed radiation pattern indicates good agreement, with a mean deviation of 0.4%. CONCLUSIONS: The results of these tests provide strong evidence that DMLC movement, variable dose-rates and gantry speeds can be precisely controlled during RapidArc.

• Intensity-Modulated Proton Therapy Versus Helical Tomotherapy in Nasopharynx Cancer: Planning Comparison and NTCP Evaluation.

  Authors: Lamberto Widesott, Alessio Pierelli, Claudio Fiorino, Italo Dell'oca, Sara Broggi, Giovanni Mauro Cattaneo, Nadia Di Muzio, Ferruccio Fazio, Riccardo Calandrino, Marco Schwarz

  International journal of radiation oncology, biology, physics. 72(2):589-96.

  PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS ANDPURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving >/=20 Gy and >/=30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving >/=50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving >/=30, >/=20, and >/=10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.

• Poor predictive value of intraoperative real-time dosimetry for prostate seed brachytherapy.

  Authors: Levon Igidbashian, David Donath, Jean-François Carrier, Stephanie Lassalle, Yannick Hervieux, Sandrine David, Jean-Paul Bahary, Daniel Taussky

  International journal of radiation oncology, biology, physics. 72(2):605-9.

  PURPOSE: To identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperativePURPOSE: To identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. METHODS AND MATERIALS: We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I(125) brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of >/=90% and a D90 of >/=140 Gy on the basis of CT-D28 values. RESULTS: On CT-D28, 72.4% of patients had a V100 of >/=90% and 74.8% had a D90 of >/=140 Gy. AUROC for a V100 of >/=90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of >/=140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. CONCLUSIONS: Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry.

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