International journal of radiation oncology, biology, physics

Publications in this journal

• Article: In Regard to Pinn-Bingham et al.

  Ajeet Kumar Gandhi, Daya Nand Sharma, Goura Kisor Rath, Pramod Kumar Julka
  International journal of radiation oncology, biology, physics 07/2013; 86(3):399.
• Article: National Residency Matching Program Results for Radiation Oncology: 2012 Update.

  Sanjay Aneja, Lynn D Wilson, Bruce G Haffty, James B Yu
  International journal of radiation oncology, biology, physics 07/2013; 86(3):402-404.
• Article: In Regard to Reuther et al.

  Shailendra Kapoor
  International journal of radiation oncology, biology, physics 07/2013; 86(3):400-401.
• Article: Oncology Scan-Improvements in Dose Calculation, Deformable Registration, and MR-Guided Radiation Delivery.

  Eric E Klein, Indra J Das, Lei Dong, Mark J Rivard
  International journal of radiation oncology, biology, physics 07/2013; 86(3):395-397.
• Article: In Regard to Chakravarti et al.

  John A Vargo, John C Flickinger, Sushil Beriwal
  International journal of radiation oncology, biology, physics 07/2013; 86(3):398-399.
• Article: In Reply to Kapoor.

  Ekkehard Dikomey, Annette Raabe, Sebastian Reuther
  International journal of radiation oncology, biology, physics 07/2013; 86(3):401.
• Article: Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis.

  Eileen Rakovitch, Steven A Narod, Sharon Nofech-Moses, Wedad Hanna, Deva Thiruchelvam, Refik Saskin, Carole Taylor, Alan Tuck, Bruce Youngson, Naomi Miller, Susan J Done, Sandip Sengupta, Leela Elavathil, Prashant A Jani, Michel Bonin, Stephanie Metcalfe, Lawrence Paszat
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  ABSTRACT: PURPOSE: To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. METHODS AND MATERIALS: All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. RESULTS: We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). CONCLUSIONS: Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.
  International journal of radiation oncology, biology, physics 07/2013; 86(3):491-497.
• Article: Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel Radiosensitizer for the Treatment of Non-Small Cell Lung Cancer.

  Michael E Werner, Natalie D Cummings, Manish Sethi, Edina C Wang, Rohit Sukumar, Dominic T Moore, Andrew Z Wang
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  ABSTRACT: PURPOSE: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease. METHODS AND MATERIALS: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration. RESULTS: Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration. CONCLUSIONS: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.
  International journal of radiation oncology, biology, physics 07/2013; 86(3):463-468.
• Article: In Reply to Gandhi et al.

  Ajmel Puthawala, A M Nisar Syed, Anil Sharma
  International journal of radiation oncology, biology, physics 07/2013; 86(3):399-400.
• Article: Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy.

  Yutaka Shiraishi, Takashi Hanada, Toshio Ohashi, Atsunori Yorozu, Kazuhito Toya, Shiro Saito, Naoyuki Shigematsu
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  ABSTRACT: PURPOSE: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after (125)I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. METHODS AND MATERIALS: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose-volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUDsum) was determined by a summation of the brachytherapy and external-beam radiation therapy components. RESULTS: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUDsum increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUDsum (P=.000) as risk factors for grade 2+ rectal bleeding. CONCLUSIONS: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up.

  Jee Suk Chang, Won Park, Yong Bae Kim, Ik Jae Lee, Ki Chang Keum, Chang Geol Lee, Doo Ho Choi, Chang-Ok Suh, Seung Jae Huh
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  ABSTRACT: PURPOSE: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. METHODS AND MATERIALS: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. RESULTS: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. CONCLUSIONS: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: In Regard to Kim et al.

  Sujith M Kumar, M A Laviraj, G K Rath
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy.

  Ingeborg Fraunholz, Franz Rödel, Daniela Kohler, Margarita Diallo-Georgiopoulou, Luitpold Distel, Stefan Falk, Claus Rödel
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  ABSTRACT: PURPOSE: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). METHODS AND MATERIALS: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients' sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). CONCLUSION: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Results of a 5-Week Schedule of Modern Total Skin Electron Beam Radiation Therapy.

  Stephen Lloyd Morris, Mark McGovern, Sally Bayne, Mary Wain, Fiona Child, Sean Whittaker
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  ABSTRACT: PURPOSE: To report the outcomes of a 5-week schedule of total skin electron beam radiation therapy (TSEB) for mycosis fungoides (MF). METHODS: Over 5 years, 41 patients with confirmed MF were treated with a modern TSEB technique delivering 30 Gy in 20 fractions over 5 weeks to the whole skin surface. Data were collected prospectively and entered into the skin tumor unit research database. Skin modified skin weighted assessment tool score data were collected to determine response, duration of response, survival, and toxicity. The outcomes were analyzed according to the patient's stage before TSEB, prognostic factors, and adjuvant treatments. RESULTS: Seventeen patients were stage 1B, 19 were stage IIB, 3 were stage III, and 2 were stage IV. The overall response rate was 95%, with a complete response rate of 51%. Seventy-six percent of patients had relapsed at median follow-up of 18 months. The median time to relapse was 12 months, to systemic therapy was 15 months, and to modified skin weighted assessment tool progression above baseline was 44 months. The complete response rate was 59% in stage IB and 47% in stage IIB patients. The median time to skin relapse was longer in stage IB compared with stage IIB, 18 months versus 9 months. The median time to systemic therapy was longer in stage IB compared with stage IIB, >56 months versus 8 months. The median overall survival was 35 months: >56 months for stage IB, 25 months for stage IIB, 46 months for stage III, and 23.5 months for stage IV. Fifteen patients received adjuvant psoralen + ultraviolet A treatment with no difference seen in the time to relapse. CONCLUSIONS: This 5-week schedule of TSEB for MF has a high response rate with comparable duration of response to other regimens. Future studies are needed to find adjuvant and combination treatments to improve the duration of response.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin.

  Mariateresa Mancuso, Simona Leonardi, Paola Giardullo, Emanuela Pasquali, Mirella Tanori, Ilaria De Stefano, Arianna Casciati, Christian C Naus, Simonetta Pazzaglia, Anna Saran
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  ABSTRACT: PURPOSE: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin. METHODS AND MATERIALS: Patched1 heterozygous (Ptch1(+/-)) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1(+/-) and Cx43(+/-) mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas. RESULTS: We report abscopal tumor induction in the shielded skin of Ptch1(+/-) mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin. CONCLUSIONS: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy.

  Stephen J Freedland, Leah Gerber, Julia Reid, William Welbourn, Eliso Tikishvili, Jimmy Park, Adib Younus, Alexander Gutin, Zaina Sangale, Jerry S Lanchbury, Joseph K Salama, Steven Stone
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  ABSTRACT: PURPOSE: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. METHODS AND MATERIALS: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. RESULTS: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. CONCLUSIONS: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.
  International journal of radiation oncology, biology, physics 06/2013;
• Article: Health-related quality of life in elderly patients with newly diagnosed glioblastoma treated with short-course radiation therapy plus concomitant and adjuvant temozolomide.

  Giuseppe Minniti, Claudia Scaringi, Alessandra Baldoni, Gaetano Lanzetta, Vitaliana De Sanctis, Vincenzo Esposito, Riccardo Maurizi Enrici
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  ABSTRACT: To describe the quality of life (QOL) in elderly patients with glioblastoma (GBM) treated with an abbreviated course of radiation therapy (RT; 40 Gy in 15 fractions) plus concomitant and adjuvant temozolomide (TMZ). Health-related QOL (HRQOL) was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30, version 3) and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). Changes from baseline in the score of 9 preselected domains (global QLQ, social functioning, cognitive functioning, emotional functioning, physical functioning, motor dysfunction, communication deficit, fatigue, insomnia) were determined 4 weeks after RT and thereafter every 8 weeks during the treatment until disease progression. The proportion of patients with improved HRQOL scores, defined as a change of 10 points or more, and duration of changes were recorded. Sixty-five patients completed the questionnaires at baseline. The treatment was consistently associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time; mean score differed by 9.6 points between baseline and 6-month follow-up (P=.03). For social functioning and cognitive functioning, mean scores improved over time, with a maximum difference of 10.4 points and 9.5 points between baseline and 6-month follow-up (P=.01 and P=.02), respectively. By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02). A short course of RT in combination with TMZ in elderly patients with GBM was associated with survival benefit without a negative effect on HRQOL until the time of disease progression.
  International journal of radiation oncology, biology, physics 06/2013; 86(2):285-91.
• Article: Research funding for radiation oncology: an unfortunately small sliver of an inadequate pie.

  Reshma Jagsi, Lynn D Wilson
  International journal of radiation oncology, biology, physics 06/2013; 86(2):216-7.
• Article: Oncology scan - gynecological cancers: new treatments, old treatments, imaging, and meta-analyses.

  Arno J Mundt, Catheryn Yashar, Loren Mell, Nina Mayr, Michael Milosevic
  International journal of radiation oncology, biology, physics 06/2013; 86(2):207-10.
• Article: Chemoradiation with Paclitaxel and Carboplatin in high-risk cervical cancer patients after radical hysterectomy: a korean gynecologic oncology group study.

  Taek Sang Lee, Soon Beom Kang, Young Tak Kim, Byung Joo Park, Yong Man Kim, Jong Min Lee, Seok Mo Kim, Young Tae Kim, Jae Hoon Kim, Kyung Tai Kim
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  ABSTRACT: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m(2), carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.
  International journal of radiation oncology, biology, physics 06/2013; 86(2):304-10.