International Journal of Radiation Oncology * Biology * Physics

Issue Highlights

2010-09-01

G. Arcangeli, B. Saracino, S. Gomellini, M. G. Petrongari, S. Arcangeli, S. Sentinelli, S. Marzi, V. Landoni, J. Fowler, and L. Strigari This study was designed to ascertain whether a hypofractionated radiation regime of 62 Gy given in 5 weeks, at 3.1 Gy/fraction, thought to be biologically equivalent with regard to tumor control to a conventional fractionation course of 80 Gy given in 8 weeks at 2.0 Gy/fraction, can result in decreased late toxicity without decreasing the tumor control in patients with high risk prostate cancer, based on the assumption that the α/β ratio (Radiosensitivity/Repair capacity ratio) for these tumors would be less than the α/β ratio for late complications. The findings of this study not only suggest that the hypofractionated regime improves the control of prostate cancer without increasing the late complications, but also that the number of treatment visits can be reduced by half, which is an important benefit for these patients who are typically an older, less mobile population.

The Beginning of a New Journal

W. Robert Lee — 2010-09-01

Look with favor upon a bold beginning. —Virgil, Georgics

Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer: Report of the ASTRO Emerging Technology Committee

2010-07-20

This report evaluates stereotactic body radiotherapy (SBRT) in the treatment of early-stage non-small-cell lung cancer (NSCLC). Stereotactic refers to precise positioning of the target volume in three dimensions. The target volume is usually localized by using some external frame of reference related to the treatment delivery system. The term “body” is used to distinguish the technique from treatments performed in the brain and skull base called intracranial stereotactic radiosurgery (SRS) or intracranial stereotactic RT (SRT). In contrast to SRS and SRT, SBRT requires special evaluation of and accounting of target motion in the absence of a reliable bony surrogate such as the skull. Stereotactic positioning is more precise than standard treatment immobilization processes, and as a result, SRS and SBRT commonly employ much higher doses per fraction and fewer fractions than conventional radiotherapy. Based on the definition of the SBRT method as approved by the Common Procedural Terminology (CPT) editorial panel, SBRT consists of a full course of treatment administered in five or fewer fractions. Because SBRT concentrates therapeutic doses of radiotherapy into a few, high-dose, highly conformal, precisely targeted treatments, it is a highly specialized technology that requires a significant quality assurance program in order to be effectively used to benefit patients. Given the scope of quality issues involved, the quality assurance program would need to address setup, testing, maintenance and interoperability of equipment, treatment planning, patient positioning, and process of care, as well as staffing, education, training, and appropriate supervision. While these aspects of SBRT are important, they are outside the scope of this paper.

A Prospective Phase III Randomized Trial of Hypofractionation Versus Conventional Fractionation in Patients With High-Risk Prostate Cancer

2010-01-04

Purpose: To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer.Methods and Materials: From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter.Results: The median (range) follow-up was 32 (8–66) and 35 (7–64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively (p = 0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score ≥8, or T ≥2c), were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors.Conclusions: Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF.

Urinary Obstruction in Prostate Cancer Patients From the Dutch Trial (68 Gy vs. 78 Gy): Relationships With Local Dose, Acute Effects, and Baseline Characteristics

2010-01-07

Purpose: To investigate the relationship between late urinary obstruction and the details of the dose distribution of irradiated prostate cancer patients, taking into account their baseline symptoms and acute complaints.Patients and Methods: We selected patients from the Dutch multicenter trial randomized between 68 Gy and 78 Gy, for whom toxicity data and dose data were available (n = 557). The absolute dose surface parameters of the delineated bladder were calculated. Next, we constructed three-dimensional dose maps of the area around the prostate, providing an approximate identification of the corresponding anatomic locations. The dose difference maps were constructed by subtracting the mean dose maps of the patients with and without late urinary obstruction. Selected local dose points were analyzed using Cox regression analysis.Results: Urinary obstruction was scored for 40 patients, including 19 of 296 patients who received 68–72 Gy and 21 of 261 patients who received 76–78 Gy. A total of 19 events occurred within 2 years after irradiation and 21 events after 2 years. The bladder surface receiving ≥80 Gy predicted (p <.01) the occurrence of obstruction within 2 years. The dose difference map indicated highly significant differences in the bladder neck situated in the trigonal region (p < .001) that were especially predictive of obstruction after 2 years and of the diagnosis of bladder neck obstruction. Baseline complaints and transurethral resection of the prostate and acute complaints were mainly predictive for obstruction within 2 years.Conclusion: Relatively early events of urinary obstruction were associated with urinary problems existing before RT, acute toxicity, previous transurethral resection of the prostate, and hotspots in the bladder. Events after 2 years were associated with the local dose in the trigonal area.

Correlation Between Acute and Late Toxicity in 973 Prostate Cancer Patients Treated With Three-Dimensional Conformal External Beam Radiotherapy

2010-02-03

Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity.Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed.Results: Multivariate analysis showed that age ≤65 years (p = .06) and use of the three-dimensional, six-field technique (p 70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001).Conclusion: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

2010-01-20

Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation.Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome.Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5–76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2–positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2–negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression.Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

2009-12-09

Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer.Methods and Materials: A total of 42 patients with T2–T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0–1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1α (IL-1α), and IL-6 in serum.Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses.Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

Hypofractionated Boost to the Dominant Tumor Region With Intensity Modulated Stereotactic Radiotherapy for Prostate Cancer: A Sequential Dose Escalation Pilot Study

2009-11-11

Purpose: To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate.Methods and Materials: After conventional fractionated external radiotherapy to 64 to 64.4Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7Gy, respectively (normalized total dose in 2Gy/fraction [NTD2Gy] < 100Gy, low-dose group), whereas 29 patients received two fractions of 8Gy each (NTD2Gy > 100Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system.Results: Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of ≥Grade 2 late urinary and late low gastrointestinal (GI) toxicity–free survival were 82.2% ± 7.4% and 72.2% ± 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease–free survival (b-DFS) and disease-specific survival were 98% ± 1.9% and 100%, respectively.Conclusion: Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

Dose Gradient Near Target–Normal Structure Interface for Nonisocentric CyberKnife and Isocentric Intensity-Modulated Body Radiotherapy for Prostate Cancer

2010-02-03

Purpose: The treatment planning quality between nonisocentric CyberKnife (CK) and isocentric intensity modulation treatment was studied for hypofractionated prostate body radiotherapy. In particular, the dose gradient across the target and the critical structures such as the rectum and bladder was characterized.Methods and Materials: In the present study, patients treated with CK underwent repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT) using identical contour sets and dose–volume constraints. To calculate the dose falloff, the clinical target volume contours were expanded 30 mm anteriorly and posteriorly and 50 mm uniformly in other directions for all patients in the CK and IMRT plans.Results: We found that all the plans satisfied the dose–volume constraints, with the CK plans showing significantly better conformity than the IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder volumes receiving a low dose were also lower for CK than for IMRT. The average conformity index, the ratio of the prescription isodose volume and clinical target volume, was 1.18 ± 0.08 for the CK plans vs. 1.44 ± 0.11 for the IMRT plans. The average homogeneity index, the ratio of the maximal dose and the prescribed dose to the clinical target volume, was 1.45 ± 0.12 for the CK plans vs. 1.28 ± 0.06 for the IMRT plans. The average percentage of dose falloff was 2.9% ± 0.8%/mm for CK and 3.1% ± 1.0%/mm for IMRT in the anterior direction, 3.8% ± 1.6%/mm for CK and 3.2% ± 1.9%/mm for IMRT in the posterior direction, and 3.6% ± 0.4% for CK and 3.6% ± 0.4% for IMRT in all directions.Conclusion: Nonisocentric CK was as capable of producing equivalent fast dose falloff as high-number fixed-field IMRT delivery.

Radiosurgery for Craniopharyngioma

2009-12-14

Purpose: To analyze the outcomes of gamma knife stereotactic radiosurgery (SRS) for residual or recurrent craniopharyngiomas and evaluate the factors that optimized the tumor control rates.Methods and Materials: A total of 46 patients with craniopharyngiomas underwent 51 SRS procedures at University of Pittsburgh between 1988 and 2007. The median tumor volume was 1.0 cm3 (range, 0.07–8.0). The median prescription dose delivered to the tumor margin was 13.0 Gy (range, 9–20). The median maximal dose was 26.0 Gy (range, 20–50). The mean follow-up time was 62.2 months (range, 12–232).Results: The overall survival rate after SRS was 97.1% at 5 years. The 3- and 5-year progression-free survival rates (solid tumor control) were both 91.6%. The overall local control rate (for both solid tumor and cyst control) was 91%, 81%, and 68% at 1, 3, and 5 years, respectively. No patients with normal pituitary function developed hypopopituitarism after SRS. Two patients developed homonymous hemianopsia owing to tumor progression after SRS. Among the factors examined, complete radiosurgical coverage was a significant favorable prognostic factor.Conclusion: SRS is a safe and effective minimally invasive option for the management of residual or recurrent craniopharyngiomas. Complete radiosurgical coverage of the tumor was associated with better tumor control.

Prognostic Factors After Extraneural Metastasis of Medulloblastoma

Ali Mazloom, Azy H. Zangeneh, Arnold C. Paulino — 2010-02-03

Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM).Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome.Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Median survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS.Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.

The Impact of Radiotherapy Fields in the Treatment of Patients With Choroid Plexus Carcinoma

Ali Mazloom, Johannes E. Wolff, Arnold C. Paulino — 2009-12-09

Purpose: To perform a comprehensive literature review and analysis of cases dealing with choroid plexus carcinoma (CPC) to determine the optimal radiotherapy (RT) treatment field.Methods and Materials: A PubMed search of English language articles from 1979 to 2008 was performed, yielding 33 articles with 56 patients who had available data regarding RT treatment field. The median age at diagnosis was 2.7 years (range, 1 month–53 years). Of 54 patients with data regarding type of surgery, 21 (38.9%) had complete resection. Chemotherapy was delivered to 27 (48%) as part of initial therapy. The RT treatment volume was the craniospinal axis in 38 (68%), whole brain in 9 (16%), and tumor/tumor bed in 9 (16%). Median follow-up for surviving patients was 40 months.Results: The 5-year overall survival and progression-free survival (PFS) rates were 59.5% and 37.2%, respectively. Complete resection (p = 0.035) and use of craniospinal irradiation (CSI; p = 0.025) were found to positively affect PFS. The 5-year PFS for patients who had CSI vs. whole brain and tumor/tumor bed RT were 44.2% and 15.3%. For the 19 patients who relapsed, 9 (47%) had a recurrence in the RT field, 6 (32%) had a recurrence outside the RT field, and 4 (21%) had a recurrence inside and outside the irradiated field.Conclusion: Patients with CPC who received CSI had better PFS compared with those receiving less than CSI. This study supports the use of CSI in the multimodality management of patients with CPC.

Phase I Study of Vandetanib With Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma

2010-02-04

Purpose: Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ).Methods and Materials: A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvant TMZ, using a standard “3 + 3” dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of ≥60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs.Results: Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT.Conclusion: Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway.

Single-Isocenter Frameless Intensity-Modulated Stereotactic Radiosurgery for Simultaneous Treatment of Multiple Brain Metastases: Clinical Experience

2010-01-21

Purpose: To describe our clinical experience using a unique single-isocenter technique for frameless intensity-modulated stereotactic radiosurgery (IM-SRS) to treat multiple brain metastases.Methods and Materials: Twenty-six patients with a median of 5 metastases (range, 2–13) underwent optically guided frameless IM-SRS using a single, centrally located isocenter. Median prescription dose was 18 Gy (range, 14–25). Follow-up magnetic resonance imaging (MRI) and clinical examination occurred every 2–4 months.Results: Median follow-up for all patients was 3.3 months (range, 0.2–21.3), with 20 of 26 patients (77%) followed up until their death. For the remaining 6 patients alive at the time of analysis, median follow-up was 14.6 months (range, 9.3–18.0). Total treatment time ranged from 9.0 to 38.9 minutes (median, 21.0). Actuarial 6- and 12-month overall survivals were 50% (95% confidence interval [C.I.], 31–70%) and 38% (95% C.I., 19–56%), respectively. Actuarial 6- and 12-month local control (LC) rates were 97% (95% C.I., 93–100%) and 83% (95% C.I., 71–96%), respectively. Tumors ≤1.5 cm had a better 6-month LC than those >1.5 cm (98% vs. 90%, p = 0.008). New intracranial metastatic disease occurring outside of the treatment volume was observed in 7 patients. Grade ≥3 toxicity occurred in 2 patients (8%).Conclusion: Frameless IM-SRS using a single-isocenter approach for treating multiple intracranial metastases can produce clinical outcomes that compare favorably with those of conventional SRS in a much shorter treatment time (<40 minutes). Given its faster treatment time, this technique is appealing to both patients and personnel in busy clinics.

Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

2009-11-11

Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital.Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model.Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years.Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.

Tomotherapy and Multifield Intensity-Modulated Radiotherapy Planning Reduce Cardiac Doses in Left-Sided Breast Cancer Patients With Unfavorable Cardiac Anatomy

2009-12-09

Purpose: For patients with left-sided breast cancers, radiation treatment to the intact breast results in high doses to significant volumes of the heart, increasing the risk of cardiac morbidity, particularly in women with unfavorable cardiac anatomy. We compare helical tomotherapy (TOMO) and inverse planned intensity modulated radiation therapy (IMRT) with three-dimensional conformal radiotherapy using opposed tangents (3D-CRT) for reductions in cardiac volumes receiving high doses.Methods and Materials: Fifteen patients with left-sided breast cancers and unfavorable cardiac anatomy, determined by a maximum heart depth (MHD) of ≥1.0 cm within the tangent fields, were planned for TOMO and IMRT with five to seven beam angles, in addition to 3D-CRT. The volumes of heart and left ventricle receiving ≥35 Gy (V35) were compared for the plans, as were the mean doses to the contralateral breast and the volume receiving ≥20 Gy (V20) for the ipsilateral lung.Results: The mean MHD was 1.7 cm, and a significant correlation was observed between MHD and both heart and left ventricle V35. The V35s for IMRT (0.7%) and TOMO (0.5%) were significantly lower than for 3D-CRT (3.6%). The V20 for IMRT (22%) was significantly higher than for 3D-CRT (15%) or TOMO (18%), but the contralateral breast mean dose for TOMO (2.48 Gy) was significantly higher than for 3D-CRT (0.93 Gy) or IMRT (1.38 Gy).Conclusions: Both TOMO and IMRT can significantly reduce cardiac doses, with modest increases in dose to other tissues in left-sided breast cancer patients with unfavorable cardiac anatomy.

Preliminary Results on Setup Precision of Prone-Lateral Patient Positioning for Whole Breast Irradiation

2010-02-05

Purpose: The aim of this study was to develop a rapid and reproducible technique for prone positioning and to compare dose–volume indices in prone and supine positions.Methods and Materials: Eighteen patients underwent computed tomography imaging for radiotherapy planning in prone and supine position. Experience was gained in the first eight patients, which lead to modifications of the Horizon prone breast board (Civco Medical Solutions, Orange City, Iowa, USA) and the patient setup technique. A unilateral breast holder (U-BH) was developed (Van de Velde, Schellebelle, Belgium) to retract the contralateral breast away from the treated breast.The technique was then applied to an additional 10 patients. The setup precision was evaluated using daily cone-beam CT.Results: Modifications to the breast board were made to secure a prone-lateral rather then a pure prone position. We evolved from a classical setup using laser marks on the patients' body to a direct breast setup using marks on the breast only. The setup precision of the direct positioning procedure with the modified breast board and the U-BH is comparable to supine setup data in the literature. Dose–volume indices for heart and lung show significantly better results for prone than for supine position, and dose homogeneity within the treated breast did not differ according to the treatment position.Conclusions: The setup precision of our prone-lateral positioning technique is comparable to supine data in literature. Our data show the advantage of prone radiotherapy to spare the lung and heart. Further research is necessary to reduce the duration of prone setup.

Clinical Applicability of Cone-Beam Computed Tomography in Monitoring Seroma Volume Change During Breast Irradiation

2009-12-09

Purpose: To determine whether cone-beam CT (CBCT) is effective in monitoring seroma reduction during breast irradiation when compared with conventional CT.Patients and Methods: This study included 19 women with Stage T1-2 breast cancer treated with breast-conserving therapy. Each patient underwent two to four CT and multiple CBCT scans (mean, 8; range, 7–13 scans) at various time intervals during radiotherapy. Seroma were contoured by two observers on all scans and checked by one radiation oncologist. Seroma clarity was determined according to The British Columbia Cancer Agency Seroma Clarity Score scale, and conformity index (CI) of the two observers was evaluated. Correlations in seroma contours and seroma characteristics between CBCT and CT, as well as interobserver variation, were examined.Results: The mean differences in seroma volume between CT and CBCT (3%, p = 0.3) and between the two observers (6%, p = 0.2) were not statistically significant. Seroma clarity correlated significantly with CI for both CT and CBCT (p = 0.02 and p = 0.001, respectively), indicating the higher the seroma clarity score, the greater the CI between the observers. With seroma clarity 3 or higher for CT and CBCT, a high level of observer concordance was shown (all CI of these scans were ≥50%).Conclusion: Volume discrepancy between CBCT and CT and between the two observers was not statistically significant. Seroma clarity influenced observers' ability to contour on CT or CBCT equally. Therefore, CBCT is a good clinical surrogate for CT in monitoring seroma reduction during breast radiotherapy, especially for patients with seroma clarity score 3 or higher.

A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

2009-11-11

Purpose: To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer.Methods and Materials: The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites.Results: Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03–2.05), colon (O/E = 1.16; CI, 1.09–1.24), vagina (O/E = 2.71; CI, 1.86–3.8), and urinary bladder (O/E = 1.41; CI, 1.25–1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6–0.93), lung and bronchus (O/E = 0.78; CI, 0.72–0.84), and esophagus (O/E = 0.58; CI, 0.37–0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers.Conclusions: Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.

High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non–Small Cell Lung Cancer and Lung Metastases

2009-11-11

Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase.Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV.Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of ≥20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5.Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.

Incidence and Correlates of Radiation Pneumonitis in Pediatric Patients With Partial Lung Irradiation

2010-01-07

Purpose: To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation.Methods and Materials: A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V10–V25, mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis.Results: The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin (χ2 test, p = 0.027) and V24 (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V24 in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without.Conclusions: The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors.

Concurrent Liposomal Cisplatin (Lipoplatin), 5-Fluorouracil and Radiotherapy for the Treatment of Locally Advanced Gastric Cancer: A Phase I/II Study

2010-02-05

Purpose: Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin–based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin™).Methods and Materials: Lipoplatin was given at a dose of 120mg/m2/week, 5-fluorouracil at 400mg/m2/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively.Results: Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles.Conclusions: Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.

Complications After Sphincter-Saving Resection in Rectal Cancer Patients According to Whether Chemoradiotherapy Is Performed Before or After Surgery

2010-01-27

Purpose: The aim of the present study was to compare the influence of preoperative chemoradiotherapy (CRT) with postoperative CRT on the incidence and types of postoperative complications in rectal cancer patients who underwent sphincter-saving resection.Patients and Methods: We reviewed 285 patients who received preoperative CRT and 418 patients who received postoperative CRT between January 2000 and December 2006.Results: There was no between-group difference in age, gender, or cancer stage. In the pre-CRT group, the mean level of anastomosis from the anal verge was lower (3.5 ± 1.4 cm vs. 4.3 ± 1.7 cm, p < 0.001) and the rate of T4 lesion and temporary diverting ileostomy was higher than in the post-CRT group. Delayed anastomotic leakage and rectovaginal fistulae developed more frequently in the pre-CRT group than in the post-CRT group (3.9% vs. 1.2%, p = 0.020, 6.5% vs. 1.3%, p = 0.027, respectively). Small bowel obstruction (arising from radiation enteritis) requiring surgical intervention was more frequent in the post-CRT group (0% in the pre-CRT group vs. 1.4% in the post-CRT group, p = 0.042). Multivariate analysis identified preoperative CRT as an independent risk factor for fistulous complications (delayed anastomotic leakage, rectovaginal fistula, rectovesical fistula), and postoperative CRT as a risk factor for obstructive complications (anastomotic stricture, small bowel obstruction). The stoma-free rates were significantly lower in the pre-CRT group than in the post-CRT group (5-year stoma-free rates: 92.8% vs. 97.0%, p = 0.008).Conclusion: The overall postoperative complication rates were similar between the pre-CRT and the Post-CRT groups. However, the pattern of postoperative complications seen after sphincter- saving resection differed with reference to the timing of CRT.

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

2009-12-09

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer.Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used.Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05).Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

Computed Tomography–Guided High-Dose-Rate Brachytherapy in Hepatocellular Carcinoma: Safety, Efficacy, and Effect on Survival

2010-01-07

Purpose: To determine the saftety and efficacy of computed tomography (CT)–guided brachytherapy in hepatocellular carcinoma (HCC).Methods and Materials: A total of 83 patients were recruited, presenting with 140 HCC- lesions. Treatment was performed by CT-guided high-dose-rate (HDR) brachytherapy with an iridium—192 source. The primary endpoint was time to progression; secondary endpoints included local tumor control and overall survival (OS). A matched-pair analysis with patients not receiving brachytherapy was performed. Match criteria included the Cancer of the Liver Italian Program (CLIP) score, alpha-fetoprotein, presence, and extent of multifocal disease. For statistical analysis, Kaplan-Meier and Cox regression were performed.Results: Mean and median cumulative TTP for all patients (n = 75) were 17.7 and 10.4 months. Five local recurrences were observed. The OS after inclusion reached median times of 19.4 months (all patients), 46.3 months (CLIP score, 0), 20.6 months (CLIP score, 1) 12.7 months, (CLIP score, 2), and 8.3 months (CLIP score, ≥3). The 1— and 3—year OS were 94% and 65% (CLIP score, 0), 69% and 12% (CLIP score, 1), and 48% and 19% (CLIP score, 2), respectively. Nine complications requiring intervention were encountered in 124 interventions. Matched-pair analysis revealed a significantly longer OS for patients undergoing CT-guided brachytherapy.Conclusion: Based on our results the study treatment could be safely performed. The study treatment had a beneficial effect on OS in patients with advanced HCC, with respect to (and depending on) the CLIP score and compared with OS in a historical control group. A high rate of local control was also observed, regardless of applied dose in a range of 15 to 25 Gy.

Combination of Transarterial Chemoembolization and Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus

2009-11-18

Purpose: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT).Methods and Materials: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range, 28–50 Gy).Results: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20–0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00–8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79–6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19–4.50) were identified as independent predictors of mortality by multivariable analysis.Conclusions: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.

Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma

2010-02-03

Purpose: We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC.Methods and Materials: Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial α-fetoprotein (AFP) kinetics, and survival.Results: Of 23 evaluable patients, 60% had ≥2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had ≧50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had ≥Grade 2 elevation of liver enzymes, and 15 had ≥Grade 2 thrombocytopenia.Conclusions: These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.

Extrahepatic Bile Duct Cancers: Surgery Alone Versus Surgery Plus Postoperative Radiation Therapy

Hee Keun Gwak, Woo Chul Kim, Hun Jung Kim, Jeong Hoon Park — 2009-11-11

Purpose: The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bile duct (EHBD) cancers.Methods and Materials: From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors.Results: There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p = 0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival.Conclusions: Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control.

Radiation Therapy for Treatment of Pigmented Villonodular Synovitis: Results of a National Patterns of Care Study

2010-05-19

Purpose: The German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) conducted a pattern-of-care study (PCS) to analyze the radiation therapy (RT) practice for pigmented villonodular synovitis (PVNS).Methods and Materials: In 2007, a structured questionnaire to assess the number of patients, the pretreatments, the RT indication, technique, target volume concepts, outcome data, and possible early or late toxicity was circulated to 227 institutions.Results: Until August 2008, a response was available from 189 institutions (83.2 %), of whom 19 (10.0 %) experienced RT for PVNS. Complete clinical information was available for 41 patients from 14 RT departments. Thirty patients (73.2 %) received postsurgical RT because of primary incomplete resection, 11 patients (26.8 %) as an adjunct after complete resections of recurrences or unclear resection status. The total doses ranged from 30 to 50 Gy (median, 36 Gy), the median single dose was 2.0 Gy. Local control was achieved 95.1%, and 82.9% had no or only slight functional impairment. The early and late toxicity was mild (≤RTOG Grade II).Conclusions: Radiation therapy is a safe and effective treatment for PVNS in the postoperative setting after incomplete resection, and also as a salvage option for treatment of recurrences it provides a high rate of local control.

Ras-Related Small GTPases RalA and RalB Regulate Cellular Survival After Ionizing Radiation

2010-07-08

Purpose: Oncogenic activation of Ras renders cancer cells resistant to ionizing radiation (IR), but the mechanisms have not been fully characterized. The Ras-like small GTPases RalA and RalB are downstream effectors of Ras function and are critical for both tumor growth and survival. The Ral effector RalBP1/RLIP76 mediates survival of mice after whole-body irradiation, but the role of the Ral GTPases themselves in response to IR is unknown. We have investigated the role of RalA and RalB in cellular responses to IR.Methods and Materials: RalA, RalB, and their major effectors RalBP1 and Sec5 were knocked down by stable expression of short hairpin RNAs in the K-Ras-dependent pancreatic cancer-derived cell line MIA PaCa-2. Radiation responses were measured by standard clonogenic survival assays for reproductive survival, γH2AX expression for double-strand DNA breaks (DSBs), and poly(ADP-ribose)polymerase (PARP) cleavage for apoptosis.Results: Knockdown of K-Ras, RalA, or RalB reduced colony-forming ability post-IR, and knockdown of either Ral isoform decreased the rate of DSB repair post-IR. However, knockdown of RalB, but not RalA, increased cell death. Surprisingly, neither RalBP1 nor Sec5 suppression affected colony formation post-IR.Conclusions: Both RalA and RalB contribute to K-Ras-dependent IR resistance of MIA PaCa-2 cells. Sensitization due to suppressed Ral expression is likely due in part to decreased efficiency of DNA repair (RalA and RalB) and increased susceptibility to apoptosis (RalB). Ral-mediated radioresistance does not depend on either the RalBP1 or the exocyst complex, the two best-characterized Ral effectors, and instead may utilize an atypical or novel effector.

Sorafenib and Radiation: A Promising Combination in Colorectal Cancer

2010-09-01

Purpose: To examine the combination of radiation and the multikinase inhibitor sorafenib in human colorectal cancer cell lines and xenografts.Methods and Materials: HT29 and SW48 colorectal cancer cells were studied in vitro using MTT assays to establish the optimal timing of radiation and sorafenib. This optimal timing was then investigated in clonogenic survival assays. Xenografts were established, and the effect of a 3-week schedule of daily radiation and sorafenib was studied by growth delay.Results: Sorafenib predominantly had minimal effects on cell growth or radiation response in MTT growth assays, though growth inhibition was significantly enhanced in HT29 cells when sorafenib was administered after radiation. The highest dose of sorafenib altered the α component of the cell survival curve in clonogenic assays. The combination of radiation and sorafenib was synergistic in SW48 xenografts, with a mean time to threshold tumor size of 11.4 ± 1.0 days, 37.0 ± 9.5 days, 15.5 ± 3.2 days, and 98.0 ± 11.7 days in the control, radiation, sorafenib, and combined treatment group, respectively. The effect on HT29 tumors was additive, with mean time to threshold volume of 12.6 ± 1.1 days, 61.0 ± 4.3 days, 42.6 ± 11.7 days, and 100.2 ± 12.4 days.Conclusions: Sorafenib had little effect on radiation response in vitro but was highly effective when combined with radiation in vivo, suggesting that inhibition of proliferation and interference with angiogenesis may be the basis for the interaction.

Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

2010-07-08

Purpose: Adenosine monophosphate (AMP)–activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells.Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (2–8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis.Results: IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti–AMPK α subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21waf/cip as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further.Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21waf/cip and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM–AMPK–p21waf/cip pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.

Sodium Selenite Radiosensitizes Hormone-Refractory Prostate Cancer Xenograft Tumors but Not Intestinal Crypt Cells In Vivo

Junqiang Tian, Shouchen Ning, Susan J. Knox — 2010-07-08

Purpose: We have previously shown that sodium selenite (SSE) increases radiation-induced cell killing of human prostate carcinoma cells in vitro. In this study we further evaluated the in vivo radiosensitizing effect of SSE in prostate cancer xenograft tumors and normal radiosensitive intestinal crypt cells.Methods and Materials: Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI–LAPC-4) and PC-3 xenograft tumors (approximately 200 mm3) were divided into four groups: control (untreated), radiation therapy (XRT, local irradiation), SSE (2 mg/kg, intraperitoneally, 3 times/week), and XRT plus SSE. The XRT was given at the beginning of the regimen as a single dose of 5 Gy for HI–LAPC-4 tumors and a single dose of 7 Gy followed by a fractional dose of 3 Gy/d for 5 days for PC-3 tumors. The tumor volume was measured 3 times per week. The radiosensitizing effect of SSE on normal intestinal epithelial cells was assessed by use of a crypt cell microcolony assay.Results: In the efficacy study, SSE alone significantly inhibited the tumor growth in HI–LAPC-4 tumors but not PC-3 tumors. Sodium selenite significantly enhanced the XRT-induced tumor growth inhibition in both HI–LAPC-4 and PC-3 tumors. In the toxicity study, SSE did not affect the intestinal crypt cell survival either alone or in combination with XRT.Conclusions: Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer.

Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition

2010-06-21

Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines.Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry.Results: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80).Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.

Proteomics of the Radioresistant Phenotype in Head-and-Neck Cancer: Gp96 as a Novel Prediction Marker and Sensitizing Target for Radiotherapy

2010-07-07

Purpose: Radiotherapy is an integral part of the treatment modality for head-neck cancer (HNC), but in some cases the disease is radioresistant. We designed this study to identify molecules that may be involved in this resistance.Methods and Materials: Two radioresistant sublines were established by fractionated irradiation of the HNC cell lines, to determine differentially proteins between parental and radioresistant cells. Proteomic analysis and reverse-transcription polymerase chain reaction were used to identify and confirm the differential proteins. The siRNA knockdown experiments were applied to examine cellular functions of a radioresistant gene, with investigation of the alterations in colonogenic survival, cell cycle status, and reactive oxygen species levels. Xenografted mouse tumors were studied to validate the results.Results: IN all, 64 proteins were identified as being potentially associated with radioresistance, which are involved in several cellular pathways, including regulation of stimulus response, cell apoptosis, and glycolysis. Six genes were confirmed to be differentially expressed in both radioresistant sublines, with Gp96, Grp78, HSP60, Rab40B, and GDF-15 upregulated, and annexin V downregulated. Gp96 was further investigated for its functions in response to radiation. Gp96-siRNA transfectants displayed a radiation-induced growth delay, reduction in colonogenic survival, increased cellular reactive oxygen species levels, and increased proportion of the cells in the G2/M phase. Xenograft mice administered Gp96-siRNA showed significantly enhanced growth suppression in comparison with radiation treatment alone (p = 0.009).Conclusions: We identified 64 proteins and verified 6 genes that are potentially involved in the radioresistant phenotype. We further demonstrated that Gp96 knockdown enhances radiosensitivity both in cells and in vivo, which may lead to a better prognosis of HNC treatment.

Integration of Functional MRI and White Matter Tractography in Stereotactic Radiosurgery Clinical Practice

2010-04-26

Purpose: To study the efficacy of the integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging tractography data into stereotactic radiosurgery clinical practice.Methods and Materials: fMRI and tractography data sets were acquired and fused with corresponding anatomical MR and computed tomography images of patients with arteriovenous malformation (AVM), astrocytoma, brain metastasis, or hemangioma and referred for stereotactic radiosurgery. The acquired data sets were imported into a CyberKnife stereotactic radiosurgery system and used to delineate the target, organs at risk, and nearby functional structures and fiber tracts. Treatment plans with and without the incorporation of the functional structures and the fiber tracts into the optimization process were developed and compared.Results: The nearby functional structures and fiber tracts could receive doses of >50% of the maximum dose if they were excluded from the planning process. In the AVM case, the doses received by the Broadmann-17 structure and the optic tract were reduced to 700 cGy from 1,400 cGy and to 1,200 cGy from 2,000 cGy, respectively, upon inclusion into the optimization process. In the metastasis case, the motor cortex received 850 cGy instead of 1,400 cGy; and in the hemangioma case, the pyramidal tracts received 780 cGy instead of 990 cGy. In the astrocytoma case, the dose to the motor cortex bordering the lesion was reduced to 1,900 cGy from 2,100 cGy, and therefore, the biologically equivalent dose in three fractions was delivered instead.Conclusions: Functional structures and fiber tracts could receive high doses if they were not considered during treatment planning. With the aid of fMRI and tractography images, they can be delineated and spared.

In Vivo Proton Beam Range Verification Using Spine MRI Changes

2010-05-17

Purpose: In proton therapy, uncertainty in the location of the distal dose edge can lead to cautious treatment plans that reduce the dosimetric advantage of protons. After radiation exposure, vertebral bone marrow undergoes fatty replacement that is visible on magnetic resonance imaging (MRI). This presents an exciting opportunity to observe radiation dose distribution in vivo. We used quantitative spine MRI changes to precisely detect the distal dose edge in proton radiation patients.Methods and Materials: We registered follow-up T1-weighted MRI images to planning computed tomography scans from 10 patients who received proton spine irradiation. A radiation dose-MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to measure range errors in the lumbar spine.Results: In the lateral penumbra, there was an increase in signal intensity with higher dose throughout the full range of 0–37.5 Gy (RBE). In the distal fall-off region, the beam sometimes appeared to penetrate farther than planned. The mean overshoot in 10 patients was 1.9 mm (95% confidence interval, 0.8–3.1 mm), on the order of the uncertainties inherent to our range verification method.Conclusions: We have demonstrated in vivo proton range verification using posttreatment spine MRI changes. Our analysis suggests the presence of a systematic overshoot of a few millimeters in some proton spine treatments, but the range error does not exceed the uncertainty incorporated into the treatment planning margin. It may be possible to extend our technique to MRI sequences that show early bone marrow changes, enabling adaptive treatment modification.

Dosimetric Effects of Air Pockets Around High–Dose Rate Brachytherapy Vaginal Cylinders

Susan Richardson, Geethpriya Palaniswaamy, Perry W. Grigsby — 2010-04-14

Purpose: Most physicians use a single-channel vaginal cylinder for postoperative endometrial cancer brachytherapy. Recent published data have identified air pockets between the vaginal cylinders and the vaginal mucosa. The purpose of this research was to evaluate the incidence, size, and dosimetric effects of these air pockets.Methods and Materials: 25 patients receiving postoperative vaginal cuff brachytherapy with a high–dose rate vaginal cylinders were enrolled in this prospective data collection study. Patients were treated with 6 fractions of 200 to 400 cGy per fraction prescribed at 5 mm depth. Computed tomography simulation for brachytherapy treatment planning was performed for each fraction. The quantity, volume, and dosimetric impact of the air pockets surrounding the cylinder were quantified.Results: In 25 patients, a total of 90 air pockets were present in 150 procedures (60%). Five patients had no air pockets present during any of their treatments. The average number of air pockets per patient was 3.6, with the average total air pocket volume being 0.34 cm3 (range, 0.01–1.32 cm3). The average dose reduction to the vaginal mucosa at the air pocket was 27% (range, 9–58%). Ten patients had no air pockets on their first fraction but air pockets occurred in subsequent fractions.Conclusion: Air pockets between high–dose rate vaginal cylinder applicators and the vaginal mucosa are present in the majority of fractions of therapy, and their presence varies from patient to patient and fraction to fraction. The existence of air pockets results in reduced radiation dose to the vaginal mucosa.

Toward a Real-Time In Vivo Dosimetry System Using Plastic Scintillation Detectors

2010-03-15

Purpose: In the present study, we have presented and validated a plastic scintillation detector (PSD) system designed for real-time multiprobe in vivo measurements.Methods and Materials: The PSDs were built with a dose-sensitive volume of 0.4 mm3. The PSDs were assembled into modular detector patches, each containing five closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of <0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms.Results: The PSDs were compatible with clinical rectal balloons and were easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal/noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with the ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy.Conclusion: Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiotherapy should help radiation oncologists protect this sensitive normal structure.

Impact of Volumetric Modulated Arc Therapy Technique on Treatment With Partial Breast Irradiation

Jian-Jian Qiu, Zheng Chang, Q. Jackie Wu, Sua Yoo, Janet Horton, Fang-Fang Yin — 2010-05-04

Purpose: To investigate the technical feasibility of volumetric modulated arc therapy (V-MAT) in the delivery of partial breast irradiation (PBI).Methods and Materials: V-MAT and the standard, three-dimensional conformal radiotherapy (3D-CRT), were compared retrospectively in 8 patients previously treated with PBI. These patients' plans were replanned with a single partial arc using V-MAT that included partial blocking to minimize normal tissue dose. Dosimetric parameters were calculated to evaluate plan quality. Quality assurance studies included verifying both the point and the multiple planar doses. Total monitor units and delivery time were also evaluated, and collision clearance was analyzed.Results: Volumes of ipsilateral lung irradiated to 10 Gy (V10) and 20 Gy (V20) by V-MAT were significantly less than those of 3D-CRT (p = 0.03 for V10 and p = 0.025 for V20). The volume of ipsilateral breast irradiated to 5 Gy was significantly less by using V-MAT than with 3D-CRT (p = 0.02), with a ratio of integrated dose of <1.00. The total mean monitor units (489 ± 38) for V-MAT were significantly less than those for 3D-CRT (634 ± 123) (p = 0.017), with a 23% reduction. The average machine delivery time was 1.21 ± 0.10 min for the V-MAT plans and 6.28 ± 1.40 min for the 3D-CRT plans, resulting in a reduction factor of 80.1%. The conformity indexes were 1.3 in the V-MAT plans and 1.5 in the 3D-CRT plans (p = 0.102).Conclusions: V-MAT technology is feasible for PBI patients. Compared to a conventional 3D-CRT technique, it is more efficient, offers equivalent or better dose conformity, delivers lower doses to the ipsilateral lung and breast, and may potentially reduce intrafractional motion.

Development of a Micro-Computed Tomography–Based Image-Guided Conformal Radiotherapy System for Small Animals

2010-04-14

Purpose: To report on the physical aspects of a system in which radiotherapy functionality was added to a micro-computed tomography (microCT) scanner, to evaluate the accuracy of this instrument, and to and demonstrate the application of this technology for irradiating tumors growing within the lungs of mice.Methods and Materials: A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the X-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of γH2AX foci.Results: The positioning error of the translation stage was found to be <0.05 mm, whereas after alignment of the collimator with the X-ray axis through adjustment of its displacement and rotation, the collimator aperture error was <0.1 mm measured at isocenter. Computed tomography image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. Gamma-H2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining.Conclusions: Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small-animal conformal radiotherapy while leveraging existing technology.

Performance of a Novel Repositioning Head Frame for Gamma Knife Perfexion and Image-Guided Linac-Based Intracranial Stereotactic Radiotherapy

2010-04-12

Purpose: To evaluate the geometric positioning and immobilization performance of a vacuum bite-block repositioning head frame (RHF) system for Perfexion (PFX-SRT) and linac-based intracranial image-guided stereotactic radiotherapy (SRT).Methods and Materials: Patients with intracranial tumors received linac-based image-guided SRT using the RHF for setup and immobilization. Three hundred thirty-three fractions of radiation were delivered in 12 patients. The accuracy of the RHF was estimated for linac-based SRT with online cone-beam CT (CBCT) and for PFX-SRT with a repositioning check tool (RCT) and offline CBCT. The RCT's ability to act as a surrogate for anatomic position was estimated through comparison to CBCT image matching. Immobilization performance was evaluated daily with pre- and postdose delivery CBCT scans and RCT measurements.Results: The correlation coefficient between RCT- and CBCT-reported displacements was 0.59, 0.75, 0.79 (Right, Superior, and Anterior, respectively). For image-guided linac-based SRT, the mean three-dimensional (3D) setup error was 0.8 mm with interpatient (Σ) and interfraction (σ) variations of 0.1 and 0.4 mm, respectively. For PFX-SRT, the initial, uncorrected mean 3D positioning displacement in stereotactic coordinates was 2.0 mm, with Σ = 1.1 mm and σ = 0.8 mm. Considering only RCT setups <1mm (PFX action level) the mean 3D positioning displacement reduced to 1.3 mm, with Σ = 0.9 mm and σ = 0.4 mm. The largest contributing systematic uncertainty was in the superior-inferior direction (mean displacement = –0.5 mm; Σ = 0.9 mm). The largest mean rotation was 0.6° in pitch. The mean 3D intrafraction motion was 0.4 ± 0.3 mm.Conclusion: The RHF provides excellent immobilization for intracranial SRT and PFX-SRT. Some small systematic uncertainties in stereotactic positioning exist and must be considered when generating PFX-SRT treatment plans. The RCT provides reasonable surrogacy for internal anatomic displacement.

Reporting of True Spinal Cord Dose Is Encouraged for Stereotactic Body Radiation Therapy for Spinal Tumors. In Regard to Sahgal et al. (Int J Radiat Oncol Biol Phys 2010;77:548–553)

Simon S. Lo, Jian Z. Wang, Jeffrey D. Radawski, Nina A. Mayr — 2010-09-01

To the Editor: In the dosimetric study by Sahgal et al. , it was determined that a maximum point dose of 10 Gy in one fraction and in up to five fractions a normalized 2-Gy-equivalent biologically effective dose of 30–35 Gy 2/2 to the thecal sac were safe in terms of radiation-induced myelopathy caused by stereotactic body radiotherapy (SBRT) for spinal tumors. In those cases included in the study, the thecal sac, instead of the spinal cord, was contoured as organ at risk (OAR). Although contouring of the thecal sac may provide extra safety margin in treatment planning, the true radiation dose delivered to the spinal cord cannot be accurately and reliably estimated because the relative volume of the thecal sac to the spinal cord differs at different vertebral levels. For instance, the true spinal cord dose will be significantly overestimated if the thecal sac is contoured as an OAR in the upper cervical spine, where the thecal sac is much larger than the spinal cord (). Furthermore, there may be a risk of significantly underdosing the posterior edge of the vertebra and the pedicles, which are sites known to be at risk for recurrence .

In Reply to Dr. Lo et al.

Arjun Sahgal, David A. Larson — 2010-06-14

To the Editor: We appreciate the thoughtful response of Dr. Lo, who recommends calculating spinal cord dose after delineating the spinal cord rather than delineating the thecal sac as a surrogate, and we look forward to his or other investigators' analysis of “true” cord dose and complications or lack thereof. Until definitive data become available, we prefer the more conservative approach, because the spinal cord can move with respect to the thecal sac and spine . Even very small cord positional deviations during imaging may make it difficult to calculate the “true” cord dose, and cord positional deviations at the time of treatment may result in delivery of more than the planned cord dose .

The Rate of Secondary Malignancies After Radical Prostatectomy Versus External Beam Radiation Therapy for Localized Prostate Cancer: A Population-Based Study On 17,845 Patients. In Regard to Bhojani et al. (Int J Radiat Oncol Biol Phys 2010;76:342–348.)

Damien C. Weber, Christophe Combescure — 2010-09-01

To the Editor: We read with interest the paper by Bohjani et al. . The use of observational data to detect an effect of a treatment is needed when data stemming from randomized trials are lacking , and studies from Registries are essential . Uncontrolled attribution of the treatment, however, renders the interpretation of these data problematic, and such analyses should be made cautiously . The relationship between prognostic factors and treatment attribution has to be explored, as severe imbalance between the treatment groups, even with adjustment, may lead to biased results. The authors conclude that external beam radiotherapy (EBRT) predisposed to higher rates of secondary cancers (SC) based on 10- and 15-year events provided from Kaplan-Meier curves. A difference of age and Charlson index was detected, however: patients treated with EBRT were older and had higher Charlson indexes. The Cox regression model was adjusted on these factors, but we believe that the analyses performed were inadequate to support their affirmative conclusion. The use of propensity scoring methods should be applied to estimate the potential causal effect . Moreover, if some factors could explain the attribution of the treatment but are not collected in the Registry, biased estimated will be produced. For example, the attribution of EBRT may vary as a function of the calendar year and pooling patients may consequentially bias results.

In Response to Drs. Weber and Combescure

Naeem Bhojani, Maxine Sun, Rodolphe Thuret, Lars Budaus, Pierre I. Karakiewicz — 2010-09-01

To the Editor: We read with interest the comments of Drs. Weber and Combescure. First, they suggest the use of propensity scoring to better adjust for potential differences that might exist between radiation and prostatectomy patients. Second, they state that calendar year differences in treatment rates may confound the observed rates of secondary malignancies. Third, they state that poor endpoint definition may undermine the validity of reported rates. Finally, they state that our results may be invalidated by substantial loss to follow-up. We thank Drs. Weber and Combescure for bringing out those points and for their interest in our manuscript.

Response to “Dosimetric Study of Pelvic Radiotherapy for High-Risk Prostate Cancer.” (Int J Radiat Oncol Biol Phys 2009;75:994–1002)

Dimitri A. Dimitroyannis — 2010-09-01

To the Editor: With proton radiotherapy (PRT) being a relatively new modality, it was pleasantly instructive to read the article by Chera and coworkers on a dosimetric study comparing three pelvic treatment techniques available to them: intensity-modulated radiotherapy, intensity-modulated radiotherapy combined with three-dimensional PRT, and exclusive three-dimensional PRT . The crux of the paper is technique intercomparison, based on dose coverage for target and selected organs at risks, for a few high-risk prostate cancer cases.

In Response to “In Regards to Chera BS et al”

Nancy P. Mendenhall, Zuofeng Li — 2010-09-01

To the Editor: Thank you for the opportunity to respond to Dr. Dimitroyannis's comments. Dr. Dimitroyannis is correct to mention that there is some uncertainty about the distal range of proton beams in tissue. A major source of this uncertainty is the accuracy of the conversion of CT Hounsfield units (HU) to proton stopping power in a treatment planning system. There is a body of literature dealing with this issue summarized in the International Commission on Radiation Units and Measurements Report No. 78. As stated in our article, because of this acknowledged uncertainty, a minimum of 8–10 mm proximal and 3–5 mm distal margins were applied to the planning target volume (PTV) to account for a worst-case scenario in proton range. The margins applied in this study are based on the estimated uncertainties of our CT HU-proton stopping power conversions and are consistent with recommendations in the International Commission on Radiation Units and Measurements report. Even with these margins, the proton dosimetry offered substantial improvements in normal tissue exposure over intensity-modulated radiotherapy. It is important to note that with treatment planning systems and proton delivery improvements already underway, there will be even less uncertainty, permitting smaller margins and enhancing the already significant dosimetric advantages of proton therapy over intensity-modulated radiotherapy or other forms of X-ray delivery.

Erratum

2010-09-01

Re: Tucker SL, Liu HH, Liao Z, et al. Analysis of radiation pneumonitis risk using a generalized Lyman model. Int J Radiat Oncol Biol Phys 2008;72:568–574. During a recent review of our dosimetric data, we found an error in the method by which treatment plans were de-archived for calculation of the lung dose–volume histograms (DVHs) used in this retrospective analysis. We wish to emphasize that all DVHs were correct at the time of treatment delivery; the error affected only the retrospective de-archiving process. We have now correctly de-archived the plans for all but 1 patient, leaving data from 575 patients available for reanalysis.

Meetings

2010-09-01

September 9-12, 2010 16th International Society of Radiographers and Radiological Technologists World Congress

ASTRO News

2010-09-01

Join us on October 1-3, 2010, in suburban Washington (National Harbor, Md.) for an interactive, discussion-based meeting that will highlight the most clinically relevant and translational science in breast cancer. Education sessions will feature a variety of topics including biology of metastases, cosmetic outcome with breast surgery, controversies in radiation therapy and many more. To register and reserve housing, visit www.breastcasymposium.org. The housing and early registration deadline is August 25, 2010.