International Journal of Radiation Oncology * Biology * Physics

Issue Highlights

2010-03-15

X.-W. Cai, L.-Y. Xu, L. Wang, J. A. Hayman, A. C. Chang, A. Pickens, K. B. Cease, M. B. Orringer, and F.-M. Kong This study, through survival analysis of 661 consecutive patients treated in 2 medical centers, demonstrates that patients with post-resection recurrent non-small cell lung cancer (54 patients) achieved comparable survival to those with the newly diagnosed disease (607 patients) when they both were treated with radiotherapy or chemoradiotherapy. Chemotherapy was also a significant factor in predicting 5-year progression free survival for patients with recurrent disease. These findings suggest that patients with post-resection recurrent non-small cell lung cancer should be treated as aggressively as those with newly diagnosed disease.

American Society for Therapeutic Radiology and Oncology (ASTRO) Emerging Technology Committee Report on Electronic Brachytherapy

2010-03-15

The development of novel technologies for the safe and effective delivery of radiation is critical to advancing the field of radiation oncology. The Emerging Technology Committee of the American Society for Therapeutic Radiology and Oncology appointed a Task Group within its Evaluation Subcommittee to evaluate new electronic brachytherapy methods that are being developed for, or are already in, clinical use. The Task Group evaluated two devices, the Axxent Electronic Brachytherapy System by Xoft, Inc. (Fremont, CA), and the Intrabeam Photon Radiosurgery Device by Carl Zeiss Surgical (Oberkochen, Germany). These devices are designed to deliver electronically generated radiation, and because of their relatively low energy output, they do not fall under existing regulatory scrutiny of radioactive sources that are used for conventional radioisotope brachytherapy. This report provides a descriptive overview of the technologies, current and future projected applications, comparison of competing technologies, potential impact, and potential safety issues. The full Emerging Technology Committee report is available on the American Society for Therapeutic Radiology and Oncology Web site.

Imaging Primary Lung Cancers in Mice to Study Radiation Biology

2010-03-15

Purpose: To image a genetically engineered mouse model of non–small-cell lung cancer with micro–computed tomography (micro-CT) to measure tumor response to radiation therapy.Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT.Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold.Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

Outcome After Conservative Surgery and Breast Irradiation in 5,717 Patients With Breast Cancer: Implications for Supraclavicular Nodal Irradiation

2009-06-19

Purpose: To evaluate the outcome and predictive factors of patients who underwent breast-conserving surgery and adjuvant radiotherapy to the whole breast only, without supraclavicular nodal irradiation.Methods and Materials: A total of 5,717 patients with pT1–T4 breast cancer were treated at the University of Florence. The median age of the patient population was 55 years (range, 30–80 years). All patients were followed for a median of 6.8 years (range, 1–27 years). Adjuvant chemotherapy was recommended in 1,535 patients (26.9%). Tamoxifen was prescribed in 2,951 patients (51.6%). The patients were split into three groups according to number of positive axillary nodes (PAN): P1, negative axillary lymph nodes; P2, one to three PAN; P3, more than three PAN.Results: The P3 patients had a higher incidence of supraclavicular fossa recurrence (SFR) compared with P2 and P1 patients. However, the incidence of SFR in P3 patients was low (only 5.5%), whereas the incidence of distant metastases (DM) was 27.2%. Distant metastasis was the only independent prognostic factor for breast cancer survival. Additionally, in the subgroup of patients who developed local recurrence, DM was the most important death predictor.Conclusion: Our series suggests that isolated SFR in patients who did not receive supraclavicular radiotherapy is infrequent, as well as in those patients who have more than three PAN, and SFR seems not to influence the outcome, which depends on DM occurrence.

True Local Recurrence Rate in the Conserved Breast After Magnetic Resonance Imaging–Targeted Radiotherapy

Elisabeth Whipp, Mark Beresford, Elinor Sawyer, Michael Halliwell — 2009-07-06

Purpose: Better accuracy of local radiotherapy may substantially improve local control and thus long-term breast cancer survival. Magnetic resonance imaging (MRI) has high resolution and sensitivity in breast tissue and may depict the tumor bed more accurately than conventional planning techniques. A postoperative complex (POCx) comprises all visible changes thought to be related to surgery within the breast and acts as a surrogate for the tumor bed. This study reports on local recurrence rates after MRI-assisted radiotherapy planning to ensure adequate coverage of the POCx.Methods and Materials: Simple opposed tangential fields were defined by surface anatomy in the conventional manner in 221 consecutive patients. After MRI, fields were modified by a single radiation oncologist to ensure encompassment of the POCx with a 10-mm margin. Genetic analysis was performed on all local relapses (LRs) to distinguish true recurrences (TRs) from new primaries (NPs).Results: This was a high risk cohort at 5 years: only 9.5% were classified as low risk (St Gallen): 43.4% were Grade 3 and 19.9% had surgical margins <1 mm; 62.4% of patients received boosts. Adjustments of standard field margins were required in 69%. After a median follow-up of 5 years, there were 3 LRs (1.3%) as the site of first relapse in 221 patients, comprising two TRs (0.9%) and one NP (0.4%).Conclusions: Accurate targeting of the true tumor bed is critical. MRI may better define the tumor bed.

Four-Year Efficacy, Cosmesis, and Toxicity Using Three-Dimensional Conformal External Beam Radiation Therapy to Deliver Accelerated Partial Breast Irradiation

2009-06-09

Purpose: This prospective study examines the use of three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Four-year data on efficacy, cosmesis, and toxicity are presented.Methods: Patients with Stage O, I, or II breast cancer with lesions ≤3 cm, negative margins, and negative nodes were eligible. The 3D-CRT delivered was 38.5 Gy in 3.85 Gy/fraction. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) toxicity scale was used to grade acute and late toxicities.Results: Ninety-four patients are evaluable for efficacy. Median patient age was 62 years with the following characteristics: 68% tumor size <1 cm, 72% invasive ductal histology, 77% estrogen receptor (ER) (+), 88% postmenopausal; 88% no chemotherapy and 44% with no hormone therapy. Median follow-up was 4.2 years (range, 1.3–8.3). Four-year estimates of efficacy were IBF: 1.1% (one local recurrence); INF: 0%; CBF: 1.1%; DF: 3.9%; DFS: 95%; OS: 97%; and CSS: 99%. Four (4%) Grade 3 toxicities (one transient breast pain and three fibrosis) were observed. Cosmesis was rated good/excellent in 89% of patients at 4 years.Conclusions: Four-year efficacy, cosmesis, and toxicity using 3D-CRT to deliver APBI appear comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate thoroughly the extent of application, limitations, and complete value of this particular form of APBI.

Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

2009-06-29

Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer.Methods and Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression).Results: Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months.Conclusion: This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.

Late Side Effects and Quality of Life After Radiotherapy for Rectal Cancer

2009-06-19

Purpose: There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535).Methods and Materials: All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30).Results: Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non–radiation-treated (RT−) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT− patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT− patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001).Conclusions: Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

Sexual Function in Males After Radiotherapy for Rectal Cancer

2009-11-02

Purpose: Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer.Methods and Materials: Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured.Results: Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT– patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate–severe erectile dysfunction in RT+ patients was 7.3 compared with RT– patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01).Conclusion: RT for rectal cancer is associated with significant long-term effects on sexual function in males.

Tumor Volume Changes Assessed by Three-Dimensional Magnetic Resonance Volumetry in Rectal Cancer Patients After Preoperative Chemoradiation: The Impact of the Volume Reduction Ratio on the Prediction of Pathologic Complete Response

2009-08-03

Purpose: The aim of this study was to determine the correlation between tumor volume changes assessed by three-dimensional (3D) magnetic resonance (MR) volumetry and the histopathologic tumor response in rectal cancer patients undergoing preoperative chemoradiation therapy (CRT).Methods and Materials: A total of 84 patients who underwent preoperative CRT followed by radical surgery were prospectively enrolled in the study. The post-treatment tumor volume and tumor volume reduction ratio (% decrease ratio), as shown by 3D MR volumetry, were compared with the histopathologic response, as shown by T and N downstaging and the tumor regression grade (TRG).Results: There were no significant differences in the post-treatment tumor volume and the volume reduction ratio shown by 3D MR volumetry with respect to T and N downstaging and the tumor regression grade. In a multivariate analysis, the tumor volume reduction ratio was not significantly associated with T and N downstaging. The volume reduction ratio (>75%, p = 0.01) and the pretreatment carcinoembryonic antigen level (≤3 ng/ml, p = 0.01), but not the post-treatment volume shown by 3D MR (≤ 5ml), were, however, significantly associated with an increased pathologic complete response rate.Conclusion: More than 75% of the tumor volume reduction ratios were significantly associated with a high pathologic complete response rate. Therefore, limited treatment options such as local excision or simple observation might be considered after preoperative CRT in this patient population.

Clinical Utility of the Modified Segmental Boost Technique for Treatment of the Pelvis and Inguinal Nodes

2009-07-13

Purpose: Low-lying pelvic malignancies often require simultaneous radiation to pelvis and inguinal nodes. We previously reported improved homogeneity with the modified segmental boost technique (MSBT) compared to that with traditional methods, using phantom models. Here we report our institutional clinical experience with MSBT.Methods and Materials: MSBT patients from May 2001 to March 2007 were evaluated. Parameters analyzed included isocenter/multileaf collimation shifts, time per fraction (four fields), monitor units (MU)/fraction, femoral doses, maximal dose relative to body mass index, and inguinal node depth. In addition, a dosimetric comparison of the MSBT versus intensity modulated radiation therapy (IMRT) was conducted.Results: Of the 37 MSBT patients identified, 32 were evaluable. Port film adjustments were required in 6% of films. Median values for each analyzed parameter were as follows: MU/fraction, 298 (range, 226–348); delivery time, 4 minutes; inguinal depth, 4.5 cm; volume receiving 45 Gy (V45), 7%; V27.5, 87%; body mass index, 25 (range, 16.0–33.8). Inguinal dose was 100% in all cases; in-field inhomogeneity ranged from 111% to 118%. IMRT resulted in significantly decreased dose to normal tissue but required more time for treatment planning and a higher number of MUs (1,184 vs. 313 MU).Conclusions: In our clinical experience, the mono-isocentric MSBT provides a high degree of accuracy, improved homogeneity compared with traditional techniques, ease of simulation, treatment planning, treatment delivery, and acceptable femoral doses for pelvic/inguinal radiation fields requiring 45 to 50.4 Gy. In addition, the MSBT delivers a relatively uniform dose distribution throughout the treatment volume, despite varying body habitus. Clinical scenarios for the use of MSBT vs. intensity-modulated radiation therapy are discussed. To our knowledge, this is the first study reporting the utility of MSBT in the clinical setting.

Feasibility and Efficacy of Single Photon Emission Computed Tomography-Based Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma 8 cm or More With Portal Vein Tumor Thrombus in Combination With Transcatheter Arterial Chemoembolization

2009-06-19

Purpose: To assess the feasibility and efficacy of single photon emission computed tomography–based three-dimensional conformal radiotherapy (SPECT-B 3D-CRT) for large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Methods and Materials: HCC patients with PVTT in the first branch or main trunk, 8 cm or greater in size, were admitted to the study. SPECT, using Tc-99m-galactosyl human serum albumin, was used in radiation treatment planning to explore the optimal irradiation beam angle. SPECT enabled the minimum possible irradiation of functional liver (FL). Clinical target volume (CTV) included the main tumor and PVTT. SPECT-B 3D-CRT targeted the CTV to a total dose of 45 Gy/18 fractions. HCC outside the CTV was treated by transcatheter arterial chemoembolization (TACE).Results: Nineteen cases were enrolled in this study. The mean maximum dimension, mean CTV, and mean dose to FL were 11.0 cm (range, 8.0–20.0), 435 cm3 (range, 60–2,535), and 1,102 cGy (range, 691–1,695), respectively. Follow-up SPECT demonstrated radiation-induced dysfunctional liver. Despite the inclusion of 6 cases of Child-Pugh B or C, no patients experienced Grade 3 or worse radiation-induced liver disease. The cumulative non-progression rates of PVTT and PVTT plus main tumor were 78.0 and 43.2%, respectively. Survival rates at 1 and 2 years were 47.4 and 23.7%, respectively.Conclusions: SPECT-B 3D-CRT with TACE appears to be tolerable to cirrhotic liver and to provide promising prognosis for patients with HCC sized 8 cm or more, in comparison with previous treatment methods. A longer follow-up period is required to evaluate these findings.

Cone Beam CT Imaging Analysis of Interfractional Variations in Bladder Volume and Position During Radiotherapy for Bladder Cancer

2009-06-19

Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy.Methods and Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions.Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, −0.32 cm). The anterior bladder wall shifted the most (mean, −0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (± standard deviation [SD]) outside the planning CT counterpart was 29.24 cm3 (SD, 29.71 cm3). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm3 (SD, 21.64 cm3). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm3 (SD, 36.51 cm3). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm3 (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm3 (SD, 3.97 cm3). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047).Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.

Health-Related Quality of Life up to Six Years After 125I Brachytherapy for Early-Stage Prostate Cancer

2010-01-25

Purpose: Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after 125I prostate brachytherapy.Methods and Materials: A total of 127 patients treated with 125I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of ≥10 points was considered clinically relevant.Results: Overall, the HRQOL at 6 years after 125I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity.Conclusion: This is the first study presenting prospective HRQOL data up to 6 years after 125I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. 125I prostate brachytherapy did not adversely affect patients' long-term HRQOL.

Postoperative Nomogram Predicting the 9-Year Probability of Prostate Cancer Recurrence After Permanent Prostate Brachytherapy Using Radiation Dose as a Prognostic Variable

2009-06-19

Purpose: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence.Methods and Materials: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an α/β of 2.Results: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73–81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710.Conclusion: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient.

A Small Tolerance for Catheter Displacement in High–Dose Rate Prostate Brachytherapy is Necessary and Feasible

2009-07-21

Purpose: We examined catheter displacement in patients treated with fractionated high–dose rate (HDR) brachytherapy boost for prostate cancer and the impact this had on tumor control probability (TCP). These data were used to make conclusions on an acceptable amount of displacement.Methods and Materials: The last 20 patients treated with HDR brachytherapy boost for prostate cancer at our center in 2007 were replanned using simulated interstitial catheter displacements of 3, 6, 9, and 12 mm with originally planned dwell times. The computer-modeled dose–volume histograms for the clinical target volumes were exported and used to calculate the TCP of plans with displaced needles relative to the original plan. Actual catheter displacements were also measured before and after manual adjustment in all patients treated in 2007.Results: In the 20 patients who were replanned for caudal catheter displacements of 3, 6, 9, and 12 mm, the median relative TCP was 0.998, 0.964, 0.797, and 0.265, respectively (p < 0.01 when all medians were compared). All patients replanned with a 3-mm displacement, compared with only 75% with a 6-mm displacement, had a relative TCP greater than 0.950. In the 91 patients treated in 2007, before adjustment, 82.3% of fractions had a displacement greater than 3 mm compared with 12.2% of fractions after adjustment.Conclusions: Catheter displacement in HDR brachytherapy significantly compromises the TCP. The tolerance for these movements should be small (≤3 mm). Correcting these displacements to within acceptable limits is feasible.

Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

2009-07-21

Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy.Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Adminstration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy.Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4–8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15–45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity.Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

Whole-Pelvis Radiotherapy in Combination With Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High-Risk Prostate Cancer?

2009-06-24

Purpose: To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field.Methods and Materials: From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of ≥20 ng/ml.Results: With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results.Conclusions: For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naïve patients, for whom a significant improvement in OS was observed.

Phase II Study of Vinorelbine and Estramustine in Combination With Conformational Radiotherapy for Patients With High-Risk Prostate Cancer

2009-07-06

Purpose: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer.Methods and Materials: Fifty patients received estramustine, 600 mg/m2 daily, and vinorelbine, 25 mg/m2, on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years.Results: All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52–86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction.Conclusions: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.

Daily Isocenter Correction With Electromagnetic-Based Localization Improves Target Coverage and Rectal Sparing During Prostate Radiotherapy

2009-07-21

Purpose: To evaluate dosimetric consequences of daily isocenter correction during prostate cancer radiation therapy using the Calypso 4D localization system.Methods and Materials: Data were analyzed from 28 patients with electromagnetic transponders implanted in their prostates for daily target localization and tracking. Treatment planning isocenters were recorded based on the values of the vertical, longitudinal, and lateral axes. Isocenter location obtained via alignment with skin tattoos was compared with that obtained via the electromagnetic localization system. Daily isocenter shifts, based on the isocenter location differences between the two alignment methods in each spatial axis, were calculated for each patient over their entire course. The mean isocenter shifts were used to determine dosimetric consequences of treatment based on skin tattoo alignments alone.Results: The mean ⩲ SD of the percentages of treatment days with shifts beyond ⩲ 0.5 cm for vertical, longitudinal and lateral shifts were 62% ⩲ 28%, 35% ⩲ 26%, and 38% ⩲21%, respectively. If daily electromagnetic localization was not used, the excess in prescribed dose delivered to 70% of the rectum was 10 Gy and the deficit in prescribed dose delivered to 95% of the planning target volume was 10 Gy. The mean isocenter shift was not associated with the volumes of the prostate, rectum, or bladder, or with patient body mass index.Conclusions: Daily isocenter localization can reduce the treatment dose to the rectum. Correcting for this variability could lead to improved dose delivery, reduced side effects, and potentially improved treatment outcomes.

Comparative Survival in Patients With Postresection Recurrent Versus Newly Diagnosed Non–Small-Cell Lung Cancer Treated With Radiotherapy

2009-06-19

Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non–small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy.Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses.Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9–25.7) and 14.8% (95% confidence interval, 5.4–24.2%) vs. 12.2 months (95% CI, 10.8–13.6) and 11.0% (95% CI, 8.5–13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224–0.914; p = .027).Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.

Variations in Target Volume Definition for Postoperative Radiotherapy in Stage III Non–Small-Cell Lung Cancer: Analysis of an International Contouring Study

2009-06-29

Purpose: Postoperative radiotherapy (PORT) in patients with completely resected non–small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART).Methods and Materials: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM–based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed.Results: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V20 values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations.Conclusion: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.

Permanent Iodine-125 Interstitial Planar Seed Brachytherapy for Close or Positive Margins for Thoracic Malignancies

2009-06-19

Purpose: To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy.Methods and Materials: An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded.Results: Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year Kaplan-Meier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year.Conclusions: This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation.

The Impact of Radiation Dose and Fractionation on Outcomes for Limited-Stage Small-Cell Lung Cancer

2009-08-07

Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and ≥54 Gy with SF.Methods and Materials: LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF ≥54 Gy group.Results: Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3–43.7) for the AHF group, 14.0 months (CI 6.6–21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9–48.1) for the SF ≥ 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF ≥54 Gy groups.Conclusions: These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation.

Quantitative Analysis of Extracapsular Extension of Metastatic Lymph Nodes and its Significance in Radiotherapy Planning in Head and Neck Squamous Cell Carcinoma

2009-08-03

Purpose: We performed a histopathologic analysis to assess the extent of the extracapsular extension (ECE) beyond the capsule of metastatic lymph nodes (LN) in head and neck cancer to determine appropriate clinical target volume (CTV) expansions.Methods and Materials: All tumor-positive LN of 98 patients who underwent a neck dissection with evidence of ECE in at least one LN were analyzed by a single pathologist. The largest diameters of all LN, and in the case of ECE, the maximal linear distance, from the capsule to the farthest extent of tumor or tumoral reaction were recorded.Results: A total of 231 LN with ECE and 200 tumor-positive LN without ECE were analyzed. The incidence of ECE was associated with larger LN size (p < 0.001). Of all tumor-positive LN with a diameter of < 10 mm or < 5 mm, 105/220 (48%) nodes or 17/59 (29%) nodes, respectively, showed evidence of ECE. The mean and median extent values of ECE were 2 and 1 mm (range, 1–10 mm) and the ECE was ≤ 5 mm in 97% and ≤ 3 mm in 91% of the LN, respectively. Overall, the extent of ECE was significantly correlated with larger LN size (Spearman's correlation coefficient = 0.21; p = 0.001).Conclusions: The incidence of ECE is associated with larger LN size. However, ECE is found in a substantial number of LN with a diameter of < 10 mm. The use of 10-mm CTV margins around the gross tumor volume seems appropriate to account for ECE in radiotherapy planning of head and neck cancer.

Hypothyroidism After Radiotherapy for Nasopharyngeal Cancer Patients

2009-07-13

Purpose: The aim of this study was to determine the long-term incidence and possible predictive factors for posttreatment hypothyroidism in nasopharyngeal carcinoma (NPC) patients after radiotherapy.Methods and Materials: Four hundred and eight sequential NPC patients who had received regular annual thyroid hormone surveys prospectively after radiotherapy were included in this study. Median patient age was 47.3 years, and 286 patients were male. Thyroid function was prospectively evaluated by measuring thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) levels. Low FT4 levels indicated clinical hypothyroidism in this study.Results: With a median follow-up of 4.3 years (range, 0.54–19.7 years), the incidence of low FT4 level was 5.3%, 9.0%, and 19.1% at 3, 5, and 10 years after radiotherapy, respectively. Hypothyroidism was more common with early T stage (p = 0.044), female sex (p = 0.037), and three-dimensional conformal therapy with the altered fractionation technique (p = 0.005) after univariate analysis. N stage, chemotherapy, reirradiation, and neck electron boost did not affect the incidence of hypothyroidism. Younger age and conformal therapy were significant factors that determined clinical hypothyroidism after multivariate analysis. Overall, patients presented with a low FT4 level about 1 year after presenting with an elevated TSH level.Conclusion: Among our study group of NPC patients, 19.1% experienced clinical hypothyroidism by 10 years after treatment. Younger age and conformal therapy increased the risk of hypothyroidism. We suggest routine evaluation of thyroid function in NPC patients after radiotherapy. The impact of pituitary injury should be also considered.

High-Dose-Rate Intraoperative Radiation Therapy for Recurrent Head-and-Neck Cancer

2009-06-29

Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution.Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10–20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24–74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated.Results: With a median follow-up for surviving patients of 23 months (range, 6–54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient).Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure.

Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

2009-07-06

Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago.Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy.Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (≥90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom–from–distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02).Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

Intraoperative Electron Radiotherapy for the Management of Aggressive Fibromatosis

2009-08-03

Purpose: We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis.Methods and Materials: Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy. Median age was 31 years (range, 13–59 years). Resection status was close margin in six lesions, microscopically positive in 13, and macroscopically positive in 12. Median tumor size was 9 cm. In all, 25 patients received additional EBRT, with a median dose of 45 Gy (range, 36–54 Gy).Results: After a median follow-up of 32 months (range, 3–139 months), no disease-related deaths occurred. A total of five local recurrences were seen, resulting in actuarial 3-year local control rates of 82% overall and 91% inside the IOERT areas. Trends to improved local control were seen for older age (>31 years) and negative margins, but none of these factors reached significance. Perioperative complications were found in six patients, in particular as wound healing disturbances in five patients and venous thrombosis in one patient. Late toxicity was seen in five patients.Conclusion: Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity and yielded good local control rates even in patients with microscopical or gross residual disease.

Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

2009-08-12

Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival.Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)–based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control.Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival.Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

Comparison of Favorable Early-Stage Hodgkin's Lymphoma Treatments: A Single-Institution Review

2009-08-20

Purpose: To compare outcomes of patients receiving combined-modality chemotherapy and radiation (CMT) vs. other approaches for early-stage Hodgkin's lymphoma (HL).Methods and Materials: A review of patients with nonbulky, early-stage (IA/IIA) HL treated between 1984 and 2002 was performed to determine the treatment approaches used and the outcomes obtained.Results: There were 173 adult patients with newly diagnosed early-stage HL (49% men, 51% women, median age 33 [range 17–82] years). Treatment was as follows: extended-field radiotherapy alone (EFRT) 49%; chemotherapy alone (CTA) 13%; and CMT 38%. Among CMT patients, 36% received abbreviated doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy (three to four cycles) followed by involved-field radiotherapy. With a median follow-up of 8.3 years, the estimated 10-year relapse-free survival (RFS) and overall survival (OS) rates for the entire cohort were 78% and 85%, respectively. The 10-year RFS and OS rates for the various groups were as follows: 69% and 81% for EFRT; 78% and 84% for CTA; and 87% and 89% for CMT. The 10-year RFS rate was significantly higher (p < 0.01) among CMT patients. The use of EFRT has diminished from approximately 90% in the 1980s to virtually no use at present, whereas the use of CTA and CMT has increased significantly (p < 0.01).Conclusion: Early-stage HL treatment has changed dramatically over the past 2 decades, and our results support the superiority and continued use of CMT, specifically abbreviated-course chemotherapy and involved-field radiotherapy, as an appropriate treatment approach.

Early Expansion of the Intracranial CSF Volume After Palliative Whole-Brain Radiotherapy: Results of a Longitudinal CT Segmentation Analysis

Paul Sanghera, Sandra L. Gardner, Daryl Scora, Phillip Davey — 2009-06-29

Purpose: To assess cerebral atrophy after radiotherapy, we measured intracranial cerebrospinal fluid volume (ICSFV) over time after whole-brain radiotherapy (WBRT) and compared it with published normal-population data.Methods and Materials: We identified 9 patients receiving a single course of WBRT (30 Gy in 10 fractions over 2 weeks) for ipsilateral brain metastases with at least 3 years of computed tomography follow-up. Segmentation analysis was confined to the tumor-free hemi-cranium. The technique was semiautomated by use of thresholds based on scanned image intensity. The ICSFV percentage (ratio of ICSFV to brain volume) was used for modeling purposes. Published normal-population ICSFV percentages as a function of age were used as a control. A repeated-measures model with cross-sectional (between individuals) and longitudinal (within individuals) quadratic components was fitted to the collected data. The influence of clinical factors including the use of subependymal plate shielding was studied.Results: The median imaging follow-up was 6.25 years. There was an immediate increase (p < 0.0001) in ICSFV percentage, which decelerated over time. The clinical factors studied had no significant effect on the model.Conclusions: WBRT immediately accelerates the rate of brain atrophy. This longitudinal study in patients with brain metastases provides a baseline against which the potential benefits of more localized radiotherapeutic techniques such as radiosurgery may be compared.

A Comparison of Volumetric Modulated Arc Therapy and Conventional Intensity-Modulated Radiotherapy for Frontal and Temporal High-Grade Gliomas

2009-06-29

Purpose: Volumetric modulated arc therapy (VMAT), the predecessor to Varian's RapidArc, is a novel extension of intensity-modulated radiotherapy (IMRT) wherein the dose is delivered in a single gantry rotation while the multileaf collimator leaves are in motion. Leaf positions and the weights of field samples along the arc are directly optimized, and a variable dose rate is used. This planning study compared seven-field coplanar IMRT (cIMRT) with VMAT for high-grade gliomas that had planning target volumes (PTVs) overlapping organs at risk (OARs).Methods and Materials: 10 previously treated patients were replanned to 60 Gy in 30 fractions with cIMRT and VMAT using the following planning objectives: 98% of PTV covered by 95% isodose without violating OAR and hotspot dose constraints. Mean OAR doses were maximally decreased without reducing PTV coverage or violating hotspot constraints. We compared dose–volume histogram data, monitor units, and treatment times.Results: There was equivalent PTV coverage, homogeneity, and conformality. VMAT significantly reduced maximum and mean retinal, lens, and contralateral optic nerve doses compared with IMRT (p < 0.05). Brainstem, chiasm, and ipsilateral optic nerve doses were similar. For 2-Gy fractions, mean monitor units were as follows: cIMRT = 789 ± 112 and VMAT = 363 ± 45 (relative reduction 54%, p = 0.002), and mean treatment times (min) were as follows: cIMRT = 5.1 ± 0.4 and VMAT = 1.8 ± 0.1 (relative reduction 65%, p = 0.002).Conclusions: Compared with cIMRT, VMAT achieved equal or better PTV coverage and OAR sparing while using fewer monitor units and less time to treat high-grade gliomas.

Management of Spinal Metastases From Renal Cell Carcinoma Using Stereotactic Body Radiotherapy

2009-07-24

Purpose: To evaluate the outcomes associated with stereotactic body radiotherapy (SBRT) in the management of spinal metastases from renal cell carcinoma (RCC).Methods and Materials: SBRT was used in the treatment of patients with spinal metastases from RCC. Patients received either 24 Gy in a single fraction, 27 Gy in three fractions, or 30 Gy delivered in five fractions. Effectiveness of SBRT with respect to tumor control and palliation of pain was assessed using patient-reported outcomes.Results: A total of 48 patients with 55 spinal metastases were treated with SBRT with a median follow-up time of 13.1 months (range, 3.3–54.5 months). The actuarial 1-year spine tumor progression free survival was 82.1%. At pretreatment baseline, 23% patients were pain free; at 1 month and 12 months post-SBRT, 44% and 52% patients were pain free, respectively. No Grade 3-4 neurologic toxicity was observed.Conclusions: The data support SBRT as a safe and effective treatment modality that can be used to achieve good tumor control and palliation of pain associated with RCC spinal metastases. Further evaluation with randomized trials comparing SBRT to conventional radiotherapy may be warranted.

Analysis of Clinical and Dosimetric Factors Associated With Change in Renal Function in Patients With Gastrointestinal Malignancies After Chemoradiation to the Abdomen

2009-06-19

Purpose: To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen.Methods and Materials: A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose–volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema.Results: Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p < 0.0001). Mean decrease in CrCl was 21.37%. Pre-RT CrCl, percentage of bilateral renal volume receiving at least 10 Gy (V10), and mean kidney dose were significantly associated with development of Grade ≥2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively).Conclusions: We observed correlation between pre-RT CrCl, V10, and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

Increased Chromosomal Radiosensitivity in Women Carrying BRCA1/BRCA2 Mutations Assessed With the G2 Assay

2010-03-15

Purpose: Several in vitro studies suggest that BRCA1 and BRCA2 mutation carriers present increased sensitivity to ionizing radiation. Different assays for the assessment of deoxyribonucleic acid double-strand break repair capacity have been used, but results are rather inconsistent. Given the concerns about the possible risks of breast screening with mammography in mutation carrier women and the potentially damaging effects of radiotherapy, the purpose of this study was to further investigate the radiosensitivity of this population.Methods and Materials: The G2 chromosomal radiosensitivity assay was used to assess chromosomal breaks in lymphocyte cultures after exposure to 1 Gy. A group of familiar breast cancer patients carrying a mutation in the BRCA1 or BRCA2 gene (n = 15) and a group of healthy mutation carriers (n = 5) were investigated and compared with a reference group of healthy women carrying no mutation (n = 21).Results: BRCA1 and BRCA2 mutation carriers had a significantly higher number of mean chromatid breaks per cell (p = 0.006) and a higher maximum number of breaks (p = 0.0001) as compared with their matched controls. Both healthy carriers and carriers with a cancer history were more radiosensitive than controls (p = 0.002 and p = 0.025, respectively). Age was not associated with increased radiosensitivity (p = 0.868).Conclusions: Our results indicate that BRCA1 and BRCA2 mutation carriers show enhanced radiosensitivity, presumably because of the involvement of the BRCA genes in deoxyribonucleic acid repair and cell cycle control mechanisms.

Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

2010-03-15

Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation.Material and Methods: Different strains of mice with defined genetic backgrounds (SCID−/− homozygous, ATM−/− homozygous, ATM+/−heterozygous, and ATM+/+wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 × 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart).Results: In repair-deficient SCID−/− and ATM−/−homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM+/−heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme.Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical radiotherapy.

Significance of Interleukin-6 Signaling in the Resistance of Pharyngeal Cancer to Irradiation and the Epidermal Growth Factor Receptor Inhibitor

2010-03-15

Purpose: Tumor eradication by chemoradiotherapy for pharyngeal cancer has not been particularly successful. Targeting epithelial growth factor receptor (EGFR) could be a potential treatment strategy providing additional benefits, but only a subset of these tumors gives a clinically significant response to EGFR inhibitors. The aim has been to identify the role of interleukin-6 (IL-6) signaling and its predictive power in the treatment response of pharyngeal cancer.Methods and Materials: Human pharyngeal cancer cell lines, including the hypopharyngeal cancer cell line FaDu and its derived cell line FaDu-C225-R, were selected. Changes in tumor growth, response to treatment, and responsible signaling pathway were investigated in vitro. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining, and correlations were made between levels of IL-6, IL-6 receptor (IL-6R), p-AKT, and p-STAT3 expression and the clinical outcome of patients.Results: In vitro, either extrinsic IL-6 stimulation of cancer cells or intrinsically activated IL-6 signaling detected in FADu-C225-R cells results in resistance to irradiation and EGFR inhibitor. Blocking IL-6 signaling attenuated aggressive tumor behavior and sensitized the cells to treatments. The responsible mechanisms included decreased p-STAT3, less nuclear translocation of EGFR, and subsequently attenuated epithelial-mesenchymal transition. Regarding clinical data, staining of p-STAT3 and IL-6 was significantly linked with lower response rates to treatments and shorter survival in pharyngeal cancer patients.Conclusions: IL-6 and p-STAT3 may be significant predictors of pharyngeal carcinoma, and regulating IL-6 signaling can be considered a promising therapeutic approach.

Inactivation of Kupffer Cells by Gadolinium Chloride Protects Murine Liver From Radiation-Induced Apoptosis

2010-03-15

Purpose: To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis.Materials and Methods: A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining.Results: The expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3.Conclusion: Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage.

Comparison of 18F-Fluorothymidine and 18F-Fluorodeoxyglucose PET/CT in Delineating Gross Tumor Volume by Optimal Threshold in Patients With Squamous Cell Carcinoma of Thoracic Esophagus

2009-11-11

Purpose: To determine the optimal method of using 18F-fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) simulation to delineate the gross tumor volume (GTV) in esophageal squamous cell carcinoma verified by pathologic examination and compare the results with those using 18F-fluorodeoxyglucose (FDG) PET/CT.Methods and Materials: A total of 22 patients were enrolled and underwent both FLT and FDG PET/CT. The GTVs with biologic information were delineated using seven different methods in FLT PET/CT and three different methods in FDG PET/CT. The results were compared with the pathologic gross tumor length, and the optimal threshold was obtained. Next, we compared the simulation plans using the optimal threshold of FLT and FDG PET/CT. The radiation dose was prescribed as 60 Gy in 30 fractions with a precise radiotherapy technique.Results: The mean ± standard deviation pathologic gross tumor length was 4.94 ± 2.21 cm. On FLT PET/CT, the length of the standardized uptake value 1.4 was 4.91 ± 2.43 cm. On FDG PET/CT, the length of the standardized uptake value 2.5 was 5.10 ± 2.18 cm, both of which seemed more approximate to the pathologic gross tumor length. The differences in the bilateral lung volume receiving ≥20 Gy, heart volume receiving ≥40 Gy, and the maximal dose received by spinal cord between FLT and FDG were not significant. However, the values for mean lung dose, bilateral lung volume receiving ≥5, ≥10, ≥30, ≥40, and ≥50 Gy, mean heart dose, and heart volume receiving ≥30 Gy using FLT PET/CT-based planning were significant lower than those using FDG PET/CT.Conclusion: A standardized uptake value cutoff of 1.4 on FLT PET/CT and one of 2.5 on FDG PET/CT provided the closest estimation of GTV length. Finally, FLT PET/CT-based treatment planning provided potential benefits to the lungs and heart.

Quantification of Artifact Reduction With Real-Time Cine Four-Dimensional Computed Tomography Acquisition Methods

Ulrich W. Langner, Paul J. Keall — 2009-11-24

Purpose: To quantify the magnitude and frequency of artifacts in simulated four-dimensional computed tomography (4D CT) images using three real-time acquisition methods- direction-dependent displacement acquisition, simultaneous displacement and phase acquisition, and simultaneous displacement and velocity acquisition- and to compare these methods with commonly used retrospective phase sorting.Methods and Materials: Image acquisition for the four 4D CT methods was simulated with different displacement and velocity tolerances for spheres with radii of 0.5 cm, 1.5 cm, and 2.5 cm, using 58 patient-measured tumors and respiratory motion traces. The magnitude and frequency of artifacts, CT doses, and acquisition times were computed for each method.Results: The mean artifact magnitude was 50% smaller for the three real-time methods than for retrospective phase sorting. The dose was ∼50% lower, but the acquisition time was 20% to 100% longer for the real-time methods than for retrospective phase sorting.Conclusions: Real-time acquisition methods can reduce the frequency and magnitude of artifacts in 4D CT images, as well as the imaging dose, but they increase the image acquisition time. The results suggest that direction-dependent displacement acquisition is the preferred real-time 4D CT acquisition method, because on average, the lowest dose is delivered to the patient and the acquisition time is the shortest for the resulting number and magnitude of artifacts.

Effects of Prostate-Rectum Separation on Rectal Dose From External Beam Radiotherapy

Robert C. Susil, Todd R. McNutt, Theodore L. DeWeese, Danny Song — 2009-11-24

Purpose: In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate (e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice.Methods and Materials: Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans.Results: In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% (p < .05). In the simulation studies, a prostate-rectum separation of 10 mm was sufficient to reduce the mean rectal volume receiving 70 Gy by 83.1% (p <.05). No additional reduction in the average rectal volume receiving 70 Gy was noted after 15 mm of separation. In addition, spacer placement allowed for increased planning target volume margins without exceeding the rectal dose tolerance.Conclusion: Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.

A Comparison of Dose–Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

2009-12-14

Purpose: The dose–response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy.Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose–response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose–volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulated salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose–threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC).Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD50 in these models was approximately 39 Gy.Conclusions: The mean dose model was preferred for describing the dose–response relationship of the parotid gland.

Dynamic Jaws and Dynamic Couch in Helical Tomotherapy

2009-11-11

Purpose: To investigate the next generation of helical tomotherapy delivery with dynamic jaw and dynamic couch movements.Methods and Materials: The new technique of dynamic jaw and dynamic couch movements is described, and a comparative planning study is performed. Ten nasopharyngeal cancer patients with skull base infiltration were chosen for this comparison of longitudinal dose profiles using regular tomotherapy delivery, running-start-stop treatment, and dynamic jaw and dynamic couch delivery. A multifocal simultaneous integrated boost concept was used (70.4Gy to the primary tumor and involved lymph nodes; 57.4Gy to the bilateral cervical lymphatic drainage pathways, 32 fractions). Target coverage, conformity, homogeneity, sparing of organs at risk, integral dose, and radiation delivery time were evaluated.Results: Mean parotid dose for all different deliveries was between 24.8 and 26.1Gy, without significant differences. The mean integral dose was lowered by 6.3% by using the dynamic technique, in comparison with a 2.5-cm-field width for regular delivery and 16.7% with 5-cm-field width for regular delivery. Dynamic jaw and couch movements reduced the calculated radiation time by 66% of the time required with regular 2.5-cm-field width delivery (199 sec vs. 595 sec, p < 0.001).Conclusions: The current delivery mode of helical tomotherapy produces dose distributions with conformal avoidance of parotid glands, brain stem, and spinal cord. The new technology with dynamic jaw and couch movements improves the plan quality by reducing the dose penumbra and thereby reducing the integral dose. In addition, radiation time is reduced by 66% of the regular delivery time.

Response to “Predictors of Prostate Cancer–Specific Mortality in Elderly Men With Intermediate-Risk Prostate Cancer Treated With Brachytherapy With or Without External Beam Radiation Therapy” (Int J Radiat Oncol Biol Phys 2009, in press)

Michael Froehner, Rainer Koch, Rainer J. Litz, Manfred P. Wirth — 2010-03-15

To the Editor: We read with great interest the article by Nanda et al. suggesting a decreased prostate cancer–specific mortality in elderly men with cardiovascular disease treated by brachytherapy with or without external beam radiation therapy for intermediate-risk prostate cancer. Attracted by this surprising finding, we performed an exploratory analysis of our sample of 2,205 consecutive patients who underwent radical prostatectomy in the years 1992–2005 (median follow-up, 5.4 years; median age, 65 years) stratified by several possible definitions of cardiovascular disease (the way of comorbidity assessment has previously been described in detail ). In all stratifications, cardiovascular disease was associated with increased overall mortality, and there was no detectable protective impact of cardiovascular disease on prostate cancer–specific mortality. Conversely, the 5-year cumulative mortality rates tended to be (nonsignificantly) higher in patients with cardiovascular disease (). Restricting the analysis to elderly patients (65 years or older; median age, 68 years) yielded similar results (data not shown). It is conceivable that the presence of cardiovascular disease might impair survival in the case of progressive prostate cancer, but there is no easy explanation for the opposite. To convincingly demonstrate a relationship between comorbid disease and prostate cancer–specific mortality, probably a large number of events would be needed. At present (with only 15 observed deaths resulting from prostate cancer ), the relatively weak association between cardiovascular disease and prostate cancer–specific mortality should be interpreted with great caution.

In Reply to Dr. Froehner et al

Akash Nanda, Ming-Hui Chen, Anthony V. D'Amico — 2010-03-15

To the Editor: We thank Dr. Froehner and colleagues for their interest in our recently published article . To assess the impact of cardiovascular disease on the risk of prostate cancer–specific mortality in men with intermediate-risk prostate cancer, an adjusted analysis using a multivariable competing risks regression model is necessary as performed in our study to avoid confounding by factors such as age and known prostate cancer prognostic factors. We do agree with Dr. Froehner and colleagues that our study is limited, given its retrospective design, and as a result our conclusions are hypothesis generating and require prospective validation.

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer. In Regard to MG Zampino et al. (Int J Radiat Oncol Biol Phys 2009;75:421-427)

Mutahir A. Tunio, Altaf H. Hashmi — 2010-03-15

To the Editor: We read with great interest the article by Zampino et al. on administration of oral capecitabine concomitant to radiotherapy, followed by two courses as monotherapy prior to surgery in locally advanced rectal cancers. We would like to express some comments and reservations about the certain aspects of the study.

In Reply to Drs. Mutahir and Hashmi

Maria Giulia Zampino, Elena Magni, Maria Cristina Leonardi, Fabrizio Luca — 2010-03-15

To the Editor: We appreciate the opportunity to respond to Drs. Mutahir and Hashmi's comments regarding our article in Int J Radiat Oncol Biol Phys . Our postsurgical complications, recovered without reinterventions, were higher than in previously published studies due to a higher percentage of locally advanced rectal cancer needing an abdominal--perineal resection (20% vs. 11%--15%) and hence were commensurate with published data . If a possible role for capecitabine is not excluded, the typology/entity of such complications do not arouse major interest.

Response to “Helical Tomotherapy for Simultaneous Multitarget Radiotherapy for Pulmonary Metastasis.” (Int J Radiat Oncol Biol Phys 2009;75:703–710)

Hideya Yamazaki — 2010-03-15

To the Editor: We read the study of Kim and colleagues with great interest. This report has a potential merit to widen the role of radiotherapy from local therapy to regional or nearly systemic radiotherapy.

In Reply to Dr. Yamazaki

Chul-Seung Kay — 2010-03-15

To the Editor: In Dr. Yamazaki's letter, he pointed to the limitation of our study , that is, jumping constraint application from conventional to stereotactic body radiation therapy (SBRT), and he took the Radiation Therapy Oncology Group 0236 protocol as an example. However, the dose schedules were different in the studies. The fractional dose and total dose were 5 Gy and 50 Gy with 10 fractions in our study and 20 Gy and 60 Gy with 3 fractions in Radiation Therapy Oncology Group 0236, respectively. The biologic isoeffective dose can be differently predicted in regard to different dose schedules. The prediction of isoeffective dose is appropriate in a certain dose range or inappropriate in another dose schedule such as radiosurgery . Milano et al. recently reported the recommendations consisting of the fractional dose from 5 Gy to 7 Gy in 10 fractions with SBRT, at least 700–1000 mL of lung not involved with gross disease and V20 of 25–30% for safe hypofractionated SBRT in lung tumor , but they did not comment about the patients' pulmonary condition.

Response to “Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects” (Int J Radiat Oncol Biol Phys 2009; in press)

John Thoms, Robert Bristow, Padraig Warde, Stéphane Supiot — 2010-03-15

To the Editor: With interest, we read the article by Krengli et al. exploring the use of intraoperative radiotherapy during radical prostatectomy for locally advanced prostate cancer. We were pleased to see the low level of intra-operative and postoperative toxicity associated with this technique. This parallels our published findings using preoperative prostate radiotherapy (25 Gy in 5 fractions) in a Phase I trial at the Princess Margaret Hospital (PMH) and provides further support for the use of intraoperative or preoperative radiotherapy in combined-modality treatment of prostate cancer.

In Reply to Dr. Thoms et al.

2010-03-15

To the Editor: We were very pleased to read the letter by Thoms et al. about our article on intraoperative radiotherapy (IORT) for prostate cancer. As the authors underline, there is an interest to explore new combined approaches in locally advanced disease based on the radiobiologic characteristics of prostate cancer cells that show a relatively low α/β ratio measured by the linear-quadratic model . In this sense, the use of high dose per fraction may represent an advantageous approach, especially when the target can be selectively irradiated by using highly conformal techniques with adequate image guidance.

Fractionated Stereotactic Radiotherapy as Reirradiation for Locally Recurrent Head and Neck Cancer: In Regard to Roh et al (Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1348-55

Gozde Yazici, Mustafa Cengiz, Fadil Akyol — 2010-03-15

To the Editor: We have read the article entitled “Fractionated Stereotactic Radiotherapy as Reirradiation for Locally Recurrent Head and Neck Cancer” with great interest. The authors have reported their experience with CyberKnife radiosurgery as salvage treatment for locally recurrent head-and-neck cancer. In the discussion, they suggested that their late complication rate was higher compared to other CyberKnife results. The authors calculated the biologic effective dose of 30–39 Gy in three fractions for late responding tissues using the linear quadratic (LQ) model. They concluded that this dose was equivalent to 80–130 Gy in 1.8–2 Gy fractions.

In Reply to Dr. Yazici et al.

Yeon-Sil Kim, Kwang-Won Roh — 2010-03-15

To the Editor: We thank Yazici et al. for their interest on our article. They raised the point that the linear-quadratic (LQ) model is not suitable for calculating the biologic effective dose (BED) in hypofractionated radiotherapy because it underestimates the effect of radiation both in tumor cells and normal tissue. We do not agree with their comments.

Meetings

2010-03-15

March 15-18, 2010 5th Latin American Congress for Palliative Care

ASTRO News

2010-03-15

ASTRO is looking for support groups who offer services to Southern California/San Diego to apply for the 2010 Survivor Circle Grant, which will be presented at ASTRO's 2010 Annual Meeting in San Diego. The grant is awarded to two organizations in amounts of up to $10,000 each. Information can be found at www.astro.org/Patients/SurvivorCircle/HowToParticipate.