Neutrophil-to-lymphocyte ratio for the prediction of soft tissue sarcomas response to pre-operative radiation therapy.

PURPOSE/OBJECTIVE: This study aims to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in soft tissue sarcomas (STS) treated with pre-operative hypofractionated radiotherapy (HFRT). MATERIALS/METHODS: This retrospective analysis included patients treated with pre-operative HFRT of 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, and complete blood count (CBC) data were collected. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Only patients with CBCs conducted within 6 months after radiotherapy were included. Cox proportional-hazard regression models were used to assess the impact of NLR and different variables on outcomes. Kaplan Meier were used to illustrate survival curves. A p-value < 0.05 was considered significant, and 95 % confidence intervals (CI) were employed. RESULTS: A total of 40 patients received HFRT and had CBCs within 6 months after radiotherapy. There were 17 (42.5 %) females and 23 (57.5 %) males with a mean age of 66 years. The mean largest tumor size dimension was 7.1 cm, and the mean NLR post-RT was 5.3. The most frequent histological subtypes were myxofibrosarcoma (17.5 %), pleomorphic spindle cell sarcoma (10 %), leiomyosarcoma (7.5 %), and myxoid liposarcoma (5 %). The median follow-up period was 15.4 months. From all patients, 14 patients had disease progression, 12 metastatic disease and 3 died of disease. Multivariable Cox proportional-hazards regression analysis displayed that a higher post-RT NLR was associated with worse disease-free survival (DFS) (HR: 1.303 [1.098-1.548], p = 0.003), and distant metastasis-free survival (DMFS) (HR: 1.38 [1.115-1.710], p = 0.003). Moreover, post-NLR ≥ 4 as a single variable was associated with worse DFS, DMFS, but not worse local recurrence or overall survival. CONCLUSION: This study is the first to evaluate NLR as a prognostic biomarker in STS patients treated with pre-operative radiotherapy. A higher NLR after pre-operative radiotherapy was associated with increased disease progression.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Implementation of a DVH Registry to provide constraints and continuous quality monitoring for pediatric CSI treatment planning.

Craniospinal irradiation (CSI) is a complex radiation therapy technique that is used for patients, often children and teenagers/young adults, with tumors that have a propensity to spread throughout the central nervous system such as medulloblastoma. CSI is associated with important long-term side effects, the risk of which may be affected by numerous factors including radiation modality and technique. Lack of standardization for a technique that is used even in larger radiation oncology departments only a few times each year may be one such factor and the current ad hoc manner of planning new CSI patients may be greatly improved by implementing a dose-volume histogram registry (DVHR) to use previous patient data to facilitate prospective constraint guidance for organs at risk. In this work, we implemented a DVHR and used it to provide standardized constraints for CSI planning. Mann-Whitney U tests and mean differences at 95% confidence intervals were used to compare two cohorts (pre- and post-DVHR intervention) at specific dosimetric points to determine if observed improvements in standardization were statistically significant. Through this approach, we have shown that the implementation of dosimetric constraints based on DVHR-derived data helped improve the standardization of pediatric CSI planning at our center. The DVHR also provided guidance for a change in CSI technique, helping to achieve practice standardization across TomoTherapy and IMRT.

Probabilistic classification of tumour habitats in soft tissue sarcoma.

The purpose of this work is to propose a method to characterize tumour heterogeneity on MRI, using probabilistic classification based on a reference tissue. The method uses maps of the apparent diffusion coefficient (ADC), T2 relaxation, and a calculated map representing high-b-value diffusion-weighted MRI (denoted simDWI) to identify up to five habitats (i.e. sub-regions) of tumours. In this classification method, the parameter values (ADC, T2 , and simDWI) from each tumour voxel are compared against the corresponding parameter probability distributions in a reference tissue. The probability that a tumour voxel belongs to a specific habitat is the joint probability for all parameters. The classification can be visualized using a custom colour scheme. The proposed method was applied to data from seven patients with biopsy-confirmed soft tissue sarcoma, at three time-points over the course of pre-operative radiotherapy. Fast-spin-echo images with two different echo times and diffusion MRI with three b-values were obtained and used as inputs to the method. Imaging findings were compared with pathology reports from pre-radiotherapy biopsy and post-surgical resection. Regions of hypercellularity, high-T2 proteinaceous fluid, necrosis, collagenous stroma, and fibrosis were identified within soft tissue sarcoma. The classifications were qualitatively consistent with pathological observations. The percentage of necrosis on imaging correlated strongly with necrosis estimated from FDG-PET before radiotherapy (R2  = 0.97) and after radiotherapy (R2  = 0.96). The probabilistic classification method identifies realistic habitats and reflects the complex microenvironment of tumours, as demonstrated in soft tissue sarcoma.

Investigating the role of functional imaging in the management of soft-tissue sarcomas of the extremities.

BACKGROUND AND PURPOSE: In this work, we validate a texture-based model computed from positron emission tomography (PET) and magnetic resonance imaging (MRI) for the prediction of lung metastases in soft-tissue sarcomas (STS). We explore functional imaging at different treatment time points and evaluate the feasibility of radiotherapy dose painting as a potential treatment strategy for patients with higher metastatic risk. MATERIALS AND METHODS: We acquired fluorodeoxyglucose (FDG)-PET, fluoromisonidazole (FMISO)-PET, diffusion weighting (DW)-MRI and dynamic contrast enhanced (DCE)-MRI data for 18 patients with extremity STS before, during, and after pre-operative radiotherapy. We tested the lung metastases prediction model using pre-treatment images. We evaluated the feasibility of dose painting using volumetric arc therapy (VMAT) via treatment re-planning with a prescription of 50 Gy to the planning target volume (PTV50Gy) and boost doses of 60 Gy to the FDG hypermetabolic gross tumour volume (GTV60Gy) and 65 Gy to the low-perfusion DCE-MRI hypoxic GTV contained within the GTV60Gy (GTV65Gy). RESULTS: The texture-based model for lung metastases prediction reached an area under the curve (AUC), sensitivity, specificity and accuracy of 0.71, 0.75, 0.85 and 0.82, respectively. Dose painting resulted in adequate coverage and homogeneity in the re-planned treatments: D95% to the PTV50Gy, GTV60Gy and GTV65Gy were 50.0 Gy, 60.3 Gy and 65.4 Gy, respectively. CONCLUSIONS: Textural biomarkers extracted from FDG-PET and MRI could be useful to identify STS patients that might benefit from dose escalation. The feasibility of treatment planning with double boost levels to intratumoural GTV functional sub-volumes was established.

Development and implementation of a radiation therapy incident learning system compatible with local workflow and a national taxonomy.

PURPOSE: Collaborative incident learning initiatives in radiation therapy promise to improve and standardize the quality of care provided by participating institutions. However, the software interfaces provided with such initiatives must accommodate all participants and thus are not optimized for the workflows of individual radiation therapy centers. This article describes the development and implementation of a radiation therapy incident learning system that is optimized for a clinical workflow and uses the taxonomy of the Canadian National System for Incident Reporting - Radiation Treatment (NSIR-RT). METHODS: The described incident learning system is a novel version of an open-source software called the Safety and Incident Learning System (SaILS). A needs assessment was conducted prior to development to ensure SaILS (a) was intuitive and efficient (b) met changing staff needs and (c) accommodated revisions to NSIR-RT. The core functionality of SaILS includes incident reporting, investigations, tracking, and data visualization. Postlaunch modifications of SaILS were informed by discussion and a survey of radiation therapy staff. RESULTS: There were 240 incidents detected and reported using SaILS in 2016 and the number of incidents per month tended to increase throughout the year. An increase in incident reporting occurred after switching to fully online incident reporting from an initial hybrid paper-electronic system. Incident templating functionality and a connection with our center's oncology information system were incorporated into the investigation interface to minimize repetitive data entry. A taskable actions feature was also incorporated to document outcomes of incident reports and has since been utilized for 36% of reported incidents. CONCLUSIONS: Use of SaILS and the NSIR-RT taxonomy has improved the structure of, and staff engagement with, incident learning in our center. Software and workflow modifications informed by staff feedback improved the utility of SaILS and yielded an efficient and transparent solution to categorize incidents with the NSIR-RT taxonomy.

Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results.

PURPOSE: Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. METHODS AND MATERIALS: Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. RESULTS: The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. CONCLUSIONS: The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

Late radiation toxicity in Hodgkin lymphoma patients: proton therapy's potential.

In 2010, all young patients treated for intrathoracic Hodgkin lymphoma (HL) at one of 10 radiotherapy centers in the province of Quebec received 3D conformal photon therapy. These patients may now be at risk for late effects of their treatment, notably secondary malignancies and cardiac toxicity. We hypothesized that more complex radiotherapy, including intensity-modulated proton therapy (IMPT) and possibly IMRT (in the form of helical tomotherapy (HT)), could benefit these patients. With institutional review board approval at 10 institutions, all treatment plans for patients under the age of 30 treated for HL during a six-month consecutive period of 2010 were retrieved. Twenty-six patients were identified, and after excluding patients with extrathoracic radiation or treatment of recurrence, 20 patients were replanned for HT and IMPT. Neutron dose for IMPT plans was estimated from published measurements. The relative seriality model was used to predict excess risk of cardiac mortality. A modified linear quadratic model was used to predict the excess absolute risk for induction of lung cancer and, in female patients, breast cancer. Model parameters were derived from published data. Predicted risk for cardiac mortality was similar among the three treatment techniques (absolute excess risk of cardiac mortality was not reduced for HT or IMPT (p > 0.05, p > 0.05) as compared to 3D CRT). Predicted risks were increased for HT and reduced for IMPT for secondary lung cancer (p < 0.001, p < 0.001) and breast cancers (p< 0.001, p< 0.001) as compared to 3D CRT.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PURPOSE: We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. PATIENTS AND METHODS: Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. RESULTS: In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). CONCLUSION: The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.

A novel approach to total skin irradiation using helical TomoTherapy.

PURPOSE: To describe our experience with a novel technique for total skin irradiation using helical TomoTherapy (Accuray, Sunnyvale, CA). METHODS AND MATERIALS: An infant with refractory acute myelogenous leukemia with extensive cutaneous involvement was given total skin irradiation using inverse-planned helical tomotherapy. Quality assurance tests to determine the deliverability of the technique and the accuracy of dose estimation at the superficial skin level were devised and performed. Daily megavoltage imaging, tomotherapy plan adaptive evaluation, in vivo skin dose measurements, and cumulative dose summation were tools employed to assess the quality of treatment and positioning reproducibility on a daily basis. RESULTS: The quality assurance checks showed that tomotherapy can indeed be used for total skin irradiation in cases where conventional electron treatment delivery is not possible. However, the overestimation of absorbed dose near surface by the treatment planning software must be quantified and taken into account using in-phantom and in vivo dosimetry techniques with appropriate detectors. Daily imaging allows for superior positioning, while daily plan adaptive and dose summations based on the plan adaptive calculations allow for evaluation of the treatment delivery. CONCLUSIONS: An infant has been treated successfully using helical TomoTherapy for total skin irradiation prior to allogeneic stem cell transplant. The course of treatment was uncomplicated and the patient is doing well more than 15 months following therapy.

Institutional experience with a rotational total skin electron irradiation (RTSEI) technique-A three decade review (1981-2012).

Total skin electron irradiation (TSEI) for patients with cutaneous lymphomas is technically challenging, and numerous approaches have been developed to overcome the many field matching problems associated with such a large and complex treatment volume. Since 1981 we have delivered TSEI using a rotational total skin electron irradiation (RTSEI) technique in conjunction with patch, treat and boost fields in order to provide complete skin and dose coverage. Initially we used a 6 MeV electron beam at an extended source-skin distance (SSD) on a modified linear accelerator. More recently we began using a high dose rate electron mode on a commercially available linear accelerator. The RTSEI technique allows the delivery of a seamless surface dose to the majority of the patient's skin surface in a single treatment. In this review paper we present our three-decade experience with the technical development, dosimetry, treatment delivery and clinical outcomes of our RTSEI technique.

Skin elasticity as a measure of radiation fibrosis: is it reproducible and does it correlate with patient and physician-reported measures?

Current means of measuring RT-induced fibrosis are subjective. We evaluated the DermaLab suction cup system to measure objectively skin deflection as a surrogate for fibrosis. Sixty-nine patients with E-STS were treated with limb-sparing surgery and 50-66 Grays (Gy) of RT. Using a "scleroderma" DermaLab Suction Cup, the skin stiffness was measured by two clinicians. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale, the Musculoskeletal Tumor Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) questionnaires were completed for each patient. Levels of agreement between measurers were estimated using the Kappa (k) coefficient and the concordance correlation coefficient (CCC). All sixty-nine patients were included. The level of agreement between measurers for NCI-CTCAE grading was moderate (range k = 0.41-0.59). The CCC for the elasticity measurements were higher, with CCC = 0.82 for fibrotic skin and CCC 5 0.84 for normal skin. The elasticity measurements were significantly higher when MSTS scores were <30 and or TESS scores were <90. Suction Cup measurement of skin elasticity is more reproducible than CTCAE grading and shows promise in generating reproducible measurements for radiation-induced skin fibrosis. Furthermore, it correlates well with the MSTS and TESS.

FDG PET/CT in Initial Staging of Adult Soft-Tissue Sarcoma.

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.

Dosimetric study of current treatment options for radiotherapy in retinoblastoma.

PURPOSE: To determine the best treatment technique for patients with retinoblastoma requiring radiotherapy to the whole eye. METHODS AND MATERIALS: Treatment plans for 3 patients with retinoblastoma were developed using 10 radiotherapy techniques including electron beams, photon beam wedge pair (WP), photon beam three-dimensional conformal radiotherapy (3D-CRT), fixed gantry intensity-modulated radiotherapy (IMRT), photon volumetric arc therapy (VMAT), fractionated stereotactic radiotherapy, and helical tomotherapy (HT). Dose-volume analyses were carried out for each technique. RESULTS: All techniques provided similar target coverage; conformity was highest for VMAT, nine-field (9F) IMRT, and HT (conformity index [CI] = 1.3) and lowest for the WP and two electron techniques (CI = 1.8). The electron techniques had the highest planning target volume dose gradient (131% of maximum dose received [D(max)]), and the CRT techniques had the lowest (103% D(max)) gradient. The volume receiving at least 20 Gy (V(20Gy)) for the ipsilateral bony orbit was lowest for the VMAT and HT techniques (56%) and highest for the CRT techniques (90%). Generally, the electron beam techniques were superior in terms of brain sparing and delivered approximately one-third of the integral dose of the photon techniques. CONCLUSIONS: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques.

Ductal carcinoma in situ--the influence of the radiotherapy boost on local control.

PURPOSE: Local recurrence (LR) of ductal carcinoma in situ (DCIS) is reduced by whole-breast irradiation after breast-conserving surgery (BCS). However, the benefit of adding a radiotherapy boost to the surgical cavity for DCIS is unclear. We sought to determine the impact of the boost on LR in patients with DCIS treated at the McGill University Health Centre. METHODS AND MATERIALS: A total of 220 consecutive cases of DCIS treated with BCS and radiotherapy between January 2000 and December 2006 were reviewed. Of the patients, 36% received a radiotherapy boost to the surgical cavity. Median follow-up was 46 months for the boost and no-boost groups. Kaplan-Meier survival analyses and Cox regression analyses were performed. RESULTS: Compared with the no-boost group, patients in the boost group more frequently had positive and <0.1-cm margins (48% vs. 8%) (p < 0.0001) and more frequently were in higher-risk categories as defined by the Van Nuys Prognostic (VNP) index (p = 0.006). Despite being at higher risk for LR, none (0/79) of the patients who received a boost experienced LR, whereas 8 of 141 patients who did not receive a boost experienced an in-breast LR (log-rank p = 0.03). Univariate analysis of prognostic factors (age, tumor size, margin status, histological grade, necrosis, and VNP risk category) revealed only the presence of necrosis to significantly correlate with LR (log-rank p = 0.003). The whole-breast irradiation dose and fractionation schedule did not affect LR rate. CONCLUSIONS: Our results suggest that the use of a radiotherapy boost improves local control in DCIS and may outweigh the poor prognostic effect of necrosis.

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone.

PURPOSE: Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients. MATERIAL AND METHODS: Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA+2 ng/mL. RESULTS: With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ≥ 2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity. CONCLUSION: HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.

Adjuvant radiotherapy in the treatment of pediatric myxopapillary ependymomas.

OBJECTIVES: Assess the role of radiotherapy (RT) in the management of primary and recurrent myxopapillary ependymoma (MPE). MATERIALS AND METHODS: We conducted a retrospective review of patients with MPE treated at the Montreal Children's Hospital/McGill University Health Centre between 1985 and 2008. RESULTS: Seven children under the age of 18 were diagnosed and treated for MPE. All patients were treated with surgery to the primary site. Three patients underwent subtotal resection (STR) and received adjuvant post-operative RT. Only one patient who had spinal drop metastases received post-operative RT to the lumbosacral region following complete resection of the primary tumor. After a median follow up of 78 months (range 24-180 months), all patients were alive with controlled disease. The single patient treated with gross total resection (GTR) and adjuvant local radiation remained recurrence free. One of the three patients treated with STR and adjuvant RT had disease progression that was controlled with re-resection and further RT. Two of the three patients treated with surgery alone developed local and disseminated recurrent spinal disease that was controlled by salvage RT. CONCLUSION: Our data support the evolving literature which suggests that GTR alone provides suboptimal disease control in MPE. In our patients, RT resulted in control of residual, metastatic and/or recurrent disease. Routine adjuvant RT may improve outcomes in pediatric MPE.

Feasibility and early outcomes of supine-position craniospinal irradiation.

From 2000-2007, we treated 14 patients (median age 5.8 years) with medulloblastoma (MB) with craniospinal irradiation (CSI) in the supine position for comfort, setup reproducibility and anaesthesia airway access. Acute toxicity included nausea/vomiting (N = 9), weight loss (median 10.3% (2.2-18.2), N = 10), lymphopenia (all), neutropenia (N = 3) and pancreatitis with Mallory-Weiss tear (N = 1). Five children required hospitalization during treatment. Chemotherapy was adjusted in 6, without CSI delay. After a median follow-up of 32.4 months (13.3-83.2), two patients recurred, two died of a second CNS malignancy, and one developed leukaemia. All others remain in complete remission. In this small series, CSI was delivered safely in the supine position with early outcomes in line with classical CSI literature.

PET/CT for radiotherapy treatment planning in patients with soft tissue sarcomas.

PURPOSE: To study the possibility of incorporating positron emission tomography/computed tomography (PET/CT) information into radiotherapy treatment planning in patients with high-grade soft tissue sarcomas (STS). METHODS AND MATERIALS: We studied 17 patients treated with preoperative radiotherapy at our institution from 2005 to 2007. All patients had a high-grade STS and had had a staging PET/CT scan. For each patient, an MRI-based gross tumor volume (GTV), considered to be the contemporary standard for radiotherapy treatment planning, was outlined on a T1-gadolinium enhanced axial MRI (GTV(MRI)), and a second set of GTVs were outlined using different threshold values on PET images (GTV(PET)). PET-based target volumes were compared with the MRI-based GTV. Threshold values for target contouring were determined as a multiple (from 2 to 10 times) of the background soft tissue uptake values (B) sampled over healthy tissue. RESULTS: PET-based GTVs contoured using a threshold value of 2 or 2.5 most closely resembled the GTV(MRI) volumes. Higher threshold values lead to PET volumes much smaller than the GTV(MRI). The standard deviations between the average volumes of GTV(PET) and GTV(MRI) ratios for all thresholds were large, ranging from 36% for 2 xB up to 93% for 10 xB. Maximum uptake-to-background ratio correlated poorly with the maximum standardized uptake values. CONCLUSIONS: It is unlikely that PET/CT will make a significant contribution in GTV definition for radiotherapy treatment planning in patients with STS using threshold methods on PET images. Future studies will focus on molecular imaging and tumor physiology.