Estimating dose delivery accuracy in stereotactic body radiation therapy: A review of in-vivo measurement methods.

Stereotactic body radiation therapy (SBRT) has been recognized as a standard treatment option for many anatomical sites. Sophisticated radiation therapy techniques have been developed for carrying out these treatments and new quality assurance (QA) programs are therefore required to guarantee high geometrical and dosimetric accuracy. This paper focuses on recent advances on in-vivo measurements methods (IVM) for SBRT treatment. More specifically, all of the online QA methods for estimating the effective dose delivered to patients were compared. Determining the optimal IVM for performing SBRT treatments would reduce the risk of errors that could jeopardize treatment outcome. A total of 89 papers were included. The papers were subdivided into the following topics: point dosimeters (PD), transmission detectors (TD), log file analysis (LFA), electronic portal imaging device dosimetry (EPID), dose accumulation methods (DAM). The detectability capability of the main IVM detectors/devices were evaluated. All of the systems have some limitations: PD has no spatial data, EPID has limited sensitivity towards set-up errors and intra-fraction motion in some anatomical sites, TD is insensitive towards patient related errors, LFA is not an independent measure, DAMs are not always based on measures. In order to minimize errors in SBRT dose delivery, we recommend using synergic combinations of two or more of the systems described in our review: on-line tumor position and patient information should be combined with MLC position and linac output detection accuracy. In this way the effects of SBRT dose delivery errors will be reduced.

Salvage radiation therapy after radical prostatectomy: survival analysis.

BACKGROUND: To evaluate the outcome of patients treated with salvage radiotherapy after radical prostatectomy and to investigate the effects of independent predictors on survival. METHODS: From January 2000 to December 2015, 234 patients with biochemical/clinical recurrences after radical prostatectomy were submitted to salvage radiotherapy (SRT). One hundred and fifty-seven patients (67%) received three-dimensional (3D) conformal radiotherapy while 77 patients (33%) were treated with intensity-modulated radiotherapy (IMRT) or IMRT/image-guided radiotherapy by tomotherapy. The median RT dose to prostate bed was 70.2 Gy (range: 66-79 Gy). The investigated endpoints were biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS). Different covariates were considered to investigate predictors of survival. RESULTS: With a median follow-up of 117 months the BRFS, CRFS, DMFS and PCSS at 10 years were 54%, 84%, 90%, and 94%, respectively. In multivariate analysis (MVA), the pathological Gleason Score (pGS) was the most important factor affecting BRFS, CRFS, DMFS and PCSS (P<0.007, HR>1.55); pathological stage (pT) was predictor of BRFS (P=0.007, HR=1.7) and PCSS (P=0.02, HR=4.2), and the last prostate-specific antigen during follow-up was an important survival predictor of CRFS (P=0.004, HR=1.26) and PCSS (P<0.0001, HR=1.04). The time between surgery and the start of SRT was correlated with BRFS (P<0.0001, HR=0.987) and CRFS (P=0.047, HR=0.989). In univariate analysis (UVA), positive surgical margins at the prostatectomy specimen improved BRFS (P=0.01, HR=0.54), CRFS (P=0.05, HR=0.46) and DMFS (P=0.005, HR=0.13) after SRT. CONCLUSIONS: At long-term follow-up, excellent outcome results of SRT on BRFS, CRFS, DMFS, and PCSS were obtained. Several prognostic factors such as pGS, pT and surgical margin status were found to be predictors of survival.

Comparison of two different EPID-based solutions performing pretreatment quality assurance: 2D portal dosimetry versus 3D forward projection method.

PURPOSE: The aim of this paper is to characterize two different EPID-based solutions for pre-treatment VMAT quality assurance, the 2D portal dosimetry and the 3D projection technique. Their ability to catch the main critical delivery errors was studied. METHODS: Measurements were performed with a linac accelerator equipped with EPID aSi1000, Portal Dose Image Prediction (PDIP), and PerFRACTION softwares. Their performances were studied simulating perturbations of a reference plan through systematic variations in dose values and micromultileaf collimator position. The performance of PDIP, based on 2D forward method, was evaluated calculating gamma passing rate (%GP) between no-error and error-simulated measurements. The impact of errors with PerFRACTION, based on 3D projection technique, was analyzed by calculating the difference between reference and perturbed DVH (%ΔD). Subsequently pre-treatment verification with PerFRACTION was done for 27 patients of different pathologies. RESULTS: The sensitivity of PerFRACTION was slightly higher than sensitivity of PDIP, reaching a maximum of 0.9. Specificity was 1 for PerFRACTION and 0.6 for PDIP. The analysis of patients' DVHs indicated that the mean %ΔD was (1.2 ±â€¯1.9)% for D2%, (0.6 ±â€¯1.7)% for D95% and (-0.0 ±â€¯1.2)% for Dmean of PTV. Regarding OARs, we observed important discrepancies on DVH but that the higher dose variations were in low dose area (<10 Gy). CONCLUSIONS: This study supports the introduction of the new 3D forward projection method for pretreatment QA raising the claim that the visualization of the delivered dose distribution on patient anatomy has major advantages over traditional portal dosimetry QA systems.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

BACKGROUND: The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). METHODS: From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. RESULTS: The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. CONCLUSIONS: The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Technical Note: Multicenter study of TrueBeam FFF beams with a new stereotactic diode: Can a common small field signal ratio curve be defined?

PURPOSE: Small radiation fields (<30 mm) are typically involved in stereotactic body radiation therapy procedures. Output factor measurements are subjected to large uncertainties. The signal ratio (SR) readings, defined as the ratio of central axis reading, respectively, in the actual field size and in the reference field size, were evaluated in several centers and a common mathematical description of the SR curve was investigated. METHODS: A couple of new unshielded stereotactic diodes (Razor, IBA) was tested under eight different TrueBeams using 10 MV flattering filter free beams with high dose rate (2400 MU/min). Small fields, ranging from 6 to 50 mm, were analyzed in terms of profiles and central axis point measurements. SRs were normalized to 30 mm field and were calculated as a function of nominal field size (NFS) and effective field size (EFS). From SRs acquired using Razor1 (four centers), a theoretical equation was extrapolated. Three centers with Razor2 were used to test the mathematical relationship. Finally, the two diodes were directly compared in the last center. RESULTS: The EFS was systematically smaller than NFS (p < 0.01) for all field size ranges, with mean difference of 0.9 ± 0.5 mm. The SR fits using the NFS and EFS had, respectively, R2 = 0.989 and R2 ≫ 0.999. The Razor2 centers' mean deviation from the predicted SRs, using the NFS and EFS fits, was, respectively, 3.4% and 0.5%. The maximum deviations were 5.0% (6 mm field size) for NFS and 1.9% for EFS. Maximum deviation of 0.5% between the two Razors was observed. CONCLUSIONS: EFS measurements were confirmed to be mandatory when comparing SRs over different centers. An equation establishing a functional relation between SRs and the EFS was obtained and tested for the new Razor diode.

Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology).

PURPOSE: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care. MATERIAL AND METHODS: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1. Taking care and multidisciplinary approach, 2. Radiotherapy treatment and brachytherapy, 3. Follow-up. RESULTS: Nineteen centers treated gynecological malignancies and 12 of these had a multidisciplinary dedicated team. Radiotherapy option has been used in all clinical setting: definitive, adjuvant, and palliative. In general, 1978 patients were treated. There were 834 brachytherapy (BRT) treatments. The fusion between diagnostic imaging (magnetic resonance imaging - MRI, positron emission tomography - PET) and computed tomography (CT) simulation was used for contouring in all centers. Conformal RT and intensity modulated radiation therapy (IMRT) were the most frequent techniques. The image guided radiation therapy (IGRT) was used in 10/19 centers. There were 8 active BRT centers. Brachytherapy was performed both with radical intent and as boost, mostly by HDR (6/8 centers). The doses for exclusive BRT were between 20 to 30 Gy. The doses for BRT boost were between 10 and 20 Gy. Four centers used CT-MRI compatible applicators but only one used MRI for planning. The BRT plans on vaginal cuff were still performed on traditional radiographies in 2 centers. The plan sum was evaluated in only 1 center. Only 1 center performed in vivo dosimetry. CONCLUSIONS: In the last three years, multidisciplinary approach, contouring, treatment techniques, doses, and control systems were similar in Liguria-Piedmont and Valle d'Aosta. However, the technology implementation didn't translate in a real treatment innovation so far.

External beam radiotherapy with dose escalation in 1080 prostate cancer patients: definitive outcome and dose impact.

BACKGROUND: The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years. METHODS: From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months. RESULTS: For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%. CONCLUSIONS: The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.

A pre-treatment quality assurance survey on 384 patients treated with helical intensity-modulated radiotherapy.

The gamma index pass rate (%GP) of 384 helical Tomotherapy pre-patient quality assurance, acquired with ArcCHECK, is presented, analyzed, and correlated to plan characteristics. Average %GP was higher than 90% and correlated strongly with gamma method, irradiated length, pitch, maximum dose to diodes, and dose per fraction.

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally. METHODS: A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities. RESULTS: Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication. CONCLUSIONS: In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.

Clinical and technical feasibility of ultra-boost irradiation in Dominant Intraprostatic Lesion by Tomotherapy: preliminary experience and revision of literature.

BACKGROUND: The aim of this paper was to present our experience of dominant intraprostatic lesions (DIL) irradiation up to an EQD2 of 93,2 Gy with helical tomotherapy. METHODS: Between March 2012 and December 2014, 15 staged II-III patients with intermediate-high risk prostate cancer were enrolled in our protocol of DIL dose escalation by Tomotherapy. All patients were submitted to a multiparametric MRI (including DCE and DWI series), in order to visualize DILs. Considering a mean α/ß ratio of 3 for prostate cancer the prescribed doses were: 83.2 Gy in 32 fractions of 2.6 per fraction (EQD2=93.2 Gy) on the DILs, 75.2 Gy in 32 fractions of 2.35 Gy per fraction (EQD2=80.5 Gy) on the prostate gland and 67.2 Gy in 32 fraction of 2.1 (EQD2=68.5 Gy) on the seminal vesicles. RESULTS: With a mean follow-up of 16 months (range 2-39), no overall severe acute toxicities >G3 were observed; one patient out of 15 (6.6%) had acute gastrointestinal (GI) toxicity equal to G2, while two cases (13.3%) had G2 acute genitourinary (GU) toxicity. No >G2 late toxicity was observed. At last follow-up, for all patients, the biochemical disease free survival was 100%. CONCLUSIONS: The irradiation of the whole prostate and seminal vesicles up to an EQD2 of 80.5 Gy and of DILs up to 93.2 Gy was clinically feasible and safe, without acute severe toxicity. Although with a short follow-up, late toxicities are currently absent and no patient relapsed.

Tomotherapy PET-guided dose escalation: A dosimetric feasibility study for patients with malignant pleural mesothelioma.

AIM: The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). MATERIAL AND METHODS: We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV1) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV2). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV1 and 56 Gy (2.24 Gy/fraction) to the PTV2, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. RESULTS: For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V20, V30, and V40 DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). CONCLUSION: The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs.

Erratum to: Tomotherapy PET-guided dose escalation--A dosimetric feasibility study for patients with malignant pleural mesothelioma.

Unfortunately, erroneous author affiliations were published in the article "Tomotherapy PET-guided dose escalation ­ A dosimetric feasibility study for patients with malignant pleural mesothelioma". The correct list of author affiliations reads as follows: Angelo Maggio 1, Claudia Cutaia 1, Amalia Di Dia 1, Sara Bresciani 1, Anna Miranti 1, Matteo Poli 1, Elena Delmastro 2, Elisabetta Garibaldi 2, Pietro Gabriele 2 and Michele Stasi 1. 1: Medical Physics Department, Candiolo Cancer Institute ­ FPO, IRCCS, Turin, Italy. 2: Radiotherapy Department, Candiolo Cancer Institute ­ FPO, IRCCS, Turin, Italy. We apologize for any inconveniences caused.

Tomotherapy treatment plan quality assurance: the impact of applied criteria on passing rate in gamma index method.

PURPOSE: Pretreatment patient plan verification with gamma index (GI) metric analysis is standard procedure for intensity modulated radiation therapy (IMRT) treatment. The aim of this paper is to evaluate the variability of the local and global gamma index obtained during standard pretreatment quality assurance (QA) measurements for plans performed with Tomotherapy unit. The QA measurements were performed with a 3D diode array, using variable passing criteria: 3%∕3 mm, 2%∕2 mm, 1%∕1 mm, each with both local and global normalization. METHODS: The authors analyzed the pretreatment QA results for 73 verifications; 37 were prostate cancer plans, 16 were head and neck plans, and 20 were other clinical sites. All plans were treated using the Tomotherapy Hi-Art System. Pretreatment QA plans were performed with the commercially available 3D diode array ArcCHECK™. This device has 1386 diodes arranged in a helical geometry spaced 1 cm apart. The dose measurements were acquired on the ArcCHECK™ and then compared with the calculated dose using the standard gamma analysis method. The gamma passing rate (%GP), defined as the percentage of points satisfying the condition GI < 1, was calculated for different criteria (3%∕3 mm, 2%∕2 mm, 1%∕1 mm) and for both global and local normalization. In the case of local normalization method, the authors set three dose difference threshold (DDT) values of 2, 3, and 5 cGy. Dose difference threshold is defined as the minimum absolute dose error considered in the analysis when using local normalization. Low-dose thresholds (TH) of 5% and 10% were also applied and analyzed. RESULTS: Performing a paired-t-test, the authors determined that the gamma passing rate is independent of the threshold values for all of the adopted criteria (5%TH vs 10%TH, p > 0.1). Our findings showed that mean %GPs for local (or global) normalization for the entire study group were 93% (98%), 84% (92%), and 66% (61%) for 3%∕3 mm, 2%∕2 mm, and 1%∕1 mm criteria, respectively. DDT was equal to 2 cGy for the local normalization analysis cases. The authors observed great variability in the resulting %GP. With 3%∕3 mm gamma criteria, the overall passing rate with local normalization was 4.6% less on the average than with global one, as expected. The wide difference between %GP calculated with global or local approach is also confirmed by an unpaired t-test statistical analysis. CONCLUSIONS: The variability of %GP obtained confirmed the necessity to establish defined agreement criteria that could be universal and comparable between institutions. In particular, while the gamma passing rate does not depend on the choice of threshold, the choice of DDT strongly influences the gamma passing rate for local calculations. The difference between global and local %GP was statistically significant for prostate and other treatment sites when DDT was changed from 2 to 3 cGy.

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study.

BACKGROUND: The aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated. METHODS: Twenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60-70.5 Gy (2-2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6-22 months). RESULTS: The treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity). CONCLUSIONS: With our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area.

Impact of age at diagnosis on overall and disease-free survival in men with prostate cancer following conformal 3D radiation therapy.

AIMS AND BACKGROUND: The impact of age on prostate cancer outcome has been controversial. The aim of the study was to evaluate the role of age on overall survival and disease-free survival in patients affected by prostate cancer when treated with 3D conformal radiation therapy. METHODS AND STUDY DESIGN: From 1999 to 2005, 1002 patients with T1-T3 prostate cancer were treated with 3D conformal radiation therapy, delivering a median dose of 75.6, 66.6 and 45 Gy to the prostate, seminal vesicles and pelvic nodes (if necessary), respectively. Patients were divided into four groups (<65, 65-70, 70-75, >75 years) according to age at diagnosis. The relationship between age and both overall survival and disease-free survival was calculated with Kaplan-Meier analysis and the comparison between curves was performed by the logrank test. ROC analysis allowed assessment of the best age cutoff. RESULTS: Mean age was 71 ± 6 years (median, 72). Median and mean follow-up was 71.4 and 69 months, respectively. In multivariate analysis, there was no significant difference in the distribution of disease risk between age groups. Analysis demonstrated that older age is a strong positive predictor of survival (odds ratio for stratified patients older than 70 years was <1). In fact, at the 90 month follow-up, overall survival and disease-free survival varied with age, increasing from 85% to 95% and from 78% to 94%, respectively. ROC curve analysis yielded a cutoff age value discriminating overall survival and disease-free survival of 72 years. CONCLUSIONS: Age is a strong positive predictor of overall survival and disease-free survival, playing a protective role for stratified patients up to 72 years of age.

Hereditary paraganglioma syndrome associated with SDHD gene mutations: a patient with multicentric presentation treated with radiotherapy. Case report.

INTRODUCTION: Extra-adrenal paragangliomas are rare tumors arising from neuroendocrine cells. Sporadic and hereditary forms have been recognized. Among the latter, the PGL1 and PGL4 syndromes are associated with a high risk of multiple localizations. The treatment of choice for paragangliomas is surgical resection, but in some cases surgery can be difficult due to particular or multiple tumor sites or may result in severe neurological deficits. In such cases radiotherapy can be an effective alternative. In this paper we describe the case of a patient affected by hereditary paraganglioma syndrome with multicentric presentation who was treated at our center by external radiotherapy. CASE REPORT: A 55-year-old man presented in April 2008 with multiple paragangliomas: one in the left pontocerebellar angle, two in the middle neck, one mediastinal paraaortic mass, and an abdominal paraaortic lesion. The left pontocerebellar and mediastinal tumors were treated with three-dimensional conformal radiotherapy (3D-CRT) at total doses of 50.40 Gy and 55.80 Gy, respectively. The neck lesions were treated with intensity-modulated radiotherapy (IMRT) at a total dose of 55.80 Gy. The abdominal paraaortic lesion was surgically resected. RESULTS: No severe acute or late toxicity as evaluated with the EORTC-RTOG scale was observed. Fourteen months after the end of radiotherapy a whole body CT scan showed that the tumor lesions were stable in size and in their relations to contiguous structures. The arterial pressure was controlled by medical therapy and urine catecholamine levels were within the normal range. CONCLUSIONS: We believe that in patients affected by unresectable paragangliomas radiotherapy is a safe and effective alternative to surgery. The use of high-dose conformity techniques such as 3D-CRT and IMRT will allow higher local control rates with relatively few side effects thanks to the possibility of dose escalation and reduction of the amount of irradiated healthy tissues.

Quality assurance of a record-and-verify system.

AIMS AND BACKGROUND: With the introduction of more complex three-dimensional conformal radiotherapy and intensity-modulated radiotherapy techniques in clinical practice, the use of record-and-verify systems is recommended to improve the accuracy of radiotherapy treatments. The aim of the present study was to evaluate, for a commercial record-and-verify system, the efficiency, integration with the treatment planning system, and impact of manual checking of data. The most frequent errors or misses were also evaluated. MATERIALS AND METHODS: The development of internal protocols to systematically implement new technologies has been identified as a priority in the departmental quality assurance process. Data electronically fed into the record-and-verify system were compared with those manually recorded in the clinical paper chart over a period of almost 6 years (October 2000 to December 2006). A total of 7768 treated patients was reviewed. The check was performed by using a homemade data base in which the errors are stratified as follows: 1) general section, 2) geometric and dosimetric section, and 3) delivered dose section. RESULTS: On a total of 7768 checked patients, one or more mismatches between treatment planning system data and record-and-verify system data or paper chart data were observed for 452 patients (5.8% of total number of inspected patients). The percentage of discrepancies out of the total was: 2.2% in the general section, 3.3% in the dosimetric and geometric section, and 4.2% in the delivered-dose section. CONCLUSIONS: Although record-and-verify systems assume a crucial role in the accuracy and reproducibility of radiation treatment, their inability to eradicate all the errors requires vigilance on the part of the radiation therapy and physics team.

Radiotherapy after partial laryngectomy: an analysis of 36 cases and a proposal to optimize radiotherapy.

AIMS AND BACKGROUND: Laryngeal cancer treatment options include radical surgery, "organ preservation surgery", radiotherapy and chemotherapy. There is no proven evidence of a significant increase in late toxicity with adjuvant radiotherapy after conservative surgery. The aim of this retrospective study was to evaluate the toxicity, local-regional control and overall survival of adjuvant radiotherapy after conservative surgery. METHODS: A total of 36 patients was treated with radiotherapy after partial laryngectomy at the Radiotherapy Department of the Institute for Cancer Treatment and Research (IRCC) of Candiolo and of the Mauriziano Hospital in Turin, between 1994 and 2007. The postoperative treatment doses ranged from 45 to 70.2 Gy with conventional fractionation. The Kaplan-Meier method was applied for statistical analysis. The RTOG-EORTC scale was used to evaluate late and acute toxicity. RESULTS: Overall 5- and 10-year survival was 93% and 47%, respectively. Local control was 93.5% at 5 and was unchanged at 10 years. Grade 2 acute cutaneous and mucous toxicity was 41% and 62%, and grade 3, 6.9% and 3.5%, respectively. Only one patient required percutaneous endoscopic gastrostomy due to severe dysphagia and one patient required temporary tracheostomy for severe acute laryngeal edema (grade 3). Two patients experienced late toxicity greater than grade 3. The median dose to the residual larynx was 59.5 Gy (range, 45-70.2), and the median dose to the neck was 50.4 Gy (range, 39.6 -55.8). CONCLUSIONS: The results of our study showed a dose-dependent increase in the late toxicity trend at doses over and above 60 Gy, which is higher than the cutoff dose reported in the literature. There was no indication from our data that adjuvant postoperative radiotherapy means additional toxicity. The use of highly conformal techniques can further reduce toxicity of the radiotherapy.

Dosimetric evaluation of a commercial 3D treatment planning system using the AAPM Task Group 23 test package.

The accuracy of the dose calculation algorithm is one of the most critical steps in assessing the radiotherapy treatment to achieve the 5% accuracy in dose delivery, which represents the suggested limit to increase the complication-free local control of tumor. We have used the AAPM Task Group 23 (TG-23) test package for clinical photon external beam therapy to evaluate the accuracy of the new version of the PLATO TPS algorithm. The comparison between tabulated values and calculated ones has been performed for 266 and 297 dose values for the 4 and 18 MV photon beams, respectively. Dose deviations less than 2% were found in the 98.5%- and 90.6% analyzed dose points for the two considered energies, respectively. Larger deviations were obtained for both energies, in large dose gradients, such as the build-up region or near the field edges and blocks. As far as the radiological field width is concerned, 64 points were analyzed for both the energies: 53 points (83%) and 64 points (100%) were within +/-2 millimeters for the 4 and 18 MV photon beams, respectively. The results show the good accuracy of the algorithm either in simple geometry beam conditions or in complex ones, in homogeneous medium, and in the presence of inhomogeneities, for low and high energy beams. Our results fit well the data reported by several authors related to the calculation accuracy of different treatment planning systems (TPSs) (within a mean value of 0.7% and 1.2% for 4 and 18 MV respectively). The TG-23 test package can be considered a powerful instrument to evaluate dose calculation accuracy, and as such may play an important role in a quality assurance program related to the commissioning of a new TPS.