Diarrhoea in irradiated patients: a prospective multicentre observational study.

AIMS: To determine the incidence of cancer treatment-induced diarrhoea in patients submitted to irradiation. METHODS: Forty-five Italian radiation oncology departments took part in this prospective observational study and a total of 1020 patients were enrolled. The accrual lasted three consecutive weeks; evaluation was based on diary cards filled in daily by patients during radiotherapy and one week after cessation. Diary cards recorded both the onset and intensity of diarrhoea. RESULTS: A total of 1004 patients were eligible for this analysis. 147/1004 (14.6%) patients had diarrhoea. The median minimum number of daily events was 1 (range 1-7) with a median maximum events of 3 (range 1-23). 82/147 patients (56.2%) had a drug prescription for diarrhoea. In the evaluation of the onset of diarrhoea, in multivariate analysis, we found the following factors to be statistically significant predictors of an increased likelihood of diarrhoea: primitive tumour site, therapeutic purpose and field size. CONCLUSIONS: Patients with abdominal-pelvic cancer, treated with curative purpose and using large field sizes are at high risk of cancer treatment-induced diarrhoea. Diarrhoea was also observed in patients treated at other sites. In this population group there is the need for more stringent monitoring during the delivery of radiation therapy.

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.

Irradiation of pacemakers and cardio-defibrillators in patients submitted to radiotherapy: a clinical experience.

AIMS AND BACKGROUND: A prospective analysis was carried out on a group of irradiated patients with pacemakers or implantable cardioverter-defibrillators to identify any relationship between the various types of devices and physical and dosimetric parameters. Cardiac toxicity of the treatment was also investigated. METHODS AND STUDY DESIGN: Forty-five irradiated patients, implanted with pacemakers or implantable cardioverter-defibrillators, were prospectively investigated from 1999 to 2007. An analysis of radiation damage to pacemakers, depending on the geometric and dosimetric characteristics of the radiation beams, was carried out. The electric and magnetic fields of linear accelerators (LINACs) were measured to evaluate any interference. The calculation of dose received by pacemakers was evaluated by dose-volume histograms. RESULTS: No dysfunction was observed in any pacemaker, nor were the substitution times negatively affected. We did not find problems with the devices due to the interaction with the electromagnetic fields. Dose-volume histograms calculated for patients treated in regions close to devices (head & neck, thorax) showed an average maximum dose equal to 2.5 Gy for the head & neck area and equal to 1.8 Gy for the thoracic area. Acute (3 cases) and late (2 cases) cardiac events were observed only in 5 patients who underwent chemoradiation treatment, but no dysfunction was observed in any pacemaker. CONCLUSIONS: Our study confirms the safety of radiotherapy for patients implanted with pacemakers or implantable cardioverter-defibrillators but suggests that chemoradiation represents a probable risk factor for cardiac toxicity. Furthermore, all cardiac events were observed in patients treated in the head and'neck or left thoracic areas. A standardized protocol is advisable in order to improve patient control during the radiotherapy treatment. It is mandatory to calculate the dose received at the pacemaker/heart, even in the case of palliative treatment.

A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres.

PURPOSE: A prospective observational multicentre trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and to evaluate the use of antiemetic drugs in patients treated with radiotherapy or concomitant radio-chemotherapy. The application in clinical practice of the Multinational Association of Supportive Care in Cancer guidelines was also studied. MATERIALS AND METHODS: Forty-five Italian radiation oncology centres took part in this trial. The accrual lasted for 3 consecutive weeks and only patients starting radiotherapy or concomitant radio-chemotherapy in this period were enrolled. Evaluation was based on diary card filled in daily by patients during treatment and one week after stopping it. Diary card recorded the intensity of nausea/vomiting and prophylactic/symptomatic antiemetic drug prescriptions. RESULTS: A total of 1020 patients entered into the trial, and 1004 were evaluable. Vomiting and nausea occurred in 11.0% and 27.1% of patients, respectively, and 27.9% patients had both vomiting and nausea. In multifactorial analysis, the only statistically significant patient-related risk factors were concomitant chemotherapy and previous experience of vomiting induced by chemotherapy. Moreover, two radiotherapy-related factors were significant risk factors for RIE, the irradiated site (upper abdomen) and field size (>400 cm(2)). An antiemetic drug was given only to a minority (17%) of patients receiving RT, and the prescriptions were prophylactic in 12.4% and symptomatic in 4.6%. Different compounds and a wide range of doses and schedules were used. CONCLUSIONS: These data were similar to those registered in our previous observational trial, and the radiation oncologists' attitude in underestimating RIE and under prescribing antiemetics was confirmed.

Comparison of endorectal magnetic resonance imaging, clinical prognostic factors and nomograms in the local staging of prostate cancer patients treated with radiotherapy.

AIMS AND BACKGROUND: To determine retrospectively the role of endorectal magnetic resonance in the staging of prostate cancer. The aim of the study was to assess whether it is possible to identify a group of patients with prostate cancer, chosen for certain prognostic factors, eligible for radiotherapy that could take advantage of endorectal magnetic resonance in staging and therapy management. METHODS: Between January 2002 and December 2005, 143 patients with biopsy proven prostate cancer underwent endorectal magnetic resonance. All patients were initially evaluated considering the following prognostic factors: serum prostate-specific antigen at diagnosis, Gleason score, histological grade, involvement of the seminal vesicle and extracapsular extension using the Roach III and ECE equations. The findings were then compared to the results of endorectal magnetic resonance. RESULTS: The relationship between the variable post-endorectal magnetic resonance stage modification and Gleason score was statistically significant (P = 0.02847). In addition, our study showed a statistically significant correlation between the risk of seminal vesicle involvement according to the Roach III formula and post-endorectal magnetic resonance stage modification (P = 0.01305). Conversely, statistical analysis showed no significant correlation between post-endorectal magnetic resonance stage modification and prostate-specific antigen values (P = 0.83440) or between post-endorectal magnetic resonance stage modification and the risk of extracapsular extension according to the extracapsular extension formula (P = 0.42748). CONCLUSIONS: Our data suggest that endorectal magnetic resonance could be used for staging of the subgroup of patients at high risk of seminal vesicle involvement (> 15%). Although we found a statistical correlation between Gleason score and post-endorectal magnetic resonance stage modification, statistical analysis showed no correlation between any of the subgroups. Therefore, it is not possible at the moment to identify a subgroup of patients by Gleason score that may benefit from endorectal magnetic resonance. In our opinion, extracapsular extension values were not useful to select patients for endorectal magnetic resonance.

Emptying the rectum before treatment delivery limits the variations of rectal dose - volume parameters during 3DCRT of prostate cancer.

PURPOSE: To investigate the impact of rectum motion on dose - volume histograms of the rectum including filling and of the wall (DVH and DWH, respectively), during 3D-conformal radiotherapy (3DCRT) for localized prostate cancer. MATERIALS AND METHODS: Ten patients received a planning CT scan (CT(0)) and 11-14 CT during 3DCRT for prostate cancer (total CT scans=126). CT images were 3D matched using bony anatomy. A single observer drew the external contours of rectum and rectum wall and the CTV (prostate + seminal vesicles) on CT(0). Patients were asked to empty their rectum before every CT, as generally performed at the Institute for Cancer Research and Treatment (IRCC) before treatment delivery. Bladder was kept full by drinking 500 cm(3) of water 60 min before the scan, according to our protocol. A 4-field box 3DCRT technique was planned and dose statistics/dose - volume histograms of the rectum were calculated for each contour referred to CT(0),CT(1),...,CT(n) for each patient. Average DVHs during treatment were calculated along with their standard deviation (SD(rand)) and compared to the planned DVH. The analyses on the patient population included the assessment of systematic deviation (average difference and SD, named SD(sys)) as well as the average SD(rand) value expressing the random component of organ motion. Rectum shifts were also assessed by anterior and lateral BEV projections. RESULTS: As to the rectum, 8/10 patients showed a "better" average DVH than DVH on CT(0). Wilcoxon test showed a statistically significant reduction when correlating the difference Delta between the average DVH during therapy and planning DVH at CT(0): for instance V(70)Delta = -3.6% and p = 0.022, V(50)Delta = -5.5% and p = 0.022, D(med)Delta = -3.2 Gy and p = 0.007. Average values of DVH systematic difference (average difference between planning scan and treatment), standard deviations (SD(sys)) and average standard deviations of the random fluctuation (SD(random)) were -4.0%, 4.7% and 6.6%, respectively. Whilst the fluctuation results were slightly smaller for DWH. Volume analysis showed a slight systematic variation of the rectal volume between planning and treatment BEV. The average rectal volume during therapy was larger than at the planning CT in 8/10 patients. The systematic shifts of the rectal wall between the planning phase and the treatment were rather small, both below and above the flexure. The larger random fluctuation of the rectum shape was found to be in the cranial half (1 SD=4.4 mm). CONCLUSIONS: The practice of carefully emptying the rectum during simulation and therapy for prostate cancer, which is a safe and simple procedure, reduces the impact of organ motion on dose - volume parameters of the rectum.

Are quality indicators for radiotherapy useful in the evaluation of service efficacy in a new based radiotherapy institution?

AIMS AND BACKGROUND: A number of documents assess the need for quality assurance in radiotherapy, which must be constantly monitored and possibly improved. In this regard, a system that confirms the quality of a department has been suggested and quality indicators have been used to improve the quality of the service. The National Health Service (Istituto Superiore di Sanità) approved a National Research Project to increase the quality of radiotherapy. The aim of the present study was to analyze the practical feasibility and efficacy of the quality indicators elaborated by the National Health Service study group in a radiotherapy unit. PATIENTS AND METHODS: The voluntary accredited program was carried out by the Radiotherapy Department of IRCC in Candiolo from June to August 2002. We analyzed 8 of the 13 indicators according to the National Health Service Project. For this purpose, 133 consecutive patients treated in our Unit were analyzed, and the results are reported according to the appropriate indicator (number of staff related to patients treated, waiting list, case history accuracy, multidisciplinary approach, number of treatment plans performed by CT, number of fields per fraction, number of portal imaging performed per overall treatment, and patient satisfaction). RESULTS: The number of professional staff related to the number of patients treated was easy to calculate and it could be the basis for further evaluation. The overall waiting time was 55.4 days, and it changed for different radiotherapy goals. We obtained 80% conformity in case-history accuracy. The number of multidisciplinary consultations performed ranged between 50% and 100%. The number of CT plans was about 1.6 +/- 0.9 plans per patient. The mean number of fields performed per day and per patient is 3.5 +/- 1.7 and was in agreement with the fact that more than 50% of treatments in our Center were performed with conformal radiotherapy. An average of 16.7 +/- 10.0 portal imaging per case was performed. The percentage of patient satisfaction with the staff obtained a very high compliance. CONCLUSIONS: The self evaluation promoted by the National Health Service Project allows the monitoring of the activities of the service in order to asses critical factors and it can be the starting point to improve the quality of the service and to compare national and international quality assurance results.

Italian survey in postoperative radiation therapy for prostate carcinoma by the AIRO National Working Group on Prostate Radiotherapy: definitive results.

AIMS AND BACKGROUND: The National Working Group on Prostate Radiotherapy of AIRO (Associazione Italiana Radioterapia Oncologica, Italian Association of Radiotherapeutic Oncology) was established in March 2001. A retrospective multi-center survey was performed to analyze the patterns of care for prostate cancer patients treated with postoperative radiotherapy following radical prostatectomy in Italy with regard to the year 2000. MATERIALS AND METHODS: A structured questionnaire was mailed to 47 Italian radiotherapy centers to assess patient accrual in the postoperative setting in the interval comprised between period January-December 2000. Numbers of patients treated for different stages, specific prognostic factors indicating the need for adjuvant radiotherapy, fractionation schedules and prescription doses were acquired as well as other clinically important factors such as radiotherapy timing and the use of hormone therapy. More technical features of the treatment, such as patient positioning, mode of simulation, typical field setup and dose prescription criteria were also included in the questionnaire. RESULTS: The questionnaire was returned by 24 radiotherapy Institutions (51%) with a total number of 470 patients treated postoperatively in the year 2000. An average of about 20 patients were enrolled by each radiotherapy center. The age range was 45-81 years. Radiotherapy was delivered within 6 months of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157 (34.6%), the treatment was delivered as a salvage approach for biochemical or micro-macroscopic recurrence. Most of patients had locally advanced stage disease (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins, capsular invasion, Gleason pattern score > 7 were present in about 50% of patients. CONCLUSIONS: The study confirmed that important risk factors for recurrences are present in a significant percentage of patients treated by radical prostatectomy. The number of patients that would benefit from adjuvant radiotherapy is therefore potentially very large. Future prospective studies should be conducted to assess and to clarify the respective roles of adjuvant and salvage radiotherapy in prostate cancer patients.

The impact of 18F-deoxyglucose positron emission tomography on tumor staging, treatment strategy and treatment planning for radiotherapy in a department of radiation oncology.

AIMS AND BACKGROUND: The study analyzed the potential contribution of positron emission tomography (PET) in patient selection for radiotherapy and in radiation therapy planning. METHODS: Eighty-seven patients with a histological cancer diagnosis were accrued for the study from December 2000 to December 2001. Demographic characteristics included a median age of 54 years and male/female ratio of 51/36. All patients staged by conventional workup who were candidates for radiotherapy had PET imaging and were allocated to a conventional "pre/post-PET stage". The treatment protocol and the shape and/or size of the portals was directly related to PET results. We examined 26 lung cancers, 15 gastrointestinal tumors, 22 genitourinary cancers and 24 hematologic malignancies. RESULTS: In the lung cancer group, the stage was modified in 10/26 patients (38.5%) by PET, with a change in management in 13 (50%) and a change in radiotherapy planning in 6 (23.1%). In the hematological group, stage was modified by PET in 8/24 cases (33.3%), with a change in treatment strategy in 9 (37.5%) and a change in radiotherapy planning in 3 (12.5%). In the gastrointestinal group, the stage was modified by PET in 2/15 cases (13.4%), with a change inn treatment strategy in 4 (26.7%) and a change in the decision for radiotherapy in 8 (no radiotherapy in 53.3%). In the mixed group (genitourinary, breast and other), the stage was modified by PET in 6/22 cases (27.3%), with a change in treatment strategy in 11 (50%) and a very low rate of change in radiotherapy planning. CONCLUSIONS: PET contributed to a modification of stage in 26/87 patients (30%), to a changing in treatment strategy in 37/87 (42.5%), and to a substantial change of the shape and/or size of radiotherapy portals in 13/43 (30%) who underwent radiotherapy.

Clinical application and dosimetric calibration procedure of the superficial and orthovoltage therapy unit Therapax DXT300.

AIMS AND BACKGROUND: The aim of this study was to configure a new superficial and orthovoltage therapy unit for clinical use and discuss the clinical indications for this kind of energy. There is renewed interest in radiotherapy using photon beams in the range from 40 to 300 kVp, in particular for the treatment of non-neoplastic diseases and superficial lesions. This is due to the fact that the latest units are of good quality, relatively cheap and reliable in comparison with alternative equipment. It is therefore necessary to document the steps involved in the clinical application of this therapeutic equipment. METHODS: The calibration procedure for a new superficial/orthovoltage therapy unit, Therapax DXT300 (Pantak, USA), installed at the Radiotherapy Department of the Mauriziano Hospital in Turin, was carried out by measurement of beam quality (half-value layer, HVL), percentage depth dose (PDD), profiles, internal dosimetry system, dose rate calibration and output factors. The Therapax DXT300 can be programmed to stop treatment either by time or dose, like a linear accelerator. It is equipped with one adjustable collimator (2 x 2 divided by 20 x 20 cm2) for orthovoltage therapy (focus skin distance, FSD = 50 cm) and six fixed applicators for superficial and orthovoltage therapy (FSD = 30 and 50 cm, respectively). Up to eight combinations of generating potential, tube current and added beam filter can be set. RESULTS: In the range of accelerating potentials from 40 to 300 kVp the Therapax provides beams with HVL ranging from 1.48 mm Al to 3.68 mm Cu. As regards the PDD curves, a slight difference between PDD values has been observed with potentials ranging from 200 to 300 kVp. The beam symmetry and flatness are almost the same in Y and X plane directions for accelerating potentials of less than 200 kVp. At higher kVp values these parameters are significantly worse in the anode-cathode axis direction, because the useful X-ray beam is extracted perpendicular to the anode-cathode axis direction: as the energy increases, the bremsstrahlung becomes more forward directed, resulting in a higher dose rate on the anode side. CONCLUSION: The present paper suggests a methodological approach for the clinical application of an orthovoltage/superficial therapy unit and discusses its current indications. It is necessary to maintain the performance of the equipment within predefined limits in order to meet the requirements of an efficient quality assurance program. This unit is particularly useful in the treatment of superficial lesions and non-neoplastic diseases and in palliative care (eg for bone metastases).