Dose reduction in LDR brachytherapy by implanted prostate gold fiducial markers.

PURPOSE: The dosimetric impact of gold fiducial markers (FM) implanted prior to external beam radiotherapy of prostate cancer on low dose rate (LDR) brachytherapy seed implants performed in the context of combined therapy was investigated. METHODS: A virtual water phantom was designed containing a single FM. Single and multi source scenarios were investigated by performing Monte Carlo dose calculations, along with the influence of varying orientation and distance of the FM with respect to the sources. Three prostate cancer patients treated with LDR brachytherapy for a recurrence following external beam radiotherapy with implanted FM were studied as surrogate cases to combined therapy. FM and brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose calculations were performed with and without FM. The dosimetric impact of the FM was evaluated by quantifying the amplitude of dose shadows and the volume of cold spots. D(90) was reported based on the post implant CT prostate contour. RESULTS: Large shadows are observed in the single source-FM scenarios. As expected from geometric considerations, the shadows are dependent on source-FM distance and orientation. Large dose reductions are observed at the distal side of FM, while at the proximal side a dose enhancement is observed. In multisource scenarios, the importance of shadows appears mitigated, although FM at the periphery of the seed distribution caused underdosage (

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands.

PURPOSE: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer. METHODS AND MATERIALS: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed. RESULTS: The average delineated CTV volume decreased from 620 to 460 cc (p<0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p=0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively. CONCLUSIONS: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.

Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma.

BACKGROUND: Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervix carcinoma (LACC). OBJECTIVES: To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity. SEARCH STRATEGY: The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN RESULTS: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 4 to 6). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significantly better overall survival (OS) following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments. AUTHORS' CONCLUSIONS: The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Combined use of hyperthermia and radiation therapy for treating locally advanced cervical carcinoma.

BACKGROUND: Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervical carcinoma (LACC). OBJECTIVES: To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity. SEARCH STRATEGY: The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN RESULTS: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 1 to 3). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate at 3 years (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significanly better overall survival (OS) at three years following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments. AUTHORS' CONCLUSIONS: The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervical carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer.

BACKGROUND: Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect. OBJECTIVES: To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy. SEARCH STRATEGY: We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study. SELECTION CRITERIA: Only phase II and III randomised controlled clinical trials were included in the analysis. DATA COLLECTION AND ANALYSIS: All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan). MAIN RESULTS: Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS). All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported. AUTHORS' CONCLUSIONS: Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

Multislice CT as a primary screening tool for the prediction of an involved mesorectal fascia and distant metastases in primary rectal cancer: a multicenter study.

PURPOSE: The purposes of this study were to assess whether multislice CT can identify tumors having a free or involved circumferential margin, to investigate the additional role of multislice CT as a "one-stop shopping" staging tool for staging nodal and distant metastases. METHODS: A total of 250 patients with adenocarcinoma of the rectum underwent multislice CT scans of the chest and abdomen before undergoing total mesorectal excision. The scans were scored by two teams. The main outcome was yes/no involvement of the mesorectal fascia. Histology was taken as the standard for determining the involvement. RESULTS: The overall sensitivity for predicting an involved mesorectal fascia was 74.2 percent and the overall specificity was 93.9 percent. The overall sensitivity for low tumors was 65.6 percent and the overall specificity was 81.5 percent. The overall sensitivity for mid-/high rectal tumors was 76.1 percent and the overall specificity was 96.3 percent. The interobserver agreement was substantial (kappa 0.695). The overall sensitivity for the prediction of liver metastases was 64.3 percent and the overall specificity was 94.4 percent with kappa 0.82. The accuracy in predicting lymph node metastases was low. CONCLUSIONS: Multislice CT can be used for the assessment of mesorectal fascia involvement in primary rectal cancer, especially those located in the middle rectum and the high rectum; however, in the prediction of an involved margin of tumors located in the distal rectum, the accuracy of multislice CT falls short.

Conventional CT for the prediction of an involved circumferential resection margin in primary rectal cancer.

PURPOSE: To determine the accuracy of conventional computed tomography (CT) scan in the preoperative prediction of an involved circumferential resection margin (CRM) in primary rectal cancer. METHODS: 125 patients with biopsy-proven adenocarcinoma of the rectum underwent CT of the abdomen before undergoing total mesorectal excision. Scans were scored by three observers, differing in experience. The main outcome was yes/no involvement of the CRM. Histology was taken as reference standard. RESULTS: For the most experienced observer, observer A, sensitivity was 46.7% and specificity 92.6%. For observer B, sensitivity was 46.7% and specificity 89.5%. For the least experienced observer C, sensitivity was 43.3% and specificity 92.6%. Inter-observer variability was good between observers A and B (kappa 0.648), B and C (kappa 0.648), and intermediate between A and C (kappa 0.542). Discrepancies occurred in a total of 34 patients; 25 had a CT scan of low technical quality, 10 an anteriorly located distal tumor. CONCLUSION: Conventional CT scan lacks sensitivity for a clinical use in the preoperative assessment of an involved CRM in primary rectal cancer. Modern multislice spiral CT will probably resolve some of the problems of conventional CT; however, further research is needed to establish its role.

Audit of effectiveness of routine follow-up clinics after radiotherapy for cancer: a report of the REACT working group of ESTRO.

BACKGROUND AND PURPOSE: The European Society for Therapeutic Radiology and Oncology was funded by the EU for a project on recording providing education, and ameliorating the consequences of treatment (REACT). An European audit was carried out as part of which to assess the usefulness of current follow-up practices. PATIENTS AND METHODS: Over a 4-month period in 15 cancer centres in 10 countries, patients attending for routine follow-up completed a questionnaire covering their expectations of and satisfaction with the visit. This was matched with a questionnaire completed by the physician about the content and usefulness of the consultation. The feasibility of a short toxicity scale developed by Dische and Saunders was also investigated. RESULTS: In total, 2303 matched questionnaires were analysed. Forty percent of the patients had symptoms or medical problems related to their disease. In 18% there was a positive finding on clinical examination. In 28% investigations were undertaken part of departmental routine practice. Ten percent of the investigations showed an abnormal result. Ninety nine percent of physicians and 85% of the patients expressed satisfaction. Using the short toxicity scale rates of recording toxicity could be increased from 28 to 93%. CONCLUSIONS: There is wide variation in follow-up practices among European centres. There was a low incidence of positive findings clinically or with routine investigations. A simple scale for recording morbidity has proved easy to use by departments, which have not routinely used one of the standard measures. Further work will attempt to produce an European guideline for effective routine follow-up after radiotherapy.