UZ Leuven

Towards videncebased guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project. Bentzen S, Heeren G, Cottier B, Slotman B, Glimelius B, Lievens Y, Van den Bogaert W.Radiother Oncol 2005;75,355-365. Abstract: BACKGROUND AND PURPOSE: Adequate and equitable access to radiotherapy (RT) must be a reasonable health care goal for the EU. However, there are large variations among the EU countries and even regional variations within countries in the provision of RT. In this report, we combine the best available evidence on the indications for RT with national epidemiological data to arrive at estimates for the appropriate level of RT infrastructure in the 25 EU countries. PATIENTS AND METHODS: Data from three systematic overviews of the best available evidence for the indication for RT in 23 main cancer types are combined with epidemiological data from the EUCAN and GLOBOCAN databases on the crude incidence of each of these cancers in the 25 EU countries. Together with published benchmarks for accelerator throughput this allows estimation of the number of linear accelerators per million people required to facilitate appropriate RT utilization rates in each country. Where possible, the estimates are compared with the detailed data available from Sweden. RESULTS: The crude incidence of the main cancer types shows large variation among the 25 EU countries. This reflects in part differences in exposure to aetiological risk factors and partly differences among the countries in population age structure. Correspondingly, the estimate of the required number of linear accelerators per million people showed considerable variation: ranging from 4.0 in Cyprus to 8.1 in Hungary. The average for the 25 countries was 5.9 per million people. These estimates were compared with available national guidelines and actual data on RT infrastructure and large shortfalls were found in many countries. Implications for health economics and capacity planning are briefly discussed. CONCLUSIONS: The QUARTS project has developed a model that establishes a direct and transparent link between epidemiological data and indications for RT based on the best available evidence. Comparison of the model estimates with current levels of RT infrastructure has revealed major inequalities in provision of RT in the 25 EU countries. Continuation of this study is recommended as a way of improving RT provision on rational grounds throughout the European community and as a model for health care planning in the EU.

A new approach to the validation of tissue microarrays. Goethals L, Perneel C, Debucquoy A, De Schutter H, Borghys D, Ectors N, Geboes K, McBride WH, Haustermans KM.J Pathol 2006;208:607-614. Abstract: Although tissue microarrays (TMA) have been widely used for a number of years, it is still not clear how many core biopsies should be taken to determine a reliable value for percentage positivity or how much heterogeneity in marker expression influences this number. The first aim of this study was to validate the human visual semi-quantitative scoring system for positive staining of tumour tissue with the exact values determined from computer-generated images. The second aim was to determine the minimum number of core biopsies needed to estimate percentage positivity reliably when the immunohistochemical staining pattern is heterogeneous and scored in a non-binary way. Tissue sections from ten colorectal cancer specimens were stained for carbonic anhydrase IX (CA IX). The staining patterns were digitized and 400 artificial computer-generated images were generated to test the accuracy of the human scoring system. To determine the minimal number of core biopsies needed to account for tumour heterogeneity, 50 (artificial) core biopsies per section were taken from the tumoural region of the ten digitally recorded full tissue sections. Based on the semi-quantitative scores from the 50 core biopsies per section, 2500 x n (n = 1-10 core biopsies) experimental core biopsies were then generated and scores recorded. After comparison with field-by-field analysis from the tumoural region of the whole tissue section, the number of core biopsies that need to be taken to minimize the influence of heterogeneity could be determined. In conclusion, visual scoring accurately estimated the percentage positivity and the percentage tumour present in a section, as judged by comparison with the artificial images. The exact number of core biopsies that has to be examined to determine tumour marker positivity using TMAs is affected by the degree of heterogeneity in the expression pattern of the protein, but for most purposes at least four is recommended.

Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer. Bussels B, Maes A, Hermans R, Nuyts S, Weltens C, Van den Bogaert W. Radiother and Oncol 2004;72, 119-127. Abstract: BACKGROUND AND PURPOSE: Evaluation of loco-regional failure patterns and survival after parotid- sparing three-dimensional conformal and intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: From June 1999 to July 2002, seventy-two patients with lateralised head and neck tumours, excluding nasopharyngeal tumours and patients with bilateral or contralateral neck disease, were irradiated with a parotid-sparing technique. Three-dimensional conformal planning was used in 68 patients, 4 patients were treated with dynamic IMRT. Bilateral neck node irradiation was performed in all patients, the junctional (or high level II) nodes, contralateral to the tumour, however, were excluded from the clinical target volume to spare the adjacent parotid from irradiation. In 20 patients with persistent or recurrent loco-regional disease, the localisation and volume of the treatment failure, as determined by computed tomography (CT), was copied on the pre-treatment CT-study used for treatment planning. Minimum, mean and maximum doses administered to the region of the failure were calculated and dose--volume histograms were computed of each failure. The failures were divided in three groups depending on the percentage of their volume receiving 95% of the prescribed dose. Recurrences were defined to be in-field (IF) if >95% of their volume received 95% of the prescribed dose and out-field (OF) if < 20% of their volume received 95% of the prescribed dose. When 20-95% of the volume of the recurrence received 95% of the prescribed dose, this recurrence was defined as extending outside the field (EOF). RESULTS: With a median follow-up time of 19 months, the 2-year loco-regional control rate was 69% with primary radiotherapy and 63.5% with surgery followed by irradiation (P=0.77). The 2-year overall survival rate for the entire patient population was 67.4%. At the time of analysis, 20 of the 72 patients had developed a loco-regional failure; 2 patients (2/20) presented with a loco-regional relapse combined with distant metastasis. Fifteen of the 20 locoregional failures (15/20) occurred within the high dose region (IF). Five patients (5/20) developed a failure of which the bulky tumour mass was located within the high dose region but extending outside the treatment volume (EOF). No relapses were seen out-field (OF) and no patients relapsed in the spared junctional area contralateral to the tumour. CONCLUSIONS: The selection of patients treated with parotid-sparing radiotherapy, by omitting irradiation to the junctional nodes contralateral to the tumour, proved to be safe in our hands, since no recurrences developed in the spared area. As this parotid-sparing technique reduces significantly the dose to the contralateral parotid and is easy to perform, it should be considered for all selected patients.

Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. Bartelink H, Horiot JC, Poortmans Ph, Struikmans H, Van den Bogaert W, Barillot I, Fourquet A, Borger J, Jager J, Hoogenraad W, Collette L, Pierart M. N Engl J Med 2001;345:1378-1387. Abstract: BACKGROUND: Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery. We evaluated the effect of a supplementary dose of radiation to the tumor bed on the rates of local recurrence among patients who received radiotherapy after breast-conserving surgery for early breast cancer. METHODS: After lumpectomy and axillary dissection, patients with stage I or II breast cancer received 50 Gy of radiation to the whole breast in 2-Gy fractions over a five-week period. Patients with a microscopically complete excision were randomly assigned to receive either no further local treatment (2657 patients) or an additional localized dose of 16 Gy, usually given in eight fractions by means of an external electron beam (2661 patients). RESULTS: During a median follow-up period of 5.1 years, local recurrences were observed in 182 of the 2657 patients in the standard-treatment group and 109 of the 2661 patients in the additional-radiation group. The five-year actuarial rates of local recurrence were 7.3 percent (95 percent confidence interval, 6.8 to 7.6 percent) and 4.3 percent (95 percent confidence interval, 3.8 to 4.7 percent), respectively (P < 0.001), yielding a hazard ratio for local recurrence of 0.59 (99 percent confidence interval, 0.43 to 0.81) associated with an additional dose. Patients 40 years old or younger benefited most; at five years, their rate of local recurrence was 19.5 percent with standard treatment and 10.2 percent with additional radiation (hazard ratio, 0.46 [99 percent confidence interval, 0.23 to 0.89]; P=0.002). At five years in the age group 41 to 50 years old, no differences were found in rates of metastasis or overall survival (which were 87 and 91 percent, respectively). CONCLUSIONS: In patients with early breast cancer who undergo breast-conserving surgery and receive 50 Gy of radiation to the whole breast, an additional dose of 16 Gy of radiation to the tumor bed reduces the risk of local recurrence, especially in patients younger than 50 years of age. 

Is there a role for FDG-PET in radiotherapy planning in esophageal carcinoma? Vrieze O, Haustermans K, De Wever W, Lerut T, Van Cutsem E, Ectors N, Hiele M, Van den Bogaert W, Flamen P. Radiother Oncol 2004;73(3):269-75. Abstract: BACKGROUND AND PURPOSE: To determine the additional value of FDG-positron emission tomography (PET) to optimize delineation of the clinical target volume (CTV) in patients with advanced esophageal carcinoma. METHODS AND MATERIALS: The imaging and radiotherapy data from 30 patients with an advanced esophageal carcinoma were analysed. The lymph node classification for esophageal cancer was modified and translated into anatomical volumes on computed tomography (CT). The so defined 14 different regions were scored individually for lymph node involvement on CT, endoscopic ultrasound (EUS) and FDG-PET. The influence of discordant findings between conventional and functional imaging on the decision as to what should be irradiated was assessed. RESULTS: In 14 of the 30 patients (47%) discordances were found in detection of the pathological lymph nodes between CT/EUS and FDGPET. In 8 patients, 9 lymph node regions were found with pathologic nodes on conventional imaging only. In three of these patients the influence of FDG-PET findings would have led to a decrease of the irradiated volume. In 6 patients, 8 lymph node regions were found with a normal CT/EUS and pathologic nodes on FDG-PET. In three of these patients (10%) the influence of the FDG-PET would have led to enlargement of the irradiated volume. CONCLUSIONS: The chance of a false negative result on FGD-PET is not negligible; therefore, the irradiated volume should not be reduced based on a negative FDG-PET in a region with suspect nodes on other investigations. However, due to the high specificity of FDG-PET enlarging the irradiated volume based on a positive FDG-PET in a region without suspected lymph nodes on CT and/or EUS should be considered. This indicates a role for FDG-PET in radiotherapy planning for esophageal cancer.

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