Breast-conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients.
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Adult↗
Biomedical subjects
János Fodor
Publications and source records attributed to János Fodor.
Is boost irradiation with interstitial brachytherapy less favourable than with teletherapy after breast conserving surgery?
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Brachytherapy↗
Sole brachytherapy of the tumor bed after conservative surgery for T1 breast cancer: five-year results of a phase I-II study and initial findings of a randomized phase III trial.
BACKGROUND AND OBJECTIVES: The objectives of this study were to test the feasibility of sole interstitial high-dose-rate brachytherapy (HDR-BT) after breast-conserving surgery (BCS) for T1 breast cancer in a phase I-II study, and to present the initial findings of a phase III trial comparing the efficacy of tumor bed radiotherapy (TBRT) alone with conventional whole breast radiotherapy (WBRT). METHODS: Forty-five prospectively selected patients with T1 breast cancer undergoing BCS were enrolled into a phase I-II study of TBRT alone, using interstitial HDR implants. HDR-BT of 7 x 4.33 Gy (n = 8) and 7 x 5.2 Gy (n = 37) was delivered to the tumor bed. Based on the results of this phase I-II study, a further 126 patients were randomized to receive 50 Gy WBRT (n = 63) or TBRT alone (n = 63); the latter consisted of either 7 x 5.2 Gy HDR-BT (n = 46) or 50-Gy wide-field electron irradiation (n = 17). Breast cancer related events and side effects were assessed. RESULTS: In the phase I-II study, at a median follow-up of 57 months, 2 (4.4%) local, 3 (6.7%) axillary, and 3 (6.7%) distant failures were observed. Two patients (4.4%) died of breast cancer. The 5-year probability of cancer-specific, relapse-free and local recurrence-free survival was 90.0%, 85.9%, and 95.6%, respectively. The cosmetic results were judged to be excellent in 44 of 45 patients (97.8%). Severe (higher than grade 2) skin sequelae or fibrosis was not found. Symptomatic fat necrosis occurred in one patient (2.2%). In the phase III study, at a median follow-up of 30 months, the locoregional tumor control was 100% in both arms. The 3-year probability of cancer-specific and relapse-free survival was 98.1% and 98.4% in the WBRT group and 100% and 94.4% in the TBRT group, respectively (P = NS). There was no significant difference between the two treatment arms regarding the incidence of radiation side effects. CONCLUSIONS: Five-year results of our phase I-II study prove that sole HDR-BT of the tumor bed with careful patient selection and adequate quality assurance is a feasible alternative to WBRT. However, long-term results of phase III trials are required to determine the equivalence of TBRT alone, compared with WBRT in the management of selected patients with early breast cancer.
Adult↗
Radiotherapy confined to the tumor bed following breast conserving surgery current status, controversies, and future projects.
BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.
Brachytherapy↗
Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer first results of the randomized Budapest boost trial.
BACKGROUND AND AIMS: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. PATIENTS AND METHODS: 207 women with stage I-II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n = 104) or no further radiotherapy (n = 103). Boost treatments consisted of either 16 Gy electron irradiation (n = 52) or 12-14,25 Gy HDR BT (n = 52). Breast cancer-related events, side effects, and cosmetic results were assessed. RESULTS: At a median follow-up of 5.3 years, the crude rate of local recurrences was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs. 84.9% (p = 0.049), 76.6% vs. 66.2% (p = 0.044), and 90.4% vs. 82.1% (p = 0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs. 91.4%; p = 0.74). On multivariate analysis, patient age < 40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2-3 side effects was higher in the boost arm (17.3% vs. 7.8%; p = 0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p = 0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p = 0.29). CONCLUSIONS: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age should be viewed as absolute indications for tumor bed boost. LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons.
Brachytherapy↗
Conformality and homogeneity of dose distributions in interstitial implants at idealized target volumes: a comparison between the Paris and dose-point optimized systems.
BACKGROUND AND PURPOSE: The use of high dose rate stepping source in interstitial brachytherapy provides more possibility to conform the dose distribution to the target volume compared to the classical systems. The purpose of this study was to evaluate implants made according to the Paris, the stepping source and the conformal dosimetry system with respect to dose homogeneity and conformality, and to compare these systems using volumetric parameters. MATERIALS AND METHODS: Single-plane and double-plane implants with catheters arranged in square and triangle pattern were used in the analysis. Twenty-seven idealized planning target volumes (PTV) were generated. They formed slabs with rectangular or trapezoidal cross-section. The lengths were 3, 5 and 7 cm, the widths and heights were determined according to the Paris system for catheter separation of 1, 1.5 and 2 cm. The dose specification was selected such that the coverage index was 0.95 for each implant. Optimal active lengths were determined according to the best conformality at the optimized implants. From the dose-volume histogram (DVH) the following indices were calculated for every implant: conformal (COIN), external volume (EI), relative dose homogeneity (HI) and overdose volume (OI). Furthermore, the mean central dose (MCD) and minimum target dose (MTD) was also determined. The dosimetry systems were compared through the mean values of these parameters and the volumetric indices were analyzed according to the geometry of the PTV. RESULTS: For the optimized systems the optimal active length was 0.5-1.0 cm shorter than the target volume length, depending on the catheter separation and geometry of the PTV. For the Paris, the stepping source and the conformal dosimetry system, the mean COIN was 0.66, 0.82 and 0.82; the mean HI was 0.71, 0.68 and 0.68; the mean EI was 0.44, 0.17 and 0.17; the mean OI was 0.11, 0.13 and 0.12, respectively. The statistical analysis showed that the Paris system differed from the optimized systems significantly. For the Paris, the stepping source and the conformal dosimetry system, the mean reference isodose was 85, 90 and 95%, the MCD was 100, 100 and 109%, the MTD was 67, 71 and 73%, respectively. Regarding geometry of the PTV, the most conformal and homogeneous dose distributions occurred when the catheter separation was small, the target volume was long and its shape was a thick rectangular slab. CONCLUSIONS: Positioning the catheters according to the rules of the Paris system, but applying optimization on dose points placed either between the catheters in the whole target volume or on the surface of the target volume, and selecting the reference isodose by DVH, can provide highly conformal dose distribution to the target volume, with only a slightly worsened dose homogeneity compared to the Paris system.
Brachytherapy↗
Modelling normal tissue isoeffect distribution in conformal radiotherapy of glioblastoma provides an alternative dose escalation pattern through hypofractionation without reducing the total dose.
The purpose of this study was to prove that by using conformal external beam radiotherapy (RT) normal brain structures can be protected even when applying an alternative approach of biological dose escalation: hypofractionation (HOF) without total dose reduction (TDR). Traditional 2-dimensional (2D) and conformal 3-dimensional (3D) treatment plans were prepared for 10 gliomas representing the subanatomical sites of the supratentorial brain. Isoeffect distributions were generated by the biologically effective dose (BED) formula to analyse the effect of conventionally fractionated (CF) and HOF schedules on both the spatial biological dose distribution and biological dose-volume histograms. A comparison was made between 2D-CF (2.0 Gy/day) and 3D-HOF (2.5 Gy/day) regimens, applying the same 60 Gy total doses. Integral biologically effective dose (IBED) and volumes received biologically equivalent to a dose of 54 Gy or more (V-BED54) were calculated for the lower and upper brain stem as organs of risk. The IBED values were lower with the 3D-HOF than with the 2D-CF schedule in each tumour location, means 22.7+/-17.1 and 40.4+/-16.9 in Gy, respectively (p < 0.0001). The V-BED54 values were also smaller or equal in 90% of the cases favouring the 3D-HOF scheme. The means were 2.7+/-4.8 ccm for 3D-HOF and 10.7+/-12.7 ccm for 2D-CF (p = 0.0006). Our results suggest that with conformal RT, fraction size can gradually be increased. HOF radiotherapy regimens without TDR shorten the treatment time and seem to be an alternative way of dose escalation in the treatment of glioblastoma.
Brain↗
Bioinformatical results based on statistical methods for endectocide products against fly-larvae.
The larvicide effects of three endecticide products were studied against house fly larvae. Repeated-measure design was used for the analysis of variance. The observed data followed different distributions. For this reason, instead of the repeated measure ANOVA, three fast statistical methods were applied simultaneously. First, the test for homogeneity was carried out for registered samples by using the Friedman test, and the Wilcoxon-Wilcox test was applied for pairwise comparisons. Secondly, an extended median test was applied for the same problem of test for homogeneity, and the Neményi test was used for pairwise comparisons. Thirdly, a 2 x 2 contingency table analysis was carried out, exploiting the specific feature of the database and informatical tools. The three simultaneous evaluations enabled us to come to sound, affirmative conclusions. In the course of veterinary-biological interpretation we demonstrated the statistically reliable temporal efficiency of the three products. We also presented the relative efficiency and recognizable features of the products. We highlighted the significantly prompt and long release larvicide effects of the drugs. We discussed and compared the information content of the applied statistical methods.
Analysis of Variance↗
[Angiosarcomas of the chest wall and breast after radiotherapy: The questions of radiogenic origin, diagnosis and treatment]
PURPOSE: To present medical history of secondary chest wall and breast angiosarcomas (AS) developed after radiotherapy, and to discuss the questions of radiogenic origin, diagnosis and treatment by the review of the literature. METHODS: Report of two cases and MEDLINE search for relevant publications. RESULTS: Secondary AS occured in a previously irradiated field after a long (6 and 8 years) latency period in both cases. Detailed histopathological and immunohistochemical examinations from the biopsy and/or surgical specimens confirmed the diagnosis as AS. The first patient with moderately differentiated AS was treated successfully with radical surgery. The second patient with irresecable AS died of rapid local progression within 4 months. The incidence of chest wall and breast AS is increased after irradiation, however, controversial data exist in the literature. The incidence of chest wall and breast AS after radiotherapy was found to be 0.39% in our patient population, which means an estimated odds ratio of 2.4 for secondary AS. Stewart-Treves syndrome is not of radiogenic origin, since postoperative lymphoedema has been considered as primary etiological factor. CONCLUSIONS: Patients treated with surgery and/or radiotherapy for primary breast cancer are at higher risk for developing secondary AS, compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long term survival. Further adjuvant radiotherapy is no longer feasible, due to the previous irradiation. Chemotherapy has only palliative effect. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.
Journal Article↗
Successful treatment of a T1 cancer of the pancreatic head with high dose rate brachytherapy and external radiotherapy.
In this report, a unique case of a localized (T1N0M0) adenocarcinoma of the head of the pancreas is presented, which was successfully treated with interstitial high dose rate brachytherapy combined with percutan irradiation after biopsy. A total dose of 18 Gy was delivered with brachytherapy (6 Gy per fraction on three consecutive days) to the tumor via after-loading catheter. Brachytherapy was followed by external radiotherapy, delivering an additional dose of 46 Gy (18 MV-x) with four-field technique using conventional fractionation (2 Gy/day). Thirty-six months after completion of the treatment the patient is alive with no evidence of disease. The combination of interstitial high dose rate brachytherapy and external beam radiation therapy may be an effective tool to deliver curative dose without any significant sequelae in the treatment of operable pancreatic carcinoma, when the patient's condition contraindicates surgery.
Adenocarcinoma↗