Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

BACKGROUND: Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. METHODS: We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). INTERPRETATION: APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. FUNDING: German Cancer Aid.

[Image-guided radiotherapy for muscle invasive bladder cancer with intravesical lipiodol injection. A new option for bladder sparing treatment]. / Izominvazív hólyagrák képvezérelt sugárkezelése intravesicalisan befecskendezett lipiodolos jelöléssel. A hólyagmegtartó kezelés új lehetosége.

INTRODUCTION AND AIM: To implement lipiodol as a fiducial marker of the tumor bed for image-guided radiotherapy with simultaneous integrated boost technique as part of radiochemotherapy for muscle invasive bladder tumors. METHOD: Since April 2016, radiochemotherapy was performed in 3 male patients with muscle invasive, transitional cell bladder carcinoma. Prior to radiochemotherapy, tumor bed resection was performed for each patient, at the same time 10 ml of lipiodol solution was injected submucosally into the resection site, thus marking the tumor bed for escalated dose irradiation. During radiochemotherapy 51 Gy (1.7 Gy/die) to the pelvis, 57 Gy (1.9 Gy/die) to the whole bladder, and 63 Gy (2.1 Gy/die) to the lipiodol-labeled tumor bed was delivered with simultaneous integrated boost technique. The accuracy of the irradiation was controlled by daily kilovoltage CT. Early radiogenic urogenital and gastrointestinal side effects were recorded according to Radiation Therapy Oncology Group side-effects grading recommendation. RESULTS: Substantial perioperative side effect or toxicity were not observed during and after the injection of lipiodol. The prescribed dose was successfully delivered in all patients. Radiotherapy duration was 6 weeks. The lipiodol-labeled tumor bed was clearly visible on daily kilovoltage cone beam CT. In one patient grade II cystitis and proctitis was observed, another patient experienced only grade I cystitis. These complaints improved with symptomatic medication. In the third patient no significant side effect occurred. CONCLUSIONS: The injection of lipiodol into the bladder wall is a safe technique, without any perioperative toxicity or complication. The tumor bed demarcated by lipiodol was visible both on treatment planning and kilovoltage CTs. The total treatment time was shortened by 4 days. The treatment was well tolerated, early side effects were moderate, or slight. Orv Hetil. 2017; 158(51): 2041-2047.

[Measurement of peak correction factor of Farmer chamber for calibration of flattening filter free (FFF) clinical photon beams]. / Kiegyenlítõ szûrõ nélküli mezõk Farmer-kamrával történõ kalibrációjánál alkalmazandó csúcshatás-korrekció mérése.

Farmer-type ionization chambers are considered the most reliable detectors and for this reason they are most frequently used for the calibration of photon beams of medical linear accelerators. Flattening filter free (FFF) photon beams of linear accelerators have recently started to be used in radiotherapy. The dose profile of FFF beams is peaked in the center of the field and the dose distribution will be inhomogeneous along the axis of the 2.3 cm long measuring volume of the Farmer chamber. The peaked radiation field will result in volume averaging effects in the large Farmer chamber, therefore this chamber will underestimate the true central axis dose. Our objective was to determine the value of the peak correction factor (Kp) of Farmer-type chamber with measurements to avoid the underestimation of the central axis dose during the calibration of FFF radiation fields. Measurements were made with 6 MV and 10 MV flattened (6X and 10X) and FFF beams (6XFFF and 10XFFF) of a Varian TrueBeam medical linear accelerator in a solid water phantom at 10 cm depth. The source surface distance (SSD) was 100 cm, the field size was 10×10 cm and the dose rate was always 400 MU/min during the measurements. We delivered 100 MU in each measurement and the absorbed dose to water was calculated according to the IAEA TRS-398 dosimetry protocol. The measured signals of the ionization chambers were always corrected for the ion recombination loss. The ion recombination correction factors (Kr) were determined with the two-voltage method separately for the used ion chambers and for flattened and unflattened beams. First, we measured the dose to water with PTW TM30012 Farmer chamber in 6XFFF and 6X beams, then calculated the ratio of doses of 6XFFF and 6X beams (R6,Farmer). Immediately after this we repeated the above measurements with PTW TM31010 Semiflex chamber and determined the ratio of doses of 6XFFF and 6X beams again (R6,Semiflex). The length of the sensitive volume of the Semiflex chamber is only 6.5 mm. According to our dose profile measurements the peak correction factor of this chamber equals to unity for both photon energies. As a consequence R6,Semiflex is larger than R6,Farmer and Kp6XFFF = R6,Semiflex / R6,Farmer, where Kp6XFFF is the peak correction factor of the Farmer chamber in 6XFFF beam. The advantage of this method is that we have to calculate ratio of doses, so it is not necessary to know the calibration factors of the chambers. Repeating the above measurements with 10X and 10XFFF beams we determined the peak correction factor of Farmer chamber for 10XFFF beam, too (Kp10XFFF). According to our measurements Kp6XFFF = 1.0025 and Kp10XFFF = 1.009. The bigger peak correction factor for 10XFFF beam is in accordance with the fact that the peak of dose profile is steeper for higher photon energy. The above described method for the determination of Kp can be used for other photon energies and other large volume ionization chambers.

[Salvage 125I brachytherapy of locally recurrent prostate cancer]. / Prosztatadaganat sugárkezelését követo helyi kiújulás "salvage" kezelése 125I brachyterápiával.

The purpose of the study is to report a case of salvage low dose rate (LDR) prostate brachytherapy in a patient with locally recurrent prostate cancer, four years after his first treatment with combined external beam radiation therapy (EBRT) and high dose rate (HDR) brachytherapy. A 61-year-old man was treated with 1x10 Gy HDR brachytherapy and a total of 60 Gy EBRT for an organ confined intermediate risk carcinoma of the prostate in 2009. The patient's tumor had been in regression with the lowest PSA level of 0.09 ng/ml, till the end of 2013. After slow but continuous elevation, his PSA level had reached 1.46 ng/ml by February 2014. Pelvis MRI and whole body acetate PET/CT showed recurrent tumor in the dorsal-right region of the prostate. Bone scan was negative. After discussing the possible salvage treatment options with the patient, he chose LDR brachytherapy. In 2014, in spinal anesthesia 21 125I "seeds" were implanted with transrectal ultrasound guidance into the prostate. The prescribed dose to the whole prostate was 100 Gy, to the volume of the recurrent tumor was 140 Gy. The patient tolerated the salvage brachytherapy well. The postimplant dosimetry was evaluated using magnetic resonance imaging-computed tomography (MR-CT) fusion and appeared satisfactory. PSA level decreased from the pre-salvage value of 1.46 ng/ml to 0.42 ng/ml by one month and 0.18 ng/ml by two months after the brachytherapy. No gastrointestinal side effects appeared, the patient's urination became slightly more frequent. In selected patients, salvage LDR brachytherapy can be a good choice for curative treatment of locally recurrent prostate cancer, after primary radiation therapy. Multiparametric MRI is fundamental, acetate PET/CT can play an important role when defining the localization of the recurrent tumor.

Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

PURPOSE: To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. MATERIAL AND METHODS: Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. RESULTS: The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. CONCLUSION: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.