Georgina Fröhlich

Moderate dose escalation with single-fraction high-dose-rate brachytherapy boost for clinically localized intermediate- and high-risk prostate cancer: 5-year outcome of the first 100 consecutively treated patients

PURPOSE To analyze the clinical outcome and toxicity data of the first 100 consecutive patients treated with a single-fraction high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT). METHODS AND MATERIALS Two-hundred eighty patients have been treated with HDR-BT boost for localized intermediate- to high-risk prostate cancer. Among these, the outcome and toxicity of the first 100 patients treated with a single HDR-BT fraction were assessed. A median dose of 60Gy EBRT was given to the prostate and vesicles. Interstitial HDR-BT of 10Gy was performed during the course of EBRT. RESULTS Median followup time was 61.5 months. The 5-year actuarial rates of overall survival, cause-specific survival, disease-free survival, and biochemical no evidence of disease (bNED) for the entire cohort were 93.3%, 99.0%, 89.3%, and 85.5%, respectively. The 7-year actuarial rate of bNED was 84.2% for the intermediate-risk group and 81.6% for the high-risk group (p=0.8464). The 7-year actuarial rates of bNED for Grade 1, 2, and 3 tumors were 97.5%, 80.0%, and 67.1%, respectively. The 5-year probability for developing late Grade 3 gastrointestinal and genitourinary (GU) toxicity was 2.1% and 14.4%, respectively. Grade 3 GU complications occurred significantly more frequently in patients with a history of preirradiation transurethral resection (29.1% vs. 8.8%; p=0.0047). CONCLUSIONS Five-year outcome after 60Gy EBRT plus a single fraction of 10Gy HDR-BT boost is encouraging. Preradiation transurethral resection significantly increases the risk of late severe GU complications.

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, Dmin) 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 (Dr) and urethra (Du), dose to volume of 2 cm3 of the rectum (D2ccm), and 0.1 cm3 and 1% of the urethra (D0.1ccm and D1) were determined. Nonparametric correlation analysis was performed between these parameters.Results:The median number of needles was 16, the mean prostate volume (Vp) was 27.1 cm3. The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the Dmin was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D2ccm = 49% for the rectum, D0.1ccm = 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(Dr,D2ccm) = 0.69, R(Du,D0.1ccm) = 0.64, R(Du,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.ZusammenfassungZiel:Quantitative Auswertung der Dosisverteilungen von High-Dose-Rate-(HDR-)Brachytherapie-Multikatheterimplantaten bezüglich Zielvolumenerfassung, Dosishomogenität und Dosisbelastung kritischer Organe.Material und Methodik:Zur Beurteilung wurden die Dosis-Volumen-Histogramme (DVH) der Bestrahlungspläne von 174 Patienten herangezogen. Die verschriebene Dosierung der auf transrektalem Ultraschall basierenden Bestrahlungspläne betrug 10 Gy (= 100%) als mittlere Dosis an der Zielvolumenoberfläche (Abbildung 1). Die Toleranzdosis für Rektum und Urethra wurde mit 80% bzw. 120% definiert. Dosis-Volumen-Parameter für das Zielvolumen (V90, V100, V150, V200, D90, Dmin) und die Qualitätsindizes (DNR [„dose nonuniformity ratio“], DHI [Dosishomogenitätsindex], CI [„coverage index“], COIN [Konformitätsindex]) wurden berechnet (Tabelle 5). Sowohl die maximale Dosis in Referenzpunkten des Rektums (Dr) und der Urethra (Du) als auch die Dosis im absoluten Volumen von 2 cm3 des Rektums (D2ccm; Abbildung 2a) und die Dosiswerte für Volumina von 0,1 cm3 und 1% der Urethra (D0.1ccm und D1; Abbildung 2b) wurden bestimmt (Tabelle 4). Anschließend wurde eine parameterfreie Korrelationsanalyse zwischen diesen Parametern durchgeführt.Ergebnisse:Es wurden im Mittel 16 Nadeln pro Applikation implantiert, das mittlere Volumen der Prostata (Vp) wurde mit 27,1 cm3 bestimmt. Die Mittelwerte der relativen Dosis-Volumen-Parameter der Prostata für V90, V100, V150 und V200 wurden mit 99%, 97%, 39% und 13% berechnet. Das mittlere Volumen für die D90 wurde mit 109%, die minimale Dosis im Zielvolumen Dmin mit 87% bestimmt (Tabelle 1). Für die Dosis in den Referenzpunkten an Rektum und Urethra wurden als Mittelwerte 75% bzw. 119% erreicht. Die gemittelten Volumendosiswerte wurden mit D2ccm = 49% für das Rektum sowie mit D0.1ccm = 126% und D1 = 140% für die Urethra berechnet (Tabelle 3). Die mittlere DNR betrug 0,37, wobei sich ein DHI von 0,60 ergab. Der Mittelwert für den COIN lag bei 0,66 (Tabelle 2). Die Spearman-Rangkorrelationskoeffizienten für die Volumendosis von Rektum und Urethra ergaben sich mit R(Dr ,D2ccm) = 0.69 (Abbildung 3), R(Du,D0.1ccm) = 0,64 und R(Du,D1) = 0,23 (Abbildungen 4a und 4b).Schlussfolgerung:Die ultraschallbasierte Bestrahlungsplanung für die HDR-Brachytherapie der Prostata ermöglicht die genaue Definition der Implantatgeometrie und liefert akzeptable Dosisverteilungen. In der Mehrzahl der betrachteten Fälle konnte so die Dosis an Urethra und Rektum unterhalb der Toleranzdosis gehalten werden. Die Dosis an den Referenzpunkten des Rektums korrelierte gut mit den Dosis-Volumen-Parametern. Für die charakteristische Dosisbeschreibung an der Urethra wird der Dosis- Volumen-Parameter D1 empfohlen.

Assessment of dose homogeneity in conformal interstitial breast brachytherapy with special respect to ICRU recommendations

Purpose To present the results of dose homogeneity analysis for breast cancer patients treated with image-based conformal interstitial brachytherapy, and to investigate the usefulness of the ICRU recommendations. Material and methods Treatment plans of forty-nine patients who underwent partial breast irradiation with interstitial brachytherapy were analyzed. Quantitative parameters were used to characterize dose homogeneity. Dose non-uniformity ratio (DNR), dose homogeneity index (DHI), uniformity index (UI) and quality index (QI) were calculated. Furthermore, parameters recommended by the ICRU 58 such as minimum target dose (MTD), mean central dose (MCD), high dose volume, low dose volume and the spread between local minimum doses were determined. Correlations between the calculated homogeneity parameters and usefulness of the ICRU parameters in image-based brachytherapy were investigated. Results Catheters with mean number of 15 (range: 6-25) were implanted in median 4 (range: 3-6) planes. The volume of the PTV ranged from 15.5 cm3 to 176 cm3. The mean DNR was 0.32, the DHI 0.66, the UI 1.49 and the QI 1.94. Related to the prescribed dose, the MTD was 69% and the MCD 135%. The mean high dose volume was 8.1 cm3 (10%), while the low dose volume was 63.8 cm3 (96%). The spread between minimum doses in central plane ranged from −14% to +20%. Good correlation was found between the DNR and the DHI (R2=0.7874), and the DNR correlated well with the UI (R2=0.7615) also. No correlation was found between the ICRU parameters and any other volumetric parameters. Conclusions To characterize the dose uniformity in high-dose rate breast implants, DVH-related homogeneity parameters representing the full 3D dose distributions are mandatory to be used. In many respects the current recommendations of the ICRU Report 58 are already outdated, and it is well-timed to set up new recommendations, which are more feasible for image-guided conformal interstitial brachytherapy.

Pathologic Complete Remission after Preoperative High-Dose-Rate Brachytherapy in Patients with Operable Cervical Cancer: Preliminary Results of a Prospective Randomized Multicenter Study

The role of preoperative intrauterine brachytherapy (BT) in the multidisciplinary treatment of early stage cervical carcinoma (ESCC) is controversial. In 2005, a prospective randomized multicenter study was initiated in Hungary in order to explore the potential advantages of preoperative high-dose-rate (HDR) BT. In this article we evaluate the efficiency of preoperative HDR BT by the rate of pathologic complete remission (pCR) in the first 185 patients enrolled in the study at the National Institute of Oncology and at the Uzsoki Municipal Cancer Center in collaboration with the 1st Department of Gynaecology and Obstetrics of Semmelweis University, Budapest, Hungary. In arm A, patients received 2x8Gy preoperative intracavitary HDR BT, while in arm B no preoperative treatment was given. In both arms patients underwent radical Wertheim (Piver III) hysterectomy. The pCR rate was 25.7% after preoperative HDR BT, while it was only 11.2% with surgery alone (p=0.03), in these cases the tumor was eliminated during the diagnostic excision or conisation. The rate of positive surgical margins was 1.5% after preoperative BT, while it was as high as 11.4% without preoperative RT (p=0.02). There was no significant difference in the local tumor control (LTC), distant metastases free survival (DMFS) and overall survival (OS) between the two arms. According to our preliminary results preoperative intracavitary HDR BT significantly increases the rate of pCR and decreases the rate of positive surgical margins in patients with ESCC. Longer follow-up is required to establish the possible impact of pCR on the ultimate LTC and OS.

Második emlőmegtartó műtét és szövetközi sugárkezelés az emlődaganat lokális kiújulásának kezelésére. Ötéves eredmények

INTRODUCTION AND AIM To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. METHOD Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1-2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan-Meier method. Late side effects and cosmetic results were also registered. RESULTS The median follow-up time following the second breast conserving therapy was 61 months (range: 26-189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. CONCLUSION Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430-438.Absztrakt: Bevezetes es celkitűzes: Masodik emlőmegtarto műtet es nagy dozisteljesitmenyű szovetkozi sugarkezeles eredmenyeinek bemutatasa azonos oldali emlődaganat kiujulasa miatt kezelt betegeknel. Modszer: Korai invaziv emlőrak előzetes emlőmegtarto kezelese utan jelentkező helyi daganatkiujulas miatt 1999 es 2015 kozott 33 betegnel vegeztunk masodik emlőmegtarto műtetet perioperativ szovetkozi sugarkezelessel. A masodik emlőmegtarto műtet soran a tumoragyba atlagosan 8 (tartomany: 4–24) darab flexibilis katetert ultettunk be. A perioperativ időszakban a tumoragy es annak 1–2 cm-es biztonsagi zonajanak teruletere adott osszdozis 22 Gy volt (5 × 4,4 Gy, 3 nap alatt). Adjuvans szisztemas kezeleskent 24 beteg (73%) egyeduli endokrin kezelesben, 6 beteg (18%) pedig kemoterapiaban reszesult. A tulelesi eredmenyeket a Kaplan–Meier-modszerrel elemeztuk. A kesői mellekhatasokat es a kozmetikai eredmenyeket feljegyeztuk. Eredmenyek: A masodik emlőmegtarto kezelestől szamitott kovetesi idő kozeperteke 61 honap (...