A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial.

BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

Overall survival, disease-specific survival and local recurrence outcomes in patients with muscle-invasive bladder cancer treated with external beam radiotherapy and brachytherapy: a systematic review.

INTRODUCTION: Neoadjuvant chemotherapy followed by radical cystectomy (RC) and pelvic lymph node dissection is the standard radical management for muscle-invasive bladder cancer (MIBC). However, major pelvic surgery is not suitable for all patients and combined modality therapy (CMT) offers an alternative for patients who want to retain their bladder. Brachytherapy (BT), as part of CMT, has been offered in selective cases of bladder cancer. OBJECTIVES: To evaluate the clinical effectiveness of BT for solitary urinary bladder tumours in terms of survival, local recurrence (LR) rates, and adverse events. METHODS: A systematic review was conducted using defined search terms using online databases. Articles that discussed the use of BT as part of multi-modality treatments for MIBC were included. RESULTS: Searches returned 112 articles of which 20 were deemed suitable for analysis. In all, 15 of the 20 articles reported overall survival (OS) at 5 years, 2747 patients were at risk and 1670 were alive after 5 years (60%): seven studies reported OS at 10 years, with 817 patients at risk and 350 alive at 10 years (42%). Disease-specific survival at 5 years was reported in four studies, with 371 patients at risk and 279 alive (75%) at 5 years. LR rates were reported across all 20 studies and ranged from 0% to 32%. CONCLUSION: Brachytherapy as part of CMT for MIBC is not a standard technique. It is an effective treatment in experienced centres for a selected patient population who wish to preserve their bladder. In such patients, CMT-BT is well tolerated with an acceptable safety profile.

Dosimetric analysis of urethral strictures following HDR (192)Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer.

BACKGROUND AND PURPOSE: To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer. MATERIAL AND METHODS: Ten strictures were identified in 213 patients treated with HDRBT alone receiving 34Gy in four fractions, 36Gy in four fractions, 31.5Gy in 3 fractions or 26Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra. RESULTS: Stricture rates were 3% in the 34Gy group, 4% in the 36Gy group, 6% in the 31.5Gy group and 4% in the 26Gy group. The median time to stricture formation was 26months (range 8-40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule. CONCLUSIONS: Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.

Image-guided vulvovaginal interstitial brachytherapy in the treatment of primary and recurrent gynecological malignancies.

PURPOSE: Evaluation of interstitial high-dose-rate brachytherapy (HDRB) to the vulvovaginal region both alone and in combination with external beam radiotherapy (EBRT) for primary or recurrent gynecological malignancy. METHODS AND MATERIALS: From 1998 to 2009, 37 women with a mean age of 68 years were treated with transperineal interstitial HDRB. Fifteen patients (40.5%) were treated for primary disease, whereas 22 (59.5%) patients were treated for recurrent disease. Median time to local recurrence was 31 months (2-312 months). Primary sites included endometrium (12), vulva (11), vagina (10), vulvovagina (1), cervix (1), and bladder (2). Thirty-one patients (83.7%) in this series were treated with radical intent, whereas 6 (16.3%) were treated with palliative intent. Radically treated patients received between 45 and 60Gy (median, 45Gy) of EBRT. The median number of days from EBRT to HDR boost was 5 days (1-35 days). The HDRB doses ranged from 11Gy in two fractions to 42Gy in six fractions (dose per fraction varied from 4 to 8.5Gy) and fractions were given at least 6-8h apart. RESULTS: Eight of the 31 patients (26%) treated with radical intent relapsed locally. Eleven of 37 patients (30%) treated with either radical or palliative intent recurred locally. The 2- and 5-year local progression-free survival was 74% and 63.4%, respectively. The total progression-free survival, which includes local, locoregional/nodal, and distant recurrence, at 2 and 5 years, was 73.6% and 45.6%, respectively. With a mean follow-up of 27 months (3.8-111.9 months), the median survival for the patient group was 16.6 months with a 2- and 5-year overall survival of 47.7% and 36.4%, respectively. Acute Grade 3 toxicity was seen in 13 (35%) of the 37 patients (skin: 10, urinary: 2, genital: 2, gastrointestinal: 0). No acute Grade 4 toxicities were seen. A total of 10 of the 37 patients (27%) developed late Grade 3 toxicities. Five of the 22 patients (22%) treated for recurrent disease with radical intent developed Grade 3 toxicity (skin: 4, urinary: 2, genital: 1, radiation-induced fracture of acetabulum: 1, and gastrointestinal: 0), whereas 1 of the 6 patients treated with palliative intent had Grade 3 toxicity affecting skin. No late Grade 4 toxicities were seen. CONCLUSION: This retrospective series suggests that interstitial perineal HDRB is a safe and effective treatment option for primary or locally recurrent gynecological malignancies. It is a valuable option in patients who have received previous EBRT to the pelvis, achieving good local control with acceptable late treatment-related side effects.