Prospective, Randomized, Controlled Pivotal Trial of Biodegradable Balloon Rectal Spacer for Prostate Radiation Therapy.

PURPOSE/OBJECTIVES: Rectal spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We evaluated efficacy and safety of a novel rectoprostatic spacer balloon which allows potential for controlled, adaptable deployment. This study tested co-primary hypotheses: 1) Balloon spacer would result in ≥ 25% reduction of rectal V70 in > 75% of subjects, and 2) Implantation procedure-related and rectal ≥ Grade 1 adverse events within 6 months (duration ≥ 2 days, CTCAE 4.0) would be non-inferior in balloon vs control subjects. MATERIALS/METHODS: 222 subjects were enrolled at 16 centers. All patients had T1-T3 prostate cancer without MRI evidence of posterior extraprostatic invasion. Randomization was 2:1 (balloon: control) and subject-blinded. Patients underwent transperineal TRUS-guided fiducial placement +/- balloon, followed by IMRT (81 Gy in 1.8 Gy fractions or biologically equivalent hypofractionated dose). For efficacy comparisons, plans were generated by a central core lab on pre- and post-implant CT scans. RESULTS: The primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction >25% (p<0.001). Mean V70 was 7.0 % pre- vs 1.1% post- implant. The primary safety endpoint was met with balloon subjects experiencing fewer ≥ Grade 1 events, 18% vs 23% (p < 0.001 for non-inferiority). On pre-defined secondary endpoint of ≥ Grade 2 events, rates trended lower in balloon subjects (4.3% vs 6.5%, p=0.527). Mean perirectal spacing was 19 ±3.7mm and maintained through radiation treatment (18 ±3.9mm). Balloon resorption was observed on 6-month CT in 98.5% (133/135) of subjects. The EPIC QOL instrument was collected throughout study, and did not differ statistically between the study arms. CONCLUSIONS: Biodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months.

Image-guided high-dose-rate brachytherapy for prostate cancer patients with previous rectal resection and pelvic irradiation: feasibility study.

PURPOSE: The aim of this study was to describe treatment procedure and early clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy (BT) in clinically localized prostate cancer patients previously treated for rectal cancer with abdominoperineal rectal resection and external beam radiation therapy (EBRT). MATERIAL AND METHODS: Between February and July 2015, two patients with clinically localized prostate cancer without rectal access were treated in our brachytherapy department. HDR interstitial brachytherapy was conducted with the guidance of fluoroscopy and computed tomography (CT) imaging. Brachytherapy was combined with hormonal therapy. RESULTS: Follow-up lasted for 34 and 39 months for patient 1 and 2, respectively. Both patients remained free from biochemical recurrence according to the Phoenix definition. No severe G3/G4 late toxicity was observed, and neither patient experienced any gastrointestinal morbidity. Acute and late urinary toxicities were at an acceptance level, and were scored G1 and G2 for patient 1, and G3 and G1 for patient 2, respectively. CONCLUSIONS: Fluoroscopy and 3D CT image-guided interstitial brachytherapy is feasible and appears to be a suitable treatment technique for patients with clinically localized prostate cancer after previous rectal resection and external beam radiation therapy.

New therapeutic approaches in the treatment of node-positive cervical cancer patients based on molecular targets: a systematic review.

Cervical uterine cancer is the second most frequent female cancer worldwide and a substantial burden for low-income societies and the patients themselves. Understanding the molecular mechanisms of metastasis permits the development of therapies that limit tumor progression, as well as providing health and social benefits. Pathomorphology is still the basis of research and a reference standard for molecular analysis. The aim of our study was to research and critically evaluate clinical trials that use new oncological approaches for node-positive cervical cancer to gain an insight into the molecular mechanisms of tumor metastasis. INCLUSION CRITERIA: node-positive disease at baseline; at least a first phase clinical study comprising adult female patients; novel clinical approach (e.g., radiotherapy, immunotherapy, targeted therapy, vaccines, radiosurgery); histologic measurement of treatment efficacy (preferably lymph node ultrastaging); and publications in English language only. INFORMATION SOURCES: US Clinical trials registry, EU Clinical trials register, ISRCTN registry, and Ovid, EBSCO and Cochrane Collaboration databases. Access dates: from January 2010 to April 2018. EXCLUSIONS: Abstracts that did not meet the inclusion criteria or with unreliable data. We collected complete data (e.g., the entire publication associated with included abstracts, heterogeneity examination of individual studies, and validity measurement of the statistical methods used). Results were analyzed in relation to the most recent understanding of the pathogenesis of cervical cancer metastasis. We proposed a possible direction for drug treatment of epithelial tumors based on the mechanisms of metastasis.

Computed Tomography-Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer.

PURPOSE: To evaluate the long-term results of computed tomography (CT)-planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. METHODS AND MATERIALS: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. RESULTS: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. CONCLUSIONS: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography-CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.

HDR brachytherapy as a solution in recurrences of locally advanced prostate cancer.

PURPOSE: The object of this study was to analyze the outcome of salvage HDR brachytherapy treatment after local failure, for patients with prostate specific antigen (PSA) failure without distant metastasis, after external beam radiation and HDR brachytherapy treatment, or after radical prostatectomy, with or without hormonal therapy. MATERIAL AND METHODS: The group of 115 patients, without distant metastasis, after local failure and external beam radiation, followed by HDR brachytherapy treatment, or after radical prostatectomy, with hormonal therapy and without, have been enrolled to salvage HDR brachytherapy (SBR). All patients had minimum 3 months androgen deprivation therapy before salvage brachytherapy, which was continued until the next 9 months after SBR. Brachytherapy was administered in three 10 Gy fractions with 3 weeks gap between them. Each session of SBR was supported by trans-rectal USG real time pictures. The treatment planning was done on the base of Abacus system from Sauerwein® or with SWIFT system from Nucletron®. The following data were collected: Gleason score, clinical staging, the volume of the prostate, PSA before and after the initial treatment and periodically during the follow-up period. Also the time during which the PSA stays at the nadir level, patient's age and toxicity of treatments were taken into consideration. RESULTS: Doses from external radiotherapy or from HDR brachytherapy were recalculated to equivalent biological dose (EBD). The independence from biochemical progression in our group of patients after retreatment was 46% for patients with PSA ≤ 6 and 18% for patients with PSA > 6. Overall survival for patients with PSA ≤ 6 was 86% and 48% for patients with PSA > 6, respectively. CONCLUSIONS: Salvage prostate brachytherapy (SBR) can be safely performed with acceptable biochemical control and toxicity.