Mathieu Gautier

Interstitial high-dose rate brachytherapy as boost for anal canal cancer

AimTo assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC).MethodsFrom August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed.ResultsMedian age was 60.6 years [34 - 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 - 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation.ConclusionHigh-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time.

Interstitial preoperative high-dose-rate brachytherapy for early stage cervical cancer: Dose–volume histogram parameters, pathologic response and early clinical outcome

PURPOSE To analyze dose-volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). METHODS AND MATERIALS From June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. RESULTS With a median clinical target volume of 50cc (minimum-maximum, 42-74), the median V100 was 49cc (minimum-maximum, 42-50). Median D90 was 45Gy (equivalent dose at 2Gy per fraction, 56Gyαβ10). Median D2cc was 34Gy, 31Gy, 28Gy, and 38Gyαβ3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum-maximum, 5-48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2-G3 toxicities were noticed. CONCLUSIONS Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose-volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.

Combination of phosphotidylinositol‐3‐kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer

The purpose of this study was to investigate the effects of combining the phosphotidylinositol‐3‐kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti‐epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC).

Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer.

Purpose There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB) boost for locally advanced cervical cancer. Material and methods From 01.2011 to 12.2014, 33 patients (pts) presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid) and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results Median age was 56.4 years (27-79). Clinical stages were: T2b = 23 pts (69.7%), T3a = 1 pt (3%), T3b = 6 pts (18.2%), and T4a = 3 pts (9.1%). Median HDRB prescribed dose was 21 Gy (21-27). Median CTVCT (16 pts) and HR-CTVMRI (17 pts) were 52.6 cc (28.5-74.3), 31.9 cc (17.1-58), respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5), 84.8 Gy (80.6-91.4), respectively. Median EQD2αβ3 (CT/MRI) for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9), 64.4 Gy (51.9-77.4), and 60.4 Gy (50.9-81.1), respectively. Median follow-up was 14 months (ranged 6-51). Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pts, G3 infection = 2 pts), and 27% (G1 diarrhea = 9 pts), respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion); no bleeding was observed due to the parametrial implant. Conclusions Concomitant cervical and transperineal parametrial HDRB boost for locally advanced cervical cancer appears feasible and safe with no specific acute toxicity compare to cervical HDRB alone. Longer follow-up and larger patient cohort will be needed.

Prostate cancer boost using high-dose-rate brachytherapy: early toxicity analysis of 3 different fractionation schemes

Purpose To analyse early toxicity of high-dose-rate brachytherapy (HDRB) boost for prostate cancer using 3 fractionation schemes. Material and methods From February 2009 to May 2012, after the first course of external beam radiation therapy (EBRT 46 Gy/23 f), 124 patients underwent HDRB boost for low (7%), intermediate (19%), and high-risk (73%) prostate cancers. From February to December 2009, Group 1 (G1) = 18 Gy/3 f/2 d (24%); from January 2010 to April 2011, Group 2 (G2) = 18 Gy/2 f/2 d (42%), and from May to September 2011, Group 3 (G3) = 14 Gy/1 f/1 d (34%). Planning and CT-scan was performed before each fraction. Dose constraints for G1/G2 were V100 rectum = 0 and V125 urethra = 0, while for G3 V90 rectum = 0 and V115 urethra = 0. Genito-urinary (GU) and Gastro-intestinal (GI) acute toxicities were assessed at 1 month (for the 3 fractionation schemes) and 6 months (for 18 Gy/3 f and 18 Gy/2 f) after the boost (CTCv3.0). Results Median follow-up was 25 months (8-46.9), median age was 71 years (50-82), and median CTV was 31 cc (16-71). The grades of acute GI and GU toxicities at 1 and 6 months after HDRB were mainly Grade 1 with few Grade 2 (GU: 5% at 1 month; GI: 1% at 6 months). One patient developed G4 sepsis toxicity 2 days after HDRB and recovered without after-effects. No significant differences were observed at 1 and 6 months after the HDRB between treatment groups. Conclusions The right fractionation remains under discussion, but prostate cancer HDRB boost using a single fraction (providing similar results in terms of acute toxicity) is more comfortable for the patient, and less time consuming for the medical staff.

Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial

PURPOSE/OBJECTIVE To evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation (APBI) in the elderly. MATERIAL/METHODS From November 2012 to September 2014, 26 patients (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intra-operative catheter implant was performed for post-operative APBI (single fraction 16 Gy). Surveillance was achieved at 1, 3 and 6 months after APBI, then twice a year. Acute toxicity was investigated. Early cosmetic outcome was analyzed (patient, radiation oncologist, 2 observers). Local and regional relapse-free survival, cancer specific survival and overall survival were analyzed. RESULTS Median age was 77 years [69-89]. Median CTV was 41 cc [22-95]. Acute toxicity was observed in 18 pts (70%) with a total of 44 events: G1: 75.7%; G2: 22.8%; G3: 4.5%. Breast fibrosis (31.8%), puncture site inflammation (13.6%) and skin hyperpigmentation (11.4%) were the most frequent side effects. Cosmetic evaluation at 6 months was excellent/good in 88%, 92%, 85% and 88% for patient, radiation oncologist, observer #1 and #2 respectively. With a median follow-up of 37.2 months [35.6-42.3], side effects were G1: 4 pts (15%) and G2: 1 pt (4%). Three-year Local and regional relapse-free survival, cancer specific survival and overall survival rates were 100%, 100%, 100% and 95.2% respectively. CONCLUSIONS For elderly early breast cancer, a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose (16 Gy) appears feasible. Acute toxicity is acceptable as well as early cosmetic outcome. Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI.

Second salvage treatment for local recurrence of prostate cancer using high-dose-rate brachytherapy: a case report.

Purpose Currently, there are no recommendations for the management of a second local recurrence of prostate adenocarcinoma except for the introduction of androgen deprivation therapy (ADT). Case report A 69-year-old man underwent a third salvage local treatment with high-dose-rate brachytherapy (HDRB), for a second biochemical relapse for local recurrence. Thirty-five Grays in 5 fractions were delivered on the whole prostate extended to the proximal part of left seminal vesicle. Given the availability of new treatment techniques in our radiation therapy department, a dosimetric comparison between HDRB and stereoatactic radiosurgery (SRS) was performed. Results Immediate tolerance of HDRB was acceptable with achievement of prostate specific antigen (PSA) nadir in 24 months (0.03 ng/ml). Observed late toxicities were only grade 2 urinary incontinence. Dosimetric comparison showed a slight advantage on clinical target volume coverage and rectum protection for the SRS. The HDRB showed an advantage on bone irradiation including femoral heads and the volume receiving 0.5 Gy (EQD2 = 1 Gy with α/β = 3). Conclusions A third local treatment with good tolerance could be a therapeutic option in case of a second local prostate cancer recurrence in order to delay, as long as possible, the chemical castration. Both techniques (HDRB and SRS) seem valid and should be chosen based on the availability and experience in a treatment center.

Brachytherapy versus external beam radiotherapy boost for prostate cancer: Systematic review with meta-analysis of randomized trials

BACKGROUND Brachytherapy boost after external beam radiotherapy for intermediate and high-risk prostate cancer is presented as an attractive technique in numerous retrospective and prospective studies. Currently, three randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost used non-homogenous irradiation features. Therefore, we analyzed the oncological outcomes by a systematic review with meta-analysis of the randomized controlled trials. METHODS We performed a systematic literature review of MEDLINE and COCHRANE databases up to 30/04/10 and we considered all published randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost for intermediate and high-risk prostate cancer according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The review was assessed using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT). Eight publications from 3 RCTs were selected. RESULTS There was a significant benefit in 5-year biochemical-progression-free survival in favor of BT versus EBRT boost (HR: 0.49 [95% CI, 0.37-0.66], p < 0.01). There was no difference at 5 years in overall survival (HR: 0.92 [95% CI, 0.64-1.33], p = 0.65), ≥ grade 3 late genito-urinary (RR: 2.19 [95%CI, 0.76-6.30], p = 0.15) and late gastro-intestinal toxicities (RR: 1.85 [95%CI, 1.00-3.41] p = 0.05). CONCLUSION This meta-analysis provides further evidence in favor of BT boost for intermediate and high-risk prostate cancer in terms of b-PFS improvement, leading to suggest BT boost as level I and grade A recommendation. However, the risk of grade ≥ 3 late toxicity must be carefully investigated.