High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent ¹⁹²Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.     

前列腺癌的高剂量率近距离放射治疗

放疗是前列腺癌根治的重要治疗手段，前列腺癌的近距离放射是近20年来前列腺癌治疗领域的研究热点。多年来早期局限性前列腺癌的近距离放射以低剂量率放射粒子植入为主，但近年来美国各肿瘤治疗中心已逐渐开展了针对局限性前列腺癌的高剂量率（hish-dose-rate，HDR）近距离放射。多项研究结果显示前列腺癌具有低α/β比值，故大分割放射的高剂量率近距离放射对前列腺癌可能更具疗效。HDR近距离放射治疗通常与外放疗联合应用于局部晚期的前列腺癌根治，临床研究结果已初步证实了这一治疗方案的疗效；另外，单一HDR近距离放射治疗也可用于早期前列腺癌的治疗，但其疗效仍需临床研究的进一步支持。HDR近距离放射技术需要经过特殊训练的医师方能操作，以保证良好的治疗结果。     

Percutaneous interstitial brachytherapy for adrenal metastasis: technical report

We developed and evaluated the feasibility of a brachytherapy technique as a safe and effective treatment for adrenal metastasis. Adapting a paravertebral insertion technique in radiofrequency ablation of adrenal tumors, we developed an interstitial brachytherapy for adrenal metastasis achievable on an outpatient basis. Under local anesthesia and under X-ray CT guidance, brachytherapy applicator needles were percutaneously inserted into the target. A treatment plan was created to eradicate the tumor while preserving normal organs including the spinal cord and kidney. We applied this interstitial brachytherapy technique to two patients: one who developed adrenal metastasis as the third recurrence of uterine cervical cancer after reirradiation, and one who developed metachronous multiple metastases from malignant melanoma. The whole procedure was completed in 2.5 hours. There were no procedure-related or radiation-related early/late complications. FDG PET-CT images at two and three months after treatment showed absence of FDG uptake, and no recurrence of the adrenal tumor was observed for over seven months until expiration, and for six months until the present, respectively. This interventional interstitial brachytherapy procedure may be useful as a safe and eradicative treatment for adrenal metastasis.     

A novel approach to advanced carcinoma of the tongue: cases successfully treated with combination of superselective intra-arterial chemotherapy and external/high-dose-rate interstitial radiotherapy

OBJECTIVE: This study sought to evaluate the efficacy and safety of a novel treatment regimen, intra-arterial cisplatin infusion plus external/high-dose-rate radiotherapy. METHODS: Superselective intra-arterial infusion of cisplatin (100-120 mg) was performed concomitantly with external radiotherapy in four patients with locally advanced carcinoma of the tongue. A high-dose-rate brachytherapy boost was performed after combination therapy in all patients. Brachytherapy was performed after external radiotherapy, and the treatment schedule was twice daily, with a fraction of 600 cGy up to a total of 30-48 Gy. RESULTS: All patients completed the therapy as scheduled. There were no vascular or neurological complications. Grade III acute radiation mucositis developed in all patients but this did not necessitate a treatment break. With a mean follow-up period of 35 months, loco-regional control was obtained for all patients. CONCLUSIONS: The combination of weekly administration of intra-arterial cisplatin plus external/high-dose-rate radiotherapy seems effective for advanced carcinoma of the tongue.     

高剂量率后装192Ir源剂量测试研究进展

现代后装治疗大多采用HDR(高剂量率)微型192Ir源,其近源区剂量特性常用针点电离室、热释光剂量计测量,但ESR(电子自旋共振)胶片法测量的空间分辨率更高,可达156μm,而蒙特卡罗光子输运模拟方法是衡量测量准确度的金标准.用热释光剂量计进行直肠内剂量测量是预测直肠并发症发生率的良好指针.慢感光胶片测量193Ir源二维剂量分布精度可达1%,用基于MR(核磁共振)的凝胶剂量计测量192Ir源三维剂量分布准确度可达2.5%、空间分辨率达1.56mm,光学体层成像凝胶剂量计测量三维剂量分布具有独特的优势.     

Phase II trial of image-based high-dose-rate interstitial brachytherapy for previously irradiated gynecologic cancer

PurposeTo report the disease-free Grade ≥3 complication-free survival of a Phase II protocol of reirradiation with high-dose-rate (HDR) interstitial brachytherapy (ITB) in previously irradiated gynecologic cancer.Methods and MaterialsFifteen patients with previously irradiated cervical (n = 6), endometrial (n = 6), and vulvovaginal tumors (n = 3) were treated with HDR-ITB alone to a median dose of 38 Gy in 8 b.i.d. fractions over 4 consecutive days. Prior treatments included surgery (n = 12; 80%), external irradiation (n = 15; 100%), and brachytherapy (n = 9; 60%). Average clinical target volume Size was 60.9 cc (range, 14.8–165.3 cc), and median time to reirradiation was 3.9 years (range, 0.4–22.7 years).ResultsWith a median followup of 2.8 years (range, 1.2–9.2 years), 3 patients (20.0%) developed Grade ≥3 toxicity consisting of Grade 3 intestinal obstruction (n = 1), Grade 4 rectovesical fistula (n = 1), and Grade 5 intestinal obstruction (n = 1). Six patients remain alive and without evidence of disease at last followup. Two patients are alive with disease progression, and 7 patients have died, 4 of them from disease progression and 3 from other causes. The 2-year disease-free Grade ≥3 complication-free survival was 40%.ConclusionsHDR-ITB alone is a reasonable salvage treatment option in a significant number of patients with previously irradiated gynecologic tumors.     

Definitive radiotherapy for primary vaginal cancer: correlation between treatment patterns and recurrence rate

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1–169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III–IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge.     

Factors associated with deformation accuracy and modes of failure for MRI-optimized cervical brachytherapy using deformable image registration

PurposeTo identify factors associated with MRI-to-CT image deformation accuracy and modes of failure for MRI-optimized intracavitary high-dose-rate treatment of locally advanced cervical cancer.Methods and MaterialsTwenty-six patients with locally advanced cervical cancer had preimplantation MRI registered and deformed to postimplantation CT images using anatomically constrained and biomechanical model–based deformable image registration (DIR) algorithms. Cervix (primary) and cervix plus 10-mm margin (secondary) were used as controlling regions of interest for deformation. High-risk clinical target volume defined on pre-MRI was propagated to CT and evaluated for clinical utility in optimizing target volumes using scores 0 (low performing) to 4 (high performing). Quantitative evaluation of deformation performance included Dice index, distance to agreement, center of mass (COM) differences, cervical/uterus volume, and geometric change in organ position for MR-projected structures. Statistical analysis was performed to identify predictors of clinical utility and modes of failure.ResultsAnatomically constrained and biomechanical model–based deformable image registration algorithms achieved clinical utility >3 in 65% and 81% of patients, respectively. This improved to 81% and 85%, respectively, if cervix plus margin was used to drive deformations. Total COM displacement (cervix plus uterus) had the highest sensitivity in predicting low from high clinical utility in optimizing target volumes. Deformation failure (low clinical utility) resulted from high COM displacement, high cervical volume change, and retroverted uterine anatomy.ConclusionsMRI-to-CT deformable image registration using a cervix-controlling region of interest can aid clinical target delineation in cervical brachytherapy and potentially improve brachytherapy implant quality and clinical workflow. Deformation failures warrant further study and prospective deformation validation.