An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry

Purpose

To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment.

Methods and materials

The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated.

Results and conclusions

Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.     

High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results

PURPOSE: To present the long-term outcome and morbidity of high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: Between September 1991 and December 1998, 209 consecutive patients with no prior androgen suppression were treated with HDR-BT plus EBRT. The median follow-up was 7.25 years (range, 5-12 years). The patients were stratified into three risk groups: low (Stage T2a or less, Gleason score 20). Four definitions of PSA progression were compared with the general clinical failure outcome: the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, nadir plus 2.0 ng/mL, two consecutive rises >/=0.5 ng/mL, and PSA level >0.2 ng/mL. Morbidity was scored using Radiation Therapy Oncology Group criteria. RESULTS: The general clinical control rate was 90% (188 of 209), and the general clinical failure rate was 10% (21 of 209). The overall survival rate was 79%, and the cause-specific survival rate was 97%. The PSA progression-free survival (ASTRO definition) rate was 90%, 87%, and 69% for the low-, intermediate-, and high-risk groups, respectively. The nadir plus 2 ng/mL and two rises >/=0.5 definitions correlated better with the actual clinical outcome than did the ASTRO and PSA >0.2 ng/mL definitions. The rate of Grade 3 and 4 late urinary morbidity was 6.7% and 1%, respectively, mostly occurring in patients who had undergone post-RT transurethral prostate resection. No late Grade 3 or 4 rectal morbidity developed. The sexual potency preservation rate was 67%. CONCLUSION: Our 10-year results have demonstrated HDR-BT plus EBRT is a proven treatment for all stages of localized prostate cancer. The morbidity was low, but post-RT transurethral resection should be avoided.     

Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

BACKGROUND: A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. METHODS AND MATERIALS: Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400 cGy per fraction. RESULTS: At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. CONCLUSION: HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than were indicated by previously reported data for LDR brachytherapy.     

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。     

HDR brachytherapy decreases proliferation rate and cellular progression of a radioresistant human squamous cell carcinoma in vitro

Purpose: To investigate the effects of high dose rate (HDR) brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters.

Materials and methods: An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated twice up to 1100 cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay. DNA content analysis and cell cycle phases were assessed by flow cytometry and gel electrophoresis, respectively. Cellular death patterns were measured by HOPI double-staining method.

Results: Significant decreasing cellular proliferation rate (p?<?0.05) as well as reduced survival fraction (p?<?0.001) in irradiated cells were observed. Moreover, increased percentage of cells arrested in the G₂/M phase (32.3?±?1.5%) in the irradiated group as compared with untreated cells (8.22?±?1.2%) was detected. Also, a significant (p?<?0.0001) nuclei shrinking in irradiated cells without evidence of necrosis or apoptosis was found.

Conclusion: HDR brachytherapy led to a decreased proliferation rate and cell survival and also hampered cellular progression to mitosis suggesting that tumor cell death mainly occurred due to mitotic death and G₂/M cell cycle arrest.     

Design and characterization of an intracavitary ultrasound hyperthermia applicator for recurrent or residual lesions in the vaginal cuff

For evaluating the feasibility of treating recurrent lesions in the vaginal cuff by hyperthermia, a 2-element ultrasound applicator was designed, constructed and characterized. A half-cylindrical transducer ( d = 1 cm, length = 1 cm) was used to construct the 2-element ultrasound applicator. Each element of this applicator was operated at 1.5 MHz and characterized by measuring transducer efficiency and acoustic power distribution. Thermocouple probes were used to measure the temperature rise in the phantom. The element sizes used in this study were selected to be comparable to a high dose rate brachytherapy colpostat applicator. Each element was powered separately to achieve a desired temperature pattern in a target. The acoustic output power as a function of applied electric power of elements 1 and 2 were linear over this 1-40 W range and efficiencies were 32.2 &#45 3.4% and 46.2 &#45 0.8%, respectively. The temperature measurements in the phantom showed that a 6°C temperature rise was achieved 2 cm from the applicator surface. As a conclusion, the ability of the ultrasound colpostat applicator to be used for hyperthermia was demonstrated by measuring acoustic output power, ultrasound field distribution and temperature rise in the phantom. Based on the characteristics of this applicator, it has the potential to be useful for inducing hyperthermia to the vaginal cuff in the clinic.     

宫颈癌放射治疗远期疗效的临床研究

目的：明确宫颈癌单纯放疗时低、高剂量率近距离治疗、外照射中线挡铅与否的远期疗效和放射性损伤,指导宫颈癌放射治疗技术改进。方法：回顾性分析了240例Ⅰ～Ⅲ期宫颈癌的放射治疗后的长期随访结果,比较低、高剂量率后装治疗和盆腔大野中线挡铅与否的疗效和副作用。结果：全组随访时间为13～16a,中位随访时间14.6a,随访率90%。10a总生存率为69.17%。Ⅰ期10a生存率100%,Ⅱ期83.05%,Ⅲ期46%。低剂量率组10a生存率Ⅰ期是100%,Ⅱ期64.71%,Ⅲ期42.86%。高剂量率组10a生存率是Ⅰ期92.31%,Ⅱ期62.69%,Ⅲ期41.38%。低、高剂量率组Ⅰ期中线挡铅与不挡铅的10a生存率分别为100%、100%和100%、100%;Ⅱ期的10a生存率分别是64.52%、65%和63.89%、61.29%。Ⅲ期的10a生存率分别是40%、45.45%和43.33%、39.29%。经过显著性检验,P〉0.05。本组3、4级放射性直肠炎总发生率为13.13%,其余均为1、2级放射性直肠炎,挡铅组的副反应较轻。放射性膀胱炎发生率为8.8%,多为1、2级。结论：低、高剂量率近距离治疗的疗效均较好,后者较前者具有较多的优越性,建议推广使用高剂量率近距离治疗,对经济状况不好的病人,可以采用盆腔大野照射,但应降低近距离照射的剂量。     

Perioperative morbidity and mortality of high-dose-rate gynecologic brachytherapy

Purpose: To determine the 30-day morbidity and mortality rates for patients with an intact uterus undergoing high-dose-rate (HDR) brachytherapy, and to assess risk factors which may predict for these potentially life-threatening complications.

Methods and Materials: From August 1989 to December 1994, 128 cervical and 41 medically inoperable endometrial cancer patients were treated with 5 outpatient weekly HDR brachytherapy insertions. Patients with cervical cancer also were treated with external beam radiotherapy. Acute events that resulted in either hospitalization (morbidity) or death (mortality) within 30 days of the implant were analyzed. Univariate and multivariate analyses were performed to identify risk factors.

Results: Overall there were 16 acute events in 169 patients (9.5%). The overall morbidity and mortality rates for the cervical and endometrial patients were 5.5%, 1.6%, 7.3%, and 9.8%, respectively. The following factors were significant by univariate analysis: age per decade, American Society of Anesthesiologists (ASA) score, Karnofsky Performance Status (KPS), significant medical history, diagnosis of cervical vs. endometrial cancer, and mean time exceeding 160 minutes for the procedure. Since age was the most significant predictive factor (p = 0.0003), bivariate analyses were performed by adjusting for age. In these analyses only ASA and KPS maintained significance, while a positive medical history was of borderline significance (p = 0.07).

Conclusion: The morbidity and mortality rates observed in gynecologic patients selected for HDR brachytherapy were similar to low-dose-rate, but higher than other HDR reports. Reasons for this include a higher risk population, especially those with medically inoperable endometrial cancer. In the cervical cancer patients, some of the complications may have also been a result of the external beam portion of the radiation. In order to minimize the acute complications observed in the present HDR brachytherapy system, the following changes have been implemented: appropriate patient selection, anesthesiology involvement to monitor conscious sedation for high-risk patients, external beam radiotherapy alone in patients at extremely high risk, deep vein thrombosis (DVT) prophylaxis, use of intraoperative ultrasound, shorter duration in the brachytherapy suite, and preradiation treatment plans (plans executed prior to the insertion) if applicable. Finally, this analysis suggests that these procedures should be performed in a hospital-based setting where appropriate support is available.