High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer

Purpose: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy.

Methods and Materials: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity.

Results: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded.

Conclusion: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence.     

Intravaginal high-dose-rate brachytherapy for Stage IB (FIGO Grade 1, 2) endometrial cancer

PURPOSE: To evaluate the outcome of patients with Stage IB Grades 1 and 2 endometrial cancer treated with adjuvant high-dose-rate intravaginal brachytherapy. METHODS AND MATERIALS: Between November 1987 and October 1999, 233 patients with Stage IB FIGO Grades 1 and 2 were treated with postoperative adjuvant high-dose-rate intravaginal brachytherapy. The median dose was 21 Gy in 7 Gy/fraction given at 2-week intervals. The mean age was 60 years. All patients underwent simple hysterectomy. Comprehensive surgical staging, defined as pelvic washing and pelvic and paraaortic lymph nodes sampling, was done in 9% of patients. Patients with FIGO Grade 3, papillary serous cancer, or clear-cell cancer were excluded from this analysis. Complications were assessed in terms of late Radiation Therapy Oncology Group toxicity (Grade > or =3) of the gastrointestinal tract, genitourinary tract, and vagina. RESULTS: With a median follow-up of 57 months, the 5-year vaginal/pelvic control, disease-free survival, and overall survival rate was 96% (95% confidence interval [CI] 94-99%), 94% (95% CI 91-98%), and 94% (95% CI 91-98%), respectively. The influence on outcome of age, grade (1 vs. 2), depth of invasion (one-third or less or greater than one-third), capillary space-like invasion, lower uterine segment involvement, and comprehensive surgical staging was evaluated. None of these factors significantly affected the rate of vaginal/pelvic control. Only age > or =60 years influenced the outcome for disease-free and overall survival. The 5-year rate for both disease-free and overall survival was 90% (95% CI 84-97%) for patients > or =60 years old compared with 99% (95% CI 96-100%) for those <60 years (p = 0.03 and 0.005, respectively). Of 233 patients, 3 (1%) developed Grade 3 or greater complications, with a 5-year actuarial rate of 2% (95% CI 0-5%). Two patients developed Grade 3 genitourinary toxicity, and 1 Grade 4 vaginal toxicity. CONCLUSION: On the basis of this retrospective study, adjuvant postoperative high-dose-rate intravaginal brachytherapy provides excellent outcomes and acceptable morbidity. These results compare very favorably with those reported in the literature using surgery alone or with pelvic radiation.     

Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: a randomized study of two dose-per-fraction levels

PURPOSE: To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. METHODS AND MATERIALS: In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator. Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. RESULTS: The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. CONCLUSION: The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.     

Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

PURPOSE: To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. METHODS AND MATERIALS: Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic +/- paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. RESULTS: With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. CONCLUSION: Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.     

早期子宫内膜癌术后单纯腔内近距离治疗的结果

目的 回顾分析术后单纯腔内近距离治疗的早期内膜癌患者临床结果。方法 2004—2013年在我院行术后单纯腔内近距离治疗的早期子宫内膜癌患者共158例。根据2009年FIGO手术—病理分期,Ⅰ _a期105例,Ⅰ _b期53例。主要病理类型为子宫内膜样腺癌(142例,占89.9%),病理分级为G₃级者17例(10.8%)。使用¹⁹²Ir源后装治疗机,照射区域为阴道顶端及上1/2段阴道,参考点定义为阴道黏膜下0.5 cm,照射剂量25~30 Gy分5~6次。Kaplan-Meier法计算生存率并Logrank检验差异,Cox模型进行预后多因素分析。     

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

Purpose

Intermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients.

Material and methods

Eighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66 Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b-T2c, or pre-treatment PSA between 10 and 20 ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7 mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA + 2 ng/mL.

Results

With a median follow-up of 51 months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ?2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity.

Conclusion

HyRT to a dose of 66 Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.     

Postoperative vaginal brachytherapy in endometrial cancer

Several randomized studies published in recent years have greatly changed the management of postoperative endometrial cancer, especially for lesions of intermediate prognosis. Vaginal brachytherapy is now standard treatment for these lesions at the expense of external beam radiation, which, despite an improvement in locoregional control, has no impact on overall survival. This review aims to take stock of new indications for vaginal brachytherapy detailing the trials that led to change standards or care.     

Intraoperative brachytherapy alone for incomplete resected recurrent rectal cancer.

In order to determine the impact of intraoperative brachytherapy alone in patients with recurrent rectal cancer who, due to prior pelvic radiation therapy, were ineligible to receive further external beam pelvic radiation, we retrospectively reviewed the records of 36 patients with recurrent rectal cancer who had gross residual disease remaining in the pelvis following biopsy alone or subtotal resection. The median follow-up was 24 months (6-81 months). The median survival was 27 months and the 4 year actuarial survival was 25%. There was a suggestion of lower survival in patients who underwent biopsy alone compared with those who underwent a subtotal resection (21% vs. 34%). The local failure (LF) rate was 22% as the only site of failure and 44% as a component of failure. There was a lower but non-significant LF rate in patients who underwent subtotal resection vs. biopsy alone (33% vs. 66%) and those with an 125I implant volume of less than 40 cm3 vs. greater than or equal to 40 cm3 (39% vs. 100%). Four patients (11%) developed treatment-related severe complications (without evidence of LF). Our data suggest that, although it is not clear that intraoperative brachytherapy impacts on the ultimate survival rate in this group of patients, it does offer reasonable local control with acceptable morbidity. Since local control, in and of itself is an important endpoint in the treatment of rectal cancer, we continue to recommend brachytherapy as part of an overall aggressive approach in patients who are unable to receive pelvic radiation therapy.     

Gynecologic brachytherapy-II: Intravaginal brachytherapy for carcinoma of the endometrium

Brachytherapy plays a significant role in the management of endometrial cancer. In the adjuvant setting, based on pathologic risk factors, intravaginal brachytherapy alone, external radiation therapy alone, or a combination of the two is recommended. For patients who are medically inoperable, brachytherapy with or without external beam therapy is the mainstay of treatment. In recurrent disease, to achieve improved local regional control interstitial and/or intravaginal brachytherapy is used as a boost. This article will highlight the indications and technical aspects of postoperative intravaginal brachytherapy, which is the most common application of brachytherapy in endometrial cancer.     

59例子宫内膜癌单纯放射治疗

目的 评价子宫内膜癌单纯放射治疗的效果,分析影响治疗效果的因素。方法 对５９例子宫内膜癌病例病进行回顾性分析,其中Ｉ期１７例,Ⅱ期２６例,Ⅲ期１４例,Ⅳ期２例。休外照射应用６或８ＭＶＸ射线直线加速器,后装治疗应用ＷＤ－ＨＤＲ１８及（或）Ｂｕｃｈｌｅｒ）后装治疗机。结果 该组患者５年生存率为５年生存率为６４．３％,其中Ｉ期为７９．２％,Ⅱ期为７５．３％,Ⅲ期为３１．４％,Ⅳ期为０．０％。期别、病理组     

High-dose-rate postoperative vaginal cuff irradiation alone for stage IB and IC endometrial cancer

PURPOSE: To evaluate the effectiveness of postoperative high-dose-rate (HDR) vaginal cuff irradiation alone (1500 cGy in 3 fractions) in patients with Stage Ib and Ic endometrial cancer. METHODS AND MATERIALS: This is a retrospective review of 102 patients with Stage Ib and Ic endometrial cancer treated with a hysterectomy and postoperative HDR intracavitary therapy alone during the period of 1/1/90-12/31/96. Each patient received 1500 cGy in 3 weekly treatments, dosed to a depth of 0.5 cm. Pathologic features such as depth of invasion, tumor grade, lower uterine segment (LUS) involvement, and lymphvascular invasion (LVI) were evaluated for their impact on recommended postoperative treatment. All survival curves were generated utilizing Kaplan-Meier methods and all statistical comparisons were via a Wilcoxon rank sum test. RESULTS: The 5-year actuarial overall survival (OS) is 84% and the 5-year disease-free survival (DFS) is 93%. Locoregional disease control (pelvic control) was excellent with 97% of the patients free of pelvic disease at 5 years. Of the three pelvic failures only one was in the vaginal cuff. LVI, LUS involvement, Grade 3 and/or outer third myometrial involvement were identified in 41 patients. Thirty-one of these patients underwent a lymphadenectomy and there were two regional failures within this increased-risk group. CONCLUSIONS: We obtained an excellent level of locoregional control with minimal morbidity and minimal time commitment for treatment with vaginal HDR brachytherapy alone. Our dose per fraction and total dose is lower than most reported series and there is no apparent loss in locoregional control. In addition, intermediate-risk patients and patients with an increased risk of recurrence (Grade 3, outer third myometrial involvement, LVI, LUS) may be treated with cuff irradiation alone, after surgical staging and a negative lymphadenectomy.     

Cost minimization analysis of high-dose-rate versus low-dose-rate brachytherapy in endometrial cancer

Purpose: Endometrial cancer is a common, usually curable malignancy whose treatment frequently involves low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. These treatments involve substantial resource commitments and this is increasingly important. This paper presents a cost minimization analysis of HDR versus LDR brachytherapy in the treatment of endometrial cancer.Methods and Materials: The perspective of the analysis is that of the payor, in this case the Ministry of Health. One course of LDR treatment is compared to two courses of HDR treatment. The two alternatives are considered to be comparable with respect to local control, survival, and toxicities. Labor, overhead, and capital costs are accounted for and carefully measured. A 5% inflation rate is used where applicable. A univariate sensitivity analysis is performed.Results: The HDR regime is 22% less expensive compared to the LDR regime. This is $991.66 per patient or, based on the current workload of this department (30 patients per year) over the useful lifetime of the after loader, $297,498 over 10 years in 1997 dollars.Conclusion: HDR brachytherapy minimizes costs in the treatment of endometrial cancer relative to LDR brachytherapy. These results may be used by other centers to make rational decisions regarding brachytherapy equipment replacement or acquisition.     

Interstitial brachytherapy for salvage treatment of vaginal recurrences in previously unirradiated endometrial cancer patients

PURPOSE: To evaluate whether interstitial brachytherapy can effectively salvage vaginal recurrence from endometrial carcinoma. METHODS AND MATERIALS: Between September 1989 and September 2000, 13 previously unirradiated patients (mean age 70 years) with isolated vaginal recurrences from endometrial adenocarcinoma were treated with interstitial low-dose-rate brachytherapy with or without additional external beam radiotherapy. Brachytherapy was delivered using a modified perineal Syed template loaded with (192)Ir. The central cylinder was loaded with high-activity (192)Ir (n = 12) or (137)Cs (n = 1). RESULTS: The patients had initially presented with FIGO Stage I (n = 11) or III (n = 2) cancer. Vaginal recurrences were diagnosed at a mean interval of 27.5 months after hysterectomy (range 2-83). The patients were followed for a median of 60 months (range 15-105). Ten patients had recurrence at the vaginal apex and three had recurrence in the lower two-thirds of the vagina. The median time to recurrence was 22 months. The tumor size ranged from 1.5 to 6 cm (mean 2.2, median 2.5). Eleven of 13 patients received 45-50-Gy pelvic external beam radiotherapy, followed by a mean interstitial brachytherapy boost of 28.3 Gy (range 18-35). The 2 other patients received brachytherapy only of 40 Gy and 50 Gy, respectively. All tumors were locally controlled. Three (23%) of 13 patients had a relapse at distant sites (two in the paraaortic region and one in the liver). The overall 8-year actuarial disease-specific survival rate was 77%. Major (Grade 3 and 4) long-term morbidity occurred in 2 patients (15%) and included Grade 3 vaginal ulceration in 1 patient, and Grade 4 colovesical fistula requiring surgical intervention in 1 patient. Additional long-term morbidity included Grade 2 proctitis in 1 patient. CONCLUSION: Interstitial brachytherapy with or without supplementary external beam radiotherapy can effectively salvage vaginal recurrence from endometrial cancer with very favorable local control and overall survival and acceptable morbidity.     

Clinically evident fat necrosis in women treated with high-dose-rate brachytherapy alone for early-stage breast cancer

PURPOSE: To investigate the incidence of and variables associated with clinically evident fat necrosis in women treated on a protocol of high-dose-rate (HDR) brachytherapy alone without external-beam whole-breast irradiation for early-stage breast carcinoma. METHODS AND MATERIALS: From 6/1997 until 8/1999, 30 women diagnosed with Stage I or II breast carcinoma underwent surgical excision and postoperative irradiation via HDR brachytherapy implant as part of a multi-institutional clinical Phase I/II protocol. Patients eligible included those with T1, T2, N0, N1 (< or = 3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular lymph-node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, re-excision, or at the time of axillary sampling. Direct visualization, surgical clips, ultrasound, or CT scans assisted in delineating the target volume defined as the excision cavity plus 2-cm margin. High activity (192)Ir (3-10 Ci) was used to deliver 340 cGy per fraction, 2 fractions per day, for 5 consecutive days to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. The median follow-up of all patients was 24 months (range, 12-36 months). RESULTS: Eight patients (crude incidence of 27%) developed clinically evident fat necrosis postimplant in the treated breast. Fat necrosis was determined by clinical presentation including pain and swelling in the treated volume, computed tomography, and/or biopsy. All symptomatic patients (7 of 8 cases) were successfully treated with 3 to 12 months of conservative management. Continuous variables that were found to be associated significantly with fat necrosis included the number of source dwell positions (p = 0.04), and the volume of tissue which received fractional doses of 340 cGy, 510 cGy, and 680 cGy (p = 0.03, p = 0.01, and p = 0.01, respectively). Other continuous variables including patient age, total excised tissue volume, tumor size, number of catheters, number of days the catheters were in place, planar separation, dose homogeneity index (DHI), and uniformity index (UI) were not significant. Discrete variables including the presence/absence of DCIS, sentinel versus full axillary nodal assessment, receptor status, presence/absence of diabetes, and the use of chemotherapy or hormone therapy were not found to have a significant association with the risk of fat necrosis. CONCLUSIONS: In this study of HDR brachytherapy of the breast tumor excision cavity plus margin, treatment was planned and delivered in accordance with the dosimetric parameters of the protocol resulting in a high degree of target volume dose homogeneity. Nonetheless, at a median follow-up of 24 months, a high rate of clinically definable fat necrosis occurred. The overall implant volume as reflected in the number of source dwell positions and the volume of breast tissue receiving fractional doses of 340, 510, and 680 cGy were significantly associated with fat necrosis. Future dosimetric optimization algorithms for HDR breast brachytherapy will need to include these factors to minimize the risk of fat necrosis.     

Recurrent endometrial cancer after surgery alone: results of salvage radiotherapy

PURPOSE: Postoperative irradiation of endometrial cancer patients decreases the risk of local recurrence but is associated with a number of long-term sequelae. In a proportion of patients, no immediate postoperative radiotherapy is applied and this treatment is introduced only at relapse. The aim of our study was to assess the long-term results of salvage radiotherapy in previously nonirradiated endometrial cancer patients who developed local recurrence, and to evaluate the impact of patient- and treatment-related factors on treatment efficacy. METHODS AND MATERIALS: We performed a detailed retrospective analysis of 73 endometrial cancer patients given radiotherapy for local recurrence after the initial surgery only. The mean age at diagnosis of the recurrence was 63 years (range, 39-78 years). Median time to recurrence was 11 months (range, 1-19 months). All recurrences were staged with the use of Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma. There were five (7%) Stage I patients, 43 (59%) Stage II patients, and 25 (34%) Stage III patients. Forty-four patients (60%) received both external beam irradiation (EBRT) and endovaginal brachytherapy (BRT), 17 (23%) received only BRT, and 12 (17%) received only EBRT. The mean total physical radiation dose was 75.9 Gy (range, 8-130 Gy), and the mean normalized total dose (NTD) calculated on the base of the linear-quadratic model was 86.6 Gy (range, 8.5-171.9 Gy). Median follow-up for alive patients was 8.8 years (range, 3-21 years). The impact of patient-, tumor-, and therapy-related factors on the treatment outcome was evaluated with the use of uni- and multivariate analyses. RESULTS: Three- and 5-year overall survival rates were 33% and 25%, respectively. In the univariate analysis, lower stage of recurrent disease (p < 0.0005), combined EBRT and BRT (p = 0.027), higher total radiation dose (p = 0.031), and higher NTD (p = 0.006) were significantly correlated with better survival. In the multivariate analysis, only stage of recurrent disease (p < 0.005) and high total dose (p = 0.047) were independently correlated with better survival. Lower FIGO stage of recurrence (p = 0.023) and higher total dose (p = 0.005) were also independently correlated with longer time to progression, whereas higher radiotherapy dose was the only factor correlated with better local control (p = 0.029). CONCLUSIONS: The efficacy of salvage radiotherapy in endometrial cancer patients with local failure after previous surgery is limited. Factors determining treatment outcome include advancement of the tumor at relapse and radiotherapy dose.     

Failure free survival following brachytherapy alone for prostate cancer: comparison with external beam radiotherapy.

BACKGROUND AND PURPOSE: To compare failure free survival (FFS) for brachytherapy (BT) alone and external beam radiotherapy (EBXRT) alone. MATERIALS AND METHODS: Between 12/88 and 12/95, 1527 and 695 T(1) or T(2) Nx-No Mo prostate cancer patients (from the Arizona Oncology Services database) were treated with either EBXRT or BT, respectively. The median age was 74 years. Median follow-up for EBXRT and BT patients was 41.3 and 51.3 months, respectively. RESULTS: Overall FFS at 5 years for EBXRT and BT were 69 and 71%, respectively (P=0.91). No significant difference in FFS at 5 years was observed between EBXRT and BT for either T(1) (78 vs. 83%, P=0.47) or T(2) (67 vs. 67%, P=0.89) tumours. Superior outcomes for Gleason 8-10 lesions treated with EBXRT vs. BT (5 years FFS 52 vs. 28%, P=0.04) were observed; outcomes for lower grade lesions when analysed by Gleason score alone did not significantly differ according to treatment received. Patients with initial PSA values 10-20 ng/dl had an improved FFS with EBXRT vs. BT (70 vs. 53%, P=0.001); outcomes for patients with initial PSA ranges 0-4 ng/dl, >4-10 ng/dl and >20 ng/dl did not differ significantly with treatment received. CONCLUSIONS: EBXRT and BT appear to be equally efficacious for low-risk patients having T(1)/T(2) disease with Gleason scores <6 and PSA <10 ng/dl. Patients with Gleason scores 8-10 or PSA >10 ng/dl-<20 ng/dl) appear to fare worse with BT alone compared with EBXRT. Neither EBXRT nor BT were particularly effective for patients with a presenting PSA >20 ng/dl.