Current controversies in high-dose-rate versus low-dose-rate brachytherapy for cervical cancer

The use of brachytherapy in the treatment of cervical cancer has increased worldwide since its initial introduction over 100 years ago. However, certain aspects of the use of high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy continue to be controversial, particularly the role of HDR in FIGO Stage III cervical cancer and the use of HDR with concurrent chemotherapy. This study represents a systematic literature review of prospective and retrospective series of patients with cervical carcinoma treated with external-beam radiation (EBRT) followed by either HDR or LDR radiation. The local control rates, survival rates, and treatment-related complications in patients with Stage III cervical cancer treated with HDR or LDR and those treated with concomitant chemotherapy are examined. Patients with Stage III cervical cancer treated with EBRT and brachytherapy have a local control rate of >50% in most series. Randomized prospective and retrospective studies show overall statistically equivalent local control, overall survival, and complication rates between HDR and LDR. However, LDR may be preferable for large, bulky tumors at the time of brachytherapy. Retrospective studies of HDR and concurrent chemotherapy are limited but have demonstrated toxicity rates similar to those with LDR. Selected patients with Stage III cervical carcinoma who have an adequate response to EBRT and concomitant chemotherapy may be treated with HDR brachytherapy. The existing literature shows no significant increase in complications in patients treated with HDR and concurrent chemotherapy; however, sufficient tumor shrinkage prior to HDR and careful monitoring of the dose to the normal tissues are imperative.     

FIGO 2018 ⅢC1p期宫颈癌患者的预后分析

目的:探讨FIGO 2018 ⅢC1p期宫颈癌患者的预后危险因素。方法:收集2015年1月至2018年6月在蚌埠医学院第一附属医院接受手术治疗并经病理确诊具有淋巴结转移的宫颈癌患者139例,所有患者均行广泛性全子宫切除加盆腔淋巴结±腹主动脉旁淋巴结清扫术。结果:139例患者3年无病生存期（disease-free survival,DFS）为71.4%。多因素分析显示,淋巴结转移数目≥3个和术前中性粒细胞和淋巴细胞比值（neutrophil-lymphocyte ratio,NLR）≥2.16是影响ⅢC1p期宫颈癌患者预后的独立危险因素（P＜0.05）。根据危险因素将所有患者分为三组,进一步分析显示,低风险组（无危险因素）、中风险组（1个危险因素）、高风险组（2个危险因素）的3年DFS分别为90.4%、54.3%、30.3%（P＜0.05）。结论:FIGO 2018 ⅢC1p期宫颈癌的患者是不同质的,淋巴结转移数目和术前NLR是3年DFS的独立预后因素,宫颈癌分期可考虑将此因素纳入分期范围,并对于ⅢC1p期的患者制定更加个体化的治疗方案。     

Effective Treatment of Stage I Uterine Papillary Serous Carcinoma with High Dose-Rate Vaginal Apex Radiation (192Ir) and Chemotherapy

Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC.Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using ²²⁶Ra or ¹³⁷Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using ¹⁹²Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy.Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients.Conclusion: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.     

局部晚期宫颈癌螺旋断层放疗同步化疗早晚期不良反应和疗效观察

目的：分析局部晚期宫颈癌螺旋断层调强（HT）放疗同步顺铂化疗和高剂量率（HDR）腔内照射的早晚期不良反应及疗效。方法选取接受根治性放疗的Ⅰb～Ⅲb宫颈癌患者46例。外照射采用HT-IMRT,14例盆腔淋巴结受累进行勾画定义为GTVnd,临床靶区（CTV）包括盆腔淋巴结区（6例扩大野包括腹主动脉旁淋巴结区）,GTVnd、全部子宫、宫颈及阴道,外扩0.8~1 cm构成计划靶区（PTV）。PTV中位剂量50.4 Gy（45～50.4 Gy）,常规分割;同步顺铂化疗,40 mg/m2/周;外照射30～40 Gy后联合HDR腔内照射,HDR的A点中位剂量30 Gy （30~36 Gy）,总的A点生物等效剂量（EQD2）90.3 Gy（84.9~98.3 Gy)。治疗期间每周及治疗后1~24个月评价不良反应及疗效。结果24例患者完成4～5周期同步化疗,22例患者仅完成2～3周期同步化疗。3级不良反应包括：白细胞减少9例（19.6%）,腹泻2例（4.3%）,恶心5例（10.9%）及呕吐1例（2.2%）;晚期3级不良反应2例：1例直肠出血,1例膀胱出血;无4级,5级不良反应发生。2年内无复发生存率、无病生存率及总生存率分别为91.7%、86.0%及97.1%。结论局部晚期宫颈癌螺旋断层调强放疗同步每周顺铂化疗联合HDR腔内照射,不良反应以血液学反应和恶心为主,晚期不良反应小,近期疗效较好。     

Adjuvant concurrent chemoradiotherapy with intensity-modulated pelvic radiotherapy after surgery for high-risk, early stage cervical cancer patients

PURPOSE: This study was undertaken to assess local control and toxicity with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy (CCRT) for early stage cervical cancer. PATIENTS AND METHODS: Between June 2004 and February 2007, 54 patients with early stage cervical cancer (stage IB-IIA) with high-risk factors for treatment failure after surgery were treated with adjuvant pelvic IMRT and CCRT. Adjuvant chemotherapy consisted of cisplatin (50 mg/m2) weekly for 4 to 6 courses. All the patients received 50.4 Gy of external beam radiotherapy with IMRT in 28 fractions and 6 Gy of high-dose rate vaginal cuff brachytherapy in 3 insertions. RESULTS: Adjuvant CCRT with IMRT provided good local tumor control in posthysterectomy cervical cancer patients with high-risk pathologic features. The 3-year locoregional control and disease-free survival were 93% and 78%, respectively. Histology and lymph node metastasis were indicators for disease-free survival. Low acute and chronic treatment-related toxicities were noted with IMRT. All the patients completed the radiotherapy treatment without any major toxicity. In terms of chronic toxicity, only 1 patient had grade 3 genitourinary toxicity and none had grade 3 gastrointestinal toxicity. CONCLUSION: Our results indicate that adjuvant CCRT with IMRT technique for adjuvant treatment of early stage cervical cancer is associated with excellent local control and low toxicity.     

同步放化疗和单纯放疗治疗ⅡB～ⅢB期宫颈癌的疗效比较

背景与目的:同步放化疗已成为局部晚期宫颈癌的标准治疗模式,但对于放疗联合何种方案的化疗效果最佳,目前尚无一致意见.本研究中我们比较同步放化疗与单纯放疗,以及同步放化疗不同化疗方案的疗效及毒副反应.方法:2003年1月至2004年12月江西省妇幼保健院收治的符合人组标准的ⅡB～ⅢB期宫颈癌患者285例,按住院序号随机分为单纯放疗组142例,同步放化疗组143例.同步放化疗组又按化疗方案不同分为:BP(博来霉素 顺铂)方案同步放化疗51例,TP(紫杉醇 卡铂)方案同步放化疗47例,FP(氟尿嘧啶 顺铂)方案同步放化疗45例.比较单纯放疗组与同步放化疗组患者的3年生存率和不良反应,同时对同步放化疗三种不同化疗方案组的3年生存率及不良反应进行比较.结果:全组中位随访时间为42个月,单纯放疗组与同步放化疗组的3年生存率分别为65%和75%,两组比较差异有统计学意义(P=0.042).单纯放疗组Ⅲ～Ⅳ度急性毒副反应低于同步放化疗组(P<0.001),迟发性毒副反应两组差异无统计学意义(P=0.613).同步放化疗组BP方案、TP方案、FP方案的3年生存率分别为74%、80%和71%,三组间比较差异无统计学意义(P=0.792).三组Ⅲ～Ⅳ度急性及迟发性毒副反应发生率相似.结论:与单纯放疗相比,同步放化疗可明显提高ⅡB～ⅢB期宫颈癌患者的疗效.在同步放化疗三种不同的化疗方案中,紫杉醇联合卡铂方案组患者3年生存率略高于其他两种化疗方案,毒副反应可耐受,值得进一步研究.     

新辅助放化疗联合手术治疗ⅠB2~ⅡA2期子宫颈癌临床预后因素分析

背景与目的：探讨Ⅰ_B2～Ⅱ_A2期子宫颈腺癌与腺鳞癌经新辅助放化疗联合手术治疗后的生存及复发情况,并分析其预后影响因素。方法：收集蚌埠医学院第一附属医院2005年4月—2011年10月50例Ⅰ_B2～Ⅱ_A2期患者的临床病理资料。患者均接受广泛全子宫切除+盆腔淋巴结清扫术,且术前均接受1次静脉化疗,宫颈肿瘤直径大于等于6 cm,给予阴道腔内放疗1次。回顾分析患者的生存及复发情况,探讨其预后影响因素。结果：50例Ⅰ_B2～Ⅱ_A2期子宫颈腺癌和腺鳞癌患者中,随访期内死亡15例,2年和5年无进展生存率分别是80.12%和72.24%,中位无进展生存时间为68个月;2年和5年累积总生存率分别是95.38%和73.56%,中位总生存时间为80个月。单因素分析显示,盆腔淋巴结转移、宫颈间质浸润、宫旁浸润和新辅助放化疗后肿瘤最大直径缩短小于3 cm的患者预后较差(P<0.05),而年龄、术后放化疗、淋巴管间隙受累分期、FIGO分期、是否保留卵巢和病理类型与预后无明显相关性(P>0.05)。多因素COX回归分析结果显示,盆腔淋巴结转移和放化疗后肿瘤直径缩小是宫颈腺癌和腺鳞癌的独立预后影响因素。结论：新辅助放化疗联合手术治疗提高了Ⅰ_B2～Ⅱ_A2期宫颈腺癌和腺鳞癌手术切除率,而盆腔淋巴结转移及放化疗后宫颈肿瘤最大径消退程度是宫颈腺癌和腺鳞癌的独立预后因素。     

Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification

PurposeData for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control.Materials and methodsForty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4.ResultsAt a median follow-up of 18 months (range: 3–78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%.ConclusionsSalvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.     

Preoperative concurrent radiation therapy and chemotherapy for operable bulky carcinomas of uterine cervix stages IB2, IIA, and IIB with proximal parametrial invasion]

PURPOSE: To evaluate preliminary results in terms of toxicity, local tumour control, and survival after preoperative concomitant chemoradiation for operable bulky cervical carcinomas. PATIENTS AND METHODS: Between December 1991 and October 2001, 42 patients (pts) with bulky cervical carcinomas stage IB2 (11 pts), IIA (15 pts), and IIB (16 pts) with 1/3 proximal parametrial invasion. Median age was 45 years (range: 24-75 years) and clinical median cervical tumour size was 5 cm (range: 4.1-8 cm). A clinical pelvic lymph node involvement has been observed in 10 pts. All patients underwent preoperative external beam pelvic radiation therapy (EBPRT) and concomitant chemotherapy during the first and the fourth radiation weeks combining 5-fluorouracil and cisplatin. The pelvic dose was 40.50 Gy over 4.5 weeks. EBPRT was followed by low-dose-rate uterovaginal brachytherapy with a total dose of 20 Gy in 17 pts. After a rest period of 5-6 weeks, all pts underwent class II modified radical hysterectomy with bilateral lymphadenectomy. Para-aortic lymphadenectomy was performed in eight pts without pathologic para-aortic lymph node involvement. Twenty-one of 25 pts who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy of 20 Gy. The median follow-up was 31 months (range: 3-123 months). RESULTS: Pathologic residual tumour or lymph node involvement was observed in 23 pts. Among the 22 pts with pathologic residual cervical tumour (<0.5 cm: nine pts; >or=0.5 to 1 cm: 10 pts), seven underwent preoperative EBRT followed by uterovaginal brachytherapy vs. 15 treated with preoperative EBRT alone (P = 0.23). Four pts had pathologic lymph node involvement, three pts had vaginal residual tumour, and four pts had pathologic parametrial invasion. The 2- and 5-year overall survival rates were 85% and 74%, respectively. The 2- and 5-year disease-free survival (DFS) rates were 80% and 71%, respectively. After multivariate analysis, the pathologic residual cervical tumour size was the single independent factor decreasing the probability of DFS (P = 0.0054). The 5-year local control rate and metastatic failure rate were 90% and 83.5%, respectively. Haematological effects were moderate. However, six pts had grade 3 acute intestinal toxicity. Four severe late complications requiring surgical intervention were observed (one small bowel complication, three ureteral complications). CONCLUSION: Primary concomitant chemoradiation followed surgery for bulky operable stage I-II cervical carcinomas can be employed with acceptable toxicity. However, systematic preoperative uterovaginal brachytherapy should increase local tumour control.     

Operable stage IB and II cancer of the uterine neck: retrospective comparison between preoperative utero-vaginal curietherapy and initial surgery followed by radiotherapy]

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable stages IB and II cervical carcinomas. PATIENTS AND METHODS: Between May 1972 and January 1994, 414 patients (pts) with cervical carcinoma staged according to the 1995 FIGO staging system underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection. Lateral ovarian transposition to preserve ovarian function was performed on 12 pts. The methods of radiation therapy (RT) were not randomised and depended on the usual practices of the surgical teams. Group I: 168 pts received postoperative RT (64 pts received vaginal brachytherapy alone [mean total dose (MD): 50 Gy], 93 pts had external beam pelvis RT (EBPRT) [MD: 45 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 20 Gy], and 11 pts had EBPRT alone [MD: 50 Gy over 6 weeks]. Group II: 246 pts received preoperative utero-vaginal brachytherapy [MD: 65 Gy], and 32 of theses 246 pts also received postoperative EBPRT [MD: 45 Gy over 5 weeks] delivered to the parametric and the pelvic lymph nodes with a midline pelvic shield. The mean follow-up was 106 months. RESULTS: The 10-year disease-free survival (DFS) rate was 80%. From 75 recurrences, 35 were isolated locoregional. Multivariate analysis showed that independent factors decreasing the probability of DFS were: both exo and endocervical tumour site (p = 0.047), lymph-vascular space invasion (p = 0.041), age < or = 51 yr (p = 0.013), 1995 FIGO staging system (stage IB1 vs stage IIA, p = 0.004, stage IB1 vs stage IB2, p = 0.0009, and stage IB1 vs stage IIB with 1/3 proximal parametrical infiltration, p = 0.00002), and histological pelvic involved lymph nodes (p = 0.00009). Methods of adjuvant RT did not influence the probability of DFS (group I vs group II, p = 0.10). The postoperative complication rate was 10.2% in group I and 8.9% in group II (p = 0.7) but the postoperative urethral complication rate necessitating surgical intervention with reimplantation was lower in group I than in group II (0.6% vs 2.3%, respectively, p = 0.03). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 10.4%. EPRT significantly increased the 10-year rate for grade 3 and 4 late radiation complications (yes vs no: 22% vs 7%, respectively, p = 0.0002). CONCLUSION: In our series, the methods of adjuvant RT (primary surgery vs preoperative uterovaginal brachytherapy) do not seem to influence the prognosis of the stage IB, IIA, and IIB (with 1/3 proximal parametrical involvement only) cervical carcinomas. The postoperative EPRT applied according to histopathological risk factors after surgical treatment increases the risk of late radiation complications.     

Ⅱ和Ⅲ期胃癌术后IMRT同期卡培他滨化疗前瞻性Ⅱ期研究中期评估

目的 评价Ⅱ、Ⅲ期(AJCC第7版)胃癌根治术后IMRT同期卡培他滨化疗的初步疗效和急性不良反应,以决定是否继续Ⅱ期研究。方法 2009—2011年35例Ⅱ、Ⅲ期(10、25例)胃癌患者进入前瞻性Ⅱ期研究,根治术后给予辅助放化疗或化疗。放疗采用IMRT,靶区包括吻合口、瘤床和区域淋巴结,剂量45 Gy分25次。同期化疗为卡培他滨每天1600 mg/m²分2次,连续服用5周;辅助化疗为氟尿嘧啶或卡培他滨±奥沙利铂4~8周期。采用Kaplan-Meier法计算生存率并Logrank法单因素预后分析。以DFS 52.9%为继续研究的下限。结果 全组中位随访21个月,随访率94%。3例未完成放疗,2年DFS、OS分别为70%、86%,急性3级胃肠道、血液和总不良反应分别为11%、11%和26%。预后分析显示病理印戒细胞癌成分和淋巴结阳性比是DFS不良预后因素,T₄期可预测OS下降。结论 全组胃癌根治术后IMRT同期卡培他滨化疗的2年DFS>52.9%,且不良反应可耐受,可继续Ⅱ期研究。     

Californium-252 neutron brachytherapy combined with external pelvic radiotherapy plus concurrent chemotherapy for cervicalcancer: a retrospective clinical study

Background: Cervical cancer is the sixth most common cancer in Chinese women. A standard treatment modality for cervical cancer is the combination of surgery, chemotherapy, external-beam radiotherapy and intracavitary brachytherapy. The aim of this study was to retrospectively assess the long-term treatment outcomes of patients with cervical cancer who were treated with californium-252 neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy.Methods: We retrospectively analyzed the medical records of 150 patients with primary stages IB-IVB cervical cancer who received neutron brachytherapy combined with external-beam radiotherapy concurrently with cisplatin chemotherapy.All patients were followed up. Using an actuarial analysis, patient outcomes and treatment-related adverse effects were evaluated and compared.Results: The median overall survival (OS) was 33.2 months. The 3-year progression-free survival rates for patients with stages Ⅰ—Ⅱ, Ⅲ, and Ⅳ diseases were 81.0% (68/84), 65.0% (39/60), and 0% (0/6), respectively; the 3-year OS rates were 90.5% (76/84), 85.0% (51/60), and 16.7% (1/6), respectively. Vaginal bleeding was controlled within the median time of 4.0 days. One month after treatment, 97.3% of patients achieved short-term local control. The local recurrence rates for patients with stages Ⅰ—Ⅱ, Ⅲ, and Ⅳ disease were 4.8% (4/84), 11.7% (7/60), and 33.3% (2/6), respectively, and the occurrence rates of distant metastasis were 16.7% (14/84), 25.0% (15/60), and 100.0% (6/6), respectively. Cancer stage,tumor size, and lymph node metastasis were identified as prognostic risk factors, but only lymph node metastasis was found to be an independent prognostic factor. The most common adverse effects during treatment were grades 1 and 2 irradiation-related proctitis and radiocystitis.Conclusion: For patients with cervical cancer, neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy produces a rapid response and greatly improves local control and long-term survival rates with tolerable adverse effects.     

A Phase II study of acute toxicity for Celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG 0128

PURPOSE: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. METHODS AND MATERIALS: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size > or =5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. RESULTS: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. CONCLUSIONS: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.     

Long-term results and prognostic factors in patients with stage III–IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study

Background

We evaluated the longer-term efficacy and safety of concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a lower cumulative radiotherapy (RT) protocol and analyzed prognostic risk factors for survival among patients with FIGO stage III–IVA squamous cell carcinoma (SCC) of the cervix.

Patients and methods

Ninety-nine patients with FIGO stage III–IVA SCC of the cervix between 1997 and 2008 were treated with CCRT using cisplatin 20 mg/m² for 5 days every 3 weeks or 40 mg/m² weekly. Acute and late toxicities were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.

Results

Median age was 53.5 years. Median follow-up period was 58 months (range 6–170 months). Pathologically complete response was achieved in 93 patients (96.9 %). The 5-year OS and DFS were 72.0 and 69.3 %, respectively. The 5-year local and distant DFS were 83.0 and 75.1 %, respectively. Thirty-one patients (31.3 %) experienced recurrence. Multivariate analysis showed that tumor size and pretreatment hemoglobin level remained an independent risk factor for OS and DFS. Acute toxicity was moderate. In terms of late adverse effects, 2 patients (2.0 %) suffered from grade 4 late intestinal toxicity because of radiation enterocolitis, with both requiring intestinal surgery.

Conclusions

Our study demonstrates that the CCRT schedule in patients with FIGO stage III–IVA SCC is efficacious and safe. In addition, the assessment of tumor size and pretreatment anemia can provide valuable prognostic information.     

Values of three different preoperative regimens in comprehensive treatment for young patients with stage Ib2 cervical cancer

Objective: To compare the clinical efficacy of concurrent chemoradiotherapy, neoadjuvant chemotherapy,and intracavity brachytherapy in comprehensive treatment for young patients with stage Ib2 cervical cancer.Methods: One hundred and twelve young patients with stage Ib2 cervical cancer were enrolled retrospectively inour hospital from January 2003 to June 2005. They were categorized into three groups according to preoperativeregimens, including the concurrent chemoradiotherapy group (Group 1, n=38), the neoadjuvant chemotherapy(Group 2, n=49), and the intracavity brachytherapy group (Group 3, n=25). Radical hysterectomy was performedfollowing these regimens. Chemotherapy and radiotherapy were given according to pelvic lymph node metastasis,deep cervical stromal invasion, intravascular cancer emboli, histological grading, vaginal stump and positivesurgical margin. Results: The cancer disappearance and superficial muscle invasion rates were statisticallysignificantly better in the concurrent chemoradiotherapy group than in the other two groups (P<0.01). Nostatistically significant difference was noted in the deep muscle invasion rate, surgical time and intraoperativeblood loss among three groups, but significantly more postoperative complications occurred in the concurrentchemoradiotherapy group. The 2-year pelvic recurrence was statistically significantly lower in the concurrentchemoradiotherapy group compared to other two groups, while the 5-year survival was higher. Conclusion:Concurrent chemoradiotherapy is efficacious for young patients with stage Ib2 cervical cancer.     

影响子宫内膜癌术后放疗疗效的相关因素分析

目的探讨影响子宫内膜癌术后放疗疗效的相关因素。方法对74例手术后子宫内膜癌患者,应用6-MVX线加速器盆腔照射,4500～5000cGy/4.5～5周,外照射后均联合192Ir腔内后装治疗。参考点：阴道黏膜下0.5cm。DT16～20Gy,每次4～5Gy,每周1～2次。结果子宫内膜癌手术后联合放疗2年总生存率（OS）和无病生存率（DFS）分别为91.9%和81.1%,其中ⅠB～ⅡB期患者2年DFS为90.7%。子宫内膜癌手术后联合放疗2年内阴道复发率和盆腔复发率分别为8.1%和6.8%,远处转移率为9.5%。单因素分析淋巴结转移和病理分期明显影响子宫内膜癌患者的2年OS;淋巴结转移、病理分期、病理类型、年龄明显影响子宫内膜癌患者的2年DFS。多因素分析淋巴结转移明显影响子宫内膜癌患者的2年OS,病理类型和淋巴结转移明显影响子宫内膜癌患者的2年DFS。Ⅲ期病例术后单纯放疗和放疗联合化疗比较,2年OS和DFS无统计学差异。结论子宫内膜癌以手术治疗为首选治疗方法,根据手术及术后病理检查的结果,对病变范围及影响预后相关危险因素进行全面评估,从而制定最佳的治疗方案,对子宫内膜癌患者进行个体化的治疗已成为当前的总趋势。     

Evolution in the Management of Locally Advanced Cervical Cancer: The Experience of Cancer Institute (WIA), Chennai,India

Objective: To conduct a retrospective analysis of disease free survival (DFS) of locally advanced cervical cancer (LACC) in relation to evolution of treatment and related factors. Methods: A total of 3,892 cases of LACC treated at the Cancer Institute (WIA), Chennai, India, during 1990-1999 were analyzed. Management of LACC including concurrent chemo-radiation (CCRT) has evolved through trials conducted at the institute. DFS and risk of second cancer were elicited using actuarial and Kaplan-Meier methods, respectively. Results: A majority belonged to stage III (54%) and complete follow-up at 5-years was 90%. DFS at 5, 10 and 15-years were 58%, 49% and 42% for stage IIB and 43%, 35% and 31% for stage III, respectively. External beam radiotherapy (EBRT) alone as treatment modality reported the poorest 5-year DFS (37%). Addition of chemotherapy to EBRT resulted in marginal increase in survival (41%) but inclusion of brachytherapy to EBRT enhanced survival (58%) significantly (p<0.001). CCRT with brachytherapy as a planned component resulted in the best DFS (69%), irrespective of disease stage. In a carefully selected group of patients who were suitable for salvage surgery, the long-term DFS was 71%, 63% and 63% at 5, 10 and 15 years, respectively, for stages IIB and III together. Complete response was achieved in 67% and 15% of them recurred. Remote metastasis occurred in 13%. The cumulative risk of developing any second cancer was 0.5% at 5 years, 1.9% at 10 years and 2.8% at 15 years of follow up. Conclusion: Our data indicates satisfactory treatment outcome even in advanced disease and with the present state of knowledge, the recommended standard treatment for LACC is careful pre-treatment evaluation followed by CCRT which includes brachytherapy.     

Cervical cancer: combined modality therapy

Prospective, randomized studies conducted over the past 10 years have changed the management of patients with advanced cervical cancer. The reviewed studies evaluated the use of surgery, irradiation, and chemotherapy in patients with various stages of cervical carcinoma in the absence and presence of high-risk factors for recurrence. A study by the Radiation Therapy Oncology Group (RTOG) compared pelvic with pelvic plus prophylactic para-aortic irradiation in patients with stages IB (> 4 cm), IIA, and IIB cervical cancer. The 10-year survival advantage was 11% for patients treated with prophylactic para-aortic irradiation. A follow-up study compared pelvic plus prophylactic para-aortic irradiation and brachytherapy with pelvic irradiation, brachytherapy, and chemotherapy with cisplatin and 5-FU in patients with IB-to IVA-stage cervical cancer. Overall and disease-free survivals were significantly improved in patients receiving chemotherapy. In patients with a prevalence of stage IIB and III, the Gynecologic Oncology Group (GOG) demonstrated that treatment with hydroxyurea alone was inferior to cisplatin or cisplatin, 5-FU, and hydroxy-urea in patients treated concurrently with pelvic irradiation and brachytherapy, and the GOG adopted irradiation and weekly cisplatin as standard therapy. Further GOG studies suggest that irradiation and weekly cisplatin chemotherapy without hysterectomy is the optimal treatment for patients with stage IB cervical cancer. High-risk factors for recurrence include tumor size, depth of tumor invasion, lymphovascular space involvement, and lymph node involvement. Prospective, randomized studies conducted by the GOG evaluated the effectiveness of various treatments in patients with high-risk factors. In one study that did not use chemotherapy, the recurrence-free interval was about 10% better for stage IB patients receiving postoperative irradiation after radical hysterectomy and pelvic lymphadenectomy compared with those who received no further therapy. Patients with Stages IB and IIA disease who, following radical hysterectomy and lymph node dissection, are identified as having positive pelvic lymph nodes and positive parametrial involvement, are at higher risk for recurrence and death than the high-risk group described above. An intergroup study conducted by the GOG, RTOG, and Southwest Oncology Group compared postoperative pelvic irradiation alone with postoperative pelvic irradiation plus concurrent chemotherapy in this group of patients. Overall and progression-free survivals were superior for patients receiving chemotherapy, and their greatest survival occurred in patients who received 3 or 4 chemotherapy cycles compared with 1 or 2 cycles or no chemotherapy. These findings are summarized with respect to their implications fortreatment of patients with advanced cervical cancer.     

Patterns of care for cervical cancer in Auckland, New Zealand, 2003-2007

Introduction: The purpose of this review is to document current patterns of care for the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 to IVA cervical cancer in a New Zealand cancer centre. Methods: This is a retrospective review of women with newly diagnosed FIGO Stage IB1–IVA cervical cancer in the Auckland/Northland regions between 2003 and 2007. Results: Two hundred seven patients were identified. Fifty‐three percent were stage IB, 24% stage II, 19% stage III and 3% stage IVA. Factors associated with stage ≥IIB were age >50, lack of participation in cervical screening and public first specialist assessment. Ninety percent (90/100) of stage IB1 patients and 73% (8/11) of stage IB2 patients were treated with primary surgery. Thirty‐eight percent of surgically treated stage IB1 and 100% of surgically treated stage IB2 tumours had indications for adjuvant radiotherapy. Radiotherapy utilisation rates were: stage IB 49% (IB1 44%, IB2 91%); stage II 93%; stage III 90%; and stage IVA 71%. Brachytherapy utilisation rate (BTU) for stages IIB to IVA was 64% overall and 75% in definitively treated patients. Seventy‐five percent of patients treated with definitive radiotherapy received concurrent cisplatin chemotherapy. Conclusion: Both radiotherapy and brachytherapy utilization rates were below optimal and are being addressed. No formal surgical or chemotherapy utilisation estimates exist for comparison; however, the use of concurrent cisplatin chemotherapy was similar to other groups. A high rate of adjuvant (chemo)radiotherapy was noted in surgically treated Stage IB patients, suggesting a need for an increased consideration of primary chemoradiotherapy in these patients to avoid the unnecessary toxicity of trimodality therapy. Future outcome analysis is planned.     

Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437 cases]

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. PATIENTS AND METHODS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivariate analysis showed that independent factors decreasing the probability of disease-free survival were: histologic type (clear cell carcinoma, p = 0.038), largest histologic tumor diameter > 3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.0055), and 1988 FIGO staging system (p = 9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were FIGO stage (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. EPRT independently increased the 10-year rate for grade 3 and 4 late radiation complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in a subgroup of intermediate risk patients (stage IA grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with stage III tumor are not satisfactory.