Definitive intensity-modulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer

Objective

Cervical cancer is one of the most common cancers diagnosed in women worldwide. Concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locally advanced cervical cancer. The purpose of this study was to investigate the treatment outcomes and toxicity of definitive intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for patients with locally advanced carcinoma of the cervix in a single institution.

Methods

Between January 2004 and November 2008, 109 patients with stage IB2-IVA cervical carcinoma treated with IMRT and concurrent cisplatin-based chemotherapy were evaluated retrospectively. All patients received external irradiation of 45-54 Gy with an IMRT technique. High dose rate brachytherapy of 20-33.5 Gy was prescribed to point A as a local boost. Each patient received concurrent cisplatin-based chemotherapy monthly or weekly. The endpoints were overall survival (OS), local failure-free survival (LFFS) and disease-free survival (DFS). Patients were assessed for acute toxicity weekly according to the Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0. Late toxicity was evaluated according to RTOG-EORTC Late Radiation Morbidity Scoring Schema.

Results

The median follow up time for all surviving patients was 32.5 months, with a range from 5 to 75 months. The 3-year OS, LFFS and DFS were 78.2%, 78.1% and 67.6%, respectively. Three (2.7%) patients developed grade 3 or greater acute gastrointestinal (GI) toxicity and 26 (23.9%) patients developed grade 3 or greater hematological toxicity. Five (4.6%) patients developed grade 3 or greater chronic GI toxicity and 7 (6.4%) patients developed grade 3 or greater genitourinary system toxicity.

Conclusions

Good outcomes were achieved with definitive IMRT and concurrent chemotherapy for patients with locally advanced cervical cancer and the combined treatment was well tolerated with favorable acute and late toxicity.     

Impact of para-aortic recurrence risk-guided intensity-modulated radiotherapy in locally advanced cervical cancer with positive pelvic lymph nodes

Objectives

A previous study has suggested the benefit of sub-renal vein radiotherapy (SRVRT) for pelvic lymph node (PLN)-positive cervical cancer. In order to better select patients for SRVRT, this study aimed to evaluate the value of a risk-based radiation field based on PLN location and number in PLN-positive cervical cancer.

调强放射治疗在宫颈癌术后治疗中的临床研究

目的 探讨调强放射治疗（IMRT）用于宫颈癌术后提高靶区受照射剂量,减少并发症的价值。方法 对2002年6月至2006年6月山东省肿瘤医院20例宫颈癌术后患者放疗前均给予2-3个周期化疗,并行全程IMRT,每日1次,每次1.8-2.2Gy,每周5次,给予处方剂量50-60Gy,中位剂量54.5Gy;同时拟设计该20例患者的普通2野放疗计划,拟给予相同的处方剂量,比较危险器官（OAR）受照射剂量;选取同期23例接受普通放疗的完整病例,比较调强放疗和普通放疗急、慢性毒副反应及近期存活率。结果 20例患者均完成全程IMRT,放射治疗计划靶区（planning target volume,PTV）内的平均剂量为56.2Gy,90%的等剂量曲线（中位剂量54.5Gy）可以覆盖99%以上的肉眼靶区（gross target volume,GTV）体积。IMRT与拟行普通2野放疗计划比较,小肠、直肠、膀胱的受照射剂量均明显减小,P均〈0.01;IMRT与普通放疗比较,急慢性毒副反应明显降低,但1、2、3年存活率比较差异无显著性意义,P〉0.05。结论 IMRT技术使宫颈癌术后患者的靶区获得理想的剂量分布,邻近危险器官得到很好的保护,毒副反应可以耐受,但未能提高患者近期存活率。     

The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: Outcome and toxicity

Objective: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer.Study design: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins.Results: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved.Conclusion: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.     

A phase I study of concurrent weekly topotecan and cisplatin chemotherapy with whole pelvic radiation therapy in locally advanced cervical cancer: a gynecologic oncology group study

Purpose

To determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLT) of intravenous topotecan administered with weekly cisplatin during pelvic radiation therapy in patients with locally advanced cervical cancer.

Methods

Patients were treated at one of two dose levels receiving intravenous topotecan at 0.5 mg/m² and cisplatin at either 30 or 40 mg/m² given weekly for 6 weeks concurrently with pelvic radiation and intracavitary brachytherapy. The primary endpoint for the escalation study was acute dose-limiting toxicities occurring within 30 days of completing radiation therapy.

Results

Eleven patients were enrolled. Dose-limiting toxicity consisting of Grade 3 nausea and vomiting lasting > 24 h in one patient and grade 3 febrile neutropenia in another patient occurred at the first dose level of weekly topotecan 0.5 mg/m² and cisplatin 40 mg/m². This necessitated de-escalation to weekly cisplatin 30 mg/m² in combination with topotecan 0.5 mg/m² and pelvic radiation. This dose level was tolerable in 6 evaluable patients with only one DLT consisting of grade 4 thrombocytopenia, grade 3 abdominal pain and grade 3 elevated gamma glutamyl transpeptidase (GGT).

Conclusions

In women with locally advanced cervical cancer, intravenous topotecan 0.5 mg/m² and cisplatin 30 mg/m² given weekly for 6 weeks with concurrent pelvic radiation and intracavitary brachytherapy were tolerable. Further expansion of the feasibility cohort of this study was suspended based on the results of a phase 3 trial comparing the efficacy of platinum combinations in advanced and recurrent cervical cancer.     

Intraarterial cisplatin/nedaplatin and intravenous 5-fluorouracil with concurrent radiation therapy for patients with high-risk uterine cervical cancer

OBJECTIVE: The purpose of this study was to determine the effectiveness of the combination of intraarterial and intravenous concurrent chemoradiation therapy (CIAIV-CCRT) for the treatment of high-risk uterine cervical cancer. METHODS: Between January 2000 and November 2004, we reviewed 45 cervical cancer patients treated by CIAIV-CCRT. The numbers of patients with stage IB2, IIA, IIB, IIIA, IIIB, and IVA were 3, 6, 14, 1, 17, and 4, respectively. Patients with stage III and IVA or patients with tumors >3 cm in diameter were enrolled in this study. Two sessions of CCRT were administered every 3 weeks using a combination of 70 mg/m2 x h(-1) cisplatin or 50 mg/m2 x h(-1) nedaplatin via the bilateral uterine artery and 2800 mg/m2 x 96 h(-1) 5-fluorouracil intravenously. Patients concurrently received external beam radiation therapy and brachytherapy. A nonrandomized control group of 47 patients who underwent radiation therapy alone between 1993 and 2000 was used for comparison. RESULTS: Of the 45 patients, 28 (62%) exhibited complete response and 16 (36%) exhibited partial response. One IIIB patient (2%) did not show any response. The 5-year overall survival (OAS) rates in the CCRT group and control group were 80.6% and 54.9%, respectively. With regard to late toxicities, no statistically significant differences were observed between the two groups. In uni- and multivariate analyses, positive pelvic lymph node showed a statistically significant influence on the OAS in the CIAIV-CCRT group (P = 0.049). CONCLUSION: These preliminary results suggest that CIAIV-CCRT can improve the prognosis of patients with high-risk cervical cancer.     

Indications and long-term clinical outcomes in 282 patients with pelvic exenteration for advanced or recurrent cervical cancer

Objective

The aim of this study was to summarize the clinical experience at our clinic with pelvic exenteration as a treatment for cervical cancer with special regard to the indications and outcomes of specific patient groups.

Methods

Medical records of 282 women who underwent pelvic exenteration to treat cervical cancer were analyzed.

Results

In total, 70 patients (25%) underwent primary exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The overall survival (OS) of the 282 patients was 41% at 5 years and 37% at 10 years. The disease-free survival at 5 years was 61%. For 133 patients for whom pelvic exenteration was a curative procedure, the OS was 64% at 5 years and 57% at 10 years. For cases of pelvic exenteration as a palliative intervention, the OS was 19% at 5 years and 18% at 10 years. No difference was seen in the OS at 5 years between patients who received primary and secondary operations. No significant difference in the OS was found regardless of whether the patients had positive pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS was significantly lower. Out of all of the procedures, 139 (49%) involved no perioperative or postoperative complications. One major complication was reported for 72 (26%) patients, two complications occurred for 42 patients (15%) and more than three complications were noted for 29 (10%) patients.

Conclusion

Pelvic exenteration is an effective technique with a high percentage of long-term survivors. To the best of our knowledge, our study involves the largest published number of patients treated with pelvic exenteration for a single gynecological cancer and shows that previous contraindications for pelvic exenteration, such as lymph node metastasis (especially when confined to the pelvic lymph nodes), older age or palliative intent, should be reconsidered.     

低频神经肌肉治疗在子宫颈癌术后和(或)放疗后下肢淋巴水肿的疗效研究

目的 探讨低频神经肌肉治疗在子宫颈癌术后和(或)放疗后下肢淋巴水肿治疗中的价值.方法 选取2019年11月至2020年10月南昌大学附属人民医院、九江市妇幼保健院、景德镇市第一人民医院、景德镇市第二人民医院、宜春市人民医院收治的子宫颈癌术后和(或)放疗后下肢淋巴水肿患者共308例,进行下肢淋巴水肿治疗的研究,根据子宫颈...     

甘氨双唑钠对宫颈癌放疗及同步放化疗增敏疗效的Meta分析

目的:系统评价甘氨双唑钠(CMNa)对宫颈癌放疗及同步放化疗增敏作用的临床疗效和安全性。方法:检索中国生物医学文献数据库、中国期刊全文数据库(CNKI)、万方医药期刊全文数据库、中文科技期刊数据库、Pub Med、Cochrane Library、Embase,收集放疗或同步放化疗联合CMNa与不联合CMNa治疗宫颈癌的临床随机对照研究(RCT)。根据纳入和排除标准筛选文献,对符合条件的RCT由两位研究者独立进行资料提取和质量评价后,采用Cochrane协作网提供的Rev Man 5.3及Stata 13.0进行Meta分析。结果:CMNa增敏治疗中晚期宫颈癌的完全缓解率高于非增敏组(OR=3.77,95%CI为2.60~5.47,P0.001;放疗亚组:OR=6.01,95%CI为3.26~11.08,P0.001;同步放化疗亚组:OR=2.72,95%CI为1.69~4.40,P0.001)。CMNa增敏组达到CR的剂量低于非增敏组(SMD=-1.84,95%CI为-2.47~-1.20,P0.001;放疗亚组:SMD=-1.54,95%CI为-2.02~-1.06,P0.001;同步放化疗亚组:SMD=-2.71,95%CI为-3.54~-1.88,P0.001)。CMNa增敏组与非增敏组的消化道不良反应、骨髓抑制、放射性肠炎、放射性膀胱炎、皮肤黏膜不良反应发生率比较,差异均无统计学意义。结论:CMNa对宫颈癌放疗及同步放化疗增敏作用的疗效较非增敏组好,不良反应发生率无差异,安全性好。     

Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer

Objectives

The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer.

Methods

We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups.

Results

Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p = 0.77), PFS (log-rank, p = 0.57), and OS rates (log-rank, p = 0.41) to definitive radiotherapy alone. The frequencies of acute grade 3–4 toxicities were similar between the two groups (24.2% versus 24.5%, p = 1.0), whereas the frequencies of grade 3–4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p = 0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3–4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97–5.99, p = 0.059).

Conclusions

Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer.     

Comparison of clinical outcomes of adenocarcinoma and adenosquamous carcinoma in uterine cervical cancer patients receiving surgical resection followed by radiotherapy: A multicenter retrospective study (KROG 13-10)

Objective

To evaluate the prognostic influence of adenocarcinoma (AC) and adenosquamous carcinoma (ASC) in patients with FIGO stage IB–IIA cervical cancer who received radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).

Methods

We analyzed 1323 patients who satisfied the following criteria: histologically proven squamous cell carcinoma (SCC), AC, or ASC of the uterine cervix; FIGO stage IB–IIA disease; no history of neoadjuvant chemotherapy; and a history of radical hysterectomy with pelvic lymph node (PLN) dissection, followed by postoperative pelvic RT at a dose ≥ 45 Gy. The median age was 50 years. Median RT dose delivered to the whole pelvis was 50.4 Gy, and 219 (16.6%) patients received brachytherapy at a median dose of 24 Gy. Concurrent chemotherapy was delivered to 492 (37.2%) patients.

Results

Pathologic risk factors were not different according to pathologic subtype. The median follow-up duration was 75.7 months. Locoregional recurrence-free survival, relapse-free survival (RFS), and overall survival were significantly affected by histology, tumor size, PLN metastasis, parametrial invasion, lymphovascular invasion, and deep stromal invasion. The 5-year RFS rates were 83.7%, 66.5%, and 79.6% in patients with SCC, AC, and ASC histology, respectively (P < 0.0001). By multivariate analysis, AC histology was the only significant prognostic factor affecting all survival outcomes.

Conclusions

AC histology was associated with poor survival outcomes in patients with FIGO stage IB–IIA cervical cancer who received adjuvant RT or CCRT. Prognosis of ASC histology was closer to that of SCC histology than that of AC histology.     

Oxygenated and reoxygenated tumors show better local control in radiation therapy for cervical cancer

The presence of hypoxic cells is one of the major factors affecting resistance against radiation therapy. In the clinical setting, little information exists as to the relationship between intratumoral oxygen partial pressure (pO(2)) and outcome. This study involved 30 consecutive patients with cervical cancer, who were treated with a combination of external and high-dose rate intracavitary irradiation. The pO(2) was measured before radiation therapy and at 9 Gy, using a needle-type polarographic oxygen electrode. The mean intratumoral pO(2) before radiation therapy was 17.3 +/- 10.8 mm Hg. The 3-year local control rates of patients with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg before radiation therapy were 52% and 100%, respectively, representing a significant difference (P= 0.035). At 9 Gy, mean intratumoral pO(2) was 23.6 +/- 9.1 mm Hg, a significant increase compared to the value before radiation therapy (P= 0.006). The 3-year local control rates of tumors with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg at 9 Gy were 35% and 93%, respectively, representing a significant difference (P= 0.001). The significantly better local control for oxygenated tumors at 9 Gy as well as before radiation therapy indicated that the oxygen effect and reoxygenation by radiation played an important role in local control in radiation therapy for cervical cancer.     

Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study

Objective

With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study.

Chronic fatigue and its correlates in long-term survivors of cervical cancer treated with radiotherapy

Objective  To describe the prevalence of chronic fatigue (CF) and associated variables in locoregional cervical cancer survivors (CCSs) surveyed >5 years after radiotherapy. Demographic, clinical and psychological characteristics of the CCSs were compared with normative data.
Design  Cross-sectional study.
Setting  Department of Gynaecologic Oncology at Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Population  Seventy-nine CCSs aged ≤79 years, treated between 1994 and 1999, representing 62% of those invited. Normative data were based on various population studies of Norwegian women.
Methods  Data were collected by means of a mailed questionnaire, which included demographic variables and instruments covering fatigue, mental distress, sexual functioning, somatic impairments and quality of life (QOL).
Main outcome measures  Self-reported fatigue score and caseness of CF based on the fatigue questionnaire.
Results  CCSs showed 30% CF versus 13% reported in the general population ( P = 0.001). CCSs with CF had a significantly lower QOL, higher levels of anxiety and depression and more physical impairments than those without CF. In a multivariable regression model, depression was the only variable significantly associated with CF in CCSs.
Conclusions  More CCSs have CF than age-matched women in the general population. CF should be of clinical concern since these women also frequently have treatable mental and physical problems.     

Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment

Human papillomavirus (HPV) infection plays a major role in oncogenesis of squamous cell carcinoma of the cervix. This study was performed to investigate if HPV status and E2 gene integrity are prognostic parameters for clinical outcome and predictive for radiation response. Forty women with locally advanced cervical cancer treated with curative radiotherapy were analyzed for HPV infection and E2 gene integrity by multiplex polymerase chain reaction. Statistical analyses were performed for overall survival, disease-free survival (DFS), local progression-free survival, and treatment response (clinical complete remission). Twenty-eight (70%) of 40 carcinomas were HPV positive. The only significant factor for a better overall survival, DFS, and local progression-free survival was HPV positivity (P < 0.02, P= 0.02, and P < 0.05, log-rank, respectively). HPV-positive tumors had a significantly better clinical complete remission (67% vs 33%, P= 0.04, Fisher's exact test). An intact E2 gene region showed a trend for a better DFS (P= 0.1, log-rank). This study reveals HPV as an independent prognostic parameter for outcome and radiation response. Integration of the virus genome into host cell DNA might be a molecular target to determine the treatment response of HPV-positive cancers.