术前新辅助化疗加消瘤放疗用于局部晚期宫颈癌的临床分析

目的:研究新辅助化疗加消瘤放疗后手术治疗ⅠB2～ⅡA期宫颈癌的疗效及意义,评估鳞状上皮细胞癌抗原(SCC)对该治疗方案效果的预测意义。方法:本院2003年1月至2010年6月收治的局部晚期宫颈癌(ⅠB2～ⅡA期)101例,其中研究组(术前同步放化疗组)59例,予铂类为基础的化疗1次联合腔内后装放疗2～3次(700～1200cGy/次),2～3周后行宫颈癌根治术;对照组(同步放化疗组)42例予盆腔内外照射的同步放化疗。比较两种治疗方案的近期疗效,毒副反应及患者生存情况。采用化学发光免疫分析法检测患者血清中SCC水平。结果:两组近期疗效差异无统计学意义,研究组手术切除率达100%,病理有效率93.2%。Kaplan-Meier生存分析显示,研究组及对照组的5年无瘤生存率分别为84.3%和92.8%,5年总生存率分别为87.7%和93.8%,Log rank检验显示,两组的无瘤生存及总生存无统计学差异。新辅助化疗及放疗消瘤后血清SCC阴性者有效率及病理完全反应率较阳性者高,差异均有统计学意义(P<0.05)。结论:在ⅠB2～ⅡA期宫颈癌中,应用新辅助化疗加消瘤放疗后手术疗效与同步放化疗治疗一致,副反应轻,可减少患者痛苦,提高生存质量。血清SCC对术前辅助治疗效果有良好预测作用。     

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.     

Clinical efficacy of conservative laser therapy for early-stage cervical cancer

The objective of this study was to evaluate the clinical efficacy of conservative laser therapy for early-stage cervical cancer. Seven hundred fifty-two and 271 patients with carcinoma in situ (CIS) and microinvasive squamous cell carcinoma (MIC), respectively, were treated by laser conization with vaporization. One hundred eighty-four patients with preclinical invasive diseases underwent radical surgery without conization. Their postoperative histologic findings and clinical outcomes were evaluated retrospectively. The cone specimens of 1023 cases were reported as showing that 54 had dysplasia, 663 had CIS, 239 had stage Ia1 without lymph vascular space invasion (LVSI), 14 had stage Ia1 with LVSI, 14 had stage Ia2, and 39 had stage Ib1 diseases. Incomplete excision occurred in 4 (7.4%) of 54 dysplasia, 48 (7.2%) of 663 CIS, and 16 (6.7%) of 239 stage Ia1 cases, but failure rates were only 1 (1.9%), 8 (1.2%), and 4 (1.7%), respectively. The other 67 of 1023 cases underwent abdominal operation. Final pathology results were analyzed for 67 and 184 cases with stages Ia1 to Ib1 receiving radical surgery with or without initial laser therapy. Lymph node metastasis was not observed in 154 Ia1 and 30 Ia2 with stromal invasion of under 4 mm in depth regardless of LVSI, but was detected in 2 of 16 Ia2 with stromal invasion of over 4 mm in depth and in 9 of 51 Ib1 cases. CIS and Ia1 disease without LVSI can be treated only by laser therapy. The limit of stromal invasion for conservative laser therapy in stage Ia cancer may be 4 mm in depth regardless of LVSI.     

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.     

Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (> or =40 mm), invasion (> or =15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR- (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.     

Ovarian transposition in young patients with invasive cervical cancer receiving radiation therapy

Twenty-two patients with invasive cervical cancer had ovarian transposition. Fifteen patients received whole pelvic external radiation therapy via a teletherapy unit, and nine patients also received one or two intracavitary insertions. Ovarian function was measured by serum gonadotropins, FSH, and LH. We were unable to measure gonadotropin levels in four patients because they were lost to follow-up after completion of radiation therapy. Five patients developed postmenopausal symptoms; in two the ovaries were not shielded and they received radiation by lateral ports with an average dose above 2500 cGY. Therefore, ovarian function was preserved in seven of 11 patients (64%), all of whom received 500 cGY with an average dose of 250 cGY to the ovaries via external radiation and intracavitary insertion(s). FSH values ranged from 3.3 to 38.8 mlU ml⁻¹ (mean = 17.7 mlU ml⁻¹). Two patients developed symptomatic ovarian cysts. Ovarian function can be preserved by transposing the ovaries at the time of surgery prior to radiation with adequate treatment planning which limits the radiation dose to the ovaries to 300 cGY.     

宫颈癌的放射治疗

放射治疗(以下简称放疗)是宫颈癌的主要治疗方法之一,可以作为宫颈癌的根治性、辅助性或姑息性治疗方法。本文就宫颈癌临床放疗工作中的一些具体方法、注意事项和进展进行阐述。     

Intensity-modulated radiation therapy for advanced cervical cancer: a comparison of dosimetric and clinical outcomes with conventional radiotherapy

Objective

The aim of this study is to evaluate the dosimetry, efficacy and toxicity of reduced field intensity-modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer.

Methods

From August 2005 to August 2010, 60 patients with stage IIB-IIIB cervical cancer underwent reduced field IMRT (RF-IMRT group) and 62 patients treated with conventional radiotherapy (c-RT group) were enrolled. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver a dose of 30 Gy firstly, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. The tumor coverage and normal tissue avoidance were evaluated. Treatment response, toxicities and survival were assessed.

Results

The mean dose delivered to the planning target volume was significantly higher in RF-IMRT group than in c-RT group (61.5 vs. 50.8 Gy, P = 0.046). IMRT plans yielded better dose conformity to the target and better sparing of the rectal, bladder and small intestine. The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (CR: 87.7% vs. 88.3%, P = 0.496; PR: 7.0% vs. 6.7%, P = 0.440). No significant differences were found between treatment groups for 1 year, 3 year, and 5 year overall survival (OS) levels, although the latter approached statistical significance in favor of IMRT, while a significantly higher progression-free survival (PFS; P = 0.031) was seen for IMRT.

Conclusions

RF-IMRT yields improved dose distributions, with lower toxicities, while providing comparable clinical outcomes. The increased PFS may be an advantage.     

局部晚期宫颈癌靶向治疗的现状和未来

近年来,由于宫颈癌筛查的普及,全球宫颈癌发病率呈现下降趋势,约80%以上宫颈癌患者发生在发展中国家,而且年轻妇女宫颈癌的发生率在逐渐上升。对于晚期宫颈癌患者,虽然放疗和化疗有一定的疗效,但是中位生存时间也仅1年。靶向治疗在治疗晚期肿瘤方面取得了巨大的成就,临床研究已经证实贝伐单抗联合化疗可有效延长晚期宫颈癌患者的总生存时间,而且越来越多的靶向药物也被用于研究对晚期宫颈癌的治疗上。     

Postoperative adjuvant therapy in early invasive cervical cancer patients with histopathologic high-risk factors

Abstract. Park TK, Kim SN, Kwon JY, Mo HJ. Postoperative adjuvant therapy in early invasive cervical cancer patients with histopathologic high-risk factors.
The purpose of this study is to evaluate the efficacy of postoperative adjuvant therapy in preventing treatment failure after primary treatment with surgery in early invasive cervical cancer patients associated with the following histopathologic high-risk factors: lymph node metastasis (either macroscopic or microscopic), parametrial extension, lymphovascular permeation and depth of invasion 10 mm.
Postoperative adjuvant concurrent chemoradiotherapy (PCCRT), postoperative adjuvant chemotherapy (PCT), or postoperative adjuvant radiotherapy (PRT) alone was administered to the 80 early invasive cervical cancers with at least one of the high-risk factors. Each of 61 patients received three to six cycles of chemotherapy at intervals of approximately 3 weeks. Twenty three patients were treated with PCCRT, 38 patients were treated with PCT alone, and 19 patients received PRT.
The 5-year survival rates of patients with macroscopic lymph node metastasis were 66.7% and 35.7% in PCCRT and PRT, respectively. With microscopic lymph node metastasis, the 5-year survival rates were 83.3%, 60.0%, and 70.1% in PCCRT, PCT, and PRT, respectively. With parametrial extension, the 5-year survival rate was 58.1% in PCCRT. The 5-year survival rates of patients with lymphovascular permeation were 100%, 90.9%, and 66.7% in PCCRT, PCT, and PRT, respectively. With depth of invasion 10 mm, the 5-year survival rates were 100% and 91.3%, in PCCRT and PCT, respectively.
PCCRT appears to be superior to PRT or PCT alone in early invasive cervical cancer patients with histopathologic high-risk factors.     

Hyperbaric oxygen therapy for delayed radiation injuries in gynecological cancers

Delayed radiation-induced injuries are difficult to treat. The treatment of delayed radiation injuries with hyperbaric oxygen therapy (HBOT) is reported in small case series and case reports. This study reports the experience of a single institution with HBOT in delayed radiation injuries in patients with gynecological cancers. At least 20 sessions of 100% oxygen inhalation at 2.4 Atmospheric Absolutes (ATA) for 90 min in a hyperbaric chamber were carried out. Of the 14 patients included in the study, 10 patients have healed or showed improvement of more than 50%, resulting in a success rate of 71%. Mean follow-up was 31.6 months (range 6-70 months). The adverse events were acceptable. HBOT should be considered for patients with delayed radiation injuries, not responding to other treatments.     

Topotecan for recurrent cervical cancer after platinum-based therapy

Abstract. Abu-Rustum NR, Lee S, Massad LS. Topotecan for recurrent cervical cancer after platinum-based therapy.
The activity and toxicity of topotecan in women with recurrent cervical cancer are described from a case series of women with recurrent cervical cancer who had measurable disease and were not amenable to cure by surgery or radiation. All patients had prior platinum-based chemotherapy and developed progressive disease. Topotecan was given as 1 mg/m²/day over 30 min for 5 days every 3 weeks until progression of disease or prohibitive toxicity. Between July 1998 and July 1999, 12 patients received a total of 20 cycles of topotecan. Median age was 41 years (range 21–62), and 11 (92%) patients had prior whole pelvic radiation. The mean number of topotecan cycles was 1.5 (median 1, range 1–3). There were two partial responses (16.7%; 95% CI, 2% to 48%), both in prior radiation fields. Five patients required red blood cell transfusions, four had grade II nausea and vomiting, two developed sepsis (one with neutropenia), one developed fever, and one reported hyperpigmentation. There were no treatment-related mortalities. Although topotecan appears to exhibit modest activity in recurrent cervical cancer after radiation and platinum-based therapy, bone marrow toxicity may limit the utility of this regimen without hematopoietic growth factor support.