High-risk Early-stage Cervical Cancer Research Articles

61 Do the Peters criteria hold up for adenocarcinoma? A retrospective database study evaluating the effect of histology on outcomes in surgically-treated high-risk early stage cervical cancer

61 Do the Peters criteria hold up for adenocarcinoma? A retrospective database study evaluating the effect of histology on outcomes in surgically-treated high-risk early stage cervical cancer

A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery.

The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (β) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.

Is postoperative radiotherapy (PORT) a viable option in high-risk early-stage cervical cancer after upfront or downstaged radical surgery? A comparative study.

Radical surgery for cervical cancer has inherent benefits, and as upfront or post neoadjuvant chemotherapy (NACT), is extendable to locally advanced cancer cervix (LACC), with postoperative radiotherapy (PORT) for high-risk factors. Objective of the study was to compare the effectiveness and survival between non-PORT and PORT in high-risk early stages. Radical hysterectomies conducted between January 2014 and December 2017 were evaluated and followed till December 2019. Clinical, surgical-pathologic characteristics, and oncological outcomes were compared between non-PORT and PORT groups. A similar comparison was made between alive and dead patients within each group. The impact of PORT was assessed. Of 178 radical surgeries, early-LACC constituted 70%. Most (37%) of the patients belonged to stage 1b2, while stage 2b formed 5%. Mean age of patients was 46.5 years; 69% were below 50 years of age. Abnormal bleeding (41%) was the predominant symptom, followed by postcoital (20%) and postmenopausal bleeding (12%). Upfront surgeries formed 70.2%, and the average waiting period was 1.93 months (range: 1-10 months). PORT patients were 97 (54.5%) in number and the remaining formed the non-PORT group. Mean follow-up was 34 months, with 118 (66%) alive patients. Significant adverse prognostic factors were tumors >4 cm (44.4% patients), positive margins (10%), lymphatic vascular space invasion (LVSI; 42%), malignant nodes (33%), multiple metastatic nodes averaging seven (range: 3-11), and delayed (>6 months) presentation, but not deep stromal invasion (77% patients) and positive parametrium (8.4% patients). PORT overcame the adverse effects of tumors >4 cm, multiple metastatic nodes, positive margins, and LVSI. Total recurrences (25%) were balanced for both groups, but recurrences within 2 years were significantly more for PORT. Two-year overall survival (78%) and recurrence-free survival (72%), median overall survival (21 months), and median recurrence-free interval (19 months) were significantly better for PORT, with the complication rates being similar. PORT had significantly better oncological outcomes compared to non-PORT. Multimodal management is worthwhile.

The effectiveness of consolidation chemotherapy in high-risk early-stage cervical cancer patients following concurrent chemoradiation after radical surgery.

Studies determining which early-stage cervical cancer patients with high-risk factors benefit from consolidation chemotherapy after postoperative concurrent chemoradiotherapy (CCRT) are limited and inconsistent. The aim of this study was to evaluate the value of consolidation chemotherapy in early-stage cervical cancer. From 2010 to 2019, a retrospective review was conducted among high-risk early-stage cervical cancer patients who were treated with postoperative CCRT or consolidation chemotherapy after postoperative CCRT. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared using the log-rank test. A total of 293 patients with early-stage cervical cancer were included in this study. A total of 188 patients were in the consolidation chemotherapy group, and 105 patients were in the postoperative CCRT alone group. The median follow-up was 48.3months (range: 3-123months). In the survival analyses, no significant differences in DFS (P=0.21) or OS (P=0.15) were observed between the groups. The grade 3-4 leukopenia and neutropenia rates in the consolidation group were higher than those in the concurrent chemoradiotherapy alone group (54.8% vs. 28.6%, P=0.02; 49.4% vs. 10.5%, P=0.001, respectively). For patients with ≥2 positive lymph nodes or ≥2 high-risk factors, consolidation chemotherapy significantly improved DFS (P=0.013 and P=0.002) and OS (P<0.001 and P<0.001) compared with CCRT alone. For early-stage cervical cancer, consolidation chemotherapy after postoperative CCRT improved survival outcomes in patients with ≥2 positive lymph nodes or ≥2 high-risk factors.

Preoperative high-dose-rate brachytherapy for high-risk early-stage cervical cancer: Long-term clinical outcome analysis

ObjectiveTo report long-term oncological and toxicity outcomes after high-dose-rate brachytherapy (HDB) followed by oncologic surgery for patients with early-stage cervical cancer. Methods and MaterialsFrom 2005 to 2019, all patients treated with preoperative HDB at Antoine Lacassagne Cancer Center for early-stage (IB1-IB2-IIA - FIGO 2018) cervical cancer with local relapse risk factors were included. HDB was performed followed by hysterectomy. Oncological and toxicity outcomes were evaluated prospectively. ResultsWe identified 61 patients, with a median follow-up of 84 months. Posthysterectomy complete pathological response was observed in 46 patients (75.4%). Six patients (9.8%) experienced recurrence, including 4 local relapses (6.6%), and 2 deaths (3.3%) due to cervical cancer. Five-year local, nodal and metastatic relapse-free survivals were 94% (95% CI 87−100%), 96% (95% CI 90−100%) and 93% (95% CI 86−100%) respectively. Five-year overall survival was 98% (95% CI 95−100%). No grade ≥ 3 acute toxicity was observed, and 3 patients (4.9%) experienced grade 2 acute toxicity. One patient presented grade 4 late digestive toxicity, and 6 patients had grade 2 late toxicity. Only 1 patient still had grade 2 toxicity, after 9 years follow-up. ConclusionsTo our knowledge, we are reporting the longest follow-up of a preoperative HDB cohort. With similar oncological outcomes and less morbidity compared to primary surgery treatment followed more or less by adjuvant radiotherapy, HDB followed by hysterectomy could be a promising therapeutic option for early-stage cervical cancers with poor prognostic factors.

Effect of Number of Retrieved Lymph Nodes on Prognosis in FIGO Stage IA1-IIA2 Cervical Cancer Patients Treated With Primary Radical Surgery.

Background:The influence of the number of removed lymph nodes (RLNs) on patients with early-stage cervical cancer (ESCC) is still questionable. The objective of this study was to explore the prognostic value of RLNs on ESCC patients.Methods:A retrospective study was performed including all ESCC patients who underwent radical surgery from January 2016 to December 2018. Cox regression analysis was performed to verify the correlation between the number of RLNs and the prognosis (recurrence-free survival [RFS], disease-specific survival [DSS]) of ESCC. According to the guidelines, all the patients were divided into high-risk and non-high-risk groups. The optimal cut-off values of RLNs were determined by receiver operating characteristic curve analysis and Youden index and further the prognostic value of them was explored.Results:A total 1101 patients were enrolled. The number of RLNs was an independent prognostic influence factor of the prognosis of ESCC (P < .001 for RFS, P < .001 for DSS). The optimal cut-off values of RLNs (40 in the high-risk group and 23 in the non-high-risk group) were significantly associated with the prognosis of ESCC, in the high-risk group (P < .001 for RFS, P = .002 for DSS) and non-high-risk group (P < .001 for RFS, P < .001 for DSS), respectively.Conclusions:More extensive lymph node dissection (RLNs ⩾ 40) could benefit the high-risk ESCC patients. However, in the non-high-risk group, moderate lymph node dissection (RLNs ≈23) could also benefit them and may reduce the incidence of related complications. Those findings may help to determine the scope of lymph node dissection in ESCC patients before operation.

Incorporation of vaginal brachytherapy to external beam radiotherapy in adjuvant therapy for high-risk early-stage cervical cancer: A comparative study

PURPOSETo examine trends, characteristics, and outcomes related to addition of vaginal brachytherapy (VBT) to external beam radiotherapy (EBRT) for adjuvant radiotherapy in high-risk early-stage cervical cancer. METHODS AND MATERIALSThis comparative study is a retrospective observational analysis of the National Cancer Institutes’ Surveillance, Epidemiology, and End Results Program. Surgically treated women with stage T1-2 cervical cancer who had high-risk factors (nodal metastasis and/or parametrial invasion) and received adjuvant radiotherapy from 2000 to 2018 were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for addition of VBT use. RESULTSAmong 2470 women with high-risk factors receiving EBRT, 760 (30.8%) had additional VBT. During the study period, there was an increasing trend of VBT use from 27.4% to 36.1% (p< 0.001). In a multivariable analysis, year of diagnosis and high-risk tumor factors: parametrial involvement, large tumor size, and use of chemotherapy remained independent characteristics associated with VBT use (all, p< 0.05). In propensity score-weighted models, VBT use with EBRT and EBRT alone had comparable overall survival (5-year rates 73.8% vs. 77.4%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92–1.25). Nonsignificant association was also observed in squamous or nonsquamous tumors, young or old age, low or high nodal ratio, chemotherapy use, and simple or radical hysterectomy (all, p> 0.05). Lastly, the addition of VBT was not associated with cervical cancer-specific survival (subdistribution-HR 1.15, 95% CI 0.94–1.41). CONCLUSIONSUtilization of VBT with EBRT for adjuvant radiotherapy in high-risk early-stage cervical cancer is increasing in the United States. Addition of VBT was associated with neither overall survival nor cancer-specific survival.

Utilization and outcome of systemic chemotherapy for high-risk early-stage cervical cancer.

e17521 Background: To examine trends and outcomes of systemic chemotherapy for high-risk early-stage cervical cancer. Methods: This retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000-2016. Surgically-treated women with stage T1-2 cervical cancer who had high-risk factors (lymph node metastasis and/or parametrial invasion) and received adjuvant therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for chemotherapy use versus external beam with chemotherapy (CCRT). Results: Among 2, 462 women with high-risk factor, 185 (7.5%) received systemic chemotherapy. Utilization of chemotherapy has significantly increased over time in multivariable analysis (adjusted-odds ratio per 1-year increment, 1.06, 95% confidence interval [CI] 1.02-1.09). In weighted models, adjuvant chemotherapy and CCRT had comparable survival among women aged &lt; 40 (hazard ratio [HR] for all-cause mortality 0.73, 95%CI 0.41-1.33), adenocarcinoma or adenosquamous histologies (HR 0.90, 95%CI 0.62-1.32), and high-risk group based on nodal metastasis alone (HR 1.17, 95%CI 0.84-1.62). In contrast, chemotherapy was associated with increased all-cause mortality compared to CCRT among women aged ≥40 (HR 1.57, 95%CI 1.19-2.06), squamous histology (HR 1.63, 95%CI 1.19-2.22), and high-risk group per parametrial invasion alone (HR 1.87, 95%CI 1.09-3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95%CI 1.06-2.52). Conclusions: Utilization of systemic chemotherapy for high-risk early-stage cervical cancer is increasing in the United States. Survival effects of adjuvant chemotherapy varied per patient and tumor factors, and this indication may be limited to those who are &lt; 40 years with non-squamous histology and absence of parametrial invasion.

Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy

Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3–153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.

Analysis of the prognostic factors determining the oncological outcomes in patients with high-risk early-stage cervical cancer

We aimed to evaluate clinicopathological data in high-risk early-stage cervical cancer and to define the prognostic factors determining the oncological outcomes. This retrospective study included 158 patients with stage IB–IIA cervical cancer who underwent radical hysterectomy plus lymph node dissection. Each patient had at least one high-risk factor. The median tumour diameter of the study group was 30 mm (range, 6–80). Seventy-five (47.5%) patients had parametrial invasion, 32 (20.3%) had positive surgical margins, and 108 (68.4%) had lymph node metastasis. The median duration of follow-up was 42 months (range, 1–228). During this period, 28 patients developed recurrence, and the recurrent disease occurred in a distant area in 18 patients. Five-year disease-free survival was 77.5%, and five-year disease-specific survival was 85%. In multivariate analysis, adjuvant radiotherapy was identified as an independent prognostic factor for recurrence and death. The recurrence (Odds ratio: 10.139, 95% CI: 1.477–69.590, p = .018) and mortality rates (Odds ratio: 16.485, 95% CI: 2.484–109.408, p =.004) were higher in patients who did not receive adjuvant therapy. IMPACT STATEMENT What is already known on this subject? The decision to proceed with adjuvant therapy in the patients with early-stage disease treated with surgery depends on the presence of risk factors in pathological examination. Various prognostic factors have been identified in cervical cancer (CC). However, there is a limited number of studies describing the prognostic factors in early-stage CC with high-risk factors. What do the results of this study add? In current study, the recurrence and mortality rates were higher in patients who did not receive adjuvant therapy. No relationship was found between the survival outcomes and the number of high-risk factors. Most of the patients who developed recurrence had the recurrence in the distant localisation. This result questioned the adequacy of adjuvant therapy. What are the implications of these findings for clinical practice and/or further research? There is still a debate over the prognostic factors and the adjuvant treatment options in the patients with early-stage cervical cancer who possess high-risk factors. Adjuvant RT or adjuvant concomitant chemoradiotherapy must definitely be used in this patients. However, adjuvant therapy fails approximately 14–32%, thus multimodal treatment modalities must be developed to improve the recurrence rates and the survival.

Conditional survival for high-risk early-stage cervical cancer patients with lymph node metastasis after hysterectomy

Background: To estimate conditional survival (CS) for high-risk early-stage cervical cancer patients with lymph node metastasis after hysterectomy. Methods: 1964 T1-2N1M0 cervical cancer patients who underwent primary hysterectomy from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Result (SEER) Program. Univariate and multivariate cox regression analysis were used to identify independent risk factors. 5-year conditional disease-specific survival (CDS5) and 5-year conditional relative survival (CRS5) were estimated. CDS5 and CRS5 stratified by risk factors were further calculated. Results: CDS5 and CRS5 increased from 71.0% and 73.7% at 0-year to 89.2% and 91.7% at 5-year, respectively. Inversely, the actuarial disease-specific survival and RS dropped from 71.0% and 73.7% at 5-year to 63.3% and 67.6% at 10-year, respectively. Patients with unfavorable factors had a bigger gap between actuarial survival and CS. Both CDS5 and CRS5 curves across stratas of each prognostic factor had a tendency to level off with time elapsing. Notably, CRS5 couldn't exceed 95% even after 5-year follow-up except for patients with grade I disease (CRS5 at 5-year: 100%) or tumor size less than 2 cm (CRS5 at 5-year: 96%). Conclusion: CS increased over time while actuarial survival decreased as time passed. Patients with unfavorable factors had bigger improvement in CS than those with favorable factors. Excess mortality still existed in these patients after 5-year follow-up compared to the general population except for patients with grade I disease or tumor size <2 cm, who might gradually decrease follow-up times after 5-year.

The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee.

ObjectiveThe Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery.MethodsThis analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model.ResultsFor surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078).ConclusionsSurvival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.

Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone

Pelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied. To examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy. This is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n= 729) or in combination with concurrent chemo-radiotherapy (n= 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection. Among 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P= .052), followed by a more gradual rise through 2016 (88.3%, P < .001). In a multivariable model, women with non-squamous cell carcinomas and those diagnosed more recently were more likely to receive concurrent chemo-radiotherapy, whereas older women were less likely to receive concurrent chemo-radiotherapy (all, P < .05). At the population level, the 5-year overall survival rates remained unchanged (annual percent change for 1997-2012: -0.1; 95% confidence interval, -1.2 to 1.0; P= .776). In a propensity score weighted cohort, women who received concurrent chemo-radiotherapy had a 5-year overall survival rate similar to women treated with radiotherapy alone (73.1% vs 73.6%; hazard ratio, 1.004; 95% confidence interval, 0.887-1.136; P= .955). Significant differences were also not seen in older women, nonsquamous types, stage T2 disease, and multiple node metastases (all, P > .05). Despite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodalmetastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.

Vaginal cuff brachytherapy in the adjuvant setting for patients with high-risk early-stage cervical cancer

PurposeTo evaluate local control and survival of high-risk patients with early-stage cervical cancer submitted or not to vaginal cuff brachytherapy in the postoperative setting. Methods and MaterialsIn this retrospective cohort of patients treated from 2010 to 2017, patients were eligible if they had confirmed histological diagnosis of cervical cancer treated with surgery and adjuvant radiotherapy with or without chemotherapy. Vaginal cuff brachytherapy (VCB) was indicated according to the radiation oncologist discretion. ResultsSeventy-nine patients were selected, with a median age at diagnosis of 47.5 years (26–77). Brachytherapy was delivered to 59 patients (74.7%). There were no significant differences between the VCB and the no-VCB groups. A total of 13 (16.5%) patients presented one or more events, 5 (25%) and 8 (13.5%) events in the no-VCB and VCB group, respectively. Most recurrences were pelvic and/or vaginal: 7/20 (35%) in the no-VCB group and 9/59 (10.2%) in the VCB group. There were eight systemic relapses with eight deaths. With a median followup of 45 months, mean overall survival and disease-free survival were, respectively, 85.1 and 83.8 months. No variables were correlated with overall survival. The only factor positively correlated to disease-free survival was VCB, with a mean of 86.9 and 68.4 months for patients who did and did not receive brachytherapy, respectively (p = 0.043). Vaginal recurrence was lower in the brachytherapy group, but with no statistical significance (p = 0.065). ConclusionVCB was associated with a reduced recurrence rate in the postoperative setting of high-risk patients with early-stage cervical cancer.

A comparative clinical study of postoperative intensity-modulated radiotherapy combined with concurrent and sequential chemotherapy for high-risk early-stage cervical cancer

Objective To evaluate the efficacy and acute toxicities of postoperative intensity-modulated radiotherapy (IMRT) combined with concurrent (C-IMRCT) or sequential chemotherapy (S-IMRCT) in the treatment of high-risk early-stage cervical cancer. Methods A retrospective study was performed on the clinical data of 105 patients with high-risk early-stage (ⅠB1-ⅡA2) cervical cancer from 2009 to 2017. Those patients were divided into C-IMRCT group (n=73) and S-IMRCT group (n=32). The 5-year disease-free survival (DFS) and overall survival (OS) rates, recurrence rate, metastasis rate, and acute toxicities were compared between the two groups. The survival rates were calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate prognostic analysis was performed by the log-rank test. Recurrence, metastasis, and adverse reactions were compared using continuous correction chi-square test. Results The median follow-up time was 20 and 23 months in the C-IMRCT group and the S-IMRCT group, respectively (P=0.813). There were no significant differences in the 5-year DFS and OS rates between the two groups (72.6% vs. 72.5%, P=0.918; 82.8% vs. 78.5%, P=0.504). There were no significant differences in the recurrence and metastasis rates between the two groups (P=0.598; P=1.000). The univariate prognostic analysis showed that no pathological factor affected prognosis. There were no significant differences in the incidence rates of grade 1-2 hematological toxicity, diarrhea, and urinary tract infection between the two groups (46.6% vs. 41.9%, P=0.884; P=0.854; P=0.271). Conclusions Further clinical studies are needed in terms of the survival rate in patients with high-risk early-stage cervical cancer receiving C-IMRCT. Key words: Cervical neoplasms/intensity-modulated radiotherapy; Cervical neoplasms/chemotherapy; Concurrent chemoradiotherapy; Sequence chemoradiotherapy; Prognosis

The prognosis of high-risk early-stage cervical cancer patients who did not receive postoperative concurrent chemoradiotherapy

The prognosis of high-risk early-stage cervical cancer patients who did not receive postoperative concurrent chemoradiotherapy

Research advances in postoperative concurrent chemoradiotherapy (CCRT) for high-risk early stage cervical cancer

Cervical cancer is one of the most common gynecologic malignancy, ranking fourth in new cases and deaths in 2012.High-risk early stage cervical cancer after operative need adjuvant treatment. Compared with postoperative radiotherapy alone, CCRT can reduce the pelvic recurrence rates and improve survival rates. And CCRT can extend median survival time and survival rates than sequential CRT after operative. CCRT plus consolidation chemotherapy may play a potential role in further improving survival outcomes for high-risk early stage cervical cancer patients compared with CCRT alone. Retrospective studies show that CCRT had equivalent effects with postoperative chemotherapy alone, but further research is needed. Factors influencing the efficacy of postoperative CCRT include chemotherapy regimens, radiotherapy technology, the interval time between surgery and CCRT, multiple pelvic lymph node metastasis and number of pelvic lymph node dissection. Toxicities mainly include hematologic and gastrointestinal toxicity. Hematologic toxicity is the most common. The incidence of toxicity can be reduced by improving radiotherapy techniques. Key words: Cervical neoplasms/concurrent chemoradiotherapy; High-risk; Untoward effect

A randomized controlled study of single-agent cisplatin and radiotherapy versus docetaxel/cisplatin and radiotherapy in high-risk early-stage cervical cancer after radical surgery

This study explored whether docetaxel/cisplatin and radiotherapy (TP-R) increases overall survival (OS) and recurrence-free survival (RFS) compared to single-agent cisplatin and radiotherapy (C-R) in patients with high-risk early-stage cervical cancer post surgery. Patients with clinical stage IB and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or the diameter of the primary tumor ≥4 cm and/or depth of interstitial infiltration ≥1/2 and/or lymphovascular space invasion were eligible for this study. Patients were randomized to receive C-R or TP-R. Radiotherapy in both groups was external radiation (46-54 Gy) followed by high-dose rate brachytherapy (12-24 Gy). Patients were given cisplatin (40 mg/m(2)) every week for five cycles (C-R group) or docetaxel (30 mg/m(2)) and cisplatin (30 mg/m(2)) every week for five cycles (TP-R group). Between 2003 and 2008, 320 patients were entered onto the study. Final analyses included 285 patients. One hundred and forty patients comprised the C-R group and 145 were in the TP-R group. The 5-year OS were 74.3 % in the C-R group and 82.8 % in the TP-R group. The hazard ratio (HR) for death was 0.65 in the TP-R group (95 % CI: 0.39-1.09, P = 0.098). The RFS were 69.3 % in the C-R group and 79.3 % in the TP-R group, and the HR for recurrence was 0.64 in the TP-R group (95 % CI: 0.40-1.03, P = 0.061). Recurrence rates were similar in both groups (27 in the C-R group and 18 in the TP-R group, P = 0.112). The seriousness of late side effects was similar in the two groups, with a higher rate of reversible hematological effects in the TP-R group. Compared with single-agent cisplatin and radiotherapy, docetaxel/cisplatin in combination with radiotherapy does not increase OS but has the trend of increasing RFS in patients with high-risk early-stage cervical cancer. However, docetaxel/cisplatin in combination with radiotherapy is associated with a higher incidence of side effects, this effect was reversible, and the incidence of late side effects was similar in the two treatment groups.

Postoperative pelvic intensity-modulated radiotherapy and concurrent chemotherapy in intermediate- and high-risk cervical cancer

ObjectiveAccording to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early stage cervical cancer. MethodsFrom 1/2004 to 12/2009, 34 patients underwent radical hysterectomy and pelvic lymph node dissection (28 median nodes were removed) for early stage cervical cancer. Median dose of postoperative pelvic IMRT was 50.4Gy (range, 45–50.4). All patients received concurrent cisplatin. ResultsWith a median follow-up of 44months, 3 patients have recurred; 1 vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year disease-free survival (DFS) was 91.2% (95% CI, 81.4–100%) and overall survival (OS) was 91.1% (95% CI, 81.3–100%). All failures and all deaths were in the high-risk group (n=3/26). There was 32.3% G3–4 hematologic toxicity, 2.9% acute G3 gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity. There were no chronic G3 or higher toxicities. ConclusionsOncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >90% at median follow-up of 44months, despite a preponderance (76.5%) of high-risk features. Toxicity was minimal even in the setting of an aggressive trimodality approach. Data from this study and emerging data from the Phase II RTOG study (0418) demonstrate the advantages of postoperative IMRT in early stage cervical cancer.

Feasibility and effectiveness of postoperative adjuvant concurrent chemoradiation therapy in Japanese patients with high-risk early-stage cancer of the uterine cervix

This study was undertaken to evaluate the feasibility and effectiveness of postoperative concurrent chemoradiation (CCRT) in patients with high-risk early-stage cervical cancer who were treated by radical hysterectomy and pelvic lymphadenectomy. From July 2001 to September 2005, CCRT was performed in 37 patients who had undergone radical hysterectomy with pelvic lymph node dissection at Nagoya University Hospital. Adjuvant chemotherapy consisted of cisplatin (70 mg/m(2) on day 1) and 5-fluorouracil (5-FU; 700 mg/m(2) per day on days 1-4) every 4 weeks for a total of three cycles. Pelvic radiotherapy was started concurrently with the first cycle of chemotherapy. The radiation dose was 45 Gy in 25 fractions. A nonrandomized control group of 52 patients who had undergone radiation therapy alone after radical hysterectomy between 1991 and 2000 served for historical comparison. In the CCRT group, the incidences of grade 3/4 toxicities were 24.3% for neutropenia, 8.1% for nausea and vomiting, and 18.9% for diarrhea. The 5-year progression-free survival (PFS) rates in the CCRT group and control group were 89.2% and 69.2%, respectively (P = 0.0392). This study showed that adjuvant CCRT with cisplatin and 5-FU could be safely performed and improved the prognosis in Japanese patients with high-risk early-stage cervical cancer after radical hysterectomy.