Treatment Of Locally Advanced Cervical Cancer Research Articles

Abstract 2403: Divergent evolutionary response to multiple fractions of radiation (MF2) therapy in cervical cancer cell lines (CCCL)

Abstract Introduction: Treatment for locally-advanced cervical cancer is not currently tailored based on genomic markers of treatment response. We aim to explore the potential for differential evolutionary trajectories of radiation (RT) resistance throughout treatment using two in vitro models. Methods: Sixteen cervical cancer cell lines ( CCCL) were exposed to 1.8 Gy fractions of RT radiation for five sequential days and the surviving fraction (MF2) calculated. Differential gene expression (DGE) was performed on pre and post - treatment samples. Partial least squares (PLS) regression was completed with MF2 as the endpoint . Protein-protein interaction (PPI) network and overrepresentation analysis of genes was also performed. Four CCCL (BOKU, SKG II SF, ME180, and HeLa) were serially exposed to 50 Gy of gamma radiation RT given in 2Gy fractions. Five evolutionary replicates and three passage-controls were maintained. The mean integral survival as a function of dose (AUC) was calculated and ANOVA analysis performed. Results: MF2 as the phenotypic endpoint identified 19 DE genes. PLS identified histones (H4C8, H2BC18, H2BC4) as positively associated and transcriptional regulators (NR2F1, KALRN) as negatively associated with MF2 (Figure 1AB). PPI and Reactome Pathways also highlighted histone deacetylase pathways, nucleosome assembly and regulation of membrane potentials (Figure 1BC). Longitudinal treatment RT identified differential evolutionary trajectories between CCCL replicates. Two BOKU (p = 0.005 and 0.0090), one SKG II SF (p = 0.0146), and one ME180 (p = 0.0384) replicates became resistant. Four SKG II SF (p < 0.0001), and two HeLa (p = 0.0005 and p = 0.0068) became more sensitive to radiationRT (1C). Conclusion: Divergent evolutionary trajectories under therapeutic stress can be elicited using in vitro evolutionary experimentation with cervical cancer cell linesCCCL. Genomic correlation with divergent evolutionary trajectories may allow for the identification of real-time markers of resistance or sensitivity and allow for true RT radiotherapy personalization. Citation Format: Johanna Kelley, Arda Durmaz, Michelle Kuznicki, Aaron Petty, Jacob Scott, Roberto Vargas. Divergent evolutionary response to multiple fractions of radiation (MF2) therapy in cervical cancer cell lines (CCCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2403.

Insurance status and time to radiation care after pathologic diagnosis for cervical cancer patients

Delays in starting potentially curative treatment for locally-advanced cervical cancer (LACC) decrease survival. Reasons for these delays are poorly understood. We conducted a retrospective chart review examining disparities in time from diagnosis of LACC to first clinic visit and to initiation of treatment based on insurance status within a single health system. We analyzed time to treatment using multivariate regression, adjusted for race, age, and insurance status. 25% of patients had Medicaid and 53% had private insurance. Having Medicaid was associated with delayed time from diagnosis to seeing a radiation oncologist (Mean 76.9 v. 31.3 days, p = 0.03). However, time from first radiation oncology visit to starting radiation was not delayed (Mean 22.6 v. 22.2 days, p = 0.67). Patients with locally-advanced cervical cancer and Medicaid had over double the time from pathologic diagnosis of cervical cancer to seeing radiation oncology; insurance disparities were not observed in treatment start after seeing radiation oncology. Improved referral and navigation processes for patients with Medicaid are needed to improve timely receipt of radiation and potentially improve survival.

Treatment planning computed tomography radiomics for predicting treatment outcomes and haematological toxicities in locally advanced cervical cancer treated with radiotherapy: A retrospective cohort study.

We evaluated whether radiomic features extracted from planning computed tomography (CT) scans predict clinical end points in patients with locally advanced cervical cancer (LACC) undergoing intensity-modulated radiation therapy and brachytherapy. A retrospective cohort study. Xiangya Hospital of Central South University, Changsha, Hunan, China. Two hundred and fifty-seven LACC patients who were treated with intensity-modulated radiotherapy from 2014 to 2017. Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume, pelvis and sacral vertebrae. The sequentially backward elimination support vector machine algorithm was used for feature selection and end point prediction. Clinical end points include tumour complete response (CR), 5-year overall survival (OS), anaemia, and leucopenia. A combination of ten clinicopathological parameters and 34 radiomic features performed best for predicting CR (validation balanced accuracy: 80.8%). The validation balanced accuracy of 54 radiomic features was 85.8% for OS, and their scores can stratify patients into the low-risk and high-risk groups (5-year OS: 95.5% versus 36.4%, p < 0.001). The clinical and radiomic models were also predictive of anaemia and leucopenia (validation balanced accuracies: 71.0% and 69.9%). This study demonstrated that combining clinicopathological parameters with CT-based radiomics may have value for predicting clinical end points in LACC. If validated, this model may guide therapeutic strategy to optimise the effectiveness and minimise toxicity or treatment for LACC.

Is There a Place for Adjuvant Chemotherapy in the Treatment of Locally Advanced Cervical Cancer?

Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Various substitutes of brachytherapy boost after neoadjuvant chemoradiation for locally advanced cervical cancer. Literature Review

Objective: Concurrent chemoradiotherapy (CCRT) is widely regarded as the gold standard for locally advanced cervical cancer (LACC). Radio Therapy encompasses pelvic external beam radiation therapy (EBRT), followed by intracavitary brachy therapy (BT) to boost the cervix. However, in developing countries, there is a tendency to prefer surgery over other types of treatments for several reasons - surgery is easily obtainable, more acceptable, and understandable culturally. On the other hand, in developed countries, The utilization of brachy therapy (BT) to boost the cervix in patients with Cervical Cancer (CC) has been gradually declined because of the advent of sophisticated techniques for EBRT. Recently, the treatment of LACC has been a point of controversy. We have no prospective data to justify that surgery or modern EBRT can be used in place of intracavitary BT boost in women with locally advanced CC. This study aims to review existing information about brachytherapy alternatives after neoadjuvant chemoradiation. Material and Methods: An electronic search of the PubMed database was conducted to obtain key cervical cancer literature. The MEDLINE/PubMED (www.ncbi.nlm.nih.gov) database was chosen as it remains the most widely used resource for medical literature. Additional records were searched in other resources. Results: The first phase of screening identified 18 articles for the first search term (“Adjuvant hysterectomy” AND “Cervical Cancer”), 10 article for the second search term (“IMRT boost” AND Cervical cancer”) and 11 articles for the third search term (“SBRT” AND “Cervical Cancer”). In sum 39 articles were identified to be relevant for the second phase of screening. Studies that included less than five patients with investigated intervention or did not provided enough information about at least one primary endpoint were excluded. A total of 20 (11-adjuvant hysterectomy, 4-IMRT boost, 5-SBRT boost) papers met the selection criteria and were found eligible for this review. Conclusion: When all these alternative approaches to ICB are evaluated, adjuvant hysterectomy appears to have treatment outcomes comparable to standard of care, while SBRT appears to have only modest yearly results. As a result, the majority of writers believe that neoadjuvant chemoradiation followed by radical surgery or SBRT may be a realistic therapeutic option for patients with LACC, not merely when ICB is unavailable, technically impractical, or rejected. Large, randomized-controlled trials are required to conclusively demonstrate or invalidate non-ICB alternatives for cervical cancer treatment.

Advances in Radiation Oncology for the Treatment of Cervical Cancer.

Background: Over the past two decades, there has been significant advancement in the management of cervical cancer, particularly in the domain of definitive chemoradiotherapy for locally advanced cervical cancer (LACC). Indeed, radiation treatment paradigms have shifted from a two-dimensional (2D) approach solely based on anatomical bony landmarks, to an image-guided three-dimensional (3D) approach, with the goal of delivering doses more precisely to clinical targets with an increased sparing of organs-at-risk. Methods: This is a narrative review on the advances in radiation technologies for the treatment of cervical cancer. Using the PubMed database, we identified articles published in English up until November 18, 2021 on the treatment of LACC with external beam radiotherapy (EBRT) and brachytherapy. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu retrieved information on ongoing clinical trials on the topic of combined immunotherapy and radiotherapy in cervical cancer. Results: We highlight the historical evolution from the use of 2D radiotherapy to 3D-conformal radiotherapy, and then intensity modulated radiotherapy (IMRT) for the delivery of EBRT. We also discuss advances in brachytherapy, notably the transition to 3D image-guided adaptive brachytherapy (3D-IGABT). In this context, we highlight large cohort studies that were recently constructed and have shown significant improvement in local control and treatment-related toxicities with 3D-IGABT. Finally, we discuss other advances in the field, notably the use of stereotactic body radiotherapy (SBRT) as a substitute to brachytherapy, and the addition of immunotherapy to chemoradiation. Conclusions: The use of IG-IMRT and 3D-IGABT have considerably improved treatment outcomes and toxicity profiles for patients with LACC, and are now considered the gold standard in many countries. The use of SBRT boost as a replacement for brachytherapy has been associated with increased toxicity and decreased efficacy and should be used with caution in the context of clinical trials. New experimental approaches include the addition of immunotherapy to chemoradiation regimens.

Dose-Dense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: A Meta-Analysis

Background: The benefit of neoadjuvant chemotherapy remains unclear for the treatment of locally-advanced cervical cancer. With this meta-analysis, we set out to demonstrate the benefit of using dose-dense cisplatin-based neoadjuvant chemotherapy in terms of overall survival. Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) method was applied for this meta-analysis (PROSPERO study’s registration number CRD42021245170). We searched through MEDLINE and Cochrane library databases up to December 2020 to identify randomized clinical trials. Randomized clinical trials were eligible if they intended to compare the survival benefit of using cisplatin-based neoadjuvant chemotherapy followed by local treatment versus local treatment alone for the treatment of locally-advanced cervical cancer. The primary outcome was overall survival as the time interval between the date of randomization and the date of death from any cause or the last follow-up. We used the risk-ratios (RRs) and their 95% Confidence Interval (95%CI) for the effects of neoadjuvant chemotherapy on overall survival and subgroup interactions in a forest plot using fixed or random effect. Findings: Twenty eligible randomized clinical trials were retrieved between 1991 and 2019, corresponding to 3,125 women with FIGO stages IB2-IVA cervical cancer. Median follow-up ranged from 16 to 108 months, 1584 patients were randomly assigned to receive neoadjuvant chemotherapy followed by local treatment and 1541 patients to local treatment alone. More than 50% of the randomized clinical trials were assessed as low risk of bias. There was no benefit of neoadjuvant chemotherapy in overall survival, but with significant heterogeneity across studies (I2= 49%, P < 0.01). In contrast, dose-dense cisplatin ≥ 72.5 mg/m2/3-weeks was significantly associated with increased overall survival (RR for fixed effect = 0.84, 95% CI = 0.76-0.93) with no heterogeneity across the pooled studies (I2= 39%, P= 0.10). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m2/3-weeks (RR = 0.75, 95% CI =0.65-0.87). Interpretation This meta-analysis demonstrated the survival benefit of using dose-dense cisplatin-based neoadjuvant chemotherapy for the treatment of women with locally-advanced cervical cancer, and thus opens perspectives for designing new clinical trials in this setting. Funding: INSERM, University of Paris Declaration of Interest: These authors have no conflict of interest to report.

Nimotuzumab with Concurrent Chemoradiation in the Treatment of Locally Advanced Cervical Cancer: A Single-Centre Experience

Outcomes with chemoradiation (CTRT) in the treatment of locally advanced cervical cancer (LACC) have plateaued. Combining an anti-epidermal growth factor receptor (EGFR) to CTRT could confer added advantage. Hence, we evaluated safety and efficacy of an anti-EGFR humanized monoclonal antibody-nimotuzumab, when given concurrent with CTRT in the treatment of LACC. We retrospectively collected and analysed patients with LACC treated with nimotuzumab with concurrent CTRT from 2013 to 2016 at a single centre in Jabalpur, Madhya Pradesh. A total of 13 patients were evaluated. With a median follow-up of 47 months (range 35–77), 100% patients were alive till last follow-up date. All (100%) patients achieved complete response. The 2-, 3-, 4- and 5-year follow-up data were available for 100%, 92.3%, 46.1% and 30.7% patients, respectively. The disease-free survival and overall survival rate at 2 years were 100% and 100%, at 3 years 100% and 100%, at 4 years 83.3% and 100% and at 5 years 75% and 100%, respectively. Most commonly observed adverse events were grade 1 loose motion (61.53%) and vomiting (53.84%). Grade 2 vomiting was observed in 7.67% patients. No grade 3 and 4 adverse events were observed. Nimotuzumab when given with concurrent CTRT in the treatment of LACC-improved disease-free survival, overall survival and tumour response without additional toxicity. Further studies are required in large number of patients to validate these findings.

Association of Polo-Like Kinase 3 and PhosphoT273 Caspase 8 Levels With Disease-Related Outcomes Among Cervical Squamous Cell Carcinoma Patients Treated With Chemoradiation and Brachytherapy.

Introduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT.Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset.Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses.Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.

Mind the Gap Between Scientific Literature Recommendations and Effective Implementation. Is There Still a Role for Surgery in the Treatment of Locally Advanced Cervical Carcinoma?

According to evidence accumulated in the last years, many cancer centers recommend a treatment plan based solely on chemo-radiotherapy and exclude surgery from the treatment options in locally advanced cervical cancer (LACC). In Romania, surgery was at the forefront of therapeutic options. Nevertheless, current data shows that in fact, a large number of patients are still referred to surgery in various stages of diagnosis and treatment. It was noted that recommendations may differ, in spite of the wide dissemination of the literature data.Works published so far, discussing the role of surgery in LACC treatment shows a lack of consensus. A group of experts in oncology (SURCECAN research group - Surgery of Cervical Cancer) met for a session of the Romanian Surgical Society (Bucharest) on April 18, 2018. They found that LACC therapeutic strategy in Romania may differ somewhat from the European recommendations.On top of that, late enrolement to RT and low acces to specialized centers are the problem. Performing surgery not only allows the evaluation of the pathological response to chemo-radiotherapy, but also achieves a better local control. In conclusion, there is still a place for surgery within locally advanced cervical cancer treatment options. More trials need to be carried out in order to confirm the findings and establish high levels of confidence for each piece of information provided.

Mri Guided Intracavitary/Interstitial Brachytherapy for Treatment of Locally Advanced Cervical Cancer in a Patient with Bicornuate Uterus

Definitive treatment for locally-advanced cervical cancer includes external beam radiation therapy (EBRT) with concurrent cisplatin and brachytherapy. Image-guided intracavitary brachytherapy utilizes CT and/or MRI for target and organ at risk delineation and has been shown to improve local control rates and decrease toxicity. Hybrid intracavitary/interstitial applicators can be used to improve tumor coverage for bulky residual tumors after EBRT. We describe the use of combined intracavitary/interstitial brachytherapy to treat a patient with cervical cancer with a bicornuate uterus.

Analysis of short-term efficacy and pathological outcome of paclitaxel plus platinum as neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer.

e17002 Background:The purpose of this study is to observe the short-term efficacy and pathological outcomes of paclitaxel combined with platinum (TP) as neoadjuvant chemotherapy (NACT) regimen in patients with locally advanced cervical cancer (LACC). Methods: This is a prospective study involving 61 women with histologically confirmed LACC referred for NACT at Beijing Obstetrics and Gynecology Hospital between April 2013 and January 2015. Results: The short-term efficacy of NACT was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST). The short-term efficacy of NACT was 91.8% (complete remission and partial remission). The cervical invasion ≤1/2 was 82.4% in the complete remission (CR) group, 46.2% in the partial remission(PR) group and 20% in the stable disease (SD) group. The difference between groups was statistically significant (p=0.012). The slides of all surgical specimens were reviewed and classified according to Tumor Regression Grade (TRG). The good response was defined by good short-term efficacy (RECIST) and the difference between the groups was statistically significant (p=0.042). The short-term efficacy of NACT in artery intervention (AI) group (70-80%) was better than that in intravenous (IV) group (20%-30%) and the difference was statistically significant (p=0.011). The patients with tumor diameter ≤5cm and multiple cycles of chemotherapy have good short-term efficacy of NACT in LACC. All patients were followed up to the last day of 2015 with the median follow-up time of 21.5 months for NACT. For the 61 patients referred for NACT in LACC, two patients had relapsed and 1 patient died from the disease. Conclusions: The study showed that the Paclitaxel plus platinum as NACT for LACC treatment had a significant local effects. It could reduce tumor myometrial invasion and regress tumor. The short-term efficacy of the treatment in the AI group was more effective than in the IV group, two cycles of NACT of AI treatment to LACC patients would obtain an optimal short-term efficacy. Clinical trial information: NCT02471027.

Risk Factors for Pelvic Insufficiency Fractures in Locally Advanced Cervical Cancer Following Intensity Modulated Radiation Therapy

To investigate the incidence of and risk factors for pelvic insufficiency fracture (PIF) after definitive chemoradiation therapy for locally advanced cervical cancer (LACC). We analyzed 101 patients with LACC treated from 2008-2014. Patients received weekly cisplatin and underwent external beam radiation therapy with 45Gy in 25 fractions (node-negative patients) or 50Gy in 25 fractions with a simultaneous integrated boost of 60Gy in 30 fractions (node-positive patients).Pulsed dose rate magnetic resonance imaging guided adaptive brachytherapy was given in addition. Follow-up magnetic resonance imaging was performed routinely at 3 and 12months after the end of treatment or based on clinical indication. PIF was defined as a fracture line with or without sclerotic changes in the pelvic bones. D50% and V55Gy were calculated for the os sacrum and jointly for the os ileum and pubis.Patient- and treatment-related factors including dose were analyzed for correlation with PIF. The median follow-up period was 25months. The median age was 50years. In 20 patients (20%), a median of 2 PIFs (range, 1-3 PIFs) were diagnosed; half were asymptomatic. The majority of the fractures were located in the sacrum (77%). Age was a significant risk factor (P<.001), and the incidence of PIF was 4% and 37% in patients aged ≤50years and patients aged >50years, respectively. Sacrum D50% was a significant risk factor in patients aged >50years (P=.04), whereas V55Gy of the sacrum and V55Gy of the pelvic bones were insignificant (P=.33 and P=.18, respectively). A dose-effect curve for sacrum D50% in patients aged >50years showed that reduction of sacrum D50% from 40 GyEQD2 to 35 GyEQD2 reduces PIF risk from 45% to 22%. PIF is common after treatment of LACC and is mainly seen in patients aged >50years. Our data indicate that PIFs are not related to lymph node boosts but rather to dose and volume associated with irradiation of the elective pelvic target. Reducing the prescribed elective dose from 50 to 45Gy may reduce the risk of PIF considerably.

SU-E-T-310: Dosimetric Comparison of Tandem and Ovoid (TO) Vs. Tandem and Ring (TR) Applicators in High-Dose Rate (HDR) Brachytherapy (BT) for the Treatment of Locally-Advanced Cervical-Cancer

Purpose: To investigate the dosimetric differences associated with the use of TO or TR applicators for cervical-cancer HDR BT. Methods: The records of all cervical-cancer patients treated with image-guided HDR BT in 2013 were reviewed. Image-based planning based on isodose line and DVH metrics inspections was performed following the GEC-ESTRO recommendations. CTV volume, CTV D90, and rectum, bladder and sigmoid D2cc were collected as % of the prescription dose (80Gy EQD2). Patients receiving both TO and TR were identified and plans were compared (paired analysis). A Student T-test was used to evaluate statistical significance (p ≤ 0.05). Results: Twenty-eight patients were identified (20 TR only, 4 TO only, 4 TO and TR), associated with 116 plans (109 TR, 7 TO). Overall metrics: CTV volume, 26.5±10.4 cm3 (TR) and 39.1±14.0 cm3 (TO, p < 0.01); CTV D90, 126±28% (TR) and 110±15% (TO, p = 0.15); rectum D2cc, 56±11% (TR) and 58±19% (TO, p = 0.91); bladder D2cc, 74±20% (TR) and 88±19% (TO, p = 0.09); sigmoid D2cc, 52±17% (TR) and 49±20% (TO, p = 0.63). The paired analysis results were: CTV volume, 37.3±11.9 cm3 (TR) and 51.0±23.1 cm3 (TO, p = 0.23); CTV D90, 111±12% (TR) and 101±17% (TO, p = 0.50); rectum D2cc, 56±12% (TR) and 53±16% (TO, p = 0.71); bladder D2cc, 73±14% (TR) and 90±20% (TO, p = 0.22); sigmoid D2cc, 59±10% (TR) and 59±22% (TO, p = 0.98). Conclusion: TR and TO were both used with good dosimetric results. TO were used for patients with larger CTV volumes than TR, although paired analysis suggest that tissue distortion and contouring bias may partially explain this Result. CTV D90 on average > 80 Gy EQD2 were achieved in both groups despite the different CTV volume. Higher bladder D2cc for TO than TR was observed.

Cost-Effectiveness Analysis of 3D Image-Guided Brachytherapy Compared to 2D Brachytherapy in the Treatment of Locally Advanced Cervical Cancer

3D Image-guided brachytherapy (IGBT) is a significant advancement in locally advanced cervical cancer treatment. Prospective and retrospective data have shown improved local control and decreased morbidity with this technique. However, the cost-effectiveness of this approach, which requires additional resources including repetitive cross-sectional imaging, is not known. We performed a cost-effectiveness (C/E) analysis of IGBT compared to conventional (2D) brachytherapy in the treatment of locally-advanced cervical cancer. A Markov model using a 1-month cycle with a 3-year follow-up period after completion of treatment was constructed to model locally advanced cervical cancer treated with five fractions of high-dose rate brachytherapy. The model captured clinical parameters (including improvement in survival, local control and RTOG late Grade 3 and above complication rates), quality of life utility, and cost associated with IGBT and 2D brachytherapy. Model assumptions regarding clinical outcomes and quality of life utility were obtained through a comprehensive literature review. Cost was based on Medicare reimbursement in 2013. Strategies were compared using the incremental cost effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, one-way and Monte Carlo probabilistic sensitivity analyses were performed. Strategies were evaluated from the health care system perspective with a willingness-to-pay threshold of $50,000/QALY gained. The base cost of treatment for five fractions of IGBT and 2D brachytherapy was $21000 and $17000, respectively. In the base case analysis, the IGBT strategy cost $3555 more than 2D while gaining 0.16 QALYs, resulting in an ICER of $22,453 per QALY gained. In one-way sensitivity analyses, which varied all parameters individually, results were most sensitive to variation of treatment costs (range: ICER of -$4000 to $49000/QALY gained), but the ICER remained <$50,000/QALY gained if IGBT costs were <$25,400 (baseline $21,000). Variation of survival, local control, and complication rates were less influential. A Monte Carlo probabilistic sensitivity analysis, which varied all model parameters simultaneously 5000 times, demonstrated that IGBT was favored in 63% of model iterations at a $50,000/QALY gained threshold. IGBT for locally-advanced cervical cancer is a cost effective option compared to 2D brachytherapy based upon the ICER analysis. These findings were robust to variation of parameter values, both individually and collectively, supporting the routine use of IGBT in locally-advanced cervical cancer.

Dosimetric Comparison of Tandem and Ovoids Versus Tandem Alone Intracavitary Applicators for Treatment of Locally-Advanced Cervical Cancer

Standard therapy for locally advanced cervical cancer includes intracavitary brachytherapy. Tandem and ovoids (TO) are traditionally used in the US, but when the vaginal fornices are obliterated by tumor, ovoid placement is difficult. Practice patterns surveys in Canada reveal 9% of practitioners there use tandem only. This study compares the dosimetry of TO versus tandem (T) alone insertions with respect to the dose to ICRU points A, B, bladder and rectum, volumetric dose to bladder and rectum and volume of tissue receiving various dose gradients. One hundred eight brachytherapy cases from 27 women with stage II-IV cervical cancer were treated consecutively for cervical cancer with HDR brachytherapy with 4 applicator insertions. The prescribed dose of each insertion was 7 Gy to ICRU point A with additional goals of minimizing bladder and rectal doses. Patients were treated with either TO or T alone at physician discretion based on the clinical evaluation of the vaginal fornices at the time of the procedure. Parameters compared were ICRU point A and B doses, volume receiving 95%, 85%, 50%, and 20% of the prescription dose, ICRU bladder and rectal point doses, and maximal dose to 2 cc of bladder and rectum (D2 cc). The Mann-Whitney U test was used to compare these parameters. The mean dose to ICRU point A was not significantly different between the TO and T applicators, 681 cGy vs 670 cGy (p = 0.09). The mean dose to ICRU point B was significantly higher with the TO applicator than T alone, 200 Gy vs 177 cGy (p = 10-7). Dose distribution was different between the two applicators, with significantly increased volume receiving 95%, 85%, 50%, and 20% of the prescription dose using the TO applicator. The mean V95 was 109.5 cc for TO vs 96.4 cc for T (p = 0.001) and the mean V20 was 1041.7 cc for TO vs 923.9 cc for T (p = 0.009). There was no significant difference in ICRU rectal point doses between the applicators, 361.8 cGy TO vs 375.1 cGy T (p = 0.7). However, there were significantly increased doses to the ICRU bladder point, and D2 cc of the rectum and bladder with the T alone. The bladder point dose was 294.9 cGy TO vs 360.6 cGy T (p = 0.02), bladder D2 cc 403.7 cGy TO vs 632.7 cGy T (p = 0.001) and rectal D2 cc 289.7 cGy TO vs 224.8 cGy T (p = 0.01). TO and T applicator insertions for cervix brachytherapy provide equivalent doses to the ICRU point A, however, the volumetric distribution is significantly different between the 3 channel applicator and single channel tandem. The TO applicator provides increased volumetric dose within the patient, but allows better sparing of the rectum and bladder. In trained providers, T may be considered when the vaginal fornices prohibit appropriate placement of ovoid applicators to provide equivalent Point A doses.

Basic T1 Perfusion Magnetic Resonance Imaging Evaluation of the Therapeutic Effect of Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer

The objective of this study was to evaluate the dynamic changes of blood perfusion coinciding with tumor regression after neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer (LACC). Thirty patients with LACC received conventional 3.0-T magnetic resonance imaging and perfusion-weighted imaging scans at 3 different times (before NACT, 2 weeks after the first NACT, and 2 weeks after the second NACT). Characteristics of time-intensity diagrams and patterns of blood perfusion maps according to the parameter of area under the curve (AUC) were observed. Eight perfusion parameters were compared among 3 time points at 2 different chemotherapy-sensitive groups by the software of Basic T1 Perfusion. The effective chemotherapy rate was 73.3% (22/30). The characteristic of time-intensity diagrams in cervical cancer was a rapid onset with plateau. There were 3 patterns of AUC perfusion maps. The common perfusion map was rich blood supply type in the effective chemotherapy group and peripheral blood supply type in the ineffective chemotherapy group. Four parameter values (relative enhancement, maximum enhancement, wash-in rate, and AUC) were significantly reduced 2 weeks after the second NACT than those before the therapy (P = 0.000; P = 0.009; P = 0.011; and P = 0.000) in the effective chemotherapy group, especially the value of relative enhancement 2 weeks after the first NACT, was obviously decreased compared to that before the therapy (P = 0.042). The value of time to peak 2 weeks after the second NACT was significantly longer than that before the therapy in the effective chemotherapy group (P = 0.001). There were no obvious changes of blood perfusion parameters among the 3 different times in the ineffective chemotherapy group. Tumor blood perfusion has obviously decreased after effective NACT in the treatment of LACC.

Radical treatment with weekly cisplatin (wCDDP) plus concurrent radiotherapy (XRT) in locally advanced cervical cancer (LACC) patients (pts): A mono-institutional experience.

e15556 Background: Platinum-based radical chemoradiation is the standard treatment for LACC (stage Ib2-IV) pts. We describe in this report the activity and tolerability concurrent wCDDP and XRT in ...