Definitive Treatment Of Cervical Cancer Research Articles

Abstract 1305: Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study

Abstract Cervical cancer is a significant global health issue, with oncogenic HPV-High Risk (HPV) responsible for over 99% of cases. Despite the prevalence of HPV-related malignancies, current guidelines by the National Comprehensive Cancer Center (NCCN) do not recommend post-treatment HPV-DNA testing. Instead, PET-CT imaging is recommended as a prognostic test. This retrospective proof-of-concept study aims to evaluate current NCCN guidelines and examines whether post-treatment HPV-HR DNA testing is a cost-effective, reliable alternative to PET-CT imaging in cervical cancer prognosis. Methods: The study included female patients diagnosed with cervical or vaginal carcinomas (2011-2021), ensuring comprehensive records of both pre-treatment and post-treatment high-risk HPV (HPV-HR) testing, alongside PET-CT imaging results. Utilizing the FDA-approved HPV-HR DNA test, capable of detecting 14 oncogenic HPV strains, the study conducted rigorous statistical analyses via STATA software to determine significance of the study results. Results: Our analysis of 53 patients who met the inclusion criteria demonstrated that post-treatment assessments using both HPV status and PET-CT imaging exhibited high levels of sensitivity and specificity, as well as impressive negative and positive predictive values (NPV and PPV, respectively). There was a statistically significant correlation between the likelihood of cancer recurrence and the results obtained from HPV status and PET-CT imaging post-treatment (p-value < 0.001). A critical observation was the superior sensitivity and improved NPV of post-treatment HPV status compared to PET-CT scans. Specifically, the sensitivity for HPV status post-treatment was quantified at 92.31, surpassing the 76.92 sensitivity rating of PET-CT scans. Furthermore, the NPV for post-treatment HPV status was measured at 97.44, which is better than the 92.31 NPV for PET-CT scans. Notably, no patients with negative post-treatment HPV-HR tests had a recurrence. Discussion: The results of this study underscore the clinical significance of assessing HPV-HR DNA status post-treatment, particularly when HPV-HR DNA is negative. If future prospective studies confirm these findings, it may eliminate the need for post-treatment PET-CT scans, providing significant survivorship benefits for patients by reducing follow-up visits and eliminating unnecessary imaging. This would also result in substantial financial savings, estimated to be over $75,000,000 per year in the US alone, based on 2023 data. The limitations of the study include small sample size, single-institution data, and biases associated with retrospective studies. Future multi-institutional prospective studies are necessary to improve current guidelines further and validate the findings of this study. Citation Format: Cameron Huddleston, Aya Bou Fakhreddine, Stephanie Stroever, Robert Young, Naresh Sah, Komaraiah Palle, Mark Reedy. Comparison of HPV-DNA testing to PET-CT imaging as prognostic test following definitive treatment for cervical cancer: A retrospective proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1305.

Pre-Brachytherapy Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

Chemoradiation consisting of external beam radiotherapy (EBRT) followed by brachytherapy (BT) is the standard of care for Stage IB2-IVA cervical cancer (CC). Multi-parametric MRI (mpMRI) is a valuable tool for initial staging, treatment planning and response assessment. In this study, we aim to explore the potential of mpMRI, in particular DW-MRI, to predict overall tumor control following chemoradiation in CC. We identified 78 consecutive patients treated with chemoradiation for FIGO IB2-IVA CC between 2012-2020, who had an MRI at baseline (MRb) and post-EBRT prior to brachytherapy boost (MRpb) that included DW-MRI (b-value = 0 and 800 s/mm2). Median age was 53 years, most patients had squamous cell carcinoma (76.9%) and advanced-stage disease (56.4% stage IIIA-IVA). Median time from completion of EBRT to MRpb was 3 days. Regions of interest (ROI) in primary tumor were delineated on DW image (b = 0 s/mm2) using ITK-SNAP software. DW-MRI data were fitted to a monoexponential model to calculate apparent diffusion coefficient (ADC) values using in-house software platform (MRI-QAMPER). MRpb mean ADC values (n = 78) and relative changes (%) in mean ADC values between MRb and MRpb (n = 64) were correlated with outcomes, including local failure (LF), regional or distant failure (RDF), and failure at any site (FAS), with death without failure as a competing risk. Median follow-up time was 45 months (95% CI 38, 53). At first post treatment assessment, 72 patients (92.3%) had a complete response (CR) in the cervix and 68 patients (87.2%) had CR in all disease sites. Of patients who had CR in the cervix (n = 72), only 1 patient had local recurrence. Of patients who had CR in all disease sites, 10 later recurred (1 LF only, 1 LF&RDF, 8 RDF only). Overall, 7 patients (9%) had LF, and 19 patients (24.4%) had FAS. A higher mean ADC value in MRpb was associated with LF (HR 4.3, 95% CI 1.32, 14.6; P = 0.016), but not with RDF (P = 0.4) or FAS (P = 0.5). A higher relative change in the mean ADC value between MRb and MRpb was associated with a lower risk of LF (HR 0.94, 95% CI 0.90, 0.98; P = 0.002), but not with RDF (P = 0.8) or FAS (P = 0.4). Treatment response as measured on prebrachytherapy DW-MRI is a significant predictor of local control in patients undergoing chemoradiation for stage IB2-IVA CC. ADC values, a quantitative imaging biomarker on MRpb may be instrumental in dose intensification/de-escalation efforts in CC.

Considerations for pharmacologic thromboprophylaxis following inpatient brachytherapy for gynecologic malignancies

Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01-5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22-155.18), p = 0.29. The median Caprini score was 11. VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges.

GSOR25 Presentation Time: 12:30 PM: Interim Pre-Brachytherapy Magnetic Resonance Imaging (MRpb) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

<h3>Background</h3> External beam radiotherapy (EBRT) followed by brachytherapy is standard of care in the management of cervical cancer. Whether early imaging response can predict longer term outcome is unclear. In this study, we investigated the role of interim pelvic magnetic resonance imaging (MRI), done prior to brachytherapy (BT) in predicting local tumor control. <h3>Methods</h3> We identified 87 consecutive patients who underwent definitive EBRT followed by BT for FIGO IIB-IVA cervical cancer at our institution between 2012 and 2020. The median age was 54 years (range, 23-81 years). Most patients had squamous cell carcinoma (77%), advanced stage disease (57.5% stage IIIA and higher, 51.7% nodal disease) and received concurrent cisplatin (98.8%). All patients had an MRI at baseline (MRb) and prior to brachytherapy boost (MRpb). The median time from completion of EBRT to MRpb was 3 days (IQR: -14d to +1d). EBRT included the regional LNs and primary site (median dose 45Gy, range 45-54Gy). Node positive patients also received a boost (median 5.4Gy, range 5.4-14.4Gy) Fifty-seven patients (65.5%) had intracavitary brachytherapy (median dose 28Gy, range 2-28Gy) and 30 (34.5%) had an interstitial BT (median dose 24Gy, range 20-28Gy). Adjuvant chemotherapy was delivered in 24 cases (27.6%). Patients were followed post-treatment with pelvic exams/cytology every 3 months for years 1-2 and every 6 months thereafter. PET/CT and a pelvic MRI were done 3 months posttreatment and as clinically indicated thereafter. Median follow up time was 35.5 months (range 3.8-114.2 months). Response to EBRT on MRpb was defined as residual disease > 2 cm, residual disease ≤ 2 cm and no measurable disease (complete response, CR). Local failure was defined as recurrent or persistent tumor in the cervix following all treatment and confirmed pathologically. Chi square test was used to compare categorical data. <h3>Results</h3> Overall, 19.5% of patients had a CR, 22.9% had residual disease ≤2cm and 57.5% had residual disease >2cm noted on MRpb. No patients who achieved a CR on MRpb had local recurrence. Of patients with residual disease ≤2 cm on MRpb, 19/20 patients (95%) ultimately achieved CR on subsequent imaging (median time to CR 3.1 months; range, 2.7-8.6 months), none of whom had a local failure. Of patients with residual disease >2 cm on MRpb, 40/50 (80%) ultimately achieved CR on subsequent imaging (median time to CR, 3.6 months; range, 2.1 - 18.6 months). Of the 10 patients with residual disease >2 cm on MRpb who did not achieve a CR, 4 had local failure, 1 had local and distant failure and 5 had regional or distant failure only. Overall, 6/50 (15%) patients with persistent disease >2 cm had local failure, compared with none of the patients who had more profound responses. Local disease response on MRpb did not predict regional or distant failure (p=0.35). <h3>Conclusions</h3> Interim pre-BT MRI seems promising in predicting local tumor control in the definitive management of cervical cancer and could be instrumental in dose intensification/de-escalation efforts. Further investigation of various MRI sequences in predicting response and long-term control is ongoing.

Trends in IMRT Utilization for Definitive Treatment of Cervical Cancer, 2004-2018

<h3>Purpose/Objective(s)</h3> Intensity-modulated radiation therapy (IMRT) is an advanced radiotherapy technique that delivers conformal radiation to desired targets while minimizing dose to surrounding organs at risk. In the post-operative setting, IMRT is associated with reduced acute and late genitourinary and gastrointestinal side effects for patients with cervical cancer. However, no prospective randomized data exist for the use of IMRT in the setting of definitive treatment of intact cervical cancer. The objective of this study was to identify trends in IMRT use for this population. <h3>Materials/Methods</h3> Patients with stage IB2-IVA cervical cancer diagnosed from 2004-2018 who were treated with curative intent chemoradiation were identified in the National Cancer Database. Patients who underwent primary surgical management, did not receive external beam radiation to the pelvis or received radiation outside the pelvis, or received an unspecified technique or target of radiation were excluded. The primary outcome of interest was utilization of IMRT vs 3D conformal radiotherapy (3D-CRT) over time. A Cochrane-Armitage test was performed to assess trends over time. T-tests, chi-square tests, and multivariable logistic regression with propensity score matching were used to identify factors associated with receipt of IMRT. <h3>Results</h3> Overall, 13,974 patients met inclusion criteria; 4,590 (33%) received IMRT, and 9,384 (67%) received 3DCRT. In this cohort, 65% were non-Hispanic White, 45% were early stage (I-II), 80% were squamous histology, 62% received brachytherapy, and 28% had lymph node involvement. The utilization of IMRT increased from 30% in 2004 to 71% in 2018 (p<0.001). After adjustment for clinical and demographic variables, factors associated with IMRT use were: Hispanic ethnicity (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.0-1.5), treatment in the Western U.S. (aOR 1.4, CI 1.2-1.7) and the Southern U.S. (aOR 1.3, CI 1.1-1.5), living more than 50 miles from the treatment facility (aOR 1.2, CI 1.0-1.5), stage III disease (aOR 1.3, CI 1.1-1.5), and lymph node involvement (aOR 1.4, CI 1.3-1.6). Compared to an academic medical center, patients receiving care at a comprehensive community cancer center were less likely to receive IMRT (aOR 0.66, CI 0.59-0.72). There were no differences in IMRT use by age, insurance, or medical comorbidities. <h3>Conclusion</h3> Despite the lack of prospective efficacy data supporting the use of IMRT in patients with intact cervical cancer, IMRT has dramatically increased over the last fifteen years especially for patients with advanced-stage disease or lymph node involvement. More data on the optimal use of IMRT, including appropriate target volume margins and on-board imaging, are needed.

IMRT use for locally advanced cervix cancer: Do patients at safety-net hospitals have equal access to this technology? (285)

<b>Objectives:</b> Intensity-modulated radiation therapy (IMRT) is an advanced technique that allows for conformal delivery of radiation to a planned treatment area while minimizing radiation to organs at risk. Utilization of this technique in the definitive treatment of cervical cancer can be variable but has been associated with reduction of acute and late genitourinary and gastrointestinal side effects of radiation. The objective of this study was to identify the trends associated with IMRT use for patients undergoing definitive treatment for cervical cancer. <b>Methods:</b> This was a retrospective cohort study of patients with FIGO stage IB2-IVA cervical cancer from 2009-2020. All patients receiving curative-intent treatment for locally advanced cancer were included, with chemoradiation therapy followed by brachytherapy as the standard. At our institution, patients were referred from a network of safety net hospitals and also a group of academic medical centers and received radiation at one site. The primary outcome was the rate of IMRT versus three-dimensional conformal radiotherapy (3DCRT) usage. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). We used Chi-square, logistic regression, Kaplan Meier log-rank test, and Cox regression with significance p<0.05. <b>Results:</b> One hundred thirty-eight patients were diagnosed with locally advanced cervical cancer in our cohort. The median age at diagnosis was 54 years (range: 23-83). Ninety-two (67%) patients received conventional 3CDRT, and 46 (33%) patients received IMRT. IMRT use increased from 0% in 2011 to 100% in 2020 (p<0.001). Age at diagnosis, race, insurance, and referring hospital were not correlated with IMRT use. In univariate regression, diagnosis after 2015 (OR: 34.22, 95% CI: 7.81-149.98), radiation dose greater than 50 Gray (OR: 2.60, 95% CI: 1.05-6.46), and need for paraaortic boost (OR 2.86, 95% CI: 1.09-7.52) were associated with IMRT. In multivariate regression, only diagnosis after 2015 was predictive of IMRT use (OR: 30.37, 95% CI: 6.58-140.36) when controlling for radiation dose and indication for paraaortic boost. IMRT use was not associated with a PFS benefit (p=0.903) nor an OS benefit (p=0.642). The median follow-up was 28 months (range: 3-122). Only stage was predictive of PFS (HR: 2.21, 95% CI: 1.41-3.44) and OS (HR: 2.63, 95% CI: 1.44-4.77) when controlling for race, insurance, and referring hospital. <b>Conclusions:</b> IMRT use has increased significantly over the last decade for locally advanced cervical cancer. In our care model, where patients referred from both a network of public and private hospitals undergo radiation at one central facility, there were no disparities in receipt of IMRT according to race, insurance, or referring hospital. There were no effects of IMRT on PFS or OS. Additional studies are warranted to correlate our institutional experience with national trends in IMRT usage. Table 1

Aggravation of Hemorrhoids in Patients With Cervical Cancer Undergoing Radiotherapy: A Nationwide Population-based Study.

Anal canal toxicity tends to be ignored in pelvic radiotherapy (RT). However, patients with hemorrhoids can be troubled by lower radiation dose. We tried to determine whether a correlation exists between hemorrhoids and anal symptoms in patients with cervical cancer undergoing RT. The insurance claim data of patients who underwent definitive treatment for cervical cancer from 2015 to 2019 were analyzed. Adverse events including bleeding, proctitis, and hemorrhoids, were documented for 1 year after treatment completion. Odds ratios (ORs) were estimated by unconditional Poisson regression and adjusted for age, treatments, chemotherapy, and comorbidities. Details of 67,114 insured cervical cancer patients treated between 2015 and 2019 were obtained. Among them, 5,919 patients with follow-up data for at least one year, treated with curative intent, were analyzed. The OR of the definitive radiotherapy group (DRT group) for anal bleeding was 10.57 higher than that of the operation alone group (surgical group) (p<0.01). Newly developed hemorrhoids gradually increased in the surgical group (3.17%), the postoperative radiotherapy group (5.38%), and the DRT group (7.58%). The OR of the DRT group for newly developed hemorrhoids was 2.38 higher than that of the surgical group (p<0.01), and ORs increased to 1.99 and 1.61 in patients that received chemotherapy and patients with diabetes, respectively (p<0.01). Pelvic RT increased anal bleeding and symptomatic hemorrhoids. In particular, chemotherapy and diabetes also increased the risk. If patients with hemorrhoids receive pelvic RT, attention is required to prevent hemorrhoid aggravation.

Incidence and Outcomes of Para-aortic Nodal Recurrence After Definitive Treatment for Cervical Cancer: A Single Institution Experience from South India

To analyse the patterns of para-aortic nodal recurrence in carcinoma cervix and the outcomes with various treatment options at our institution. The data of patients diagnosed to have cervical cancer between January 2012 and December 2017 were retrieved from the electronic medical records. Those with para-aortic recurrence following definitive treatment for cervical cancer were identified and were classified as isolated para-aortic nodal recurrence, para-aortic and pelvic recurrences, and para-aortic and distant metastases. Analysis was done based on demographic characteristics, disease stage at diagnosis, pathological characteristics, treatment modality, and follow-up. There were 18 isolated para-aortic recurrences (41%), 17 para-aortic with distant metastasis (39%), and 9 para-aortic with pelvic metastasis (20%). The median time to recurrence from diagnosis for isolated para-aortic recurrences, para-aortic with pelvic recurrences, and para-aortic with distant metastasis was 26 months, 14 months, and 12.5 months, respectively. The median survival of the entire cohort of patients was 36 months. The median survival of isolated para-aortic recurrence, para-aortic with pelvic recurrence, and para-aortic with distant metastasis was 45 months, 16 months, and 10 months, respectively (p = 0.001). The median survival was 45 months for those who received combined modality treatment with chemotherapy followed by RT, followed by 30 months for those who received RT alone, and 11 months for those who received chemo alone. For patients who received best supportive care alone, it was 7 months (p = 0.055). Isolated para-aortic recurrences present late and have a relatively favourable prognosis when treated with a combined modality approach. At recurrence, definitive para-aortic radiation therapy combined with chemotherapy had the best outcome. High-risk approach with prophylactic lower para-aortic radiation for high volume primary and pelvic nodal disease needs to be studied for further improvement in outcomes.

Assessment of Intrafraction Cervico-Uterine Motion in the Definitive Treatment of Locally Advanced Cervical Cancer Using MR-Guided Radiotherapy

To account for intrafraction motion, patients receiving intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer have an internal target volume (ITV) defined from bladder-full and bladder-empty CT simulation scans. We hypothesized that through daily volumetric magnetic resonance (MR) imaging for setup and treatment, we can assess cervico-uterine motion and create an intrafraction-ITV independent of interfraction bladder changes, and therefore dispense with the full-bladder to empty-bladder ITV paradigm. In this IRB-approved, study patients with locally advanced cervical cancer received IMRT with brachytherapy. IMRT was delivered on a clinical MR-guided radiotherapy (MRgRT) Linac. All patients received a pre-treatment (pre-tx) and post-treatment (post-tx) 0.35T balanced steady-state free precession MR scans in treatment position. The intrafraction cervico-uterine motion was assessed through segmentation of the clinical target volume (CTV) by a gynecological radiation oncologist on each scan. The pre-tx and post-tx MR scans were in the same frame of reference, and any residual patient motion was removed through a rigid registration of the post-tx MR scan to the pre-tx MR scan based on bony anatomy. All post-tx contours were rigidly copied to the pre-tx MR scans. The maximum and mean difference in spatial position between the pre-tx and post-tx MR scans were quantified using maximum Hausdorff distance (HD) and mean distance to agreement (MDA), respectively. Mean, standard deviation, and 95% confidence interval were calculated to determine the intrafraction MR-based internal target volume (ITVMRgRT). In total, 19 same day sessions (N = 38 scans) of intrafraction motion were assessed. Minimal patient voluntary motion was observed across rigid registrations with respect to bony anatomy. The average time between the pre-tx and post-tx MR scans was 14.3 ± 7.1 minutes (mean ± standard deviation), resembling a hypothetical time of on-table adaptation and treatment. The average maximum HD was 0.88 ± 0.46 cm (95% CI 0.668 - 1.08) and average MDA was 0.08 ± 0.07 cm (95% CI 0.05- 0.118). Due to HD’s sensitivity to outliers, a more robust metric (i.e., MDA) was utilized for margin calculation. The ITVMRgRT margin necessary to encompass the MDA for 95% of the intrafraction motion was 0.12 cm; therefore, we propose an ITVMRgRT of 0.15 cm given the non-partial voxelization of segmentation. This work supports margin reduction of the ITV to ITVMRgRT of 0.15 cm when using daily MR-guided online adaptive radiotherapy. Given the maximum setup uncertainty is limited in MRgRT to spatial resolution of the real-time cine imaging sequence, we propose an ITVMRgRT-PTV margin of 0.3 cm. Therefore, our total CTV to PTV margin is 0.45 cm.

Dosimetric Modeling of Intracavitary versus Combined Intracavitary/Interstitial Applicators During High Dose Rate Brachytherapy for Cervical Cancer

With increased adoption of image guided adaptive brachytherapy (IGABT) for definitive treatment of cervical cancer, combined intracavitary/interstitial (IC/IS) brachytherapy applicators are increasingly utilized as a means of dose escalation while minimizing exposure to organs at risk (OAR) structures compared to traditional intracavitary (IC) applicators. Aside from high risk CTV volume, little data exists to guide clinicians as to relative OAR dose reductions that might be predicted for a given patient with use of combined IC/IS vs IC applicators and tumor/target volume characteristics that correlate with greatest benefit. We performed pair-wise comparisons of IGABT treatment plans modeled with IC and IC/IS applicators to determine relative dose reductions to bladder, rectum, and sigmoid. In addition, we hypothesized that CTV asymmetry would be associated with a relatively greater degree of OAR dose reduction with use of an IC/IS applicator. Treatment planning MRI or CT images for fifteen consecutive patients treated with IC or IC/IS brachytherapy applicators as part of definitive therapy for FIGO 2018 stage IB3 to IIIC cervical cancer at a tertiary care academic medical center were obtained. For each dataset, high dose rate brachytherapy treatment plans were generated for both IC and IC/IS brachytherapy applicators using a treatment planning software. When interstitial needles were not placed at the time of applicator insertion, needle/dwell positions were modeled based on ovoid position and patient anatomy. Treatment plans were generated to minimize dose to the D2 cc volume of OAR contours while reaching an equivalent dose to the D90 of the high-risk CTV. OAR (bladder, rectum, and sigmoid colon), CTV, and GTV volumes, consistent with GEC-ESTRO guidelines, were obtained from previously administered treatment plans and were not modified. As a surrogate for target volume asymmetry, the ratio of maximum antero/posterior to lateral CTV dimension (AP:L ratio), was calculated for each patient. Paired t-tests were used to identify significant differences between IC and IC/IS treatment plans with respect to OAR doses, while Spearman correlation tests were used to assess correlations between OAR sparing and CTV AP:L ratios. Mean volumes for GTV and CTV were 7.4 (1.1 to 19.4) and 29.7 (10.4 to 52.3) cubic centimeters. Mean doses to D2 cc volumes were 15.9% lower for bladder (p<0.01); 15.3% lower for rectum(p<0.01); and 10.0% lower for sigmoid (p<0.01) with IC/IS plans. The CTV AP:L ratio demonstrated a significant inverse correlation with D2cc dose reduction for bladder (p<0.05), rectum (p<0.05), and sigmoid (p<0.05). For an equivalent prescribed radiation dose, IC/IS applicators are associated with significant reductions in bladder, rectal, and sigmoid D2cc doses. CTV asymmetry, as measured by AP:L ratio, is associated with relatively greater dose reductions to bladder, rectum, and sigmoid with use of IC/IS applicators.

Utility of MRI in the Definitive Treatment of Cervical Cancer

Utility of MRI in the Definitive Treatment of Cervical Cancer

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer

ABSTRACTCombining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose–volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70–80 , 60–70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = −0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).

Clinical Outcome of the Recurrence of Uterine Cervical Cancer in Isolated Para-aortic Lymph Node after Definitive Treatment

To evaluate the clinical outcome of the recurrence of cervical cancer in isolated para-aortic lymph nodes (PALN). The cases of 50 patients first diagnosed with isolated PALN metastasis after definitive treatment of cervical cancer from 2002 to 2016 at our institution were reviewed for this retrospective study. Forty patients presented with squamous cell carcinoma and 10 with other histopathology. Eleven patients had initial FIGO stage I disease, 24 had stage II, 10 had stage III, and 5 had stage IV. They were initially treated with radiation therapy (RT) alone, concurrent chemoradiation therapy (CCRT), or surgery for cervical cancer. Statistical analysis included construction of overall survival (OS), local control rate (LCR), and progression-free survival (PFS) curves using the Kaplan-Meier method. Possible prognostic factors, including histopathology, initial FIGO stage, initial treatment, age at recurrence, tumor marker, duration between the end of initial treatment and recurrence, maximum size of the metastatic lesion, number of metastases, SUV max of the metastases, and the treatment method for recurrence, were evaluated using the log-rank test. The median follow-up time for living patients was 52 months (range: 13-132 months). The median age at diagnosis of recurrence was 57 years (range: 26-84 years). The median duration between the end of initial treatment and recurrence was 10 months (range: 1-91 months). The median maximum size of the metastatic lesion was 17 mm (range: 8-60 mm). Twenty-five patients had one or two PALN metastases, while 25 patients had more than three. Eighteen patients were treated for recurrence with RT alone, 7 with CCRT, 3 with surgery, 17 with chemotherapy, and 5 with best supportive care (BSC). The median RT dose used for RT alone or CCRT was 55 Gy (range: 50-58 Gy). The RT target volume was the regional PALN area followed by PALN metastases, except in one patient in whom the target volume was the regional pelvic and PALN areas. The 3- and 5-year OS rates of all patients were 47.0% and 36.2%, respectively. In particular, the 3-year OS rate of patients who underwent CCRT for recurrence was 85.7%, surgery 66.7%, chemotherapy 48.8%, RT 41.3%, and BSC 0% (p= 0.014). Only the treatment method for recurrence was significantly associated with OS. The 3-year LCR and PFS for CCRT was 100% and 71.4%, for surgery, 100% and 66.7%; for chemotherapy, 33.6% and 13.7%; and for RT, 55.5% and 14.1%, respectively (LCR: p= 0.028, PFS: p= 0.059). The number of metastatic lesion and treatment method for recurrence were significantly associated with LCR. Age at recurrence, tumor marker, and number of metastatic lesion were significantly associated with PFS. Current data suggest that CCRT may be effective in preventing local progression of disease recurrence exclusively in the PALN and may improve the OS of patients.

Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis

BackgroundTo compare the efficacies and toxicities of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) or conventional two-dimensional radiotherapy (2D-RT) for definitive treatment of cervical cancer.MethodsA meta-analysis was performed using search engines, including PubMed, Cochrane Library, Web of Science, and Elsevier. In the meta-analysis, odds ratios (ORs) were compared for overall survival (OS), disease-free survival (DFS), and acute and chronic toxicities.ResultsIncluded data were analysed using RevMan 5.2 software. Six studies encompassing a total of 1008 patients who received definitive treatment (IMRT = 350, 3-DCRT/2D-RT = 658) were included in the analysis. A comparison of 3-year OS and 3-year DFS revealed no significant differences between IMRT and 3D-CRT or 2D-RT (3-year OS: OR = 2.41, 95% confidence interval [CI]: 0.62–9.39, p = 0.21; 3-year DFS: OR = 1.44, 95% CI: 0.69–3.01, p = 0.33). The incidence of acute gastrointestinal (GI) toxicity and genitourinary (GU) toxicity in patients who received IMRT was significantly lower than that in the control group (GI: Grade 2: OR = 0.5, 95% CI: 0.28–0.89, p = 0.02; Grade 3 or higher: OR = 0.55, 95% CI: 0.32–0.95, p = 0.03; GU: Grade 2: OR = 0.41, 95% CI: 0.2–0.84; p = 0.01; Grade 3 or higher: OR = 0.31, 95% CI: 0.14–0.67, p = 0.003). Moreover, the IMRT patients experienced fewer incidences of chronic GU toxicity than did the control group (Grade 3: OR = 0.09, 95% CI: 0.01–0.67, p = 0.02).ConclusionIMRT and conventional radiotherapy demonstrated equivalent efficacy in terms of 3-year OS and DFS. Additionally, IMRT significantly reduced acute GI and GU toxicities as well as chronic GU toxicity in patients with cervical cancer.

Exposing the Rectosigmoid Junction: An In-Depth Analysis of Sigmoid Complications

The dose-volume (DV) constraints related to sigmoid toxicity are not well established for the definitive treatment of cervical cancer with a combination of external beam irradiation (EBRT) and image-guided brachytherapy (IGBT). Sigmoid location on CT or MR images at the time of IGBT can be near the brachy dose distribution. The literature reported rates of sigmoid complications, however, are low, which may be due to under-reporting or misrepresentation as rectal toxicity.

Use of Synthetic CT for Magnetic Resonance–Only Based External Beam Pelvic Radiation Therapy of Cervical Cancer

The superiority of T2 MRI over CT for cervical cancer tumor delineation is established by GEC-ESTRO. With the emergence of integrated MRI/LINAC technology, MR-only pelvic radiation needs to be studied in the definitive treatment of cervical cancer. In this study, we evaluate the impact of MR on pelvic targets and organs at risk (OARs) demarcation and dose distribution. Eight patients treated for cervical cancer staged FIGO IIA2 to IIIB for which a supine CT simulation and supine MRI of pelvis was performed were reviewed. All patient data was de-identified in accordance with institutional IRB requirements. Diagnostic MR Images were acquired on a 1.5T scanner. The MR images were manually co-registered with CT using Velocity software. CT body was segmented into 3 tissue types known as Dixon map: bone, fat, muscle/organs, by thresholding of CT number, and assigned HU numbers of 300, -100, and 0, respectively, to generate synCT. Treatment planning from CT was recalculated on the synCTs. Contouring of the CTV was performed by a radiologist on CT and T2MR to ensure accuracy. OARs were contoured on both CT and registered T2-weighted MR images. Four-field box conformal 3D-CRT planning to 45 Gy was used for plan generation. Treatment plans from CT was recalculated on the synCTs using same beam arrangements and monitor units. Dosimetric statistical analysis of the targets and OARs was performed using t-test with an alpha of 0.05. The volumetric difference between CT-CTV (mean 292.70 cm3, range 68.40-1139.90 cm3) and MR-CTV (mean 88.96 cm3, range 30.30-331.70 cm3) was not statistically significant (SS) (p=0.06). The mean D99 for CT and MR uterocervix was 45.32 and 44.99 Gy, respectively, and V100 for CT and MR uterocervix was 226.00 and 176.96, respectively, with no statistical difference between D99 or V100 for CT and MRI uterocervix (p=0.26 and 0.24, respectively). All dosimetric data can be found in Table 1 demonstrating non-significant difference on max doses for all OARs.Abstract 3614; Table 1Mean dosimetry metrics and statistical analysis using student's T-test comparing CT to MRICT CTVMRCTVCT UtcxMRUtcxCT BladMR BladCT RectMR RectCT L FHMRL FHCT R FHMR R FHMean Vol cm3292.790.0292.7238.3Mean Max dose Gy47.747.747.947.341.642.340.242.2t-Test P-Value0.060.240.360.060.750.26 Open table in a new tab The use of MRI for external beam planning provides optimal tumor visualization, providing potential clinical impact by improving target coverage. Our findings suggest that defining the CTV on MRI may be more accurate given the inherent MR advantage for pelvic organ visualization. The average CTV volume was smaller on MRI, which could ultimately lead to improved OAR sparing and reduced toxicities. We feel that this small pilot study warrants further investigation in order to fully evaluate the advantage of MR only based external beam planning for cervical cancer.

Cost Analysis of an Outpatient-Based Method for Implanting Intracavitary Brachytherapy Applicators in the Definitive Treatment of Cervical Cancer

Cost Analysis of an Outpatient-Based Method for Implanting Intracavitary Brachytherapy Applicators in the Definitive Treatment of Cervical Cancer

Implementing MRI-based target delineation for cervical cancer treatment within a rapid workflow environment for image-guided brachytherapy: A practical approach for centers without in-room MRI.

Magnetic resonance imaging (MRI)-based intracavitary brachytherapy offers several advantages over computed tomography (CT)-based brachytherapy, but many centers are unable to offer it at the time of brachytherapy because of logistic and/or financial considerations. We have implemented a method of integrating MRI into a CT-guided, high-dose-rate intracavitary brachytherapy workflow in clinics that do not have immediately available MRI capability. At our institution, patients receiving high-dose-rate intracavitary brachytherapy as a component of the definitive treatment of cervical cancer have a Smit sleeve placed during the first brachytherapy fraction in a dedicated suite with in-room CT-on-rails. After the first fraction of brachytherapy, an MRI is obtained with the Smit sleeve, but no applicator, in place. For each subsequent fraction, CT scans are coregistered to the MRI scan by the Smit sleeve. The gross target volume is defined by MRI and overlaid on the CT images for each brachytherapy treatment for dose optimization. This MRI-integrated workflow adds <5 minutes to the brachytherapy session for image fusion. Our initial clinical experience suggests that this approach is feasible and results in target volume reductions compared with CT-alone brachytherapy. Our proposed combination MRI and/or CT workflow is a feasible compromise to preserve an efficient workflow while integrating MRI target delineation, and it provides many of the advantages of both MRI- and CT-based brachytherapy. The future collection and analysis of clinical data will serve to compare the proposed approach to non-MRI containing techniques.

Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and (18)F-fluorodeoxyglucose (FDG) - positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

Limitations of the bowel bag contouring technique in the definitive treatment of cervical cancer

PurposeIncidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. Methods and MaterialsBowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. ResultsInterfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. ConclusionsIn the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.