Locally Advanced Cervical Cancer Research Articles

Prognostic Value of Change in Albumin and Body Mass Index during and after Definitive Radiotherapy in Patients with Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Definitive radiotherapy (RT) is the standard treatment in patients with locally advanced cervical cancer (LACC). Many studies have shown that in addition to the intrinsic characteristics of the tumor, there are many other factors can also affect the prognosis, such as baseline nutritional and inflammation status. However, which of these factors, or their alterations during radiotherapy, has a greater impact on prognosis is unclear on survival is unknown. Therefore, the purpose of this study was to observe changes in these factors during RT and to evaluate the prognostic impact of these factors and their changes in clinical practice. <h3>Materials/Methods</h3> A total of 229 patients were involved in this retrospective study. All patients received definitive RT at a single institution. Clinical pathological characteristics and eight inflammatory and nutritional factors (albumin, weight, Body Mass Index (BMI), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, etc.) of patients were collected at pre-, during and post-radiation. Changes in those parameters at different radiotherapy periods were evaluated, and the association between those parameters and their changes with progression-free survival (PFS) and overall survival (OS) were assessed at 3 years. <h3>Results</h3> The median follow-up periods were 42.3 months for all patients. During RT, almost all the parameters reduced significantly, and after RT, albumin levels returned to pre-treatment levels, but the body weight was further significantly reduced compare with that during RT (p < 0.001). In univariate analysis, neither baseline nutritional nor inflammatory factor levels were shown to be associated with prognosis, whereas changes in albumin and body weight during RT were associated with prognosis. In multivariate analysis, non-SCC (HR 2.747 for PFS, <i>p</i> =0.016; HR 2.983 for OS, p=0.016), a decrease >0.2kg/m² in BMI during and post RT (HR 2.595 for PFS, <i>p</i> <0.001; HR 2.579 for OS, <i>p</i> =0.002), and albumin <35g/L (defined as hypoalbuminemia) during RT (HR 2.208 for PFS, <i>p</i> =0.004; HR 2.069 for OS, <i>p</i> =0.021), were independent predictors of poor prognosis for both PFS and OS, ranking with gradually decreased hazard ratios. Hypoalbuminemia during RT was more common in patients with older age, lower baseline hemoglobin and albumin levels, BMI <25kg/m², concurrent chemotherapy with weekly cisplatin and higher incidence of diarrhea during treatment. However, the decrease in BMI during and post RT showed no significant association with patients' baseline characteristics. <h3>Conclusion</h3> Changes in albumin and BMI during or after RT showed more prognostic value than their baseline levels or other hematological and inflammatory parameters in LACC. Therefore, prevention of hypoalbuminemia during RT and maintenance of BMI in the middle and later stages of RT are the management priorities in the clinical practice of LACC.

GSOR4 Presentation Time: 9:15 AM: Predicting the Benefit of Hybrid Intracavitary + Interstitial Needle Applicators in Patients with Locally Advanced Cervical Cancer

<h3>Purpose</h3> The purpose of this study is to determine whether pre-treatment and brachytherapy (BRT) characteristics are associated with benefit from hybrid intracavitary + interstitial needle (IC/IS) applicator, as opposed to IC applicator, use in patients with locally advanced cervical cancer (LACC). <h3>Methods</h3> 53 LACC patients treated with IC/IS BRT from August 2014 to March 2020 using HDR were included. Patient variables included pre-treatment characteristics (age, histology, grade, T Stage, N Stage, max lateral, A-P, S-I, and overall tumor dimensions, tumor symmetry, max distance from endometrial canal, tumor volume, tumor max SUV on PET) and BRT characteristics (max lateral, A-P, S-I, and overall tumor dimensions, tumor symmetry, max distance from tandem, GTV and high-risk CTV (CTV HR) volumes). For each patient, an IC plan prescribed to match the IC/IS plan (CTV HR) coverage and optimized based on volumes was created. In addition, a standard loading IC plan prescribed to point A was also created. These plans were compared to the IC/IS plan. Benefit for IC/IS was defined by organ at risk (OAR) D2cc's transitioning from unacceptable to acceptable based on American Brachytherapy Society (ABS) guidelines. Patients were then placed into 3 categories: those having 0, 1, or 2 or more organs that benefited from IC/IS. Wilcoxon rank sum and Fisher's exact tests, proportional odds models, and linear regression models were used to determine which characteristics were associated with benefit from IC/IS. <h3>Results</h3> Analysis showed that 33 (62%) patients showed benefit from IC/IS compared to optimized IC plans. IC/IS resulted in an average decrease in EQD2 to normal structures of 11.4 Gy (bladder), 6.2 Gy (rectum), 5.7 Gy (sigmoid), and 4.4 Gy (small bowel). No pre-treatment characteristics were associated with an increase in the number of organs benefiting from IC/IS. Increasing BRT max S-I and overall dimension as well as GTV and CTV HR volumes were associated with increased organ sparing with IC/IS. The bladder had the greatest reduction in dose from IC/IS with greater than 10 Gy benefit with S-I extension or max tumor dimension greater than 5 cm, GTV greater than 27 cc, and CTV HR greater than 35 cc. Standard IC plans prescribed to point A had inferior coverage of the CTV HR compared to IC/IS plans above 2.9 cm max distance from tandem, 5.3 cm max lateral dimension, 4.1 cm max A-P dimension, 5.4 cm max S-I dimension, and 5.6 cm overall dimension. Standard IC plans prescribed to point A also began to treat the CTV HR inferiorly to IC/IS plans above a GTV and CTV HR of 37.4 and 43.1 cc, respectively. <h3>Conclusions</h3> Various BRT characteristics are significantly associated with benefit from IC/IS, and our data suggests patients having tumors with max overall dimensions > 5 cm, CTV HR > 35 cc and GTVs > 27 cc at the time of BRT would benefit from IC/IS. However, further analysis using independent data is needed to confirm these thresholds.

GSOR22 Presentation Time: 12:15 PM: A Novel Radiosensitizer Kortuc Enhanced Brachytherapy for Unresectable Recurrent Uterine Cervical Cancer

<h3>Purpose</h3> To evaluate the tolerability, safety and efficacy of KORTUC Intratumoral injection with brachytherapy in unresectable recurrent cervical cancer. <h3>Materials and Methods</h3> A novel radiosensitizer KORTUC (Kochi Oxydol Radiation Therapy for Unresectable Carcinoma) was invested by Dr. Yasuhiro Ogawa at Kochi University (Japan) in 2006 and was developed for the treatment of malignant solid tumours that contain numerous hypoxic cancer cells and/or large quantities of antioxidative enzymes. Hydrogen peroxide is the only agent known to be capable of inactivating antioxidative enzymes and producing oxygen simultaneously when applied to tumour tissues. KORTUC is a solution that contains 3% hydrogen peroxide with 1% sodium hyaluronate. Hydrogen peroxide is the active ingredient for this radiosensitizer. Sodium hyaluronate viscosity sustains the hydrogen peroxide in the tumour as well as delays decomposition of hydrogen peroxide and maintains a high concentration of oxygen in the tumour. Injecting the two components together at a particular ratio is the key feature of this product. Currently Phase 2 clinical trial for locally advanced and recurrent breast cancer has been conducted in the United Kingdom and India. Our institution, (Osaka Medical and Pharmaceutical University, Japan) has conducted single-arm clinical research of KORTUC since May 2010, we dosed KORTUC more than 250 patients of various solid cancers including more than 40 patients of the gynecological tumors treated with brachytherapy as of today. In this study we report our experiences of KORTUC with brachytherapy in recurrent local advanced cervical cancer patients who are likely the high risk of poor prognosis.From April 2012 to January 2020, 15 female patients with recurrent cervical cancer received KORTUC with brachytherapy. Previous treatments of 15 recurrent patients were surgery (n=4), radiation therapy (n=8), surgery + radiation therapy (n=3). The primary lesion of these 15 patients were vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2), and lymph node (n=2). KORTUC was injected intratumorally under direct vision of colposcopy prior to radiation therapy. The dose of KORTUC ranged from 4 to 12 mL adjusted by tumor size. For patients who had the Interstitial brachytherapy, KORTUC was administered before and after the applicator insertion prior to irradiation. <h3>Results</h3> Intratumoral injection of KORTUC was completed without any technical and safety issues in all 15 patients. KORTUC was well tolerated and no adverse events judged to be related to KORTUC injection were observed, except the transient local pain at the injection site in some patients. KORTUC also showed efficacy in local control in recurrent patients. <h3>Conclusion</h3> Based on this result, we would like to confirm in a future study, KORTUC's efficacy with external irradiation as well as brachytherapy for the newly diagnosed unresectable locally advanced cervical cancer with high risk factors of poor prognosis. KORTUC may have potential as an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

PO35 Presentation Time: 10:30 AM: Initial Outcomes for Utilization of the Venezia Hybrid High-Dose Rate Brachytherapy Applicator in Definitive Treatment of Locally-Advanced Cervical and Endometrial Cancer

<h3>Purpose</h3> The Venezia gynecological applicator (Elekta) is a hybrid interstitial/intracavitary brachytherapy applicator used to treat cervical cancers. Previous data supporting the use of hybrid brachytherapy comes mainly from the EMBRACE cohort showing increased coverage of the high-risk CTV (HR-CTV) with decreased toxicity. Single-institution data, further supports this technique. We undertook this study to report our initial experience with the Venezia applicator for treatment of locally advanced cervical and endometrial cancers. <h3>Materials/Methods</h3> We retrospectively reviewed 21 patients who received brachytherapy using the Venezia applicator for definitive treatment of cervical or endometrial cancer, treated from June, 2021 to March, 2022. All patients completed chemoradiotherapy followed by brachytherapy boost. For each brachytherapy fraction, patients received sedation and the Venezia applicator was placed. Radiation treatment planning was performed on CT imaging fused to daily MRI, using the Oncentra® treatment planning system. If needles were required for hybrid interstitial brachytherapy, the plan was optimized first without utilizing the needles, to meet constraint to organs at risk (OARs). Subsequently, planning was performed considering the interstitial needles with a focus on optimizing the balance of target coverage and dose to organs at risk. Radiation dose to target volumes and organs at risk were recorded as equivalent dose in 2Gy fractions (EQD2). <h3>Results</h3> Median age was 54 years. Ninety percent of patients were treated for a primary cervical cancer and 10% for primary endometrial cancer. Twenty-nine percent of patients had T1 primary tumor, 48% had a primary T2 tumor and 24% had a primary T3 tumor. The most common histology was squamous cell carcinoma (SCC) in 76% of patients, with adenocarcinoma in 10% and the remaining being undifferentiated or endometrioid. Median follow up was 4.3 months. Thirty-three percent of patients experienced acute toxicity with brachytherapy, all of which were grade 1-2. Twenty-nine percent experienced acute GI toxicity, 10% experienced acute GU toxicity and 10% experienced bleeding. Median brachytherapy dose and fractionation was 28Gy delivered over 4 fractions. Sixty-two percent of patients required hybrid interstitial brachytherapy and the median number of interstitial needles placed was 4. Median volume of the Gross Tumor Volume (GTV) and HR-CTV at first fraction were respectively 5.22cm³(IQR 4.26cm³-10.28cm³) and 27.84cm³(IQR 24.71cm³-40.36cm³⁾. Median HR-CTV D90 and D98 were respectively 85.3Gy(IQR 83.1Gy-88.8Gy) and 76.8Gy (IQR 74.2Gy-79.6Gy). Median GTV D98 was 98.4Gy (IQR 94.3Gy-116.3Gy). Regarding OARs, median D2cc dose to the rectum, sigmoid and bladder were respectively 56.9Gy (IQR 53.7Gy-59.1Gy), 60Gy (IQR 55.9Gy-63.7Gy) and 75.3Gy (IQR 72.3Gy-77.6Gy). Median D1cc dose to the bowel was 50Gy (IQR 46.6Gy-56.8Gy). Median D0.1cc dose to the left and right ureter were respectively 71.8Gy (IQR 62.6Gy-85Gy) and 67.5Gy (IQR 61.6Gy-89.1Gy). <h3>Conclusions</h3> Brachytherapy using the Venezia hybrid applicator was implemented with good dosimetry and sparing of organs at risk. Procedure related complications were mild.

GSOR2 Presentation Time: 9:05 AM: Implementation of Hybrid Intracavitary and Interstitial Brachytherapy for Cervical Cancer in a Freestanding Clinic

<h3>Purpose</h3> Radiation therapy for locally-advanced cervical cancer consists of external beam radiation therapy and brachytherapy. While the recent introduction of image-guided brachytherapy and hybrid intracavitary and interstitial brachytherapy treatments (HBT) may potentially improve clinical outcomes, current literature describes the procedure requiring significant resources (such as general anesthesia, conscious sedation, and MRI-based treatment planning). With increases in treatment time and patient movements, there is greater potential for positional changes of the applicator and neighboring organs at risk (OAR), which can alter dosimetry. Furthermore, these resources might not be universally available to all radiation oncology centers that perform intracavitary cervical brachytherapy, potentially limiting the widespread implementation of HBT. Here we describe our experience with CT-guided interstitial needle placement in a typical freestanding outpatient setting, with an emphasis on minimization of patient movement and treatment duration. <h3>Materials and Methods</h3> All patients that were treated with HBT from June 2018 to May 2020 were included in this series. Initially, patients were taken to the operating room, for an exam under anesthesia and Smit sleeve placement by the radiation oncologist. The patients were determined to need interstitial brachytherapy either by exam under anesthesia, due to anatomy and tumor extent, or after the first brachytherapy treatment, due to dosimetry. All tandem, ovoid and needle insertions and HDR treatments were performed in a freestanding clinic, on the CT simulator table. The patients were treated using minimal sedation (oral lorazepam and oxycodone/acetaminophen). An indwelling urinary catheter was inserted into the bladder. The tandem and ovoids (Elekta) were inserted in the patient, and a vaginal balloon was substituted for packing. Multiple CT scans were performed while advancing the interstitial needles, the bladder was filled with 180 cc of diluted contrast, and a final CT scan was taken for planning purposes. The patients were shifted from the CT table to a surgical bed (single shift), and then transported to the treatment room while treatment planning was performed using Oncentra (Elekta) treatment planning software. After the treatment plan was approved, the bladder was refilled to 180 cc and treatment was delivered using a microSelectron HDR afterloader (Elekta). The applicator was removed and the patient was examined for bleeding. If any vaginal bleeding occurred, vaginal packing was inserted with pressure applied. Time stamps and clinical data were collected during each procedure. <h3>Results</h3> Sixty-three patients underwent placement of a total of 244 interstitial implants. The median time for the entire procedure, from the time of patient entry into the CT simulation room to exit of the HDR treatment room, was 70.0 minutes (mean 70.3, range 54-100). The median time after tandem and ovoid insertion to complete interstitial needle insertion was 9.0 minutes (mean 9.8, range 4-24), using median 2 needles (mean 1.93, range 1-3) and median 3 CT scans (mean 2.63, range 1-4). Bleeding occurred in 22.1% (54/244) of implants, which resolved after median 3 minutes (mean 3.33, range 1-8) of vaginal packing with pressure. All patients (100%) required only one total shift, from the CT table to the mobile surgical bed. <h3>Conclusions</h3> In our series, the interstitial insertion portion of the HBT added 9 minutes, with an overall procedure time of 70 minutes (including insertion, planning, treatment and removal). There was an acceptable bleeding rate which quickly resolved with vaginal packing and pressure. Combining intracavitary and interstitial implants using a hybrid applicator appears to be feasible, efficient and safe in an outpatient freestanding clinic. Further studies aimed at evaluating long-term toxicities and tumor control are warranted.

GSOR14 Presentation Time: 11:35 AM: Distribution of Centers Offering Brachytherapy Services for Patients with Cervical Cancer: A National Workforce Evaluation

<h3>Purpose</h3> Brachytherapy (BT) is an essential component of treatment for locally-advanced cervical cancers in conjunction with external beam radiation therapy (EBRT) and chemotherapy. Brachytherapy is a resource- and labor-intensive treatment not offered in all radiation facilities. Patients may be traveling great distances for treatment due to concentration of these resources. <h3>Materials and Methods</h3> The National Cancer Database (NCDB) was queried for adult women with cervical carcinomas treated with EBRT+BT from 2004-2018. Patients were dichotomized to those who received same-institution treatment (SIT) for EBRT + BT and those who had different-institution treatment (DIT), receiving BT in a reporting facility but not EBRT. Women treated with EBRT in a reporting facility but BT in a non-reporting facility were excluded due to lack of details on the BT-providing facility. One-way independent t-test and ANOVA were used to determine differences groups with respect to distance travelled. Chi-squared analysis was used to determine regional differences and patterns between academic/non-academic facilities. <h3>Results</h3> A total of 44,684 women received chemoradiation across 1,236 facilities and 29,076 (65.1%) women received brachytherapy across 1,159 facilities. Of those, 23,513 (80.9%) received brachytherapy in 887 reporting facilities. SIT was delivered to 20,125 (85.6%) and 3,388 (14.4%) received only BT at a reporting facility (DIT). 5,563 received all treatment at non-reporting facilities after diagnosis. The rate of SIT treatment was relatively stable through the reporting period, fluctuating between 82.6% and 86.5% without a trend. The median number of BT cases over the time period per institution was 11 (IQR: 3-32). Academic centers had the highest total caseload per institution (median: 39 cases) with community cancer programs having the lowest (median: 2 cases), p<0.001). Only 14 centers (1.6%) treated ≥ 1 patient/month over the reporting period. Institutions in the top quartile for treatment volume treated 75.0% of all patients while the institutions in the middle quartile treated 22.7% and bottom quartile institutions treated 1.9% of patients (p<0.001). The median crow-fly distance for SIT vs DIT was 10.3 miles vs 33.4 miles (IQR: 4.7-25.4 vs 14.5-63.0 miles, p<0.001). 13.3% of women had to travel > 50 miles for brachytherapy, mostly in the Mountain and West North/South Central regions (p<0.001) and significantly more often for DIT (p<0.001). The median differential distance traveled for patients receiving DIT vs SIT was greatest in the West North Central (IA, KS, MN, MO, ND, NE, SD) at +42.3mi and East South Central (AL, KY, MS, TN) at +43.1mi. Similarly, the differential distance traveled for patients receiving DIT in an academic center was +33.2mi compared to +15.7mi for a comprehensive community program, +13.4mi in an integrated delivery network and +0.1mi for a community program (p<0.001). <h3>Conclusions</h3> The distribution of centers offering brachytherapy services for women with cervical cancers differs widely across the country with women in some regions traveling great distances to receive care at high-volume centers.

Radiotherapy Management of Locally Advanced Cervical Cancer during the COVID-19 Era: A Single Centre Report on Treatment Approach, Brachytherapy Fractionation and Timing

Background: The COVID-19 pandemic had a catastrophic impact on healthcare. Keeping an optimal cancer care routine has been challenging. For cervical cancer (CC) patients external beam radiotherapy (EBRT) and brachytherapy (BT) are key elements for radical treatment. Oncological treatment delays have represented a major issue during the pandemic. Overall treatment time (OTT) is a well-known prognostic factor for CC. Thus, we decided to evaluate radiotherapy timing and modalities, and OTT trends for locally advanced cervical cancer (LACC) patients treated at our center during the Pandemic. Methods: We retrospectively collected and analyzed data of patients treated for LACC at our Center, (Department of Oncology, Radiation Oncology, S.Anna Hospital, Turin, Italy), during the COVID-19 pandemic. Results: Between March 2020 and March 2022, 36 patients were treated. All patients underwent EBRT (median pelvic dose 48 Gray (Gy)). Concurrent chemotherapy (ChT) was administered in 31/36 patients. High Dose Rate (HDR) BT boost was delivered to 32/36 patients. BT schedules adopted were: 28 Gy in 4 fractions (18 cases, 56.2%), 26 Gy in 4 fractions (5 cases, 15.6%), 21 Gy in 3 fractions (4 cases, 12.5%), 18 Gy in 3 fractions (3 cases, 9.3%), 24 Gy in 4 fractions (one case, 3.2%), 12 Gy in 2 fractions plus 11 Gy in 2 fractions (one case, 3.2%). Most of the patients (25/32, 78.1%) received one fraction per week; 6 patients (18.1%) 2 fractions per week and one patient 3 fractions per week. Median OTT was 74 days (57–99). The median interval from EBRT to HDR-BT was 14 days (6–54). Four patients tested positive for COVID-19 between EBRT and BT. At a median follow-up of 10.7 months (range 1.8–20.3), a complete response was obtained in 25 patients (69.5%), a partial response in 8 cases (22.2%), and a disease progression in two patients (5.5%). Conclusions: in terms of radiotherapy management of LACC, brachytherapy resulted as the most affected by the restrictions due to the pandemic. We adopted different schedules and fractionations to optimize the resources available and to keep providing an optimal care. A be-weekly fractionation emerged as a promising option for LACC during the pandemic, with a good toxicity profile.

Post treatment imaging in patients with local advanced cervical carcinoma.

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction.

Comparison of Hematotoxicity of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor (PEG-rhG-CSF) Combined with Dual-Agent Concurrent Chemoradiotherapy and Cisplatin Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) with cisplatin is the standard treatment for locally advanced cervical cancer (LACC), but there are still some patients who have poor efficacy. Though dual-agent concurrent chemoradiotherapy (dCCRT) can improve the efficacy, the higher hematotoxicity makes it difficult to be popularized in clinical. PEG-rhG-CSF has been recommended by relevant NCCN guidelines for CCRT of malignant tumors in recent years, however there are few reports in LACC. The aim of this study was to evaluate the effect of PEG-rhG-CSF on reducing hematotoxicity in LACC with dCCRT. <h3>Materials/Methods</h3> This study retrospectively analyzed the clinical data of patients with LACC treated with CCRT in the Affiliated Cancer Hospital of Guizhou Medical University. According to patients' clinical protocol, all patients were divided into three groups, single-agent concurrent chemoradiotherapy group(sCCRT), dCCRT group and PEG-rhG-CSF combined with dCCRT group (PEG+dCCRT). Patients in sCCRT received CCRT with cisplatin 40 mg/m² for four to six cycles and patients in dCCRT were treated with paclitaxel 135-175mg/m²+cisplatin 60-80mg/m² or lobaplatin 30mg/m² for two cycles. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 5ug/kg/d was given to patients in these two groups according to the instructions. Patients in PEG+dCCRT were received dCCRT, and PEG-rhG-CSF 6mg was given in 24 to 72 hours after chemotherapy each cycle. The incidence and duration of grade 3-4 leukocytopenia and neutropenia and febrile neutropenia (FN) (according to CTCAE, V5.0) were the primary endpoints. The second endpoints were completion rate of chemotherapy and radiotherapy, time to complete radiotherapy. <h3>Results</h3> A total of 192 patients were enrolled between July 2019 and December 2021. 51 patients in sCCRT, 68 patients in dCCRT and 73 patients in PEG+dCCRT. The three groups were respectively compared for primary and second endpoints, and the results were shown below. The incidences of grade 3-4 leukocytopenia and neutropenia of the three groups (sCCRT, dCCRT and PEG+dCCRT) were 41.2%, 67.2%, 27.4% and 27.5%, 48.6%, 13.7%, respectively. The incidences of PEG+dCCRT were lowest in the three groups(P<0.05). In the three groups, the duration of grade 3-4 leukocytopenia and FN of PEG+dCCRT were observably reduced(P<0.05). There was no statistical difference of other primary and second endpoints in the three groups. <h3>Conclusion</h3> Prophylactic use of PEG-rhG-CSF during dCCRT makes hematotoxicity manageable, which may make dCCRT have better promotion and improves efficacy of LACC. However, further prospective studies are needed to confirm the results.

Simultaneous or Sequential Boost to Clinically Involved Lymph Nodes in Cervical Cancer

<h3>Purpose/Objective(s)</h3> The optimal approach to metastatic lymph nodes (LNs) in locally advanced cervical cancer (LACC) is controversial. This study aimed to evaluate the efficacy and toxicity profile of dose escalation with simultaneous integrated (SIB) or sequential boost (SB) for clinically positive LNs in LACC. <h3>Materials/Methods</h3> The data of 43 patients who underwent chemoradiotherapy (CRT) with a SIB or SB dose to positive LNs between 2015 and 2021 for LACC were retrospectively analyzed. All patients were applied 50.4 Gy intensity-modulated radiotherapy (IMRT) or modulated volumetric arc therapy (VMAT) to the lymphatic and primary regions in 28 fractions with concurrent platinum-based chemotherapy followed by 28 Gy HDR intracavitary brachytherapy (BRT) in four fractions. Response evaluations were performed via magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT on the third month. <h3>Results</h3> Median age was 53 years (range: 34-80 years). The FIGO stage was IIIC1 in 30 (70%), IIIC2 in 10 (23%), and IVA in three patients (7%), respectively. Pelvic CRT was applied to 25 patients (58%), and pelvic-paraaortic CRT was applied to 18 patients (41%). A total of 94 LNs were boosted. The median longest diameter of the LNs was 1.7 cm (range: 1–7 cm) and median volume was 2.5 cc (range: 0.6-21.5 cc). A SIB was applied in 24 (56%), SB in 13 (30%), and both in 6 patients (14%), respectively. Patients in the SIB group received a total dose of 56-64 Gy in 28 fractions. The patients with SB on the other hand received 56.4-60.4 Gy in 31-33 fractions and patients with SIB+SB received 60-66 Gy in 30-32 fractions. The dose from the BRT was also calculated to the LNs and the minimum dose to LNs from BRT was between 0-7.6 Gy (median 3.6 Gy). The maximum dose from BRT was as 0-9.7 Gy (median 4.8 Gy). Median follow-up (FU) was 21 months (range: 3-77 months). Following CRT, 41 (98%) patients had a complete response (CR) and one (2%) had a partial response (PR) in boosted LNs on MRI whereas 39 (98%) patients had a CR and one (2%) had a PR on PET/CT. Recurrence occurred in 12 patients during FU: one local recurrence (LR), two regional recurrence out of the RT field, seven distant metastases (DM), and two LR+DM. There was no recurrence in any of the 94 boosted LNs and the local control (LC) rate was 100%. The 1- and 2-year rate of overall survival was 89.5% and 82.3%, disease-free survival was 80% and 65.8%, locoregional recurrence-free survival was 84.6% and 70.5%, and DM-free survival rate was 80.4% and 69.9%, respectively. Treatment was well tolerated without any serious acute toxicity. Grade 3 late toxicity was observed in two patients (1-rectovaginal fistula, 1-ureteral stenosis). <h3>Conclusion</h3> Dose escalation with IMRT/VMAT yields an excellent LC rate for the involved LNs, even for very large ones, in LACC with a low toxicity profile. Routine LN dissection may not be necessary for patients with a LACC, but prospective randomized trials are needed to clarify this.

Predictors of Interstitial Brachytherapy Utilization in Locally Advanced Cervical Cancer and Impact on Overall Survival

<h3>Purpose/Objective(s)</h3> The standard of care for locally advanced cervical cancer (LACC) is multimodality therapy with chemotherapy, external beam radiation therapy (EBRT) and brachytherapy (BT) boost. The addition of BT improves overall survival (OS); interstitial BT has been prospectively shown to improve target and organ at risk dose, especially for larger tumors. Prior research suggests declining utilization of BT particularly in patients without insurance, underrepresented minorities, and in low volume cancer centers, which may widen cancer disparities. Here we utilize the National Cancer Database (NCDB) to examine patterns and predictors of BT use, particularly interstitial BT, in patients with LACC and its impact on OS. <h3>Materials/Methods</h3> The NCDB was used to identify patients with LACC (stage IIb-IVa) diagnosed between 2004-2018 and treated with radiation that included a component of BT. A multivariable model to predict receipt of interstitial vs intracavitary BT was created including age, race, comorbidity score (CCI), stage, receipt of chemotherapy, urban-rural continuum, insurance, facility type, facility region, facility quartile of cases reported and year of diagnosis. For survival analysis, patients who received interstitial BT were propensity score matched 1:1 to intracavitary patients using the same variables and nearest neighbor matching without replacement. Log rank survival analysis was performed for the matched cohort. <h3>Results</h3> A total of 9,591 patients were included with median age of 55 years. Overall, 14% of patients who received BT as part of their radiation treatment received interstitial BT. Ninety-three percent of patients received chemotherapy. On multivariable logistic regression analysis, higher stage (stage IIIa: OR 2.04 [95% CI 1.64 to 2.54], stage IIIb: OR 1.38 [1.22-1.57], stage IVa: OR 2.09 [1.09-4.00]), treatment at an academic center (OR 1.31 [1.12-1.54]), treatment at a higher volume center (highest quartile: OR 1.38 [1.12-1.70]) and later year of diagnosis (OR 1.03 per year [1.02-1.05]) were associated with increased interstitial BT utilization. Conversely, uninsured status (OR 0.772 [0.62-0.97]) or Medicare (OR 0.78 [0.65-0.94]) were associated with decreased interstitial BT utilization. There was no significant association between age at diagnosis, race, or CCI and patterns of interstitial BT use. After propensity score matching there was no overall survival difference between patients who received interstitial vs those treated with intracavitary BT (p=0.471). <h3>Conclusion</h3> Patients with more locally advanced cervical cancer and those treated at a high volume or academic center were more likely to receive interstitial BT. This pattern likely reflects appropriate intensification of therapy for larger tumors at centers with the expertise to perform interstitial implants. Utilization of interstitial implant did not translate into an OS benefit likely due to selection of cases for interstitial implant that have poor initial response to chemoRT.

Multi-Institutional Evaluation of Health Disparities in Rural Cervical Cancer Patients

<h3>Purpose/Objective(s)</h3> Cervical cancer remains a significant concern for both rural and urban populations in the US. Overall treatment time from the start of chemoradiation to completion of brachytherapy is known to correlate with local control and overall survival. Rural populations experience health disparities which are multi-factorial and vary by region, but a commonality is lack of healthcare access and distance to tertiary care centers. The purpose of this study is to examine the health disparities due to geographic location for women with locally advanced cervical cancer (LACC) presenting to tertiary care facilities and identify factors that influence their treatment and outcomes. <h3>Materials/Methods</h3> A multi-institutional retrospective cohort study was conducted including data from 5 tertiary care centers across the United States. Women with LACC defined as FIGO 2018 IB3-IVA treated with definitive intent RT ±chemotherapy from Jan 2011 to Jan 2021 were included. Clinical, pathologic, radiologic, demographic, and treatment parameters as well as disease outcomes were collected. Geographic location was collected, and zip code was used to determine urban (pop ≥10,000) or rural (pop <10,000) residency. Univariate analyses were used to determine the effects of these variables on disease outcomes. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. <h3>Results</h3> 613 patients were included from diverse regions of the country. Median OS was 27 months (range 0-133) and median RFS was 19.4 months (range 0-123.5). Urban (N=534, 87%) or rural (N=79, 13%) residence was not correlated with overall treatment time (p = 0.50) or cervical cancer specific survival (p = 0.32). The median time from diagnosis to start of RT was significantly shorter in the rural patient population than in the urban population (28 days v. 41 days, p = 0.002). There was no significant association between time from diagnosis to start of RT and cervical cancer specific survival (p = 0.07) or between overall treatment time and cervical cancer specific survival (p = 0.26). There was, however, a significant association between overall treatment time and time to recurrence, with each day of increase in treatment time leading to a 1.1% increased risk of recurrence (p = 0.03, HR = 1.011). <h3>Conclusion</h3> In this group of patients we found no differences in treatment time or outcomes between urban and rural residents and surprisingly, rural patients had a shorter median time from diagnosis to start of treatment when compared to the urban patient group. As is already known, there was a significant relationship between treatment time and time to recurrence, highlighting the importance of timely treatment in patients with LACC. We are adding data from several more centers and will be evaluating the populations with more granularity to identify challenges faced by our patients and resources that may be helpful.

Comparison of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiotherapy vs. Concurrent Chemoradiotherapy Alone in Locally Advanced Cervical Cancer Under 2018FIGO Staging Correction

<h3>Purpose/Objective(s)</h3> According to NCCN guidelines, concurrent chemoradiation (CCRT) is the standard care for locally advanced cervical cancer (LACC) patients, but the benefit of neoadjuvant chemotherapy (NACT) before CCRT for LACC patients is still controversial, especially based on 2018FIGO staging,This study is designed to answer the question by comparing the efficacy and toxicities of neoadjuvant chemotherapy with concurrent chemoradiation (NACT+CCRT) versus concurrent chemoradiation (CCRT) alone in LACC under 2018FIGO staging correction. <h3>Materials/Methods</h3> Patients with stage IB2, IIA2, IIB-IVA (2009 FIGO staging) cervical cancer were retrospectively reviewed from January 2013 to January 2017 in China. All patients were re-staged after 2018FIGO staging correction. All patients were treated with IMRT to 50.4 Gy with concurrent weekly cisplatin 40 mg/m² followed by intra-cavitary brachytherapy. The primary endpoint was progression free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response by RECIST 1.1 criteria, and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated with Log-rank test. Toxicities were analyzed using the χ2 test. All statistical tests were two-sided. <h3>Results</h3> A total of 432 patients were identified and 406 were eligible for analysis. The 2009FIGO staging of IB2 in 81, stage IA2 and IIB in 119, stage III in 119, stage IV in 87 were corrected into 2018FIGO staging which IB3 in 58, stage IIA2 and IIB in 75, stage III in 186, and stage IV in 87. No patients were down-staged. 201 patients were treated with NACT+CCRT and 205 with CCRT. With a median follow-up of 58.6 months, 5-year PFS was 60.3% in the NACT+CCRT arm, and was 57.6% in the CCRT arm. There was no significant difference in 5-year PFS between two arms (p=0.287). 5-year OS was 68.8% and 65.0% in the NACT+CCRT arm and CCRT+ACT arm, respectively. There was no statistical difference in 5-year OS between two arms (p=0.301). Multivariate analysis showed that pathological type, FIGO stage and pelvic nodes status were associated with OS and PFS. The CR and PR in NACT group was similar to the CCRT group (196/201 versus 193/205, p=0.090). There were higher acute systemic side effects in the NACT+CCRT arm. The result of subgroup analysis showed that PFS in stage III in NACT+CCRT group was significantly higher than that in CCRT group (57.6% vs 45.4%, P=0.048), but OS had no significant difference (71.9% vs 56.3%, P=0.053). In stage III, the curative effect of IIIC1 was better than that of IIIA-B and IIIC2, with 5-year OS of 81.9%, 61.7% and 37.5% (P=0.004), and 5-year PFS of 62.6%, 48.8% and 38.4% (P=0.031), respectively. <h3>Conclusion</h3> For LACC patients with 2018 FIGO correction stage, neoadjuvant chemotherapy plus concurrent cisplatin chemoradiation did not improves RR, PFS and OS. There were more toxicities for the neoadjuvant chemotherapy group. Further research and longer follow up is needed, especially for the staging IIIC1 LACC patients.

Exploiting Pretreatment Nodal Involvement to Identify Drivers of Chemoradiation Resistance in Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Following standard-of-care chemoradiation therapy (CRT), 30-50% of locally advanced cervical cancer (LACC) patients experience recurrence. Thus, more sophisticated prognostic markers and targeted therapeutic options are needed. The Cancer Genome Atlas (TCGA) molecular classification of cervical cancer did not identify clinically significant patient strata for overall prognosis or risk of recurrence. Notably, the TCGA study did not collect data on clinical factors such as tumor size and nodal status and thus did not incorporate these into their clustering strategies. We hypothesized that at different stages of initial presentation (no nodal disease, locoregional nodal disease, distant nodal disease), different gene programs may be important for progression and resistance to standard of care therapy. <h3>Materials/Methods</h3> We utilized institutional PET and RNA-seq data (<i>N</i>=99) to separate the gene expression profiles of patients with LACC into three groups (Negative nodal (NN) disease, pelvic/locoregional nodal (LRN) disease, aortic/distant (DN) nodal disease) as assessed by pre-treatment PET imaging. Next, to globally assess gene contribution to treatment resistance, we constructed an Rscript to perform univariate Kaplan Meier (KM) analysis for disease recurrence, for all genes in each pre-treatment PET nodal group. FDR multiple hypothesis correction was employed. Lastly, the lists of genes significantly associated with treatment resistance in each PET nodal group were compared. Pathway Enrichment Analysis (PAE) was performed using EnrichR. <h3>Results</h3> When combining all genes statistically associated with recurrence following CRT in at least one nodal cohort, only 7% were shared between two groups (3% LRN-NN, 2% DN-NN, 2% LRN-DN), and <1% was shared by all three groups. Thus, the genes shown to be significant predictors of recurrence following standard of care chemoradiation therapy are largely different depending on the degree of spread of cervical cancer at the time of initiation of therapy (21% NN, 24% DN, 49% LRN). Concordantly, PAE shows striking differences in pathways associated with recurrence. The Immune Response, (p=3.9*10⁻⁶), Epithelial to Mesenchymal Transition (p=1.6*10⁻¹⁰), and MYC/E2F targets (p=5.3*10⁻⁸) were most enriched in NN, LRN, and DN, respectively. Lastly, expression levels of the top 5 genes associated with recurrence within nodal groups identifies high and low risk clusters of patients' prognostic for recurrence (p=0.00304, p=0.00137, and p=0.019 for NN, LRN, DN, respectively). <h3>Conclusion</h3> Our novel findings suggest that different genes drive cervical cancer progression following CRT depending on the degree of nodal spread at presentation. Utilizing these gene clusters identifies high and low risk groups of patients in each presenting nodal strata.

Automated Prediction of Complete Pathological Response to Neo-Adjuvant Chemoradiotherapy Using Hybrid Model-Based MRI Radiomics in Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Cervical cancer (CC) is one of the common gynecological tumors. It has been reported that patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) had better disease-free survival and longer overall survival than patients with pathological partial response (pPR). Radiomics can extract high-throughput information from medical images to quantitatively evaluate lesions. Prediction models based on deep learning may be a useful analytical tool for predicting pathological reactions of CC after radiotherapy. The model performance may be improved by combining clinical information with image information, and the decision model performance may be better by combining manual feature model with deep feature model. Therefore, this study will establish a model to automatically predict treatment response (pCR or non-pCR) for locally advanced cervical cancer (LACC) based on T2-weighted MR images and clinical parameters. <h3>Materials/Methods</h3> A total of 138 patients with LACC from 2010 to 2014 were enrolled in this study, and t2-weighted magnetic resonance images and clinical information of the patients before treatment were collected. Clinical information includes age, stage, pathological type, SCC level, and lymph node status. Combining the domain specific features from computational radiomics system, the abstract features from deep learning network and the clinical parameters, ensemble learning classifier composed of multiple weak classifiers was used to predict pCR. The area under the receiver operating characteristics curve (AUC), accuracy (ACC), true positive rate (TPR), true negative rate (TNR) and precision were used as evaluation metrics. <h3>Results</h3> Among 138 cervical cancer patients, 74 were in the pCR group and 64 were in the non-pCR group. There was no significant difference between the two cohorts in terms of tumor diameter, lymph node and stage before radiotherapy, p=0.787, 0.068, 0.846, respectively. The average AUC, ACC, TPR, TNR and precision of the proposed hybrid model was about 0.80, 0.71, 0.75, 0.66 and 0.71. The AUC values of using clinical parameters, domain specific features, abstract features alone are 0.66, 0.67 and 0.76, respectively. This shows that radiomic features extracted from MRI images are more efficient than clinical parameters in predicting treatment response, and abstract features from deep learning network are the best representation for the LACC. The AUC value of model without ensemble learning is 0.76, which shows ensemble learning classifier is better than single classifier. <h3>Conclusion</h3> The proposed hybrid model can predict well the treatment response of patients with cervical cancer, which might help radiation oncologist to make personalized treatment plans for patients.

Adaptive VMAT Radiotherapy to Avoid Brachytherapy in Cervical Cancer Treatment

<h3>Purpose/Objective(s)</h3> Concomitant chemoradiation (CRT) is the standard of care to treat patients with stage Ib1- IVb carcinoma of the cervix. External beam radiotherapy (EBRT) and brachytherapy are used. There are potential benefits of VMAT technology both in terms of an escalation of dosage and a decrease in toxicity. Non-brachytherapy treatment is an evolving alternative approach which requires adaptive external beam radiotherapy treatment to improve its accuracy and to avoid geographical miss, yet it is still unclear whether this approach could yield further improve outcomes. <h3>Materials/Methods</h3> A Prospective study was conducted between May 2015 and May 2021. Thirty-two patients with locally advanced cervical cancer (LACC) stage Ib1-IVa and three patients with stage IVb who underwent CRT using EBRT and simultaneous integrating boost (SIB) were evaluated. The median age was 53,2 years (30-76) with prevalence of squamous cell carcinoma histology (80 %). All patients had regular follow-up by gynecological examination, pelvis MRI and 18FDG-PET/CT scan. The prescribed radiation dose ranged between 60,0 to 96,6 Gy to the gross tumor volume (GTV). None of these patents received brachytherapy treatment, and eight (22,8%) patients received no chemotherapy due to other reasons. <h3>Results</h3> A total of 35 patients were recruited. The median follow-up was 38 months (range: 2-83 months). The 1, 3 and 5-year overall survival and local control were 91, 78, 74% and 100, 97, 94%, respectively. Six patients had disease progression. The median time to progression was 9 months (range: 3-16 months). Early and late toxicities were acceptable without severe events. <h3>Conclusion</h3> Non brachytherapy CRT treatment of LACC is feasible and seems that escalating the dosage provides better local control, which might be translated to favor progression free and overall survival. No serious toxicities occur and studies to establish this method are mandatory.

The Choice of 2D-Brachytherapy or 3D-Brachytherapy for Cervical Cancer Patients after External Beam Radiation Based on Residual Gross Tumor Volume

<h3>Purpose/Objective(s)</h3> The purpose of this study was to analyze the choice of 2-dimensional brachytherapy (2D-BT) or 3-dimensional brachytherapy (3D-BT) for cervical cancer patients after external beam radiotherapy (EBRT), based on residual gross tumor volume (GTV res). <h3>Materials/Methods</h3> Between September 2019 and April 2020, 106 local advanced cervical cancer patients (FIGO stage IB3-IVA) who received primary radiation or chemoradiation followed by BT were analyzed retrospectively. We divided patients into large tumor group (GTV res > 30 mm³ or the width ≥ 4 cm) and small tumor group (GTV res ≤ 30 mm³). Point A and high-risk clinical target volume (CTV_HR) planning were designed for each patient; all patients received 4–5 fractions of intra-cavity BT with a single dose of 6 Gy. The CTV_HR, the bladder, and rectum were delineated, respectively, the D2cc (minimum dosage to the most irradiated 2 cc of an organ at risk) of bladder and rectum, D90 (dose to 90% of a target) of the target, vaginal dose point, and vaginal reference length (VRL) were compared. <h3>Results</h3> The patients who received BT fewer than 4 times (n = 2), had double primary tumors (n = 1), or had incomplete data (n = 3) were excluded. Thus, 106 patients were eligible and analyzed in this study. Of the 106 patients, 45 (42.5%) had an initial tumor size of > 4 cm before EBRT. After EBRT, 92 (86.8%) patients had small GTV res, the median of GTV res and CTV_HR were 2 cm³ and 17.85 cm³. The CTV_HR does not change with GTV res (r² = 0.16, <i>P</i> < 0.001), no matter the size of GTV res, both the point A dose and CTV_HR can satisfactorily reach the prescribed tumor coverage dose. However, when evaluated by volume dose, the CTV-_HR D90 was higher than the Point A dose; with reduced organs at risk (OARs) dose (bladder, rectum-, and vaginal dose point) (<i>P</i> < 0.05). The remainder of the patients had large GTV res, with a median of 64cm³, which is not covered by the Point A dose. While evaluated by volume dose, the median of CTV_HR was 71.6 cm³; as GTV res increased, the CTV_HR increased significantly (r² = 0.68, <i>P</i> < 0.001). The CTV_HR D90 to Point A dose ratio was negatively correlated with GTV res (r = -0.61, <i>P</i> < 0.001), and the Point A dose typically varied between 47% and 230% of the CTV_HR D90. In the OARs dose evaluation, only the vaginal dose points were lower in the CTV_HR plan. The 1-year and 2-year local controls for small and large tumor groups were 94.3% versus 78.6% and 91.9% versus 70.7%, respectively. <h3>Conclusion</h3> After EBRT, 86.8% of locally advanced cervical cancer (LACC) patients had small residual tumors, and 2D-BT can achieve adequate prescription dose coverage and meet treatment needs. Only 13.2% of patients had large residual tumors, and these patients should receive 3D-BT or treatment combined with interstitial needles to deliver a higher dose to the CTV_HR. To protect the OARs and reduce radiation damage in small resident tumor patients, 3D-BT would be the best choice.

Endoscopic Assessment of Radiological Stage IVA Cervical Cancer: A Bivariate Meta-Analysis Supporting an Evidence-Based Staging Algorithm

<h3>Purpose/Objective(s)</h3> To optimize the use of confirmatory endoscopic exams (cystoscopy/proctoscopy) in the staging of locally advanced cervical cancer (LACC), the present study evaluates the predictive value of radiological exams (CT and MRI) to detect bladder/rectum invasion. <h3>Materials/Methods</h3> A systematic search of databases (PubMed and EMBASE) was performed (CRD42021270329). The inclusion criteria were: a) cervix cancer diagnosis; b) staging CT and/or MRI (index test); c) staging cystoscopy and/or proctoscopy (standard test); and d) numbers of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) provided. A random-effects bivariate meta-analysis of positive predictive value (PPV) and negative predictive value (NPV) was performed with moderator analyses by imaging modality (CT and MRI) and prevalence. <h3>Results</h3> Nineteen studies met the inclusion criteria, totaling 3480 and 1641 patients for bladder and rectum analyses, respectively. For bladder invasion (prevalence ranged from 0.9% to 34.5%), the overall PPV was 45% (95% confidence interval, 33%-57%, based on 19 studies). Per subgroup, the PPV was 31% for MRI/prevalence ≤6%, 33% for CT/prevalence ≤6%, and 69% for CT/prevalence >6%. For rectal invasion (prevalence ranged from 0.4% to 20.0%), the overall PPV was 30% (95% confidence interval, 17%-47%, based on 8 studies). Per subgroup, the PPV was 36% for MRI/prevalence ≤1%, 17% for MRI/prevalence >1%, and 38% for CT/prevalence >1%. The overall NPV for bladder invasion and rectal invasion were 98% (95% confidence interval, 97%-99%) and 100% (95% confidence interval, 99%-100%), respectively. Considering prevalence and radiological modality, the point estimate of NPV varied from 95% to 100% for bladder invasion and from 99% to 100% for rectum invasion. <h3>Conclusion</h3> Due to low PPV (<50%) of radiological staging, endoscopic exams may be necessary to correctly assess radiological stage IVA LACC. However, they are not necessary after negative radiological exam (NPV ≥95%).

Stereotactic Body Radiotherapy Boost with the CyberKnife for Locally Advanced Cervical Cancer: Dosimetric Analysis and Potential Clinical Benefits.

Simple SummaryThe recommended treatment for locally advanced cervical cancer (LACC) consists of chemoradiotherapy (CRT) followed by brachytherapy (BT). Although BT is considered a minimally invasive procedure, patients still suffer severe discomfort from it and risk uterine perforation. Dosimetric uncertainties are often inevitable due to anatomical variations and inconsistencies in applicator loadings. These issues prompted us to explore the use of stereotactic body radiotherapy (SBRT) as a viable alternative. It has been well described that the CyberKnife (CK), a robotic image-guided SBRT delivery system, is capable of producing rapidly fall-off dose gradients with submillimeter accuracy. The aim of this study was to compare the dose distributions and radiobiological effects of a CK-based SBRT boost and a BT boost. We found a tumor volume threshold target, below which the CK-based SBRT plan could result in significantly better target coverage, OAR sparing and radiobiological effects compared to the BT plan. With improved precision of target localization, a reduced PTV margin might increase the eligibility of patients to receive a CK-based SBRT boost after CRT, rather than BT. CK-based SBRT could be an alternative option for patients who are not candidate for BT.(1) Aim: To compare the treatment plans of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) and high-dose-rate (HDR) intracavitary/interstitial brachytherapy (IC/ISBT) and examine the feasibility of CK-SBRT as a viable alternative to BT in patients with locally advanced cervical cancer (LACC). (2) Methods: A BT plan of 28 Gy in four fractions delivered previously to 20 patients with LACC was compared with a CK plan based on the same CT images with structures delineation for BT. The SBRT treatment plan was further divided according to two different approaches, with the high-risk planning target volume (HR-PTV) defined by the high-risk clinical target volume (HR-CTV) without and with a 5 mm margin, which were named CK-CTV plan and CK-PTV plan, respectively. The dose distributions and dosimetric parameters of the target volumes and organs at risk (OARs) were recorded and compared for the three boost plans. Radiobiological metrics were calculated based on the EUD for the hybrid plans. Additionally, the relationship between tumor volume and tolerance doses for the OARs in the BT plan and CK-PTV plan was investigated. (3) Results: Target coverage was better with the CK plan than with the BT plan, as the D95%, D98%, HI and CI of the CK-CTV plan and CK-PTV plan were higher than those of the BT plan; an exception was the D50%. Similarly, the TCP of the target was also significantly in favor of the CK hybrid plans (p < 0.01). For the OARs, the CK-CTV plan was superior to the BT plan as regards the rectum D2cc, bladder D2cc and bladder Dmax. The CK-PTV plan could achieve dosimetric parameters comparable to those of the BT plan for OARs concerning the small residual tumor volume. The NTCP of the rectum for the WPI+CK-CTV plans was significantly lower than that of the WPI+BT plans (p < 0.01). (4) Conclusions: CK-based SBRT can achieve better target coverage, dose sparing for the OARs and radiobiological effects compared with the BT plan for tumors that are not excessively large. CK-based SBRT could be an alternative option to administer a radiation boost for patients with LACC.

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study

BackgroundThe aim of this study was to investigate the role of the lipid peak derived from 1H magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC).MethodsWe enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction ≤ 50%).ResultsOf 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality 1H-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040).ConclusionsAssessment of lipid peak at 1H-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC.