Concurrent Chemoradiotherapy For Cervical Cancer Research Articles

Nomograms combining clinical factors and apparent diffusion coefficient to predict downstaging and progression-free survival after concurrent chemoradiotherapy in patients with cervical cancer.

Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment. To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer. X-tile was used to calculate the optimal threshold for ΔADCmean(%) for prognostic stratification. Kaplan-Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model. ΔADCmean(%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADCmean(%) to diagnose prognosis was 40.8. Kaplan-Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years (P < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862. ΔADCmean(%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADCmean(%) predict PFS of patients with cervical cancer with moderate accuracy.

Prospective clinical study of the efficacy and safety of different doses of PEG recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for preventing leukopenia/neutropenia caused by concurrent chemoradiotherapy for cervical cancer

ObjectiveThe efficacy and safety of different doses of PEG recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of leukopenia/neutropenia during concurrent chemoradiotherapy for cervical cancer were investigated.MethodsThe patients who received concurrent radiotherapy and chemotherapy for cervical cancer from June 2020 to January 2023 were selected to evaluate the difference in efficacy, adverse reactions, and treatment cost of PEG-rhG-CSF in the prevention of leukopenia/neutropenia between the test group and the control group.ResultsThe minimum value of leukopenia/neutropenia in the test group was significantly higher than that in the control group (P < 0.05). The incidence of grade ≥ 3 leukopenia/neutropenia was significantly lower than that of the control group (P < 0.05). The number of interrupted days of radiotherapy was less than that of the control group (P < 0.05). PEG-rhG-CSF of different prophylactic doses (100 μg/kg dose or 50 μg/kg dose) had similar prophylactic effects in the test group, OR=1.192 (0.761, 1.868), P=0.443.ConclusionProphylactic application of PEG-rhG-CSF could reduce the incidence of leukopenia/neutropenia in cervical cancer during concurrent chemoradiotherapy. There was no significant difference in efficacy and safety with prophylactic use of drug at doses of 100 μg/kg and 50 μg/kg.

Vaginal microbial profile of cervical cancer patients receiving chemoradiotherapy: the potential involvement of Lactobacillus iners in recurrence

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB–IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

The prognostic effect of tumor volume, reduction ratio, and cumulative doses on external beam radiotherapy with central-shielding method and image-guided adaptive brachytherapy for cervical cancer.

To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTVHR D90) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer. Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression. A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm3 and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All p < 0.05). In this group, the patients with a cumulative CTVHR D90 < 69.6 GyEQD2 showed significantly worse PFS and LC (p = 0.042 and p = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors (p = 0.045, p = 0.009 and p = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor (p = 0.041). The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors.

Application of Recombinant Human Superoxide Dismutase in Radical Concurrent Chemoradiotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Acute Rectal Injury: A Multicenter, Randomized, Open-label, Prospective Trial

PurposeTo evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer. MethodsIn this phase III, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiotherapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiotherapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiotherapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea; ≥G1 and ≥G2 diarrhea lasting at least 3 days; and damage to the rectal mucosa due to radiotherapy measured by endoscopy. ResultsTwo-hundred-and-eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 140). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs. 14.8 and 4.5 days, respectively; P<0.001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs. 55.7%, P<0.001). Three patients felt intolerable or abdominal pain following rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P=0.061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P<0.001). ConclusionThe results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa.

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer

Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. ClinicalTrials.gov Identifier: NCT03239613.

Radiomics signature for dynamic changes of tumor-infiltrating CD8+ T cells and macrophages in cervical cancer during chemoradiotherapy

BackgroundOur previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes.MethodsThirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study. Pre-therapeutic CT images were acquired. And tumor biopsies with immunohistochemistry at primary sites were performed at baseline (0 fraction (F)) and immediately after 10F. Radiomics features were extracted from the region of interest (ROI) of CT images using Matlab. The LASSO regression model with ten-fold cross-validation was utilized to select features and construct an immunomarker classifier and a radiomics signature. Their performance was evaluated by the area under the curve (AUC).ResultsThe changes of tumor-infiltrating CD8+T cells and macrophages after 10F radiotherapy as compared to those at baseline were used to generate the immunomarker classifier (AUC= 0.842, 95% CI:0.680–1.000). Additionally, a radiomics signature was developed using 4 key radiomics features to predict the immunomarker classifier (AUC=0.875, 95% CI:0.753-0.997). The patients stratified based on this signature exhibited significant differences in treatment response (p = 0.004).ConclusionThe radiomics signature could be used as a potential predictor for the CCRT-induced dynamic alterations of CD8+ T cells and macrophages, which may provide a less invasive approach to appraise tumor immune status during CCRT in cervical cancer compared to tissue biopsy.

Contrast-enhanced ultrasound combined with elastic imaging for predicting the efficacy of concurrent chemoradiotherapy in cervical cancer: a feasibility study.

Contrast-enhanced ultrasound (CEUS) and elastography are of great value in the diagnosis of cervical cancer (CC). However, there is limited research on the role of contrast-enhanced ultrasound combined with elastography in predicting concurrent chemoradiotherapy and disease progression for cervical cancer. The purpose of this study was to evaluate the feasibility of contrast-enhanced ultrasound combined with elastography and tumor prognosis. MRI was performed on 98 patients with cervical cancer before and after treatment. Before, during, and 1 week after the treatment, contrast-enhanced ultrasound and elastography were conducted, and the alterations of ultrasound-related parameters at each time point of the treatment were compared. The correlation between contrast-enhanced ultrasound combined with elastic imaging and oncological outcome was assessed. There was no notable difference in overall clinical data between the complete remission (CR) group and the partial remission (PR) group (P>0.05). Before treatment, there were no statistically significant differences in elasticity score, time to peak (TTP), and peak intensity (PI) between the CR group and the PR group. However, there were no statistical differences in elastic strain ratio (SR) and area under the curve (AUC) before and after treatment between the CR group and the PR group, and there were also no statistical differences in the elastic strain ratio (SR) and area under the curve (AUC) of contrast-enhanced ultrasound parameters between the CR group and the PR group before and during treatment. There was a statistically significant difference after treatment (P<0.05).At present, the follow-up of patients is about 1 year, 7 patients were excluded due to loss to follow-up, and 91 patients were included in the follow-up study. Through the review of the cases and combined with MRI (version RECIST1.1) and serology and other related examinations, if the patient has a new lesion or the lesion is larger than before, the tumor marker Squamous cell carcinoma antigen (SCC-Ag) is significantly increased twice in a row, and the patient is divided into progressive disease (PD). Those who did not see significant changes were divided into stable disease (SD) group. The relationship between clinical characteristics, ultrasound parameters and disease progression in 91 patients was compared. There was no significant difference in age and clinical stage between the two groups (P>0.05), but there was a significant difference in the elevation of tumor marker squamous cell carcinoma antigen (SCC-Ag) between the two groups (P<0.05).With the growth of tumors, TTP decreased, elasticity score and PI increased, and the difference was statistically significant (P<0.05). The AUC of SCC-Ag was 0.655, the sensitivity was 85.3%, and the specificity was 45.6%.The AUC, sensitivity and specificity of ultrasound parameters combined with SCC-Ag predicted disease progression was 0.959, 91.2% and 94.8%. Using contrast-enhanced ultrasound and elastography to predict the efficacy and disease progression of concurrent chemoradiotherapy is feasible. In addition, the combination of SCC-Ag with contrast-enhanced ultrasound and elastography can further enhance the efficiency of predicting disease progression.

Association between IDEAL-IQ MRI fat fraction quantification and pelvic bone marrow reserve function in concurrent chemoradiotherapy for cervical cancer

ObjectiveTo analyze the association between iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification sequence (IDEAL-IQ) magnetic resonance imaging (MRI) of bone marrow fat fraction and bone marrow reserve function during concurrent chemoradiotherapy for cervical cancer. MethodsThe study retrospectively analyzed twenty-six patients with stage IB1 to IVA cervical cancer treated between February 2020 and November 2020. All patients received concurrent chemoradiotherapy that included platinum alone or combined paclitaxel and platinum. Pelvic IDEAL-IQ MRI (plain and enhanced) was performed before and after treatment. Regions of interest, including the fifth lumbar vertebra, sacrum, ilium, ischium, and femoral neck, were manually delineated, and the bone marrow fat fraction was measured. Peripheral blood cell counts were recorded during treatment, and the relationship between the fat fraction values and changes in the blood cell counts was explored. ResultsIDEAL-IQ MRI bone marrow fat fraction was associated with platelet nadir and platelet decline during treatment. The average pelvic bone marrow fat fraction before chemoradiotherapy was moderately negatively correlated with platelet count nadir during concurrent chemoradiotherapy (r ​= ​−0.450, P ​= ​0.021). The change in average pelvic bone marrow fat fraction through chemoradiotherapy was moderately positively correlated with the degree of thrombocytopenia (r ​= ​0.399, P ​= ​0.044). ConclusionBone marrow fat content quantified by IDEAL-IQ was associated with platelet count nadir and the degree of thrombocytopenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.

The efficacy of Mecapegfilgrastim therapy in the primary prevention of concurrent chemoradiotherapy-induced neutropenia

ObjectiveTo evaluate the efficacy and safety of mecapegfilgrastim therapy in primary prevention of neutropenia after concurrent chemoradiotherapy for cervical cancer. MethodsThis study was a single-center, open, one-arm clinical observation, and analyzed the effectiveness of mecapegfilgrastim primary prevention of neutropenia after concurrent chemoradiotherapy in 25 cervical cancer patients undergoing concurrent chemoradiotherapy in Tianjin Medical University Cancer Institute and Hospital from 2019 to 2021. ResultsDuring the whole concurrent chemorrhotic cycle, chemotherapy delay occurred in 8 patients, (16%). The completion rate of chemotherapy cycle was 84% (42/50). There were only 4 (8%) cases of delayed concurrent chemotherapy due to leukopenia or neutropenia. Radiotherapy delay occurred in 10 patients, (20%). None of the patients delayed radiotherapy due to leukopenia or neutropenia. The incidence of febrile neutropenia (FN) was 0%. Subgroup analysis found that after completing 1 cycle of concurrent chemoradiotherapy, 6(12%) patients with grade 3–4 leukocyte or neutropenia. After completing 2 cycles of concurrent chemoradiotherapy, 14(29%) patients with grade 3–4 leukocyte or neutropenia. ConclusionDuring the chemoradiation in patients with cervical cancer, primary prevention use of mecapegfilgrastim can significantly reduce the incidence of FN, effectively reduce the incidence of grade III-Ⅳ leukopenia or neutropenia, beneficial to ensure the smooth progress of concurrent chemoradiotherapy,and provide a new direction for primary prevention of cervical cancer chemotherapy.

The relationship between the radiation dose of pelvic-bone marrow and lymphocytic toxicity in concurrent chemoradiotherapy for cervical cancer

ObjectiveThe purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer.Materials and methodsThis research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy.ResultsDuring concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3–4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1–4 and grade 3–4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P < 0.05). Kaplan–Meier analysis shows that the incidence of both grade 1–4 and grade 3–4 lymphocytic toxicity of the small-volume subgroups is significantly lower than that of the large-volume subgroups (P < 0.05).ConclusionThere is a significant correlation between a medium and low dose of pelvic-bone-marrow radiation and incidence of lymphocytic toxicity. Reducing the volume of medium and low radiation doses could effectively reduce incidence of lymphocytic toxicity.

Functional MRI radiomics-based assessment of pelvic bone marrow changes after concurrent chemoradiotherapy for cervical cancer

ObjectivesTo quantify the dose-response relationship of changes in pelvic bone marrow (PBM) functional MR radiomic features (RF) during concurrent chemoradiotherapy (CCRT) for patients with cervical cancer and establish the correlation with hematologic toxicity to provide a basis for PBM sparing.MethodsA total of 54 cervical cancer patients who received CCRT were studied retrospectively. Patients underwent MRI IDEAL IQ and T2 fat suppression (T2fs) scanning pre- and post-CCRT. The PBM RFs were extracted from each region of interest at dose gradients of 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and > 50 Gy, and changes in peripheral blood cell (PBC) counts during radiotherapy were assessed. The dose-response relationship of RF changes and their correlation with PBC changes were investigated.ResultsWhite blood cell, neutrophils (ANC) and lymphocyte counts during treatment were decreased by 49.4%, 41.4%, and 76.3%, respectively. Most firstorder features exhibited a significant dose-response relationship, particularly FatFrac IDEAL IQ, which had a maximum dose-response curve slope of 10.09, and WATER IDEAL IQ had a slope of − 7.93. The firstorder-Range in FAT IDEAL IQ and firstorder-10Percentile in T2fs, showed a significant correlation between the changes in ANC counts under the low dose gradient of 5–10 Gy (r = 0.744, -0.654, respectively, p < 0.05).ConclusionFunctional MR radiomics can detect microscopic changes in PBM at various dose gradients and provide an objective reference for bone marrow sparing and dose limitation in cervical cancer CCRT.

A phase III randomized, controlled trial of nedaplatin versus cisplatin concurrent chemoradiotherapy in patients with cervical cancer

BackgroundWe evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients.DesignPatients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m2 or cisplatin 40 mg/m2 concurrently.ResultsOne hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness.ConclusionsOur findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin.

Pelvic bones ADC could help to predict severe hematologic toxicity in patients undergoing concurrent chemoradiotherapy for cervical cancer

BackgroundHematologic toxicity (HT) during concurrent chemoradiotherapy (CCRT) for cervical cancer can lead to treatment breaks and compromise efficacy. PurposeTo evaluate the association between severe hematologic toxicity (HT) and clinical factors and pelvic apparent diffusion coefficient (ADC) during CCRT of cervical cancer patients. MethodsData from 120 patients with cervical cancer who were treated with CCRT from January 2016 and December 2018 were retrospectively analyzed. The clinical data (age, menopausal status, clinical stage, body mass index, chemotherapy regimen and chemotherapy cycle) of the patients were collected, and the cohort were divided into two groups based on the HT grade: HT3+ group (HT grade ≥ 3; 66 patients) and HT3- group (HT grade<3; 54 patients). All patients performed MRI before CCRT, and pelvic (ilium, pubis, ischium) ADC value was measured on ADC map. The correlation between severe HT and clinical parameters and pelvic ADC value were analyzed by univariate analysis, and the diagnostic performance was further assessed by receiver operating characteristic (ROC) analysis. ResultsIn univariate analysis, the menopausal status (p = 0.012) and chemotherapy regimen (p = 0.011) were significantly correlated with severe HT in overall patients, and menopausal patients or patients receiving paclitaxel plus cisplatin (TP) regimen were more likely to develop severe HT. HT3+ group showed a significantly lower pelvic ADC value than HT3- group. The ADC value cut-offs derived from our study for predicting severe HT was 0.317 × 10−3 mm2/s in overall patients. Neither clinical parameters nor pelvic ADCs were associated with severe HT in menopausal patients when analyzed separately (p > 0.05). ConclusionsSevere HT was significantly associated with menopausal status and chemotherapy regimen in patients with cervical cancer treated with CCRT, and HT3+ group showed a lower pelvic ADC value.

PD-1/PD-L1 Correlates With the Efficacy of the Treatment of Concurrent Chemoradiotherapy in Cervical Cancer.

BackgroundCervical cancer (CC) is the third most common cancer worldwide, with high mortality rates. The programmed cell death 1 (PD-1)/(PD-1 ligand) PD-L1 has been reported to be an effective indicator in cancer development. In this study, we aim to explore the role of PD-1/PD-L1 in the evaluation of concurrent chemoradiotherapy (CCRT) efficacy and prognosis in CC patients.MethodsWe included 55 CC patients in this study. Immunohistochemistry and flow cytometry were employed to detect the expression of PD-1, Treg cells, CD8, and CD68 in tumor tissues, and the contents of PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells in the peripheral blood. The relationships of these indexes with CCRT efficacy were measured by Spearman correlation analysis, overall survival (OS), and disease-free survival (DFS) of patients were analyzed by Kaplan–Meier estimator, and the diagnostic values of these indexes in CC were assessed by a receiver operating characteristic (ROC) curve.ResultsThe clinical effectivity rate of CCRT was 89.10%. The positive expressions of PD-L1, Treg cells, PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells were reduced after CCRT, while the CD8 and CD68 increased. All 7 indexes had diagnostic values in evaluating CCRT efficacy and were considered the influencing factors of OS, DFS, and the prognosis of CC patients.ConclusionThese findings indicate that PD-1/PD-L1 may be a potential indicator for the efficacy evaluation of CCRT and the prognosis of CC. This study may offer potential targets for CC treatment.

Correlation between changes of pelvic bone marrow fat content and hematological toxicity in concurrent chemoradiotherapy for cervical cancer

ObjectivesTo quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts.MethodsThe data of 54 patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and > 50 Gy doses were analyzed. Spearman’s rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment.ResultsThe lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5–30 Gy compared to RT-end, while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5–10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5–10 Gy (r = 0.554, P = 0.017).ConclusionMRI IDEAL IQ imaging is a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention to.

Correlation of Hematological Toxicity with the Bone Marrow Radiation Dose and Volume during Concurrent Chemo Radiation in Patients with Cervical Cancer

Aims &amp; Objective: Hematological toxicity is common in patients with cervical cancer treated with concurrent chemo radiotherapy (CT-RT), so the purpose is to assess this hematological toxicity and correlate the toxicity with the dose and volume of bone marrow included in the field of radiation. Materials &amp; Methods: Twenty five patients with histologically proven cervical cancer attending to our Cancer centre from July 2018-August 2019 were the subjects of this study. Patients were treated on 6 MV linear accelerator with a radical intent with concurrent chemotherapy using cisplatin 50 mg weekly. The planning CT was done for all the patients before the treatment and contouring of the pelvic bone marrow apart from other organs at risk was done. Hematological toxicity was assessed using RTOG common toxicity criteria weekly during and at 2 weeks after the completion of the treatment. Results: A total of 25 patients on CT-RT treatment were assessed. Sixteen patients were in locally advanced stage. The variation in HB, TLC, Platelets, and ANC counts from the baseline to 2 weeks after chemo radiotherapy were assessed. Grade II anemia was observed in 12 and Grade III in 2 patients. There were no toxicity as far as WBC and platelets were considered. There was also no correlation between the volume of bone marrow included in the field of irradiation and appearance of anemia. Conclusion: CT-RT for cervical cancer is safe and is associated with minimal hematological toxicity in the form of anemia. The toxicity is same for different volumes of bone marrow included in the field of irradiation with both 3DCRT as well as IMRT technique. The toxicity observed is probably contributed by Cisplatin.

The 100 Most Cited Papers in Radiotherapy or Chemoradiotherapy for Cervical Cancer: 1990-2020.

ObjectiveThis work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer.MethodsThe 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors.ResultsThese 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer” by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper.ConclusionIn the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.

Pretreatment Neutrophil-to-Lymphocyte Ratio Combined with Platelet-to-Lymphocyte Ratio as a Predictor of Survival Outcomes after Definitive Concurrent Chemoradiotherapy for Cervical Cancer.

The aim of the study was to evaluate pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors for predicting clinical outcomes after definitive concurrent chemoradiotherapy (CCRT) for cervical cancer. The cases were divided into two groups based on the values of NLR and PLR: High NLR-PLR (high value in both NLR and PLR) and Low NLR-PLR (low value in either NLR or PLR). The relationships between survival outcomes and the pretreatment NLR-PLR were investigated. Of the 148 patients enrolled in the study, 30 patients died during the median follow-up of 75 months. Based on receiver operating curves, NLR and PLR cut-off values for survival analysis were 2.34 and 148.89. The 10-year overall survival and disease-free survival rates for high NLR-PLR vs. low NLR-PLR were 63.6% vs. 86.2% (p = 0.001) and 63.3% vs. 77.5% (p = 0.026), respectively. Based on a multivariate analysis, independent predictors of overall survival were high NLR-PLR (hazard ratio [HR], 2.435; 95% confidence interval [CI], 1.106–5.361; p = 0.027) and stage (HR 2.659; 95% CI, 1.146–6.613; p = 0.024). Increases in both NLR and PLR are associated with poor survival. Elevation in both NLR and PLR before initiation of CCRT may be a useful biomarker for predicting clinical outcomes.

Abstract PO-054: Correlation of hematological toxicity with the bone marrow radiation dose and volume during concurrent chemo radiation in patients with cervical cancer

Abstract Aims &amp; Objective: Hematological toxicity is common in patients with cervical cancer treated with concurrent chemo radiotherapy (CT-RT), so the purpose is to assess this hematological toxicity and correlate the toxicity with the dose and volume of bone marrow included in the field of radiation. Materials &amp; Methods: Twenty-five patients with histologically proven cervical cancer attending to our cancer center from July 2008-August 2009 were the subjects of this study. Patients were treated on 6 MV linear accelerator with a radical intent with concurrent chemotherapy using cisplatin 50 mg weekly. The planning CT was done for all the patients before the treatment and contouring of the pelvic bone marrow apart from other organs at risk was done. Hematological toxicity was assessed using RTOG common toxicity criteria weekly during and at 2 weeks after the completion of the treatment. Results: A total of 25 patients on CT-RT treatment were assessed. Sixteen patients were in locally advanced stage. The variation in HB, TLC, Platelets, and ANC counts from the baseline to 2 weeks after chemo radiotherapy were assessed. Grade II anemia was observed in 12 and Grade III in 2 patients. There were no toxicity as far as WBC and platelets were considered. There was also no correlation between the volume of bone marrow included in the field of irradiation and appearance of anemia. Conclusion: CT-RT for cervical cancer is safe and is associated with minimal hematological toxicity in the form of anemia. The toxicity is same for different volumes of bone marrow included in the field of irradiation with both conventional as well as 3DCRT technique. The toxicity observed is probably contributed by Cisplatin. Citation Format: Irappa Madabhavi, Ragavendra Sagar, Apurva Patel, Malay Sarkar. Correlation of hematological toxicity with the bone marrow radiation dose and volume during concurrent chemo radiation in patients with cervical cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-054.