Radiotherapy For Cervical Cancer Research Articles

Improvement of accumulated dose distribution in combined cervical cancer radiotherapy with deep learning–based dose prediction

PurposeDifficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning–based dose prediction.Materials and methodsA total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101–based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses.ResultsThe redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (−3.02%, −1.71%, and −1.19 Gy, respectively) and rectum (−4.82%, −1.97%, and −4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02‰ and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112).ConclusionThis study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.

Improvement of accumulated dose distribution in combined cervical cancer radiotherapy with deep learning-based dose prediction.

Difficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning-based dose prediction. A total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101-based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses. The redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (-3.02%, -1.71%, and -1.19 Gy, respectively) and rectum (-4.82%, -1.97%, and -4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02‰ and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112). This study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.

Selenium-Doped Nanoheterojunctions for Highly Efficient Cancer Radiosensitization.

Exploring efficient and low-toxicity radiosensitizers to break through the bottleneck of radiation tolerance, immunosuppression and poor prognosis remains one of the critical developmental challenges in radiotherapy. Nanoheterojunctions, due to their unique physicochemical properties, have demonstrated excellent radiosensitization effects in radiation energy deposition and in lifting tumor radiotherapy inhibition. Herein, they doped selenium (Se) into prussian blue (PB) to construct a nano-heterojunction (Se@PB), which could promote the increase of Fe2+/Fe3+ ratio and conversion of Se to a high valence state with Se introduction. The Fe2+-Se-Fe3+ electron transfer chain accelerates the rate of electron transfer on the surface of the nanoparticles, which in turn endows it with efficient X-ray energy transfer and electron transport capability, and enhances radiotherapy physical sensitivity. Furthermore, Se@PB induces glutathione (GSH) depletion and Fe2+ accumulation through pro-Fenton reaction, thereby disturbs the redox balance in tumor cells and enhances biochemical sensitivity of radiotherapy. As an excellent radiosensitizer, Se@PB effectively enhances X-ray induced mitochondrial dysfunction and DNA damage, thereby promotes cell apoptosis and synergistic cervical cancer radiotherapy. This study elucidates the radiosensitization mechanism of Se-doped nanoheterojunction from the perspective of the electron transfer chain and biochemistry reaction, which provides an efficient and low-toxic strategy in radiotherapy.

Zimberelimab combined with concurrent chemoradiotherapy for patients with locally advanced cervical cancer: Early results of efficacy and safety.

e17507 Background: To assess the efficacy and safety of zimberelimab combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) patients (pts). Methods: This a single arm, open label, prospective phase II study. participants aged 18-75 years of FIGO 2018 IIB-IVA LACC, with histologically confirmed adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma untreated with radiotherapy or immunotherapy for cervical cancer were included. Nineteen enrolled pts received zimberelimab (240 mg, IV, Q2W) for up to one year starting from the first week of radiotherapy, combined with CCRT, including cisplatin (25-40 mg/m2), paclitaxel (35 mg/m2), once a week for up to 5 cycles, intensity modulated radiation therapy (IMRT, 45-50 Gy/25-28 f), with a simultaneous integrated boost of 10-15 Gy to involved metastatic lymph nodes, followed by brachytherapy (30-40 Gy, 5-6 Gy/f, biw). All radiotherapy was completed within 8 weeks. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), 3-year overall survival (OS) rate and safety. Results: The median age was 57 years (range, 32 to 71), with 6 pts in stage IIB, 2 pts in stage IIIB, 8 pts in stage IIIC, and 3 pts in stage IVA. All pts completed CCRT successfully, with 18 pts completed 5 cycles of chemotherapy, while only 1 pts received 4 cycles of chemotherapy. The median cycles with zimberelimab treatment was 15 (range, 6 to 26). Grade (G) 3 and higher treatment related adverse events (TRAEs) were observed in 13 pts (13/19, 68.4%), 1 pts had G4 lymphopenia (1/19, 5.3%). The most frequent ≥G3 TRAEs was lymphopenia (11/19, 57.9%), followed by leukopenia (7/19, 36.8%). The ORR was 100%, with complete responses in 18 pts (18/19, 94.7%) and partial responses in 1 pts (1/19, 5.3%). At data cutoff (October 31, 2023), 2 pts had disease progression (2/19, 10.5%), 17 pts have been remaining in disease remission (17/19, 89.5%). Conclusions: Zimberelimab combined with CCRT achieved promising anti-tumor effects and manageable toxicities in LACC pts. Further follow-up results are expected. Trial registration: ClinicalTrials.gov Identifier: NCT05437692. Clinical trial information: NCT05437692 . [Table: see text]

Exploring the Correlation Between Health Literacy and Knowledge of Cervical Cancer and Radiotherapy Among Japanese Women: A Web-Based Survey.

Health literacy (HL) plays a vital role in an individual's ability to make informed health decisions. Japan faces several challenges in cervical cancer control, including low human papillomavirus (HPV) vaccination and screening rates, underutilization of radiotherapy, and limited HL. This study explored the association between HL and knowledge of cervical cancer and radiotherapy, particularly among young Japanese women. We conducted a web-based survey among users of LunaLuna, a popular women's healthcare application, to assess their HL and knowledge about cervical cancer and radiotherapy through a 46-question survey. We compared three groups in terms of HL (inadequate, problematic, and sufficient & excellent). Multiple regression analysis was used to identify factors associated with knowledge. In total, 1468 respondents were included in this study. HL was positively correlated with knowledge scores (inadequate: 51.8%; problematic: 56.3%; sufficient & excellent: 60%). Participants displayed relatively low accuracy for treatment-related questions. Higher HL (β = 0.15, p < 0.01), education (β = - 0.11, p < 0.01), cervical cancer screening (β = - 0.11, p < 0.01), income (β = 0.09, p < 0.01), and employment (β = - 0.06, p = 0.04) were significant factors affecting knowledge of cervical cancer and radiotherapy. Our findings underscore the pivotal role of HL in promoting cervical cancer prevention and providing a better understanding of radiotherapy. Despite factors such as age, education, and history of cervical cancer screening, HL showed the strongest association with knowledge of cervical cancer and radiotherapy. The enhancement of HL and knowledge dissemination may be critical for promoting cervical cancer prevention and radiotherapy in Japan.

Insights into pelvic insufficiency fracture following pelvic radiotherapy for cervical cancer: a comparative review

BackgroundRadiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation create uncertainty. This review examined PIF after RT in cervical patients, including its pathobiology, likely locations of fractures, incidence, clinical symptoms, and predisposing factors. We further discussed study limitations and therapeutic possibilities of PIF.MethodsThe following online resources were searched for relevant articles: Google Scholar and PubMed. The keywords ‘pelvic insufficiency fractures’, ‘cervical carcinoma’ and ‘cervical cancer’, as well as ‘chemoradiotherapy’, ‘chemoradiation’, and ‘radiotherapy’, were some of the terms that were used during the search.ResultsPatients with PIF report pelvic pain after radiation treatment for cervical cancer; the incidence of PIF ranges from 1.7 to 45.2%. Evidence also supports that among all patients treated with pelvic radiation, those who experienced pelvic insufficiency fractures invariably had at least one sacral fracture, making it the most frequently fractured bone in the body. Menopausal status, weight, BMI, age, and treatments and diagnosis modalities can influence PIF during radiotherapy.ConclusionsIn conclusion, our comparative review of the literature highlights significant heterogeneity in various aspects of PIF following radiation for patients with cervical cancer. This diversity encompasses prevalence rates, associated risk factors, symptoms, severity, diagnosis methods, preventive interventions, and follow-up periods. Such diversity underscores the complexity of PIF in this population and emphasizes the critical need for further research to elucidate optimal management strategies and improve patient outcomes.

Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy.

Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias. Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively). The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

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.

Assessment of Changes of Bladder Volume and Rectal Volume Using 4DCT Scan During External Beam Radiotherapy for Cervical Cancer- Observation Study

Assessment of Changes of Bladder Volume and Rectal Volume Using 4DCT Scan During External Beam Radiotherapy for Cervical Cancer- Observation Study

Quantified difference of the collapsed cone convolution (CCC) and Monte Carlo (MC) algorithms based on DVH and gamma analysis for cervical cancer radiation therapy

ObjectiveTo quantify the difference between the (collapsed cone convolution) CCC algorithm and the (Monte Carlo) MC algorithm and remind that the planners should pay attention to some possible uncertainties of the two algorithms when employing the two algorithms. MethodsThirty patients’ cervical cancer VMAT plans were designed with a Pinnacle TPS (Philips) and divided equally into two groups: the simple group (SG, target volume was only the PTV) and the complex group (CG, target volume included the PTV and PGTV). The plans from the Pinnacle TPS were transferred to the Monaco TPS (Elekta).The plans’ parameters all remained unchanged, and the dose was recalculated. Gamma passing rates (GPRs) obtained from dose distribution from Pinnacle TPS compared with that from Monaco TPS with SNC software based on three triaxial planes (transverse, sagittal and coronal). GPRs and DVH were used to quantify the difference between the CCC algorithm in pinnacle TPS and the MC algorithm in Monaco TPS. ResultsAmong the statistical dose indexes in DVHs from the Pinnacle and Monaco TPSs, there were 7(7/15) dose indexes difference with statistically significant differences in the SG, and 10(10/18) dose indexes difference with statistically significant differences in the CG. With 3%/3 mm criterion, the most (5/6) GPRs were greater than 95% from the SG and CG. But with 2%/2 mm criterion, the most (5/6) GPRs were less than 90% from the two groups. In addition, we found that GPRs were also related to the selected triaxial planes and the complexity of the plan (GPRs varied with the SG and CG). ConclusionsObvious difference between the CCC and MC algorithms from Pinnacle and Monaco TPS. DVH maybe better than 2D gamma analysis on quantifying difference of the CCC and MC algorithms. Some attention should be paid to the uncertainty of the TPS algorithm, especially when the indicator on the DVH is at the critical point of the threshold value, because the algorithm used may overestimate or underestimate the DVH indicator.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy

PurposeRadiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). MethodsUsing EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. ResultsThe incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. ConclusionsThe risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

Automatic segmentation of tumour and organs at risk in 3D MRI for cervical cancer radiation therapy with anatomical variations.

Cervical cancer is a common cancer in women globally, with treatment usually involving radiation therapy (RT). Accurate segmentation for the tumour site and organ-at-risks (OARs) could assist in the reduction of treatment side effects and improve treatment planning efficiency. Cervical cancer Magnetic Resonance Imaging (MRI) segmentation is challenging due to a limited amount of training data available and large inter- and intra- patient shape variation for OARs. The proposed Masked-Net consists of a masked encoder within the 3D U-Net to account for the large shape variation within the dataset, with additional dilated layers added to improve segmentation performance. A new loss function was introduced to consider the bounding box loss during training with the proposed Masked-Net. Transfer learning from a male pelvis MRI data with a similar field of view was included. The approaches were compared to the 3D U-Net which was widely used in MRI image segmentation. The data used consisted of 52 volumes obtained from 23 patients with stage IB to IVB cervical cancer across a maximum of 7 weeks of RT with manually contoured labels including the bladder, cervix, gross tumour volume, uterus and rectum. The model was trained and tested with a 5-fold cross validation. Outcomes were evaluated based on the Dice Similarity Coefficients (DSC), the Hausdorff Distance (HD) and the Mean Surface Distance (MSD). The proposed method accounted for the small dataset, large variations in OAR shape and tumour sizes with an average DSC, HD and MSD for all anatomical structures of 0.790, 30.19mm and 3.15mm respectively.

Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: A retrospective cohort and survey study

ObjectivesThis study assessed the uptake of hormone replacement therapy (HRT) in cervical cancer patients with iatrogenic menopause. Survival in relation to HRT use was assessed via a retrospective chart study, and the severity of menopausal symptoms, motivations and barriers to starting HRT were examined via questionnaires. Study designIn total, 293 women under the age of 51 and treated with radiotherapy for cervical cancer between 2010 and 2020 were identified. Medical records were searched for information on HRT use. If still living, women were sent digital questionnaires addressing menopausal symptoms, quality of life (QoL) and potential barriers and motivations concerning HRT use. Univariable data were analysed using Mann-Whitney U, chi-square, and Fisher's exact test, while logistical regression was used to analyse relationships between certain variables and use of HRT and survival. ResultsOverall HRT uptake was 78.1 %, which was related to age and Charlson Comorbidity Index, but independent of the duration of radiotherapy or FIGO stage. Overall survival was higher for HRT users (χ2(1) = 4.3, p = 0.038). Questionnaires were sent to 193 patients and 100 completed it (response rate 51.8 %). Main reasons for HRT use were relief of hot flushes and improvement in QoL. For women below age 51, QoL was indeed higher for current HRT users than for non-HRT users (EQ-index 0.8 vs. 0.7, p = 0.008). ConclusionsHRT prescription rate was inversely correlated with age. Survival was not negatively affected by HRT use. It is important to stress the benefits of HRT and address women's fears regarding its use.

The Prognostic Value of the Systemic Immune-Inflammation Index (SII) and Red Cell Distribution Width (RDW) in Patients with Cervical Cancer Treated Using Radiotherapy.

There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer. This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan-Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator. The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32-3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation.

Changes of the Vagina After Concurrent Radiochemotherapy and Brachytherapy in Cervical Cancer Anatomical and Physiological Changes

The objective of the study: The aim of our study was to highlight the anatomical and physiological changes of the vagina after external radiotherapy and brachytherapy in cervical cancer. Materials and Methods: This was a prospective descriptive study conducted over a period of 6 months, from March to August 2022. A total of 123 women with cervical cancer, treated with concurrent radiochemotherapy and uterovaginal brachytherapy, who reported having had sexual intercourse in the six months prior, were included in the study. Patients were interviewed and examined during post-therapeutic follow-up consultations. Results and Statistical Analysis: The age of the patients (n=123) ranged from 33 to 67 years, with a mean of 49.35 ± 9.84 years. The post-therapeutic follow-up duration ranged from 6 months to 7 years. The most common histological type was squamous cell carcinoma, and the most common FIGO stage was stage II. Treatment consisted of concurrent radiochemotherapy and uterovaginal brachytherapy. Interviews revealed several changes related to the vagina after treatment. More than 65% of patients (n=81) reported the onset or worsening of vaginal dryness, over 50% (n=63) reported the onset or worsening of dyspareunia. Nearly 70% (n=83) reported a decrease in sexual desire frequency or dissatisfaction, and over 60% (n=78) became indifferent to sexual life. Gynecological examination revealed a vaginal length ranging from 2 to 10 cm with a mean of 5.66 ± 2.09 cm, the presence of synechiae and/or stenosis in nearly 43% (n=53), and bleeding in nearly 40% (n=47). In univariate analysis, vaginal dryness and dyspareunia significantly increased with age. Resumption of sexual activity was slower in younger and older women. Among patients followed for two years or less, there was a significant increase in synechiae or stenosis, as well as bleeding. Conversely, the prevalence of vaginal dryness and dyspareunia increased with follow-up duration, especially in those exceeding two years. In groups with vaginal dryness or dyspareunia, a large proportion of patients reported a decrease in sexual desire and indifference to their sexual life. Conclusion: This study revealed that patients with cervical cancer experienced significant anatomical and physiological changes in the vagina after treatment with concurrent radiochemotherapy and uterovaginal brachytherapy, leading to chronic sequelae and sexual disorders. It is therefore essential to implement measures to prevent or limit certain side effects associated with these treatments.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1mm in the left, 9.8 ± 4.4mm in the right, 12.6 ± 4.0mm in the anterior, 8.8 ± 5.1mm in the posterior, 5.7 ± 5.4mm in the superior, and 3.0 ± 3.2mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2mm in the left, 8.6 ± 3.8mm in the right, 9.0 ± 6.1mm in the anterior, 8.4 ± 3.6mm in the posterior, 5.0 ± 5.0mm in the superior, and 3.0 ± 2.5mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Radiation-Related Fractures after Radical Radiotherapy for Cervical and Endometrial Cancers: Are There Any Differences?

In this study, we reviewed CT/MRI scans and studied the rates of radiation-related fractures in subjects treated for cervical cancer (CC, 63 subjects) by radical radiotherapy (RT) and in subjects treated for endometrial cancer (EC, 64 subjects) by radical surgery and RT. The differences between bone density measured in L1 on pretreatment CT, age and body mass index (BMI) were evaluated. Despite significant differences in RT total dose, age, BMI, etc., between both groups, the rate of radiation-related fractures was similar: 28.6% of CC versus 26.6% of EC subjects. CC subjects with fractures were significantly older (62.4 ± 10.1 vs. 49.0 ± 12.4 years; p < 0.001), and their bone densities were significantly lower (106.3 ± 40.0 vs. 168.2 ± 49.5 HU; p < 0.001); no difference in BMI was found. EC subjects with fractures were without significant difference in age but had significantly lower bone densities (103.8 ± 29.0 vs. 133.8 ± 42.3 HU; p = 0.009) and BMIs (26.1 ± 4.9 vs. 31.8 ± 6.9 kg/m2; p = 0.003). Bone density strongly correlated with age (r = -0.755) only in CC subjects. Subjects with fractures from both groups had similarly low bone densities (106.3 ± 40.0 vs. 103.8 ± 29.0 HU; p = 0.829); however, no correlation between bone density and BMI was found. The rate of radiation-related fractures in both groups was clearly associated only with low pretreatment bone density, reflecting osteoporosis.

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer

BackgroundMonitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer.MethodsThis prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups.ResultsThe splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different.ConclusionsThis exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy.Trial registrationClinicalTrials.gov NCT04951921, registered 7 July 2021.Relevance statementThis prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients’ immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer.Key points• Effective radiotherapy induces abscopal effect via altering immune metabolism.• Hyperpolarized 13C MRS evaluates patients’ immune potential non-invasively.• Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.Graphical

Narrative review of the utility of magnetic resonance imaging in radiotherapy for cervical cancer.

In radiotherapy (RT) for locally advanced cervical cancer, high soft tissue contrast on magnetic resonance imaging (MRI) can ensure accurate delineation of target volumes (TVs) and optimal dose distribution to the RT target and organs at risk (OAR). MRI-guided adaptive RT (MRIgART) is a novel technology that revises RT plans according to anatomical changes occurring throughout the treatment to improve target coverage and minimise OAR toxicity. This review aims to assess the evidence and gaps of MRI use in RT planning and MRIgART in the treatment of cervical cancer, as well as challenges in its clinical implementation. Ovid Medline and PubMed were searched using keywords for MRI in RT for cervical cancer. After applying the inclusion and exclusion criteria, the initial search was deduced to 32 studies. A total of 37 final studies were reviewed, including eight additional articles from references. In the primary studies, TVs and organ motion were assessed before, during, and after treatment. MRI was used to investigate dose distribution and therapeutic response to the treatment in association with its outcome. Lastly, rationales for MRIgART were evaluated. It was concluded that MRI enables accurate target delineation, assessment of organ motion and interfraction changes, and monitoring of treatment response through dynamic parameters. Enhanced target coverage and reduced OAR irradiation through MRIgART can improve local control and the overall outcome, although its rationales against the logistical challenges need to be evaluated on further research.