Radiotherapy (RT) is an established viable treatment for cervical cancer across all clinical stages. However, the therapeutic ratio of conventional techniques remains suboptimal due to the anatomical proximity of the cervix to critical pelvic organs. The current study presents a case of pathological complete response (pCR) achieved exclusively through preoperative online adaptive RT (oART) guided by fan beam computed tomography (FBCT). A 54-year-old woman presenting with irregular vaginal bleeding was diagnosed with a cervical mass via pelvic imaging. Subsequent histopathological biopsy confirmed invasive papillary squamous cell carcinoma. Preoperative evaluation, supplemented by laboratory and imaging studies, ruled out distant metastases. The patient underwent fractionated oART using a CT-linear accelerator platform. Post-treatment imaging demonstrated complete resolution of the lesion, and surgical histopathology revealed no residual malignancy. This case highlights the feasibility, safety and dosimetric precision of FBCT-guided oART in cervical cancer. The pCR achieved in this case indicates that oART has the potential to improve the treatment of cervical cancer.

Background: Cervical cancer treatment with advanced radiotherapy techniques benefits from image guidance, particularly when anatomical changes occur during therapy. This case emphasizes the need for adaptive radiotherapy when target volume shifts significantly. Methods: A 70-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) IIIC2 9th edition cervical squamous cell carcinoma presented with a distended uterine cavity due to fluid accumulation. She underwent definitive chemoradiotherapy using Volumetric Modulated Arc Therapy (VMAT) and weekly cisplatin. Results: Daily Cone Beam Computed Tomography (CBCT) imaging revealed progressive uterine shrinkage as intrauterine fluid drained, significantly altering target volume and organ-at-risk (OAR) positioning. These changes necessitated two re-planning CT scans during external beam radiotherapy to maintain accurate dosing and avoid OAR toxicity. The patient completed treatment, including image-guided brachytherapy, without complications. Adaptive planning ensured adequate tumor coverage and minimized normal tissue exposure. Conclusions: This case highlights the critical role of daily CBCT in detecting anatomical changes during radiotherapy. Adaptive re-planning, though rarely required more than once, was essential here to preserve treatment accuracy. CBCT should be considered a standard verification tool in cervical cancer radiotherapy, particularly in cases involving intrauterine fluid.

Emerging evidence has suggested the safety and efficacy of individualized-uterine radiotherapy in locally advanced cervical cancer. This study aimed to compare the clinical outcomes and gastrointestinal toxicity of whole-uterine and individualized-uterine radiotherapy in women with locally advanced cervical cancer.

A retrospective analysis was conducted on 220 patients with stage IB3 to IVA cervical cancer, treated with definitive chemoradiotherapy between 2014 and 2021 at 2 tertiary centers. The clinical target volume included the entire uterus (whole-uterine group) or an individualized-uterine volume based on the gross tumor with a 15 mm margin (individualized-uterine group). Local recurrence rate, overall survival, and progression-free survival were evaluated using the Kaplan-Meier method. The Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events was used to assess acute gastrointestinal toxicity, and a score of ≥3 indicated severe toxicity.

Overall, 128 (58.2%) and 92 (41.8%) patients received whole- and individualized-uterine radiotherapy with a median follow-up of 63.0 (interquartile range; 39.4-93.2) months and 64.8 (interquartile range; 47.3-85.6) months, respectively. Compared to the whole-uterine group, the individualized-uterine group had significantly lower volumes of small bowel, rectum, and sigmoid colon exposed to 45 Gy or 30 Gy (all p < .05). The 5-year local recurrence rate, overall survival, and progression-free survival in the whole- and individualized-uterine groups were 4.1% vs 0.0% (p = .054), 84.9% vs 87.6% (p = .48), and 74.7% vs 84.8% (p = .07), respectively. Fewer patients in the individualized group reported severe acute gastrointestinal toxicity (5.4% vs 23.4%, p < .001). The 5-year rates of severe late gastrointestinal toxicity were 7.4% and 0.0% in the whole- and individualized-uterine groups, respectively (p = .009).

Individualized-uterine radiotherapy resulted in favorable clinical outcomes and reduced acute or late gastrointestinal toxicity compared to whole-uterine radiotherapy. This approach may offer an optimized balance between outcomes and toxicity in patients with locally advanced cervical cancer.

Human cervical cancer is the fourth most common malignancies among females worldwide. Radiotherapy is crucial in the treatment of cervical cancer. REV7 is associated with the radiosensitivity of cancer cells. We aimed to investigate the relationship between the REV7 expression and the clinical outcome for patients with cervical cancer who received radiation therapy and identify new markers for studying radiosensitivity in cervical cancer.

The expression of REV7 in 71 cases of cervical squamous cell carcinoma (CSCC) tissues, 20 paracancerous tissues and 20 normal cervical epithelia tissues were analyzed by qRT-PCR and immunohistochemistry (IHC). Among them, 60 patients who underwent intensity-modulated radiation therapy (IMRT) and met the inclusion and exclusion criteria were divided into groups based on the REV7 IHC score: high-expression and low-expression. The relationship between REV7 expression level and short-term efficacy, recurrence and metastasis was investigated. Meanwhile, univariate, multivariate, and Kaplan-Meier analyses were used to analyze the association of REV7 expression with disease-free survival (DFS) and overall survival (OS).

The expression of REV7 is upregulated in CSCC tissues. There was a higher likelihood of progression (pelvic recurrence or distant metastasis) in the group with high REV7 expression (P = 0.024). Moreover, the REV7-high expression patients showed a shorter DFS than the REV7-low expression group (P = 0.011).

The higher expression level of REV7 indicates an unfavorable prognosis in cervical cancer patients undergoing IMRT treatment. REV7 could potentially serve as a novel biomarker and therapeutic target for investigating the radiosensitivity of cervical cancer.

Labeling cone-beam computed tomography (CBCT) images is challenging due to poor image quality. Training auto-segmentation models without labelled data often involves deep-learning to generate synthetic CBCTs (sCBCT) from planning CTs (pCT), which can result in anatomical mismatches and inaccurate labels. To prevent this issue, this study assesses an auto-segmentation model for female pelvic CBCT scans exclusively trained on delineated pCTs, which were transformed into sCBCT using a physics-driven approach.

To replicate CBCT noise and artefacts, a physics-driven sCBCT (Ph-sCBCT) was synthesized from pCT images using water-phantom CBCT scans. A 3D nn-UNet model was trained for auto-segmentation of cervical cancer CBCTs using Ph-sCBCT images with pCT contours. This study included female pelvic patients: 63 for training, 16 for validation and 20 each for testing on Ph-sCBCTs and clinical CBCTs. Auto-segmentations of bladder, rectum and clinical target volume (CTV) were evaluated using Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95). Initial evaluation occurred on Ph-sCBCTs before testing generalizability on clinical CBCTs.

The model auto-segmentation performed well on Ph-sCBCT images and generalized well to clinical CBCTs, yielding median DSC's of 0.96 and 0.94 for the bladder, 0.88 and 0.81 for the rectum, and 0.89 and 0.82 for the CTV on Ph-sCBCT and clinical CBCT, respectively. Median HD95's for the CTV were 5 mm on Ph-sCBCT and 7 mm on clinical CBCT.

This study demonstrates the successful training of auto-segmentation model for female pelvic CBCT images, without necessarily delineating CBCTs manually.

Cisplatin-based chemoradiation (CRT) plus brachytherapy for locally advanced cervical cancer (LACC) is standard. Intrinsic overexpression of ribonucleotide reductase (RNR) may enhance DNA damage repair from CRT. We report on outcomes of adding RNR inhibitor, triapine (T), to CRT.

NRG-GY006 is an open-label randomized phase III trial. FIGO 2009 LACC (stages IB2, II, IIIB or IVA) without para-aortic nodal involvement or stages II-IV vaginal cancer were eligible. Random assignment to CRT or in combination with thrice-weekly T (CRT + T) occurred. Radiation consisted of either 3D conformal (3DCRT) or image-guided intensity modulated RT (IG-IMRT) followed by intracavitary brachytherapy. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was secondary. Exploratory endpoints included complete metabolic response rate on post treatment PET/CT imaging and comparative toxicity and outcomes for 3DCRT vs. IG-IMRT.

Four-hundred-fifty patients were randomized including 448 eligible (224 in CRT and 224 in CRT + T). Median age was 47 (range 23-85). The majority had cervical cancer (93.3 %) with squamous histology (82 %). 52 % had FIGO stage II disease. Racial/ethnic distribution included non-Hispanic white (53.8 %), black (15.2 %) and Hispanic/Latina (22.5 %). At randomization, IG-IMRT was planned in 74.3 % and HDR brachytherapy in 98.2 %. No differences in Grade 3-5 toxicities were observed: CRT: 52 % and CRT + T: 49 %, with two G5 toxicities (cardiac arrest and acidosis) in the CRT + T arm. The median patient follow-up was 28 months (IQR 15-45). HR for death was 1.018 (95 % CI 0.634-1.635) while HR for progression was 1.021 (95 % CI 0.694-1.501).

Triapine added to CRT did not improve OS.

To evaluate acute toxicity and dosimetric outcomes in cervical cancer treated with daily iterative cone beam computed tomography (iCBCT) guided online adaptive radiation therapy (oART) using reduced planning target volume (PTV) margin.

From February 2023 to November 2023, 27 patients with stages I to III cervical cancer were prospectively enrolled in this study. All patients received daily iCBCT guided oART (prescribed 50.4 Gy in 28 fractions) with concurrent weekly chemotherapy followed by brachytherapy. A uniform 10-mm margin was used to cover more variable uterus (PTV-U), and 5-mm margin was used for other PTV. The dosimetric results for each oART fraction were recorded. Both clinician- and patient-reported acute toxicities were assessed before treatment, weekly during treatment, 1 month and 3 months after treatment.

The average total treatment time was 22 minutes and 54 seconds, and the adapted plan was selected for all fractions. The adapted plans showed superior coverage for the target volume and dosimetric improvement of organs at risk compared with the scheduled plan. Overall, no patient had grade ≥ 4 acute toxicities. Grades 1, 2, and 3 acute gastrointestinal toxicity were 26%, 19%, and 4%, respectively, among which diarrhea was the most common. Only grade 1 acute genitourinary toxicity was observed in 2 cases (7%). The low incidence of acute toxicity was supported by patient-reported outcome data, which showed significant decreases in mean standard scores on function subscales and significant increases on symptom subscales/items following the initiation of oART. Most of these scales returned to baseline average scores by the 1-month follow-up.

This prospective study of daily oART in patients with cervical cancer observed dosimetric benefits and a low incidence of acute toxicity, both in clinician- and patient-reported outcome measurements.

This study aims to investigate the feasibility of fan-beam computed tomography (FBCT)-guided online adaptive radiotherapy (oART) in radical radiotherapy for cervical cancer.

Ten patients who underwent radical radiotherapy for cervical cancer were enrolled in this study. All patients received external beam radiation therapy (EBRT) with a prescription dose of 50.4 Gy/28f, and daily oART with FBCT guidance was performed. Dosimetric analysis was conducted on 278 fractions, comparing the adaptive and scheduled plans. The γ passing rate was measured through in-vivo dose monitoring during treatment, using a 3%/3mm gamma criterion with an 88% threshold for alerts. The time invested in the oART workflow was recorded at each step. Acute toxicities were classified following the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

The adaptive plans demonstrated a dosimetric advantage in target coverage and/or organs at risk (OARs) sparing across all 278 fractions. Compared to the scheduled plan, the adaptive plan showed improved dose received by 95% (D95) of planning target volume (PTV), conformity index (CI), and homogeneity index (HI) (P<0.001). Among the three PTVs, the PTV of uterus (PTV_U) benefited most from dosimetric improvements in the adaptive plan, followed by the PTV of cervix, vagina, and parametrial tissues (PTV_C), while the PTV of lymph node (PTV_N) exhibited the least enhancement. For OARs, the adaptive plan achieved reductions in the dose to the most irradiated 2 cm³ volume (D2cc) for the rectum, bladder, and small intestine (P<0.001). For patients with ovarian conservation, the dose to the 50% volume (D50) and the mean dose of the bilateral ovaries were decreased (P<0.001). The mean γ passing rate across all fractions was 99.24%. The mean duration of the oART workflow was 22.82 ± 3.61 min, with auto-segmentation & review (44.40%) and plan generation & evaluation (22.02%) being the most time-intensive steps. The incidence of Grade 1-2 acute non-hematological toxicity was 60%, with no cases of Grade 3 or higher observed.

The implementation of FBCT-guided oART in radical radiotherapy for cervical cancer was feasible. This approach has shown significant improvements in dose distribution and the potential to provide clinical benefits by reducing acute toxicity.

Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques.

Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) International Federation of Gynecology and Obstetrics (FIGO) IIIC1 with a bulky tumor and vaginal metastasis, (2) FIGO IIB with calcified uterine fibromas, and (3) FIGO IIIC2 with large lymph nodes. The contours on all 6 data sets (3 CT simulations without diagnostic images and 3 with registered images) were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement. The contours were reviewed, discussed, and edited in a group meeting prior to finalizing.

Contours showed considerable agreement among experts in each of the cases, with kappa statistics from 0.67 to 0.72. For each case, diagnostic PET ± MRI was associated with an increase in volume. The largest increase was the clinical target volume (CTV) primary for case 2, with a 20% increase in volume and a 54% increase in simultaneous truth and performance level estimation volume, which may be due to variance in registration priorities. For the third case, 92.9% increased their CTVs based on the addition of the diagnostic PET scan. The main areas of variance were in determining the superior extent of CTV coverage, coverage of the mesorectum, and simulation and planning protocols.

This study shows the value and the challenges of using coregistered diagnostic imaging, with an average increase in volumes when incorporating MRI and PET.

Accurate segmentation of the clinical target volume (CTV) is essential to deliver an effective radiation dose to tumor tissues in cervical cancer radiotherapy. Also, although automated CTV segmentation can reduce oncologists' workload, challenges persist due to the microscopic spread of tumor cells undetectable in CT imaging, low-intensity contrast between organs, and inter-observer variability. This study aims to develop and validate a multi-task feature fusion network (MTF-Net) that uses distance-based information to enhance CTV segmentation accuracy.

We developed a dual-branch, end-to-end MTF-Net designed to address the challenges in cervical cancer CTV segmentation. The MTF-Net architecture consists of a shared encoder and two parallel decoders, one generating a distance location information map (Dimg) and the other producing CTV segmentation masks. To enhance segmentation accuracy, we introduced a distance information attention fusion module that integrates features from the Dimg into the CTV segmentation process, thus optimizing target delineation. The datasets for this study were from three centers. Data from two centers were used for model training and internal validation, and that of the third center was used as an independent dataset for external testing. To benchmark performance, we also compared MTF-Net to commercial segmentation software in a clinical setting.

MTF-Net achieved an average dice score of 84.67% on internal and 77.51% on external testing datasets. Compared with commercial software, MTF-Net demonstrated superior performance across several metrics, including Dice score, positive predictive value, and 95% Hausdorff distance, with the exception of sensitivity.

This study indicates that MTF-Net outperforms existing state-of-the-art segmentation methods and commercial software, demonstrating its potential effectiveness for clinical applications in cervical cancer radiotherapy planning.

Daily online adaptive radiotherapy (ART) improves dose metrics for gynecological cancer patients, but the on-treatment process is resource-intensive requiring longer appointments and additional time from the entire adaptive team. To optimize resource allocation, we propose a model to identify high-priority patients.

For 49 retrospective cervical and endometrial cancer patients, we calculated two initial plans: the treated standard-of-care (InitialSOC) and a reduced margin initial plan (InitialART) for adapting with the Ethos treatment planning system. Daily doses corresponding to standard and reduced margins (DailySOC and DailyART) were determined by re-segmenting the anatomy based on the treatment CBCT and calculating dose on a synthetic CT. These initial and daily doses were used to estimate the ART benefit (Δ D a i l y ${{\Delta}}Daily$ = DailySOC-DailyART) versus initial plan differences (Δ I n i t i a l ${{\Delta}}Initial$ = InitialSOC-InitialART) via multivariate linear regression. Dosimetric benefits were modeled with initial plan differences (Δ I n i t i a l ${{\Delta}}Initial$ ) ofB o w e l V 40 G y $Bowel\ {{V}_{40Gy}}$ (cc),B l a d d e r D 50 % $Bladder\ {{D}_{50{\mathrm{\% }}}}$ (Gy), andR e c t u m D 50 % $Rectum\ {{D}_{50{\mathrm{\% }}}}$ (Gy). Anatomy (intact uterus or post-hysterectomy), DoseType (simultaneous integrated boost [SIB] vs. single dose), and/or prescription value. To establish a logistic model, we classified the top 10% in each metric as high-benefit patients. We then built a logistic model to predict these patients from the previous predictors. Leave-one-out validation and ROC analysis were used to evaluate the accuracy. To improve the clinical efficiency of this predictive process, we also created knowledge-based plans for the ΔInitial plans (Δ I n i t i a l R P ${{\Delta}}Initia{{l}_{RP}}$ ) and repeated the analysis.

In bothΔ I n i t i a l O r i g ${{\Delta}}Initia{{l}_{Orig}}$ andΔ I n i t i a l R P ${{\Delta}}Initia{{l}_{RP}}$ our multivariate analysis showed low R2 values 0.34-0.52 versus 0.14-0.38. The most significant predictor in each multivariate model was the corresponding ∆Initial metric (e.g.,Δ I n i t i a l ${{\Delta}}Initial$ Bowel (V40 Gy), p < 1e-05). In the logistic model, the metrics with the strongest correlation to the high-benefit patients wereB o w e l V 40 G y $Bowel\ {{V}_{40Gy}}$ (cc),B l a d d e r D 50 % $Bladder\ {{D}_{50{\mathrm{\% }}}}$ (Gy),D o s e T y p e $DoseType$ , andS I B D o s e $SIBDose$ prescription. The models for original and knowledge-based plans had an AUC of 0.85 versus 0.78. The sensitivity and specificity were 0.92/0.72 and 0.69/0.80, respectively.

This methodology will allow clinics to prioritize patients for resource-intensive daily online ART.

This study investigates the clinical efficacy of MRI-based adaptive brachytherapy (IGABT) using combined intracavitary and interstitial techniques in the curative treatment of patients with advanced cervical cancer (LACC). A retrospective analysis was conducted on 149 LACC patients treated at a single center. The therapeutic protocol included intensity-modulated external beam radiotherapy (IMRT) and IGABT. Dosimetric parameters were evaluated for relevance for local control (LC), progression-free survival (PFS), and overall survival (OS) using Kaplan-Meier estimation, Cox regression, and log-rank test. Patients predominantly presented with stage III/IV tumors (81%, FIGO 2018). The median high-risk clinical target volume (hrCTV) was 34 cm3, with a median D90% dose of 88.9 GyEQD2. At 24 months, OS, PFS, and LC rates were 86%, 57%, and 81%, respectively. FIGO stage, tumor volume, and histology were significant predictors of PFS. Higher total hrCTV doses were strongly correlated with improved LC and PFS, emphasizing the importance of precise dosimetric optimization in IGABT and confirming the critical role of IGABT in achieving very good LC rates for LACC. The reported LC rates are comparable to landmark studies, such as INTERLACE and KEYNOTE-A18. This study validates the effectiveness of MRI-guided IGABT in enhancing local tumor control in advanced-stage cervical cancer while providing insights into the prognostic implications of dosimetric parameters such as hrCTV and point A. Future research should address the persistent challenge of distant metastases by exploring the integration of novel systemic treatment options.

This study was conducted to develop and validate a novel deep reinforcement learning (DRL) algorithm incorporating the segment anything model (SAM) to enhance the accuracy of automatic contouring organs at risk during radiotherapy for cervical cancer patients. CT images were collected from 150 cervical cancer patients treated at our hospital between 2021 and 2023. Among these images, 122 CT images were used as a training set for the algorithm training of the DRL model based on the SAM model, and 28 CT images were used for the test set. The model's performance was evaluated by comparing its segmentation results with the ground truth (manual contouring) obtained through manual contouring by expert clinicians. The test results were compared with the contouring results of commercial automatic contouring software based on the deep learning (DL) algorithm model. The Dice similarity coefficient (DSC), 95th percentile Hausdorff distance, average symmetric surface distance (ASSD), and relative absolute volume difference (RAVD) were used to quantitatively assess the contouring accuracy from different perspectives, enabling the contouring results to be comprehensively and objectively evaluated. The DRL model outperformed the DL model across all evaluated metrics. DRL achieved higher median DSC values, such as 0.97 versus 0.96 for the left kidney (P < 0.001), and demonstrated better boundary accuracy with lower HD95 values, e.g., 14.30 mm versus 17.24 mm for the rectum (P < 0.001). Moreover, DRL exhibited superior spatial agreement (median ASSD: 1.55 mm vs. 1.80 mm for the rectum, P < 0.001) and volume prediction accuracy (median RAVD: 10.25 vs. 10.64 for the duodenum, P < 0.001). These findings indicate that integrating SAM with RL (reinforcement learning) enhances segmentation accuracy and consistency compared to conventional DL methods. The proposed approach introduces a novel training strategy that improves performance without increasing model complexity, demonstrating its potential applicability in clinical practice.

Consensus contouring guidelines for intensity-modulated-radiation-therapy (IMRT) of patients with locally advanced cervix cancer (LACC) advise including the whole uterus in the target volume and adding generous planning-target-volumes (PTVs) to account for motion uncertainties of the gross-tumor-volume (GTV). The primary objective of this analysis was to assess the interfractional GTV motions using a magnetic-resonance-image (MRI) guided-Radiation-Therapy (MRgRT) system to investigate the margins required for MRgRT treatments.

125 daily set-up MRIs from five patients with LACC who received MRgRT were analyzed. The GTV, bladder, uterus, and rectum were contoured on all 125 MRIs. Tumor volume changes were calculated in cubic-centimeters (cc). The positional and volume changes of organs-at-risk (OARs) were calculated to assess their effect on GTV interfractional motion, these data were used to calculate adequate PTV margins.

The tumor volume decreased in size during the course of MRgRT for all patients, from 34.0 % to 85.2 %. The interfractional average GTV displacement ranged from 0.46 cm to 0.94 cm. The PTV margins required were: 0.78 cm Left-Right, 1.31 cm Anterior-Posterior and 1.38 cm for the Superior-Inferior directions. The proposed PTV margins, compared to those recommended by consensus guidelines, reduce the PTV by 38 % sparing both the sigmoid and bowel OARs.

By utilizing daily onboard MRI guidance, the GTV becomes readily visualized, allowing for margin reduction and potentially excluding a portion of the uterine fundus from the PTV. The amount of interfractional motion demonstrated in this study is considerable and clinically significant with the goal of decreasing treatment toxicity while maintaining tumor control.

Daily pretreatment magnetic resonance images (MRIs) from patients with locally advanced cervix cancer (LACC) treated with on-board MR-guided radiation therapy (MRgRT) were analyzed to quantify the range of interfractional motion and develop target volume guidelines for adaptive MRgRT. MRI-guidance leads to better tumor visualization in comparison to cone beam computed tomography (CBCT), and online adaptive planning can account for the interfraction motion of the tumor and surrounding tissue. MRI's ability to better visualize the disease and pelvic anatomy along with adaptive on-board MRgRT could allow for a reduction in the required setup margins as well as potentially excluding non-diseased portions of the uterus from the target volumes. These changes will lead to reduced treatment volumes and may lead to decreased treatment toxicities and allow for dose escalation in certain circumstances.

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.

The aim was to determine which immobilisation device improved inter-fraction reproducibly of pelvic tilt and required the least pre-treatment setup and planning interventions.

Sixteen patients were retrospectively reviewed, eight immobilised using the BodyFIX system (BodyFIX®, Elekta, Stockholm, Sweden) and eight using the Butterfly Board (BB) (Bionix Radiation Therapy, Toledo, OH, USA). The daily pre-treatment images were reviewed to assess setup variations between each patient and groups for pelvic tilt, pubic symphysis, sacral promontory and the fifth lumbar spine (L5).

Compared with the planning CT, pelvic tilt for most patients was within ±2° using the BodyFIX and ± 4° for the BB. The Butterfly Board had a slightly higher variance both for patient-to-patient (standard deviation of the systematic error) and day-to-day error (standard deviation of the random error). Variance in position between individual patients and the two stabilisation devices were minimal in the anterior-posterior (AP) and superior-inferior (SI) direction for the pubic symphysis, sacral promontory and L5 spine. Re-imaged fractions due to pelvic tilt reduced by about half when BodyFIX was used (39.1% BB, 19.4% BodyFIX). One patient treated with the BB required a re-scan for pelvic tilt. Three patients required a re-scan for body contour variations (two using BodyFIX and one with the BB).

BodyFIX resulted in a more accurate inter-fraction setup and efficient treatment and is used as the standard stabilisation for gynaecological patients at our centre. It reduced the pelvic tilt variance and reduced the need for re-imaging pre-treatment by half.

This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma.

Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS).

All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%.

Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.

Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients.

The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed.

The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities.

IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

Cervical cancer is one of the most frequent malignant tumors in females. Concurrent chemoradiotherapy is one of the treatment options for cervical cancer. The treatment time of conventional radiotherapy is long. Moderately hypofractionated radiotherapy (MHRT) offers the advantage of shortening the overall treatment duration and enhancing the radiobiological effects on tumors. MHRT shortens the overall treatment duration while enhancing the radiobiological effects on tumors. Previous studies have reported that MHRT of cervical cancer has relatively high toxicity. Daily online adaptive radiation therapy (oART) showed improvements in dosimetry and a decrease in toxicity. To the best of our knowledge, this case was the first reported case of moderated hypofractionated oART used in a cervical cancer patient to date in a prospective clinical trial (NCT05994300). This case serves as a critical reminder that cervical cancer is a potential tumor that may be in MHRT with iterative cone beam computed tomography-guided oART. Further data are needed to confirm the toxicity and efficacy of this technique.

The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality.

Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested.

CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes.

The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography-guided adaptive radiation therapy.

Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs).

FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years.

Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median follow-up of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years.

PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS.

The ability to visualise cancer with imaging has been crucial to the evolution of modern radiotherapy (RT) planning and delivery. And as evolving RT technologies deliver increasingly precise treatment, the importance of accurate identification and delineation of disease assumes ever greater significance. However, innovation in imaging technology has matched that seen with RT delivery platforms, and novel imaging techniques are a focus of much research activity. How these imaging modalities may alter and improve the diagnosis and staging of cancer is an important question, but already well served by the literature. What is less clear is how novel imaging techniques may influence and improve practical and technical aspects of RT planning and delivery. In this review, current gold standard approaches to integration of imaging, and potential future applications of bleeding-edge imaging technology into RT planning pathways are explored.

Activated guided irradiation by X-ray (AGuIX) nanoparticles are gadolinium-based agents that have the dual benefit of mimicking the effects of a magnetic resonance imaging (MRI) contrast agent used in a clinical routine and enhancing the radiotherapeutic activity of conventional X-rays (for cancer treatment). This "theragnostic" action is explained on the one hand by the paramagnetic properties of gadolinium and on the other hand by the generation of high densities of secondary radiation following the interaction of ionizing radiation and high-Z atoms, which leads to enhanced radiation dose deposits within the tumors where the nanoparticles accumulate. Here, we report the results of a phase I trial that aimed to assess the safety and determine the optimal dose of AGuIX nanoparticles in combination with chemoradiation and brachytherapy in patients with locally advanced cervical cancer. AGuIX nanoparticles were administered intravenously and appropriately accumulated within tumors on a dose-dependent manner, as assessed by T1-weighted MRI, with a rapid urinary clearance of uncaught nanoparticles. We show that the observed tumor accumulation of the compounds can support precise delineation of functional target volumes at the time of brachytherapy based on gadolinium enhancement. AGuIX nanoparticles combined with chemoradiation appeared well tolerated among the 12 patients treated, with no dose-limiting toxicity observed. Treatment yielded excellent local control, with all patients achieving complete remission of the primary tumor. One patient had a distant tumor recurrence. These results demonstrate the clinical feasibility of using theranostic nanoparticles to augment the accuracy of MRI-based treatments while focally enhancing the radiation activity in tumors.

Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM.

LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55-50.6 Gy at PTV1 and 45-39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients.

Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed.

CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Chemoradiotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer (LACC). In this study, we postulate that omitting an iconographical unaffected uterus (+12 mm distance from the tumour) from the treatment volume is safe and that no tumour will be found in the non-targeted uterus (NTU) leading to reduction of high-dose volumes of surrounding organs at risk (OARs).

In this single-arm phase 2 study, two sets of target volumes were delineated: one standard-volume (whole uterus) and an EXIT-volume (exclusion of non-tumour-bearing parts of the uterus with a minimum 12 mm margin from the tumour). All patients underwent chemoradiotherapy targeting the EXIT-volume, followed by completion hysterectomy. In 15 patients, a plan comparison between two treatment plans (PTV vs PTV_EXIT) was performed. The primary endpoint was the pathological absence of tumour involvement in the non-targeted uterus (NTU). Secondary endpoints included dosimetric impact of target volume reduction on OARs, acute and chronic toxicity, overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS).

In all 21 (FIGO stage I: 2; II: 14;III: 3; IV: 2) patients the NTU was pathologically negative. Ssignificant reductions in Dmean in bladder, sigmoid and rectum; V15Gy in sigmoid and rectum, V30Gy in bladder, sigmoid and rectum; V40Gy and V45Gy in bladder, bowel bag, sigmoid and rectum; V50Gy in rectum were achieved. Median follow-up was 54 months (range 7-79 months). Acute toxicity was mainly grade 2 and 5 % grade 3 urinary. The 3y- OS, PFS and LRFS were respectively 76,2%, 64,9% and 81 %.

MRI-based exclusion of the non-tumour-bearing parts of the uterus at a minimum distance of 12 mm from the tumour out of the target volume in LACC can be done without risk of residual disease in the NTU, leading to a significant reduction of the volume of surrounding OARS treated to high doses.

Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer.

All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables.

A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments ( P =0.039), older age ( P =0.049), rectal volume irradiated at 40 Gy ( P =0.01) and 30 Gy ( P =0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm 3 of rectum (D2cm 3 ) showed a potential association with the occurrence of radiation proctitis of all grades ( P =0.064).

This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.

To determine the impact of a MR-based contouring atlas for male pelvis radiotherapy delineation on inter-observer variation to support radiographer led real-time magnetic resonance image guided adaptive radiotherapy (MRgART).

Eight RTTs contoured 25 MR images in the Monaco treatment planning system (Monaco 5.40.01), from 5 patients. The prostate, seminal vesicles, bladder, and rectum were delineated before and after the introduction of an atlas developed through multi-disciplinary consensus. Inter-observer contour variations (volume), time to contour and observer contouring confidence were determined at both time-points using a 5-point Likert scale. Descriptive statistics were used to analyse both continuous and categorical variables. Dice similarity coefficient (DSC), Dice-Jaccard coefficient (DJC) and Hausdorff distance were used to calculate similarity between observers.

Although variation in volume definition decreased for all structures among all observers post intervention, the change was not statistically significant. DSC and DJC measurements remained consistent following the introduction of the atlas for all observers. The highest similarity was found in the bladder and prostate whilst the lowest was the seminal vesicles. The mean contouring time for all observers was reduced by 50% following the introduction of the atlas (53 to 27 minutes, p=0.01). For all structures across all observers, the mean contouring confidence increased significantly from 2.3 to 3.5 out of 5 (p=0.02).

Although no significant improvements were observed in contour variation amongst observers, the introduction of the consensus-based contouring atlas improved contouring confidence and speed; key factors for a real-time RTT-led MRgART.

The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients.

Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a framework for treatment of similar patients.

Treatment of gynecologic malignancies with SBRT requires many considerations, including treatment intent, optimal patient selection, fractionation selection, tumor localization, and plan optimization. Although other treatment paradigms including conventionally fractionated radiation therapy and brachytherapy remain the standard-of-care for definitive treatment of gynecologic malignancies, SBRT may have a role in palliative cases or those where high doses are not required due to the unacceptable toxicity that may occur with SBRT.

A case-based practice review was developed by the Radiosurgery Society to provide a practical guide to the common scenarios noted above affecting patients with gynecologic malignancies.

Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation.

We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point.

The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups.

Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

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 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm 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 15 mm 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.

Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography-magnetic resonance imaging) PET-MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era.

Definitive pelvic intensity modulated radiation therapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging.

In this prospective, nonrandomized phase 2 study, patients with cervical cancer International Federation of Gynecology and Obstetrics (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic chemoradiotherapy with a prespecified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive image-guided radiotherapy (IGRT), with a library of 3 IMRT (volumetric modulated arc therapy) plans with incremental expansions of clinical target volume (CTV) to planning target volume (PTV) (primary) margins (small, 0.7 cm; adequate, 1 cm; and large, 1.5 cm) and a backup motion robust 3-dimensional conformal radiotherapy plan; the appropriate plan is chosen based on pretreatment cone beam computed tomography (CBCT) ("plan of the day" approach).

Fifty patients with a median age of 49 years (IQR, 45-56 years) received definitive radiation therapy (45-46 Gy in 23-25 fractions to pelvis, with simultaneous integrated boost to gross nodes in 15 patients) with the aforementioned IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning computed tomography (CT) and CBCT bladder volumes were 417 and 373 cc, respectively. Significant interfractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were postchemotherapy sessions (P ≤ .001), pre-CBCT protocol duration (P = .001), and grades of chemotherapy induced nausea vomiting (P = .001). Significantly higher variation in bladder filling was noted in patients with older age (P = .014) and larger planning CT bladder volume (P ≤ .001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from the first to the fifth week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion and without any significant factors affecting it. Although in 19% and 2% of sessions large IMRT PTV and 3-dimensional conformal radiotherapy were necessary to cover the primary target, respectively, reduction in treated volume was possible in 43% of sessions with small PTV selection instead of standard adequate PTV (36% sessions). Plan of the day selection had a moderate to strong correlation with nonabsolute dispersion of bladder filling (Spearman ρ =0.4; P = .001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade 3 toxicity.

Interfractional variation in organ filling (especially bladder) is inevitable despite fixed pretreatment protocol in definitive settings (intact cervix). Despite the logistical challenges, adaptive IGRT in the form of plan of the day based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimize geometric uncertainties in radical IG-IMRT of cervical cancer.

Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared.

A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test.

Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART.

This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume.