Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer

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Intracavitary brachytherapy (ICBT) combined with external beam radiotherapy (EBRT) is the standard of care, optimizing tumour dose while sparing normal tissues. Plan quality indices such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-uniformity Ratio (DNR), and Conformity Index (COIN) are crucial in evaluating treatment plans, yet their predictive clinical relevance remains underexplored. Methodology In this prospective study, 84 patients with histologically confirmed cervical cancer undergoing definitive chemoradiation followed by CT-based HDR ICBT (Co-60) were evaluated. Plan indices were calculated per ICRU 89 and GEC-ESTRO guidelines. Correlation with tumour response (RECIST v1.1), toxicity (≥ grade 2 bladder/rectal), and clinical factors (FIGO stage, HRCTV volume, EQD2, BED, treatment duration) was assessed using t-tests, regression analyses, and Pearson’s correlation. Results Mean DHI was 0.403; OI 0.358; DNR 0.594; COIN 0.636. Higher DHI (p=0.019) and lower OI (p=0.004) were associated with tumour response; DNR and COIN were not significant. No plan index predicted ≥ grade 2 bladder or rectal toxicity. COIN correlated poorly with other indices. Multiple regression showed no consistent predictors of dosimetric indices. Logistic regression did not establish any index as a definitive predictor of 3-month response. Conclusion Plan quality indices provide useful quantitative insights into dose distribution in High dose rate intracavitary brachytherapy for cervical cancer. In this study, DHI and OI showed an association with early tumour response, while no significant correlation was observed between plan indices and treatment-related toxicity. 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F1000Research 2025, 14 :882 ( https://doi.org/10.12688/f1000research.166604.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] Abhishek Krishna https://orcid.org/0000-0002-9318-7024 1 , Juvie Leona Lobo 1 , Pooja MS 1 , [...] Bharat Sai Makkapati https://orcid.org/0000-0002-1635-0289 1 , Athiyamaan MS https://orcid.org/0000-0003-4691-9728 1 , Challapalli Srinivas 1 , Sourjya Banerjee 1 , Johan Sunny 1 , Paul Simon 1 , Dilson Lobo https://orcid.org/0000-0002-9222-863X 1 Abhishek Krishna https://orcid.org/0000-0002-9318-7024 1 , Juvie Leona Lobo 1 , [...] Pooja MS 1 , Bharat Sai Makkapati https://orcid.org/0000-0002-1635-0289 1 , Athiyamaan MS https://orcid.org/0000-0003-4691-9728 1 , Challapalli Srinivas 1 , Sourjya Banerjee 1 , Johan Sunny 1 , Paul Simon 1 , Dilson Lobo https://orcid.org/0000-0002-9222-863X 1 PUBLISHED 09 Sep 2025 Author details Author details 1 Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Abhishek Krishna Roles: Conceptualization, Methodology, Validation, Writing – Review & Editing Juvie Leona Lobo Roles: Data Curation, Validation Pooja MS Roles: Data Curation, Formal Analysis, Software Bharat Sai Makkapati Roles: Conceptualization, Writing – Review & Editing Athiyamaan MS Roles: Investigation, Supervision, Validation Challapalli Srinivas Roles: Formal Analysis, Methodology, Writing – Original Draft Preparation Sourjya Banerjee Roles: Formal Analysis, Supervision, Writing – Review & Editing Johan Sunny Roles: Formal Analysis, Visualization, Writing – Review & Editing Paul Simon Roles: Formal Analysis, Validation, Writing – Review & Editing Dilson Lobo Roles: Conceptualization, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. This article is included in the Manipal Academy of Higher Education gateway. Abstract Background Cervical cancer remains to be a significant health concern globally, with India contributing to nearly one-quarter of cases worldwide. Intracavitary brachytherapy (ICBT) combined with external beam radiotherapy (EBRT) is the standard of care, optimizing tumour dose while sparing normal tissues. Plan quality indices such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-uniformity Ratio (DNR), and Conformity Index (COIN) are crucial in evaluating treatment plans, yet their predictive clinical relevance remains underexplored. Methodology In this prospective study, 84 patients with histologically confirmed cervical cancer undergoing definitive chemoradiation followed by CT-based HDR ICBT (Co-60) were evaluated. Plan indices were calculated per ICRU 89 and GEC-ESTRO guidelines. Correlation with tumour response (RECIST v1.1), toxicity (≥ grade 2 bladder/rectal), and clinical factors (FIGO stage, HRCTV volume, EQD2, BED, treatment duration) was assessed using t-tests, regression analyses, and Pearson’s correlation. Results Mean DHI was 0.403; OI 0.358; DNR 0.594; COIN 0.636. Higher DHI (p=0.019) and lower OI (p=0.004) were associated with tumour response; DNR and COIN were not significant. No plan index predicted ≥ grade 2 bladder or rectal toxicity. COIN correlated poorly with other indices. Multiple regression showed no consistent predictors of dosimetric indices. Logistic regression did not establish any index as a definitive predictor of 3-month response. Conclusion Plan quality indices provide useful quantitative insights into dose distribution in High dose rate intracavitary brachytherapy for cervical cancer. In this study, DHI and OI showed an association with early tumour response, while no significant correlation was observed between plan indices and treatment-related toxicity. READ ALL READ LESS Keywords Uterine Cervical Neoplasms; Brachytherapy; Radiotherapy, High-Energy; Radiotherapy Planning, Computer-Assisted; Radiation Dosage; Treatment Outcome; Radiation Injuries. Corresponding Author(s) Dilson Lobo ( [email protected] ) Close Corresponding author: Dilson Lobo Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Krishna A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Krishna A, Lobo JL, MS P et al. Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] . F1000Research 2025, 14 :882 ( https://doi.org/10.12688/f1000research.166604.1 ) First published: 09 Sep 2025, 14 :882 ( https://doi.org/10.12688/f1000research.166604.1 ) Latest published: 09 Sep 2025, 14 :882 ( https://doi.org/10.12688/f1000research.166604.1 ) Introduction Cervical cancer continues to remain a significant public health concern globally, with an estimated 662,301 new cases and 348,874 deaths in 2022. 1 In countries like India, cervical cancer represents a major public health challenge. 2 One-quarter of all cervical cancer incidences globally have been identified in India. 1 Brachytherapy enhances local tumor control and overall survival while maintaining manageable toxicity levels. The combination of intracavitary brachytherapy (ICBT) and external beam radiotherapy (EBRT) constitutes the standard curative approach for cervical cancer. 3 This treatment approach offers a high therapeutic index by delivering a high dose to the tumour while sparing the nearby organs. 4 The global popularity of HDR brachytherapy with Co-60 is increasing. It utilizes a small Co-60 source that is similar in size to an Ir-192 source. 5 The success of ICBT depends on the precise and accurate delivery of brachytherapy to the target volume, which can be achieved through careful High Dose Rate (HDR) treatment planning. 3 Plan indices serve as important measures for evaluating the quality of radiation therapy plans and anticipating clinical outcomes. Among these, the dose-volume histogram (DVH) is frequently utilized, providing comprehensive insights into the dose distribution across both the target area and surrounding healthy tissues. 6 Additional indices include the Conformity Index (COIN), Dose Homogeneity Index (DHI), Dose Non-Homogeneity Ratio (DNHR), and Overall Index (OI). 6 – 8 The COIN measures the conformity of the radiation dose distribution to the target volume, while the DHI and DNR assess the radiation dose homogeneity and steepness of dose gradients, respectively. 7 , 8 The utilization of plan indices in radiation treatment planning offers a robust framework for objectively assessing the quality and efficacy of treatment plans. These indices, such as the dose-volume histogram (DVH), conformity index (COIN), dose homogeneity index (DHI), and others, provide quantitative metrics that evaluate various aspects of treatment plans, including precision, uniformity, and overall effectiveness. 7 By analysing the DVH, clinicians can ascertain whether the prescribed dose adequately covers the target while minimizing radiation exposure to critical structures, thus ensuring precision in treatment delivery. Only a few studies in the literature have explored the plan indices and their significance in cervical cancer patients undergoing intracavitary brachytherapy. 6 – 8 Despite the extensive research in cervical cancer treatment, there remains a lack of consensus regarding which plan indices are the most dependable and predictive for ICBT treatment planning. This uncertainty is partly due to conflicting results reported across numerous studies, which may arise from differences in the patient cohorts, treatment techniques, and evaluation criteria. The objective of the research was to evaluate and ascertain the clinical significance of multiple plan indices in predicting treatment outcomes and toxicities for cervical cancer patients undergoing ICBT. Methodology This was a prospective study conducted at a single tertiary care institution. The study enrolled patients with pathologically confirmed carcinoma of the cervix who were planned for definitive chemoradiation followed by intracavitary brachytherapy (ICBT). Institutional Ethics Committee approval was obtained before the start of the study, and all participants provided written informed consent. Eligible patients included those with histologically proven cervical cancer, deemed suitable for radical intent treatment. Exclusion criteria were metastatic disease, prior history of pelvic radiotherapy or chemotherapy, and inability to complete planned brachytherapy or follow-up assessments. Patients with incomplete medical records or inadequate imaging for plan evaluation were also excluded. All patients underwent baseline magnetic resonance imaging (MRI) for pelvic assessment before treatment initiation. External beam radiotherapy (EBRT) was delivered to the whole pelvis using 3DCRT or IMRT to a dose of 46 to 50 Gy in 23 to 25 fractions, with concurrent weekly cisplatin or carboplatin chemotherapy. In case a nodal boost was planned, an additional dose of 8 to 10 Gy in 4 to 5 fractions was delivered sequentially. Upon completion of EBRT, patients were clinically assessed for brachytherapy suitability. Those selected for intracavitary brachytherapy (ICBT) underwent the procedure under spinal anesthesia using Fletcher-Suit applicators. A dose of 7 to 7.5 Gy per fraction × 3 fractions was prescribed. Following applicator insertion, computed tomography (CT)-based simulation was performed. Delineation of high-risk clinical target volume (HRCTV), intermediate-risk clinical target volume (IRCTV), and organs at risk (OARs) was carried out according to GEC-ESTRO and IBS guidelines. 3 , 9 Treatment delivery Intracavitary brachytherapy (ICBT) treatment was administered using Cobalt 60 high dose rate brachytherapy (HDRBT) system. The prescribed dosage adhered to the recomendations outlined in the International Commission on Radiation Units and Measurements (ICRU) 38 report. 10 Following completion of the planned treatment, patients were monitored through a structured follow-up schedule. Follow-up evaluations were done every 3 months for the first 2 years, every 6 months for the subsequent 3 years, and annually thereafter. Treatment response was assessed at 3 months post-therapy using clinical and radiological with an MRI. Response evaluation adhered to the criteria defined by RECIST version 1.1. 11 In cases where residual or suspicious lesions were detected, further confirmation was sought through biopsy and histopathological examination. Plan evaluation Plan quality evaluation was performed using a set of standard dosimetric parameters derived from patients treatment plan. These parameters were used to calculate established brachytherapy plan indices as per ICRU 89 recommendations. 12 The following parameters were extracted for analysis: D90, defined as the dose received by the 90% of the target volume; V100%, representing the percentage of the total target volume receiving 100% of the total prescribed dose; V150%, the percentage of the target volume receiving at least 150% of the total prescribed dose; and V200%, the percentage of the target volume receiving at least 200% of the prescribed dose. 12 Additionally, volumetric parameters included TV (total target volume), TVDref (target volume receiving 100% of the prescribed dose), TV1.5ref (target volume receiving 150% of the prescribed dose), and TV2ref (target volume receiving 200% of the prescribed dose). The Vref parameter represented the overall volume receiving 100% of the prescribed dose, inclusive of both the target and surrounding tissues. 12 The quality of dose distribution within the planned target volume was further evaluated as per ICRU 89 and GEC ESTRO recommendations using the Dose Homogeneity Index (DHI), Dose Non-Uniformity Ratio (DNR), Overdose Index (OI), and Conformity Index (COIN). 9 , 12 The DHI was calculated as (TVDref − TV1.5ref ) divided by TVDref, providing a measure of the uniformity of dose distribution within the target volume; higher values indicated better homogeneity. The DNR was computed as the ratio of the target volume receiving ≥150% of the prescribed dose (TV1.5ref ) to the volume receiving 100% of the prescribed dose (TVref ), quantifying the extent of dose non-uniformity. The OI was defined as the ratio of the target volume receiving ≥200% of the prescribed dose (TV2ref ) to TVref, representing the extent of high-dose regions within the target. Finally, the COIN assessed both target coverage and dose conformity, calculated as the product of two factors: C1 (TVDref/TV), representing target coverage, and C2 (TVref/Vref ), reflecting dose conformity to the target volume. Statistical analysis Descriptive statistics were used to summarize patient characteristics, treatment parameters, and dosimetric indices. Continuous variables were expressed as mean, standard deviation (SD), minimum, and maximum values. Categorical variables were presented as frequencies and percentages. Correlations among dosimetric indices (DHI, OI, DNR, and COIN) were assessed using Pearson’s correlation coefficient. To compare dosimetric indices between responders and non-responders, independent samples t-tests were performed. Differences in mean DHI, OI, DNR, and COIN between the two groups were analyzed, with statistical significance set at p < 0.05. Logistic regression analysis was conducted to evaluate whether dosimetric indices (DHI, OI, DNR, and COIN) could predict response at 3 months (complete vs progressive disease; complete vs partial response). Regression coefficients, standard errors, and p-values were reported. Ordinal regression analysis was performed to assess the association between dosimetric indices and the grade of rectal and bladder toxicity. Multiple linear regression was used to explore the relationship between each dosimetric index (DHI, OI, DNR, COIN) and potential clinical or treatment-related factors, including FIGO stage, pre-treatment tumor volume, HRCTV volume, BED to tumor, EQD2 to tumor, and overall treatment time. Regression estimates, standard errors, t-values, and p-values were reported for each predictor. Finally, logistic regression analysis was performed to assess the relationship between dosimetric indices and the incidence of grade >2 bladder and rectal toxicities. The association of each index with high-grade toxicity was evaluated, and statistical significance was considered at p < 0.05. All statistical analyses were conducted using SPSS (version 24). P-values < 0.05 were considered statistically significant in all cases. Results A total of 84 patients with carcinoma of the cervix who underwent intracavitary brachytherapy were included in the study. The most common FIGO stage was IIB (45.2%), followed by IIIC1 (23.8%), IIIB (9.5%), IIA (6.0%), IVA (7.1%), IB2 (2.4%), IIIC2 (2.4%), IIA2 (1.2%), and IVA (2.4%). Histopathological evaluation showed squamous cell carcinoma in 77 patients (91.7%), adenocarcinoma in 5 patients (6.0%), and villoglandular variant in 2 patients (2.4%). Chemotherapy was administered concurrently in all patients, with 67 receiving cisplatin (79.8%) and 17 receiving carboplatin (20.2%). The average number of chemotherapy cycles was 4 (range 3–5) for carboplatin and 4 (range 1–6) for cisplatin ( Table 1 ). Table 1. Patient characteristics. Characteristics N = 84 Percentage Age in years (Median) 54 Stage IB2 2 2.4% IIA 5 6.0% IIA2 1 1.2% IIB 38 45.2% IIIB 8 9.5% IIIC1 20 23.8% IIIC2 2 2.4% IVA 2 2.4% IVA 6 7.1% Chemotherapy Carboplatin 17 20.2% Cisplatin 67 79.8% Mean Chemotherapy Cycles 4 Pathology Adenocarcinoma 5 6.0% Squamous Cell Carcinoma 77 91.7% Villoglandular Carcinoma 2 2.4% Brachytherapy Dose Fractionation 7.5Gy in 3 fractions The mean pre-treatment tumor volume was 61.66 cm 3 (SD = 60.94), with a minimum of 2.37 cm 3 and a maximum of 252.81 cm 3 . The mean brachytherapy dose per fraction was 7.72 Gy (SD = 0.34), with a range from 7.00 Gy to 8.50 Gy. The calculated biologically effective dose (BED) to the tumor was 99.85 Gy (SD = 3.58), with an equivalent dose in 2 Gy fractions (EQD2) of 83.27 Gy (SD = 2.98). The EQD2 to the bladder, rectum, and sigmoid colon were 73.37 Gy (SD = 5.93), 73.48 Gy (SD = 2.76), and 58.90 Gy (SD = 4.71), respectively ( Table 2 ). Table 2. Radiotherapy dose details. N Mean SD Minimum Maximum PRE TREATMENT TUMOUR VOLUME 84 61.66 60.942 2.37 252.81 BRACHY DOSE 84 7.72 0.341 7.00 8.50 EQD2 TUMOR (GY10) 84 83.27 2.980 76.20 92.82 BED TO TUMOR 84 99.85 3.579 91.46 111.39 EQD2 BLADDER (GY3) 84 73.37 5.932 58.97 85.19 EQD2 RECTUM (GY3) 84 73.48 2.761 64.00 84.58 EQD2 SIGMOID (GY3) 84 58.90 4.707 51.20 70.41 Dosimetric indices for all patients were calculated. The mean dose homogeneity index (DHI) was 0.403 (SD = 0.043), mean overdose index (OI) was 0.358 (SD = 0.044), mean dose non-uniformity ratio (DNR) was 0.594 (SD = 0.042), and mean conformity index (COIN) was 0.636 (SD = 0.068) ( Table 3 ). Pearson’s correlation coefficient showed a statistically significant negative correlation between DHI and OI (r = -0.899, p < .001), and between DHI and DNR (r = -0.948, p < .001). A positive correlation was seen between OI and DNR (r = 0.761, p < .001). No statistically significant correlation was observed between COIN and the other indices ( Table 4 & Figure 1 ). Table 3. Dosimetric indices details. N Mean SD Minimum Maximum MEAN DHI 84 0.403 0.0433 0.287 0.503 MEAN OI 84 0.358 0.0443 0.287 0.503 MEAN DNR 84 0.594 0.0422 0.497 0.713 MEAN COIN 84 0.636 0.0684 0.455 0.757 Table 4. Correlation of various indices. Variables Pearson’s r df p-value 95% CI Lower 95% CI Upper MEAN DHI vs MEAN OI -0.899 82 < .001 -0.933 -0.847 MEAN DHI vs MEAN DNR -0.948 82 < .001 -0.966 -0.921 MEAN DHI vs MEAN COIN -0.094 82 0.393 -0.303 0.123 MEAN OI vs MEAN DNR 0.761 82 < .001 0.653 0.839 MEAN OI vs MEAN COIN -0.034 82 0.758 -0.247 0.182 MEAN DNR vs MEAN COIN 0.106 82 0.337 -0.111 0.313 Figure 1. Correlation of various dosimetric indices. Independent samples t-test showed that DHI was significantly higher in responders compared to non-responders ( p = 0.019), while OI was significantly lower in responders ( p = 0.004). No significant differences were observed for DNR ( p = 0.085) and COIN ( p = 0.119) ( Table 5 ). Table 5. Dosimetric parameters in responders and non responders. Parameter Response Mean SD Statistic df p DHI Responders 0.406 0.0419 2.40 82.0 0.019 Non Responders 0.367 0.0350 OI Responders 0.354 0.0414 -2.96 82.0 0.004 Non Responders 0.403 0.0515 DNR Responders 0.592 0.0416 -1.74 82.0 0.085 Non Responders 0.620 0.0311 COIN Responders 0.632 0.0695 -1.57 82.0 0.119 Non Responders 0.674 0.0391 Binary logistic regression for response at 3 months (complete vs progressive disease) was conducted. None of the indices reached statistical significance. Estimates were as follows: DHI = 1.723 (p = 0.978), OI = 27.535 (p = 0.403), DNR = 10.032 (p = 0.787), and COIN = 23.174 (p = 0.067) ( Table 6 ). Table 6. Logistic regression. Response at 3 months Predictor Estimate SE Z p Complete Response - Progressive Disease Intercept -34.843 60.75 -0.57351 0.566 MEAN DHI 1.723 62.26 0.02768 0.978 MEAN OI 27.535 32.92 0.83638 0.403 MEAN DNR 10.032 37.08 0.27055 0.787 MEAN COIN 23.174 12.66 1.83108 0.067 Complete Response - Partial Response Intercept 0.750 135.32 0.00554 0.996 MEAN DHI -14.832 137.22 -0.10809 0.914 MEAN OI -28.980 33.57 -0.86325 0.388 MEAN DNR 27.812 131.39 0.21168 0.832 MEAN COIN -6.243 7.37 -0.84743 0.397 Ordinal regression analysis for grade of rectal toxicity showed no statistically significant association for any of the indices: DHI (p = 0.502), OI (p = 0.891), DNR (p = 0.636), and COIN (p = 0.258). Similarly, there was no significant association for bladder toxicity: DHI (p = 0.104), OI (p = 0.221), DNR (p = 0.186), and COIN (p = 0.364) ( Table 7 ). Table 7. Ordinal regression analysis for grade of rectal and bladder toxicity. Rectal toxicity Predictor Estimate SE Z p MEAN DHI 10.73 15.98 0.671 0.502 MEAN OI -0.647 4.70 -0.138 0.891 MEAN DNR 7.72 16.33 0.473 0.636 MEAN COIN -3.58 3.16 -1.132 0.258 Bladder toxicity Predictor Estimate SE Z p MEAN DHI 18.6 11.4 1.62 0.104 MEAN OI 13.4 11.0 1.22 0.221 MEAN DNR -7.09 5.36 -1.323 0.186 MEAN COIN 3.00 3.31 0.909 0.364 Correlation of dosimetric indices with FIGO stage, pre-treatment tumor volume, BED, EQD2, HRCTV volume, and overall treatment time was performed using multiple linear regression. For DHI, HRCTV volume showed a trend (p = 0.072), while no significant associations were seen for other variables. For OI, overall treatment time showed a borderline effect (p = 0.056). For DNR and COIN, no significant predictors were identified ( Table 8 ). Table 8. Correlation of dosimetric indices with factors. Parameter Predictor Estimate SE t p DHI INTERCEPT 0.26084 0.12661 2.060 0.043 STAGE 0.00757 0.00661 1.146 0.255 BED TO TUMOR 0.00255 0.00810 0.315 0.754 EQD2 TUMOR (GY10) -0.00134 0.00981 -0.136 0.892 HRCTV VOLUME 4.30e-4 2.36e-4 1.821 0.072 PRE TREATMENT TUMOUR VOLUME -9.74e−5 7.57e-5 -1.288 0.202 OVERALL TREATMENT TIME IN DAYS -7.04e−4 4.31e-4 -1.633 0.107 OI INTERCEPT 0.47179 0.13202 3.574 <.001 STAGE -0.00691 0.00689 -1.003 0.319 BED TO TUMOR 0.00278 0.00845 0.329 0.743 EQD2 TUMOR (GY10) -0.00507 0.01023 -0.495 0.622 HRCTV VOLUME -1.80e−4 2.46e-4 -0.730 0.468 PRE TREATMENT TUMOUR VOLUME 1.14e-4 7.89e-5 1.451 0.151 OVERALL TREATMENT TIME IN DAYS 8.71e-4 4.50e-4 1.938 0.056 DNR INTERCEPT 0.66895 0.12534 5.3372 <.001 STAGE -0.00625 0.00654 -0.9563 0.342 BED TO TUMOR -0.00156 0.00802 -0.1938 0.847 EQD2 TUMOR (GY10) 8.67e-4 0.00971 0.0892 0.929 HRCTV VOLUME -3.83e−4 2.34e-4 -1.6388 0.105 PRE TREATMENT TUMOUR VOLUME 6.88e-5 7.49e-5 0.9190 0.361 OVERALL TREATMENT TIME IN DAYS 7.45e-4 4.27e-4 1.7453 0.085 COIN INTERCEPT 0.46598 0.2186 2.132 0.036 STAGE 0.00621 0.0114 0.544 0.588 BED TO TUMOR 0.00746 0.0140 0.533 0.595 EQD2 TUMOR (GY10) -0.00744 0.0169 -0.439 0.662 HRCTV VOLUME 1.14e-4 4.08e-4 0.279 0.781 PRE TREATMENT TUMOUR VOLUME 4.27e-5 1.31e-4 0.327 0.744 OVERALL TREATMENT TIME IN DAYS 3.13e-4 7.44e-4 0.421 0.675 Toxicity analysis for grade >2 bladder and rectal events showed no statistically significant associations with any dosimetric index. For bladder: DHI (p = 0.482), OI (p = 0.624), DNR (p = 0.559), COIN (p = 0.400); and for rectum: DHI (p = 0.258), OI (p = 0.221), DNR (p = 0.460), COIN (p = 0.435) ( Table 9 ). Table 9. Toxicity analysis. Rectal toxicity > Grade 2 Predictor Estimate SE Z p Intercept -94.53 88.83 -1.064 0.287 MEAN DHI 102.65 90.73 1.131 0.258 MEAN OI 33.77 27.61 1.223 0.221 MEAN DNR 60.76 82.32 0.738 0.460 MEAN COIN 4.30 5.51 0.780 0.435 Bladder toxicity > Grade 2 Predictor Estimate SE Z p Intercept -61.55 84.09 -0.732 0.464 MEAN DHI 60.37 85.87 0.703 0.482 MEAN OI 13.07 26.68 0.490 0.624 MEAN DNR 45.65 78.14 0.584 0.559 MEAN COIN 5.01 5.96 0.842 0.400 Discussion The evolution of brachytherapy in cervical cancer has been influenced by the introduction of image-guided brachytherapy (IGBT), as advocated by the GEC-ESTRO working committee. 9 The GEC-ESTRO recommendations emphasize individualized dose optimization to achieve adequate target coverage while minimizing toxicity, which directly informs the interpretation of dosimetric indices such as DHI, DNR, OI, and COIN. The EMBRACE and EMBRACE II protocols have further standardized IGBT approaches, promoting consistent reporting of dose-volume parameters and encouraging adaptive planning based on anatomical changes during treatment. 4 The current study’s evaluation of plan quality indices within this framework aligns with the ongoing clinical emphasis on optimizing dosimetric quality and reinforcing the value of quantitative assessment in modern brachytherapy practice. This study evaluated the dosimetric parameters and clinical utility of standard brachytherapy indices in patients undergoing high dose rate (HDR) intracavitary brachytherapy (ICBT) for cervical cancer. This comprehensive analysis highlights the associations between key indices such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-Uniformity Ratio (DNR), and Conformity Index (COIN) with tumor response and toxicity outcomes. While brachytherapy remains a cornerstone in the curative management of locally advanced cervical cancer, the evolution of image-guided planning systems has made it possible to quantify dose distributions more precisely through these indices. Our findings offer valuable insights into the dosimetric quality of treatment plans and their potential impact on clinical outcomes. The mean values of the indices observed in our cohort — DHI (0.403), OI (0.358), DNR (0.594), and COIN (0.636) — suggest moderate dose uniformity and conformity in the overall treatment delivery. The moderate DHI and relatively elevated DNR and OI reflect the inherent limitations of standard tandem and ovoid-based ICBT in achieving highly homogeneous dose distributions. These findings are consistent with previous studies, which have shown that conventional intracavitary techniques, even with optimized planning, often result in significant dose gradients within the target volume due to applicator geometry and anatomical constraints. 13 , 14 The COIN value of 0.636 reflects moderate conformity, which is a function of both adequate target coverage and avoidance of normal tissues. This index gains particular importance in the era of image-guided brachytherapy (IGBT), where the goal is not merely to deliver high doses to the high-risk clinical target volume (HR-CTV) but also to minimize spillover to adjacent organs at risk (OARs). The observed strong negative correlations between DHI and both OI (r = -0.899) and DNR (r = -0.948) are expected, as a more homogeneous dose distribution (high DHI) logically coincides with lower volumes receiving excessively high doses (low OI and DNR). The positive correlation between OI and DNR (r = 0.761) further supports this dose distribution trend, where plans with more overdose zones are likely to be less uniform. These findings are supported by studies in literature who have described similar relationships in interstitial and intracavitary HDR plans. 15 , 16 Interestingly, COIN showed no statistically significant correlation with the other indices, highlighting its distinct role in plan evaluation. While DHI, OI, and DNR describe internal characteristics of dose distribution within the target, COIN encompasses spatial conformity — that is, the extent to which the high-dose volume coincides with the intended target and avoids non-target tissues. The significant association of DHI and DNR with tumor response at 3 months — with lower DHI and higher DNR seen in patients with progressive disease — underscores the importance of achieving uniform dose coverage within the target. Previous studies have emphasized that non-uniform dose distributions with hotspots or cold spots may compromise treatment efficacy, either due to undertreated areas within the tumor or over-irradiated regions that lead to tissue necrosis and impaired tumor control. 13 , 15 The trend toward statistical significance seen with COIN and OI in logistic regression models further supports their potential prognostic role. Although not reaching conventional levels of significance, these findings suggest that plans with poor conformity or higher overdose regions may influence tumor control, possibly through mechanisms such as uneven tumor sterilization or radiation-induced hypoxia in high-dose zones. The sample size of 84 patients, while adequate for exploratory analyses, may have limited the statistical power to detect small but clinically meaningful differences. These findings reinforce the need to integrate dosimetric indices into routine plan evaluation, not just as post-treatment analytics but as proactive tools to guide real-time decision-making during planning. No statistically significant associations were observed between the evaluated dosimetric indices and grade ≥2 bladder or rectal toxicity in either ordinal or binary regression models. This may appear contrary to the intuitive expectation that indices reflecting high-dose volumes (e.g., OI and DNR) would correlate with increased toxicity. However, it is important to note that OAR doses were evaluated separately through standard D2cc measurements, which were within tolerance limits in most cases (mean EQD2 to bladder and rectum ~73 Gy). Additionally, previous studies by Kirchheiner et al. and Fokdal et al. have reported that D2cc values are more sensitive predictors of toxicity than global plan indices such as DNR or COIN. 17 , 18 This suggests that while indices help in understanding dose distributions within the target, toxicity is more directly influenced by localized hot spots in the OARs. Nonetheless, the marginal trend seen for bladder toxicity with DHI (p = 0.104) in our data indicates a possible influence that warrants further investigation in larger cohorts. Our regression models exploring predictors of the indices themselves (DHI, OI, DNR, COIN) did not identify any single parameter as a statistically significant determinant, although HR-CTV volume and treatment time showed near-significant trends for DHI and OI, respectively. This may suggest that anatomical and logistical treatment factors modestly influence dose distribution but are insufficient on their own to explain dosimetric variability. It also reflects the complexity of treatment planning in HDR brachytherapy, where multiple variables — applicator geometry, dwell times, optimization techniques — interact in nuanced ways. The lack of correlation between FIGO stage and dosimetric indices is also notable, as it indicates that disease extent does not necessarily dictate the quality of dose distribution achievable with ICBT. This is likely because the applicator positioning and optimization methods are tailored to individual anatomy rather than disease stage per se. The integration of dosimetric indices into brachytherapy planning represents a significant advancement in the quality assurance of radiotherapy. Indices such as DHI and COIN serve not only as measures of plan quality but also potentially as surrogates for predicting tumor control. Their objective, quantitative nature allows for plan comparisons across institutions and operators, aiding in standardization — a key challenge in HDR brachytherapy. Moreover, the use of these indices aligns with recommendations from the GEC-ESTRO and ICRU 89 reports, which advocate for individualized, image-guided brachytherapy planning with thorough DVH-based evaluations. 9 , 12 Studies such as EMBRACE and Retro EMBRACE have already demonstrated that consistent and optimized dosimetric parameters are associated with better local control and reduced toxicity, especially when EQD2 >85 Gy is achieved for HR-CTV without exceeding constraints for bladder and rectum. 4 , 18 This study, while comprehensive, is limited by its retrospective design and single-center data. MRI-based brachytherapy planning, which is now considered standard in many centers ws used in only few patients in this study which may influence the generalizability of our results. Additionally, the small number of events in certain response and toxicity subgroups may reduce the statistical power of regression models. Future studies should focus on prospectively validating these findings in larger cohorts with MRI-guided planning, incorporating advanced tools such as automated dwell-time optimization and deformable image registration for cumulative dose assessment. Furthermore, integrating radiomics and machine learning approaches with dosimetric indices could enhance predictive modeling for response and toxicity. Conclusion In conclusion, our study underscores the importance of incorporating brachytherapy indices such as DHI, OI, DNR, and COIN into intracavitary treatment planning for cervical cancer. These indices provide a nuanced understanding of dose distribution and may aid in refining treatment plans for better tumor response while minimizing toxicity. Continued emphasis on dosimetric quality assurance and individualized planning is essential to optimize outcomes in HDR brachytherapy. Consent Written informed consent to take part in the research has been obtained from all patients when indicated. Consent for publication is not applicable as all data is anonymized, and no images are being published. Ethics statement The Institutional Ethics Committee of Kasturba Medical College approved this study, Mangalore, vide Protocol No. IEC KMC MLR 12/2022/420). The study was conducted in accordance with the ethical guidelines and regulations set forth by the institution. The study has been conducted according to the principles expressed in the Declaration of Helsinki. Data availability statement FIGSHARE: https://doi.org/10.6084/m9.figshare.29302400.v1 Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 4.0 Public domain dedication). References 1. Bray F, Mathieu L, Hyuna S, et al. : Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 09 Sep 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Abhishek Krishna Roles: Conceptualization, Methodology, Validation, Writing – Review & Editing Juvie Leona Lobo Roles: Data Curation, Validation Pooja MS Roles: Data Curation, Formal Analysis, Software Bharat Sai Makkapati Roles: Conceptualization, Writing – Review & Editing Athiyamaan MS Roles: Investigation, Supervision, Validation Challapalli Srinivas Roles: Formal Analysis, Methodology, Writing – Original Draft Preparation Sourjya Banerjee Roles: Formal Analysis, Supervision, Writing – Review & Editing Johan Sunny Roles: Formal Analysis, Visualization, Writing – Review & Editing Paul Simon Roles: Formal Analysis, Validation, Writing – Review & Editing Dilson Lobo Roles: Conceptualization, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 09 Sep 2025, 14:882 https://doi.org/10.12688/f1000research.166604.1 Copyright © 2025 Krishna A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Krishna A, Lobo JL, MS P et al. Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] . F1000Research 2025, 14 :882 ( https://doi.org/10.12688/f1000research.166604.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 09 Sep 2025 Views 0 Cite How to cite this report: Attalla EM. Reviewer Report For: Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] . F1000Research 2025, 14 :882 ( https://doi.org/10.5256/f1000research.183618.r449894 ) The direct URL for this report is: https://f1000research.com/articles/14-882/v1#referee-response-449894 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Jan 2026 Ehab Marouf Attalla , Cairo University, Cairo, Egypt Approved VIEWS 0 https://doi.org/10.5256/f1000research.183618.r449894 Dear Editor The study evaluated Plan quality indices, such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-uniformity Ratio (DNR), and Conformity Index (COIN), provide valuable insights into dose distribution in intracavitary brachytherapy (ICBT) for ... Continue reading READ ALL Dear Editor The study evaluated Plan quality indices, such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-uniformity Ratio (DNR), and Conformity Index (COIN), provide valuable insights into dose distribution in intracavitary brachytherapy (ICBT) for cervical cancer. Studies have shown that higher DHI and lower OI are associated with improved tumor response, while DNR and COIN are not significant predictors. Here are the advantages and disadvantages: Advantages: Useful quantitative insights: Plan quality indices provide valuable information about dose distribution in ICBT. Association with tumor response: DHI and OI showed significant association with early tumor response. Optimizing treatment plans: Indices can help optimize treatment plans to improve tumor control and reduce toxicity. Disadvantages: Limited predictive value: No index was a definitive predictor of 3-month response or treatment-related toxicity. Poor correlation: COIN correlated poorly with other indices, limiting its usefulness. Need for further research: More studies are needed to establish the clinical relevance of plan quality indices. The article highlights several research gaps in the field of cervical cancer treatment using intracavitary brachytherapy (ICBT): Lack of consensus on plan indices: There's no agreement on which plan indices are most dependable and predictive for ICBT treatment planning. Limited studies on plan indices: Few studies have explored plan indices and their significance in cervical cancer patients undergoing ICBT. Conflicting results: Different studies report conflicting results, possibly due to differences in patient cohorts, treatment techniques, and evaluation criteria. Limited understanding of dosimetric indices: The clinical significance of indices like DHI, OI, DNR, and COIN in predicting treatment outcomes and toxicities is not well understood. Need for individualized planning: There's a need for personalized planning approaches incorporating dosimetric indices to optimize treatment outcomes. Limited data on MRI-based brachytherapy planning: MRI-based brachytherapy planning is not widely used, and its impact on treatment outcomes is unclear. Need for prospective validation: The study's findings need prospective validation in larger cohorts with MRI-guided planning. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Bao S, Wang Y, Hu Y, Lin S, et al.: Research trends in cervical cancer brachytherapy: a bibliometric analysis. Discover Oncology . 2025; 16 (1). Publisher Full Text 2. Itami J, Murakami N, Watanabe M, Sekii S, et al.: Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer. Frontiers in Oncology . 2022; 11 . Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Medical Physics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Attalla EM. Reviewer Report For: Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] . F1000Research 2025, 14 :882 ( https://doi.org/10.5256/f1000research.183618.r449894 ) The direct URL for this report is: https://f1000research.com/articles/14-882/v1#referee-response-449894 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 09 Sep 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 09 Sep 25 read Ehab Marouf Attalla , Cairo University, Cairo, Egypt Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Attalla E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Jan 2026 | for Version 1 Ehab Marouf Attalla , Cairo University, Cairo, Egypt 0 Views copyright © 2026 Attalla E. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear Editor The study evaluated Plan quality indices, such as Dose Homogeneity Index (DHI), Overdose Index (OI), Dose Non-uniformity Ratio (DNR), and Conformity Index (COIN), provide valuable insights into dose distribution in intracavitary brachytherapy (ICBT) for cervical cancer. Studies have shown that higher DHI and lower OI are associated with improved tumor response, while DNR and COIN are not significant predictors. Here are the advantages and disadvantages: Advantages: Useful quantitative insights: Plan quality indices provide valuable information about dose distribution in ICBT. Association with tumor response: DHI and OI showed significant association with early tumor response. Optimizing treatment plans: Indices can help optimize treatment plans to improve tumor control and reduce toxicity. Disadvantages: Limited predictive value: No index was a definitive predictor of 3-month response or treatment-related toxicity. Poor correlation: COIN correlated poorly with other indices, limiting its usefulness. Need for further research: More studies are needed to establish the clinical relevance of plan quality indices. The article highlights several research gaps in the field of cervical cancer treatment using intracavitary brachytherapy (ICBT): Lack of consensus on plan indices: There's no agreement on which plan indices are most dependable and predictive for ICBT treatment planning. Limited studies on plan indices: Few studies have explored plan indices and their significance in cervical cancer patients undergoing ICBT. Conflicting results: Different studies report conflicting results, possibly due to differences in patient cohorts, treatment techniques, and evaluation criteria. Limited understanding of dosimetric indices: The clinical significance of indices like DHI, OI, DNR, and COIN in predicting treatment outcomes and toxicities is not well understood. Need for individualized planning: There's a need for personalized planning approaches incorporating dosimetric indices to optimize treatment outcomes. Limited data on MRI-based brachytherapy planning: MRI-based brachytherapy planning is not widely used, and its impact on treatment outcomes is unclear. Need for prospective validation: The study's findings need prospective validation in larger cohorts with MRI-guided planning. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Bao S, Wang Y, Hu Y, Lin S, et al.: Research trends in cervical cancer brachytherapy: a bibliometric analysis. Discover Oncology . 2025; 16 (1). Publisher Full Text 2. Itami J, Murakami N, Watanabe M, Sekii S, et al.: Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer. Frontiers in Oncology . 2022; 11 . Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Medical Physics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Attalla EM. Peer Review Report For: Evaluation and clinical relevance of plan quality indices in intracavitary brachytherapy for cervical cancer [version 1; peer review: 1 approved] . F1000Research 2025, 14 :882 ( https://doi.org/10.5256/f1000research.183618.r449894) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-882/v1#referee-response-449894 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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