Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

PURPOSE: The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. METHODS: Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. RESULTS: Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. CONCLUSION: Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

MRI-guided dynamic risk assessment in cervical cancer based on tumor hypoxia at diagnosis and volume response at brachytherapy.

BACKGROUND AND PURPOSE: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification. MATERIAL AND METHODS: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HFpre) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HFpre. In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. Change in ADC during therapy was combined with volume regression yielding functional regression as explorative response measure. Endpoint was disease free survival (DFS). RESULTS: HFpre was the strongest predictor of DFS, but a significant correlation with outcome was found also for volume regression. The combination of HFpre and volume regression showed a stronger association with DFS than HFpre alone. Patients with disease recurrence were selected to either the intermediate- or high-risk group with a 100 % accuracy. Functional regression showed a stronger correlation to HFpre than volume regression. CONCLUSION: The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter.

Integrated pretreatment diffusion kurtosis imaging and serum squamous cell carcinoma antigen levels: a biomarker strategy for early assessment of radiotherapy outcomes in cervical cancer.

OBJECTIVE: This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. MATERIALS AND METHODS: A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. RESULTS: Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. CONCLUSION: Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy.

Updated Trends in Cervical Cancer Brachytherapy Utilization and Disparities in the United States From 2004 to 2020.

PURPOSE: Lower brachytherapy utilization for cervical cancer patients is associated with decreased survival. This study examines more recent trends in brachytherapy utilization from 2004 to 2020 to assess any trend reversal after awareness increased regarding the importance of brachytherapy. METHODS AND MATERIALS: This study analyzed data from the National Cancer Database of patients with Federation of Gynecology and Obstetrics (FIGO) IB to IVA cervical cancer treated with radiation therapy between 2004 and 2020. To compare brachytherapy utilization over time, 2- to 3-year categories were created to account for potential variation seen in individual years. A multivariate log binomial regression with robust variance was used to estimate the incidence rate ratio (IRR) of brachytherapy utilization in each year category in reference to the 2004-2006 category. Additionally, risk factors for brachytherapy utilization were identified. RESULTS: Overall brachytherapy utilization for cervical cancer increased from 54.9% in 2004 to 75.7% in 2020. Compared with 2004 to 2006 when rates of utilization totaled 55.2%, brachytherapy utilization significantly increased to 63.4% in 2011 to 2014 (IRR, 1.15; 95% CI, 1.11-1.19), 66.0% in 2015 to 2017 (1.20 [1.16-1.23]), and 76.0% in 2018 to 2020 (1.38 [1.34-1.42]). Sociodemographic factors associated with lower brachytherapy utilization included Black race (0.94 [0.92-0.97]), Hispanic ethnicity (0.92 [0.90-0.95]), and age >59 years (age ≥60-69: 0.96 [0.94-0.98]; age ≥70-79: 0.89 [0.87-0.92]; age ≥80: 0.73 [0.69-0.77]). Positive predictors of brachytherapy utilization included having insurance (IRR, 1.11; 95% CI, 1.07-1.14). CONCLUSIONS: In patients with FIGO IB-IVA cervical cancer treated with radiation therapy from 2004 to 2020, brachytherapy utilization has increased during the past decade. These results are encouraging given the known benefit to cause-specific survival and overall survival provided by brachytherapy treatment and indicate a reversal in the trend of declining brachytherapy noted previously. Concerns related to disparities by race, ethnicity, and insurance status require further interventions.

Assessment of intrafractional motion of the cervix-uterus by MR-guided radiotherapy system†.

The uterus is known as one of the moving organs. We evaluated the movement of the uterus during irradiation and the effects of changes in the surrounding organs using a magnetic resonance (MR)-guided radiotherapy system. Seven patients with cervical cancer underwent pre- and posttreatment MR imaging to assess changes in the positioning of the uterus and cervix as well as the alterations in bladder and rectal volume. The study revealed that the movements of the uterus were greater than that of the cervix and showed a tendency to correlate with the bladder rather than the rectum. We also examined whether intrafractional motion could lead to insufficient dose coverage of the clinical target volume (CTV), specifically focusing on the D98% of the CTV in the uterine body and cervix. The impact of intrafractional motion on the D98% varied among patients, with one out of the seven patients experiencing an average dosimetric change of -2.6 Gy in the uterus, although larger planning target volume margins of 1.5 cm were applied, therefore, indicating the need for individualized optimal margins in each case. Online adaptive radiotherapy offers the advantage of modifying the treatment plan when irradiating moving organs, such as the uterus. However, it should be noted that this approach may result in longer overall treatment times compared with the traditional methods. Therefore, we must carefully consider the influence of intrafractional organ motions when opting for such a treatment.

[Verification of Dose Distribution in Cervical Cancer Brachytherapy Using Metal and Plastic Applicators].

PURPOSE: To validate the point-A dose and dose distribution of metal and resin applicators in comparison with those of TG-43U1. METHODS: The metal and resin applicators consisting of tandem and ovoid were modeled by the egs_brachy. The doses to point A and dose distributions considering each applicator were calculated and compared to those of TG-43U1. RESULTS: The dose to point A considering the metal applicator was 3.2% lower than that of TG-43U1, but there was no difference in the dose to point A considering the resin applicator. The dose distribution considering the metal applicator was lower than that of TG-43U1 at all calculation points, but there was no difference in the dose distribution considering the resin applicator at almost all calculation points. CONCLUSION: In this study, the dose distribution considering the metal applicator was lower than that of TG-43U1 at all calculation points, but there was no difference in the dose distribution considering the resin applicator at almost all calculation points. Therefore, TG-43U1 can accurately calculate the dose distribution when changing from the metal applicator to the resin applicator.

Three-dimensional assessment of interfractional cervical and uterine motions using daily magnetic resonance images to determine margins and timing of replanning.

PURPOSE: This study was conducted to determine the margins and timing of replanning by assessing the daily interfractional cervical and uterine motions using magnetic resonance (MR) images. METHODS: Eleven patients with cervical cancer, who underwent intensity-modulated radiotherapy (IMRT) in 23-25 fractions, were considered in this study. The daily and reference MR images were converted into three-dimensional (3D) shape models. Patient-specific anisotropic margins were calculated from the proximal 95% of vertices located outside the surface of the reference model. Population-based margins were defined as the 90th percentile values of the patient-specific margins. The expanded volume of interest (expVOI) for the cervix and uterus was generated by expanding the reference model based on the population-based margin to calculate the coverage for daily deformable mesh models. For comparison, expVOIconv was generated using conventional margins: right (R), left (L), anterior (A), posterior (P), superior (S), and inferior (I) were (5, 5, 15, 15, 10, 10) and (10, 10, 20, 20, 15, 15) mm for the cervix and uterus, respectively. Subsequently, a replanning scenario was developed based on the cervical volume change. ExpVOIini and expVOIreplan were generated before and after replanning, respectively. RESULTS: Population-based margins were (R, L, A, P, S, I) of (7, 7, 11, 6, 11, 8) and (14, 13, 27, 19, 15, 21) mm for the cervix and uterus, respectively. The timing of replanning was found to be the 16th fraction, and the volume of expVOIreplan decreased by >30% compared to that of expVOIini . However, margins cannot be reduced to ensure equivalent coverage after replanning. CONCLUSION: We determined the margins and timing of replanning through detailed daily analysis. The margins of the cervix were smaller than conventional margins in some directions, while the margins of the uterus were larger in almost all directions. A margin equivalent to that at the initial planning was required for replanning.

Biological Characterization of the Effects of Filtration on the Xoft Axxent® Electronic Brachytherapy Source for Cervical Cancer Applications.

Low-energy X-ray sources that operate in the kilovoltage energy range have been shown to induce more cellular damage when compared to their megavoltage counterparts. However, low-energy X-ray sources are more susceptible to the effects of filtration on the beam spectrum. This work sought to characterize the biological effects of the Xoft Axxent® source, a low-energy therapeutic X-ray source, both with and without the titanium vaginal applicator in place. It was hypothesized that there would be an increase in relative biological effectiveness (RBE) of the Axxent® source compared to 60Co and that the source in the titanium vaginal applicator (SIA) would have decreased biological effects compared to the bare source (BS). This hypothesis was drawn from linear energy transfer (LET) simulations performed using the TOPAS Monte Carlo user code as well a reduction in dose rate of the SIA compared to the BS. A HeLa cell line was maintained and used to evaluate these effects. Clonogenic survival assays were performed to evaluate differences in the RBE between the BS and SIA using 60Co as the reference beam quality. Neutral comet assay was used to assess induction of DNA strand damage by each beam to estimate differences in RBE. Quantification of mitotic errors was used to evaluate differences in chromosomal instability (CIN) induced by the three beam qualities. The BS was responsible for the greatest quantity of cell death due to a greater number of DNA double strand breaks (DSB) and CIN observed in the cells. The differences observed in the BS and SIA surviving fractions and RBE values were consistent with the 13% difference in LET as well as the factor of 3.5 reduction in dose rate of the SIA. Results from the comet and CIN assays were consistent with these results as well. The use of the titanium applicator results in a reduction in the biological effects observed with these sources, but still provides an advantage over megavoltage beam qualities. © 2023 by Radiation Research Society.

Assessment of Peripheral Platelet to Lymphocyte Ratio and Prognostic Nutritional Index in the Efficacy and Prognosis of Radiotherapy for Cervical Cancer.

This study aimed to evaluate the correlation between the pre-treatment peripheral platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) with the efficacy and prognosis of radiotherapy for cervical cancer. A total of 110 patients with cervical cancer who received radiotherapy at our hospital from November 2017 to November 2020 were retrospectively analysed. The cut-off values of PLR and PNI were obtained using the receive operating characteristic curve (ROC) and the Youden index. The patients were divided into high PLR and low PLR and high PNI and low PNI groups. We compared the clinical characteristics, 3-year overall survival (OS), and progression-free survival (PFS) between the high and low PLR groups, as well as the high and low PNI groups of patients. Cox regression was used to analyse the factors influencing OS and PFS. The median follow-up duration was 26 months. The optimal cut-off value for PLR was 186.88 and that for PNI was 47.35. The 3-year OS values were 81.00% and 97.10% for the high PLR (PLR > 186.88) and low PLR (PLR ≤ 186.88) groups, respectively, and the 3-year PFS values were 59.50% and 88.20% for the high PLR and low PLR groups, respectively, with statistically significant differences (p < 0.05). The 3-year OS values were 97.50% and 74.20% for the high PNI (PNI > 47.35) and the low PNI (PNI ≤ 47.35) groups, respectively, and the 3-year PFS values were 87.30% and 51.60% for the high PNI and low PNI groups, respectively, with statistically significant differences (p < 0.05). Multifactorial Cox regression analyses revealed that high PLR value (PLR > 187.88), low PNI value (PNI ≤ 47.35), histological type, and FIGO stage were independent risk factors for the OS of cervical cancer. Pretreatment PNI values and PLR values can be used as simple and feasible predictors of clinical efficacy and prognosis for patients treated with radiotherapy for cervical cancer.

Assessment of adverse events among cervical cancer patients at Kenyatta National Hospital.

INTRODUCTION: Due to their cytotoxic nature, anticancer drugs and radiotherapy have the potential to cause toxic adverse events. As a result, they can increase the risk of morbidity and mortality. However, there was a lack of data among cervical cancer patients in our setting. Hence, this study was aimed to assess the prevalence of adverse events among cervical cancer patients at Kenyatta National Hospital. METHODS: A cross-sectional study design was employed among a consecutive sample of 151 adult cervical cancer patients. The data were collected by reviewing the medical records and interviewing the patients. The data were entered and analyzed using SPSS 27.0 software. The results were presented with frequency tables and graphs. RESULTS: A total of 214 adverse events (prevalence of 100%) were identified from 151 patients. The most common adverse events identified were ulcerated sores (52.8%), dysuria (7.5%), thrombocytopenia (5.6%), and loss of appetite (5.6%). The majority of the patients (80.8%) who had adverse events were on radiotherapy. As per the Naranjo causality assessment scale, the predominant (80.1%) proportion of the adverse event was a probable adverse event with a total score of 5-8. Besides, 15.9% of the adverse events had a possible causality. The present study also reported that 61.6% of patients with a probable adverse event were treated with radiotherapy. CONCLUSION: The prevalence of adverse events among cervical patients was high in our setting. The predominant proportion of the adverse event was a probable adverse event and most of them were treated with radiotherapy.

Spare the Bowel, Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix.

PURPOSE: The standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage. METHODS AND MATERIALS: A retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART. RESULTS: The average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage. CONCLUSIONS: Based on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.

Comparison between MCNP and planning system in brachytherapy of cervical cancer.

Absorbed doses in uterus during brachytherapy were calculated with MCNP in relevant points and compared with planning system for one patients. MCNP was applied with two different humanoid phantoms in input, ORNL and voxel models, which represent human body in mathematical way. Good agreement between both phantoms, as well as, between MCNP and planning system were found. In addition the doses in critical organs (bladder and colon in this kind of therapy), were calculated and compared with maximal doses in these organs obtained from planning system for 15 other patients. MCNP doses agree well with planning system in points of uterus for those 15 patients, where radioactive source is used to apply. However, there are systematical discrepancies between doses in colon and bladder obtained by MCNP and planning system.

Pre-treatment hematological parameters as a cost effective predictive marker for response to concurrent chemo radiation in locally advanced cervical cancer.

INTRODUCTION: Locally advanced cervical cancer is still a major cause of mortality in developing countries. Recently, personalized medicine has changed the treatment paradigm for many solid cancers but no robust biomarkers has yet been validated for predicting response to chemo radiation in cervical cancer patients. AIM: To assess the role of hematological parameters as a cost-effective predictive marker of response to concurrent chemo radiation in cervical cancer patients. MATERIALS AND METHOD: This is a retrospective analysis of 90 cervical cancer patients treated with concurrent chemo radiation in a tertiary cancer center. Clinical details of the patients were extracted from the case records. For end point evaluation, the pre-treatment levels of hemoglobin, neutrophil, lymphocyte, platelet, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) were compared and statistically analyzed between responders and non-responders. The optimal cutoff values of hematological parameters were estimated by the receiver operating characteristics (ROC) curve. RESULT: Out of 90 patients, 60 (66.66%) were complete responders and remaining 30 (33.33%) were non-responders. The mean value of platelet, NLR, and PLR was significantly higher in the non-responder group. ROC curve analysis showed the optimal cut-off value of pre-treatment Hb, PLT, NLR and PLR to be 11 gm/dl, 3, 177 × 109/L, and 70 respectively. CONCLUSION: Our study suggests that simple hematological markers like NLR, PLT count and PLR could be used as a cost effective pretreatment predictive marker for response to chemo radiation in cervical cancer patients.

Better late than never: Brachytherapy is more important than timing in treatment of locally advanced cervical cancer.

PURPOSE: To evaluate the utilization of brachytherapy and duration of treatment on overall survival for locally advanced cervical cancer. METHODS: The National Cancer Database (NCDB) was queried to identify stage II-IVA cervical cancer patients diagnosed in the United States between 2004 and 2015 who were treated with definitive chemoradiation therapy. We defined standard of care (SOC) treatment as receiving external beam radiation therapy (EBRT) and concurrent chemotherapy, brachytherapy (BT), and completing treatment within 8 weeks, and compared SOC treatment to non-SOC. The primary outcome was overall survival (OS). We also evaluated the effect of sociodemographic and clinical variables on receiving SOC. RESULTS: We identified 10,172 women with locally advanced cervical cancer primarily treated with chemotherapy and concurrent EBRT of which 6047 (59.4%) patients received brachytherapy, and only 2978 (29.3%) completed treatment within 8 weeks (SOC). Receipt of SOC was associated with significantly improved overall survival (median OS 131.0 mos vs 95.5 mos, 78.1 mos, 49.2 mos; p < 0.0001). Furthemore, in patients whose treatment extended beyond 8 weeks, brachytherapy was still associated with an improved survival (median OS 95.5 vs 49.2 mos, p < 0.0001). More advanced stage, Non-Hispanic Black race, lower income, lack of insurance or government insurance, less education, and rural residence were associated with decreased likelihood of receiving SOC. CONCLUSIONS: Completing standard of care concurrent chemoradiation therapy and brachytherapy in the recommended 8 weeks was associated with a superior overall survival. Patients who received brachytherapy boost show superior survival to patients receiving EBRT alone, regardless of treatment duration. Disparities in care for vulnerable populations highlight the challenges and importance of care coordination for patients with cervical cancer.

Integration of rotatable tandem applicator to conventional ovoid applicator toward complete framework of intensity modulated brachytherapy (IMBT) for cervical cancer.

A new tandem applicator with tungsten shield for Ir-192 radiation source used in intra-cavitary brachytherapy (ICBT) enabled intensity modulated brachytherapy (IMBT) in cervical cancer treatment through fluence-modulation by rotating shield. Our previous work employed group-wise and element-wise sparsity constraints for plan optimization of tandem applicator to minimizes the number of activated angles and source dwell points for delivery efficiency. It, however, did not incorporate the ovoid applicators into the optimizing process, which is generally used to prevent cancer recurrence. To integrate ovoid applicators to the new tandem applicator, this work proposed a comprehensive framework that modifies 1) dose deposition matrix for inverse planning, and 2) plan optimizing algorithm. The dose deposition matrix was newly formulated by the Monte-Carlo simulated dose distribution for 10 positions of ovoid applicators, followed by combining those with tandem-associated dose deposition matrix. The plan optimizing algorithm decomposed entire elements into tandem and ovoid applicators, which were governed by different constraints adaptive to specified plan objectives. The integrated framework was compared against conventional ICBT, and IMBT with tandem only for three patients with asymmetric dose distributions. Integrated IMBT framework resulted in the most optimal plans. Including fluence-modulation by rotating-shield outperformed conventional ICBT in dose sparing to critical organs. Adopting ovoid applicators to the optimization yielded more conformal dose distribution around inferior, laterally expanded region of target volume. The resulting plans reduced D5cc and D2cc by 30.9% and 27.8% for critical organs over conventional ICBT, and by 20.6% and 21.5% for target volume over IMBT with tandem only.

Metal stent for the ureteral stricture after surgery and/or radiation treatment for malignancy.

BACKGROUND: To assess the efficacy and safety of self-expanding metal ureteral stent for the stricture following surgery and/or radiation for malignancy. METHODS: We performed 36 metal ureteral stent insertion procedures (32 patients) between May 2019 and June 2020. The main inclusion criterion was the patients with ureteral stricture due to surgery and/or radiation treatment for malignancy. The diagnosis of stricture was ascertained by history and radiographic imaging. The etiologies underlying the strictures were: surgery and/or radiation therapy for cervical and rectal cancer, surgery for ovarian cancer. The primary outcome was the stent patency rate, and the secondary outcomes were the postoperative complications and glomerular filtration rate (GFR). Stent patency was defined as stent in situ without evident migration, unanticipated stent exchange or recurrent ureteral obstruction. Cost analysis was calculated from stent cost, anesthesia cost and operating room fee. RESULTS: The pre-metallic stent GFR was 22.53 ± 6.55 mL/min/1.73 m2. Eight patients were on double-J stents before insertion of metallic stents. The total annual cost of per patient in our study was $10,600.2 US dollars (range $9394.4-$33,527.4 US dollars). During a median follow-up time of 16 months (range 8-21 months), 27 cases (31 sides, 84%) remained stent patency. Twelve patients died from their primary malignancy carrying a patency stent. Stent migration was observed in 4 patients within 10 months after insertion. Ectopic stents were endoscopically removed and replaced successfully. Three stents were occluded, and no encrustation was seen in our study. Three and four patients had postoperative fever and gross hematuria, respectively. Infection was observed in 2 cases, mandating antibiotics therapy. In addition, postoperative volume of hydronephrosis postoperatively was significantly reduced compared with preoperation (54.18 ± 15.42 vs 23.92 ± 8.3, P = 0.019). However, no statistically significant differences regarding GFR, creatinine levels, blood urea nitrogen and hemoglobin existed between preoperation and last follow-up. CONCLUSIONS: The current study demonstrated that metal ureteral stent is effective and safe in the treatment of stricture following surgery and/or radiation therapy for malignant cancer. Patients hydronephrosis could be improved by the stent placement.

The Cost of Locally Advanced Cervical Cancer in Thailand: an Empirical Study for Economic Analysis.

OBJECTIVE: To evaluate cost of illness of locally advanced cervical cancer patients from societal perspective in three scenarios including completely cured without severe late side effects (S1), completely cured with late grade 3-4 gastrointestinal side effects (S2.1) or genitourinary side effects (S2.2), and disease recurrence and death (S3). METHODS:  The incidence-based approach was conducted. The cost was calculated for 5-year time horizon starting for the treatment initiation. Direct medical costs were extracted from hospital database. Cost of using two-dimensional technique and three-dimensional conformal radiation therapy were calculated separately. Direct non-medical costs and indirect costs in terms of productivity loss were based on actual expenses from the interview of 194 locally advanced cervical cancer patients from two tertiary hospitals in Bangkok, during June to December 2019. All costs were converted to US dollar in 2019 values. RESULTS: For 5 years, cost of illness per patient for using two-dimensional technique and three-dimensional conformal radiation therapy were US $8,391 and US $10,418 for S1, US $18,018 and US $20,045 for S2.1, US $17,908 and US $19,936 for S2.2, and US $61,076 and US $63,103 for S3, respectively. The economic burden for newly diagnosed locally advanced cervical cancer patients in Thailand in 2018 was approximately US $129 million and US $131 million for using two-dimensional technique and three-dimensional conformal radiation therapy, respectively. Cost from S3 accounted for 70% of all total cost. Premature death was the most important cost driver of cost of illness accounted for 64 % of the total cost estimates. CONCLUSIONS: Cost of illness of locally advanced cervical cancer patients produced significant economic burden from societal perspective. Disease recurrence and early death from cancer was the most influential cause of this burden.

Initial analysis of the dosimetric benefit and clinical resource cost of CBCT-based online adaptive radiotherapy for patients with cancers of the cervix or rectum.

PURPOSE: This provides a benchmark of dosimetric benefit and clinical cost of cone-beam CT-based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients. METHODS: An emulator of a CBCT-based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans. To measure clinical resource cost, the six phases of the workflow were timed. To evaluate the dosimetric benefit, changes in dosimetric values were assessed. These included minimum dose (Dmin) and volume receiving 95% of prescription (V95%) for the planning target volume (PTV) and the clinical target volume (CTV), and maximum 2 cc's (D2cc) of the bladder, bowel, rectum, and sigmoid colon. RESULTS: The average duration of the workflow was 24.4 and 9.2 min for cervical and rectal cancer patients, respectively. A large proportion of time was dedicated to editing target contours (13.1 and 2.7 min, respectively). For cervical cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction 0.25 and 0.25 Gy, respectively. The replan changed the V95% by 9.2 and 7.9%. The D2cc to the bladder, bowel, rectum, and sigmoid colon for each fraction changed -0.02, -0.08, -0.07, and -0.04 Gy, respectively. For rectal cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction of 0.20 and 0.24 Gy, respectively. The replan changed the V95% by 4.1 and 1.5%. The D2cc to the bladder and bowel for each fraction changed 0.02 and -0.02 Gy, respectively. CONCLUSIONS: Dosimetric benefits can be achieved with CBCT-based online ART that is amenable to conventional appointment slots. The clinical significance of these benefits remains to be determined. Managing contours was the primary factor affecting the total duration and is imperative for safe and effective adaptive radiotherapy.

Development and performance assessment of an advanced Lucas-Kanade algorithm for dose mapping of cervical cancer external radiotherapy and brachytherapy plans.

PURPOSE: The aim of this study was to verify the possibility of summing the dose distributions of combined radiotherapeutic treatment of cervical cancer using the extended Lucas-Kanade algorithm for deformable image registration. MATERIALS AND METHODS: First, a deformable registration of planning computed tomography images for the external radiotherapy and brachytherapy treatment of 10 patients with different parameter settings of the Lucas-Kanade algorithm was performed. By evaluating the registered data using landmarks distance, root mean square error of Hounsfield units and 2D gamma analysis, the optimal parameter values were found. Next, with another group of 10 patients, the accuracy of the dose mapping of the optimized Lucas-Kanade algorithm was assessed and compared with Horn-Schunck and modified Demons algorithms using dose differences at landmarks. RESULTS: The best results of the Lucas-Kanade deformable registration were achieved for two pyramid levels in combination with a window size of 3 voxels. With this registration setting, the average landmarks distance was 2.35 mm, the RMSE was the smallest and the average gamma score reached a value of 86.7%. The mean dose difference at the landmarks after mapping the external radiotherapy and brachytherapy dose distributions was 1.33 Gy. A statistically significant difference was observed on comparing the Lucas-Kanade method with the Horn-Schunck and Demons algorithms, where after the deformable registration, the average difference in dose was 1.60 Gy (P-value: 0.0055) and 1.69 Gy (P-value: 0.0012), respectively. CONCLUSION: Lucas-Kanade deformable registration can lead to a more accurate model of dose accumulation and provide a more realistic idea of the dose distribution.