High-risk Clinical Target Volume Research Articles

Carbon ion radiotherapy for mesonephric adenocarcinoma of the uterine cervix: a case report

BackgroundMesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix.Case presentationWe treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life.ConclusionsThis is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.

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

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

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96±0.02, 0.91±0.02, and 0.83±0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73±0.95, 8.18±4.84, and 2.11±0.50, respectively. The mean HD95% values (mm) were 1.66±1.11, 3.07±0.94, and 1.35±0.55, respectively. The mean IoUs were 0.92±0.04, 0.84±0.03, and 0.71±0.09, respectively. A delineation time<2.35s per structure in the new model was observed, which was available to save clinician time. The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

Monocentric Retrospective Study: Efficacy, Feasibility, and Prognostic Factors of Single-Insertion High-Dose-Rate Brachytherapy With 4 Sessions for Locally Advanced Cervical Cancer

ObjectiveThis study aims to assess the feasibility and efficacy of high-dose-rate (HDR) brachytherapy (BT) administered in a single insertion with four treatment sessions for locally advanced cervical cancer (LACC), and to identify the prognostic factors influencing outcomes. MethodsWe retrospectively analyzed the clinical data of cervical cancer patients with locally advanced disease (International Federation of Gynecology and Obstetrics 2018 (FIGO) IB-IVB), treated at our institution from January 2014 through December 2021. Each patient received definitive radiotherapy with an external irradiation dosage between 45-50.4 Gy along with concurrent chemotherapy (CCRT). HDR-BT (24 Gy) was prescribed to a high-risk clinical target volume (HR-CTV). Results139 patients were included and HDR-BT program could be fully performed in 136 patients (98%). Over a median follow-up duration of 40.5 months, the two-year local control (LC), overall survival (OS), and disease-free survival (DFS) rates stood at 79.4%, 77.7%, and 61.7% respectively, with five-year rates at 78.2%, 61.6%, and 55.7%. Multivariate analysis revealed the primary determinant of LC as the tumor's response to external beam radiotherapy (EBRT) as determined via magnetic resonance imaging (MRI) prior to BT. Parametrial involvement demonstrated a significant multivariate association with DFS (p = 0.04). Regarding OS, parametrial invasion (p = 0.01) and the tumor's response post-chemoradiotherapy (p = 0.02) emerged as significant factors. Regarding chronic toxicities, 18% (25 patients) experienced grade 3 complications. An optimal D2cc (Bowel) threshold of 70 Gy (p = 0.001) was identified to limit chronic digestive complications of grade 3 or higher. ConclusionThe implementation of single-insertion, four-session HDR-BT could be performed in 98% of the patients. It yields favorable LC and OS rates, coupled with tolerable toxicity in patients with LACC. Response to initial chemoradiotherapy evaluated on pre-BT MRI is an important prognostic factor and could help to individualized therapeutic strategies.

Dosimetric and toxicity comparison between Syed-Neblett and Fletcher-Suit-Delclos Tandem and Ovoid applicators in high dose rate cervix cancer brachytherapy

PURPOSETo compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. METHODSA retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTSA total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). CONCLUSIONSSyed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer

INTRODUCTIONThe purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODSThis cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTSThe 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze (“mild/moderate” 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently “excellent/good” with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently “extremely easy” with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSIONThis randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.MethodsClinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden’s J statistic was used to identify a threshold value.ResultsAmong 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR.ConclusionsClinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy

ObjectiveThis study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality.Material and methodsTRUS was utilized during and after applicator insertion, with each needle’s visibility documented through axial images at the high-risk clinical target volume’s largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan.ResultsAnalysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ± 0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and –0.1 ± 1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases.ConclusionReal-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

Design approach and benefits of the 3D-printed vaginal individualized applicator (VIA)

PURPOSEInterstitial gynecologic brachytherapy necessitates precise needle placement, requiring time and expertise. We aimed to simplify interstitial procedures and facilitate optimal needle distribution with individualized vaginal templates to guide interstitial needles. MATERIALS/METHODSWe developed the 3D-printed vaginal individualized applicator (VIA), a cylindrical template containing individualized internal channels that guide interstitial needles to cover the tumor extent. Eight patients underwent VIA only interstitial implants (VIA only), and five intact cervical cases were treated using tandem and customized VIA (VIA + T). Procedure length, number of needles utilized and dosimetric measures were evaluated. RESULTSVIA was successfully designed and used clinically for 24 procedures (8 VIA only, 16 VIA + T). Average procedure needle insertion time reduced from 80.9 min for traditional interstitial to 42.9 min for VIA only, approximately 47% shorter with a similar mean high risk CTV volume (28.3 cc VIA only vs. 32.4 cc) and excellent dosimetry with average CTV V100% (94.3% and 94.4%). VIA + T was particularly useful in patients with small vaginal canals and large tumor size. For the five VIA + T patients average tumor size was 68.0cc (range 26.6–143.5 cc). VIA + T procedures were approximately 20% shorter than hybrid procedures with other applicators with mean length of 20.1 min and an average of 6.8 needles (range 3–12). CONCLUSIONOur novel 3D-printed VIA facilitates gynecologic interstitial brachytherapy by simplifying needle placement, reducing procedure time, and maintaining excellent dosimetry. VIA can be customized for various clinical scenarios, particularly beneficial for large tumors or small vaginal canals.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Effect of Brachytherapy Source Dwell Position on Dose Distribution in Cervical Cancer Therapy

To investigate the effect of different source dwell positions on dose distribution in the treatment of cervical cancer with brachytherapy. Treatment planning data for cervical cancer patients were used. Treatment plans were created at 1 mm intervals, varying up to 5 mm. For intracavitary brachytherapy and intracavitary and interstitial brachytherapy, the following dose parameters were evaluated: 90% high-risk clinical target volume (HR-CTV D90%), rectum 2 cm3 dose (Rectum D2 cc), small intestine 2 cm3 dose (Small D2 cc), sigmoid colon 2 cm3 dose (Sigmoid D2 cc), bladder 2 cm3 dose (Bladder D2 cc), point A dose. In intracavitary brachytherapy, the HR-CTV D90%, Rectum D2 cc, Small D2 cc, and Sigmoid D2 cc doses increased as the source dwell position changed in the direction. On the other hand, the dose of Bladder D2 cc increased when the source position changed in the outward direction. The same trend was observed in the case of intracavitary and interstitial brachytherapy. It was shown that a 1 mm change in the source dwell position can affect the dose by up to 2% or more. The accuracy of the source dwell position is very important and should be checked before using the device.

High-dose-rate brachytherapy in uterine cervix carcinoma: a comparison of dosimetry and clinical outcomes among three fractionation schedules.

To assess the differences among three dose-fractionation schedules of image-guided adaptive brachytherapy (IGABT) in cervical squamous cell carcinoma (CSCC) by comparing the dosimetry and clinical outcomes. Forty-five patients with CSCC who underwent chemoradiotherapy and IGABT were retrospectively enrolled and divided into three groups based on their dose-fractionation schedules of brachytherapy as: Group-5.5 (5.5 Gy × 6 fractions), Group-6.0 (6.0 Gy × 5 fractions), and Group-7.0 (7.0 Gy × 4 fractions). The analyzed dose-volume histogram parameters included D90% and D98% of the high-risk clinical target volume (HR-CTV), D90% and D98% of intermediate-risk clinical target volume (IR-CTV), and D0.1cc and D2cc of the organs-at-risk (OARs, namely the bladder, rectum, sigmoid and small intestine). Furthermore, the therapeutic efficacy and late toxicities were also compared among the three groups. The doses of HR-CTV and IR-CTV in Group-5.5 were found to be the highest among the three groups, followed by those in Group-6.0. Significant differences were found for the doses of HR-CTV between Group-5.5 and the other groups. There were no significant differences in the bladder, sigmoid and small intestine dose among the three groups. However, Group-6.0 yielded the lowest rectum received doses, with a significant difference in D0.1cc being detected between Group-6.0 and Group-5.5. The median follow-up time was 30.08 months [range, 6.57-46.3]. The numbers of patients with complete response in Group-5.5, Group-6.0 and Group-7.0 were 13, 14 and 14, respectively (P > 0.05). In regard to the toxicitiy, the incidence of radiation cystitis and proctitis in Group-6.0 was lower than that in Group-5.5 and Group-7.0 (P > 0.05). The dose-fractionation schedule of 6.0 Gy × 5 fractions provided the most beneficial effects with relatively low OARs doses, suggesting that this dose-fractionation schedule should be prioritized in the clinical application of brachytherapy in cervical cancer.

Brachytherapy in gynecological malignancies at a tertiary care hospital: An analysis.

Brachytherapy plays a crucial role in the standard of care for locally advanced gynecological malignancies. In this report, we present the experience from a tertiary teaching hospital, which is a referral center for image-guided brachytherapy (IGBT) in the management of locally advanced gynecological malignancies. This was a retrospective study of 130 patients referred to our hospital for IGBT after receiving initial external beam radiotherapy in their primary healthcare facilities, from January 2021 till January 2023. CT-based planning was done to delineate high-risk clinical target volume (HR-CTV). Dose of 6-7.5 Gy in 3-4 fractions was prescribed. Overall treatment time (OTT) was calculated, and patients were assessed for clinical response and toxicity after three months. All patients received IGBT using an intra-cavitary or interstitial technique. The D90 HR-CTV mean EQD2 dose was 28.34 ±2.78 Gy. The mean EQD2 dose to 2 cc of the bladder, rectum, and sigmoid was 18.31 ±5.19 Gy, 14.14 ±5.76 Gy, and 17.43 ±4.75 Gy, respectively. The median interval time between the last fraction of external beam radiation therapy (EBRT) and first evaluation in the hospital was 19 (range, 13-28) days (interquartile range [IQR]). The median time between the completion of chemoradiation and brachytherapy procedure was 25 (range, 19-33) days (IQR). The mean overall treatment time (OTT) was 63.5 ±14.7 days. This study highlights the established advantages of image-guided interstitial brachytherapy and associated challenges. To optimize the overall treatment duration, it is imperative to prioritize and update the referral processes for brachytherapy centers.

Effect of model-based dose-calculation algorithms in high dose rate brachytherapy of cervical carcinoma.

Task Group 43 (TG-43) formalism does not consider the tissue and applicator heterogeneities. This study is to compare the effect of model-based dose calculation algorithms, like Advanced Collapsed Cone Engine (ACE), on dose calculation with the TG-43 dose calculation formalism in patients with cervical carcinoma. 20 patients of cervical carcinoma treated with a high dose rate of intracavitary brachytherapy were prospectively studied. The target volume and organs at risk (OARs) were contoured in the Oncentra treatment planning system (Elekta, Veenendaal, The Netherlands). All patients were planned with cobalt-60 (Co-60) and iridium-192 (Ir-192) sources with doses of 21 Gy in 3 fractions. These plans were calculated with TG-43 formalism and a model-based dose calculation algorithm ACE. The dosimetric parameters of TG-43 and ACE-based plans were compared in terms of target coverage and OAR doses. For Co-60-based plans, the percentage differences in the D90 and V100 values for high-risk clinical target volume (HR-CTV) were 0.36 ± 0.43% and 0.17 ± 0.31%, respectively. For the bladder, rectum and sigmoid, the percentage differences for D2cc volumes were -0.50 ± 0.51%, -0.16 ± 0.53% and -0.37 ± 1.21%, respectively. For Ir-192-based plans, the percentage difference in the D90 for HR-CTV was 0.54 ± 0.79%, while V100 was 0.24 ± 0.29%. For the bladder, rectum and sigmoid, the doses to 2cc volume were 0.35 ± 1.06%, 0.99 ± 0.74% and 0.74 ± 1.92%, respectively. No significant differences were found in the dosimetric parameters calculated with ACE and TG-43. The ACE algorithm reduced doses to OARs and targets. However, ACE and TG-43 did not show significant differences in the dosimetric parameters of the target and OARs with both sources.

Dosimetric comparison of intra-cavitary brachytherapy technique with free-hand (intra-cavitary + interstitial) technique in cervical cancer.

The aim of the study was to dosimetrically compare intra-cavitary brachytherapy technique (ICBT) with free-hand (intra-cavitary + interstitial, IC + IS) technique. Twenty seven locally advanced carcinoma cervix patients were included in the study. Patients with more than medial 1/3rd parametrial residual disease without extending upto lateral pelvic wall were included, following external beam radiotherapy (EBRT), in which cobalt-60 high-dose-rate (60Co HDR) brachytherapy source was used. Dose for both plans were 6.5 Gy × 4 fractions, 2 fractions per day, 6 hours apart, over 2 days. Free-hand brachytherapy technique, consisted of placement of central tandem and 2 ovoids along with needles without using template, was applied. Two plans were generated by activating and deactivating the needles, and compared by normalizing to V100. A total of 79 needles were applied. Using paired-t test, dosimetric comparison of both the plans was done. Free-hand plan had a significant higher mean V90 (volume receiving 90% of the dose) of 94.2% compared with 87.22% in ICBT plan (p ≤ 0.0001). Free-hand and ICBT plans presented a mean V100 values of 89.06% and 81.51% (p ≤ 0.0001), respectively, favoring free-hand plan. The mean D90 (dose to 90% volume), D98, and D100 of free-hand plan were 6.28 Gray (Gy), 4.91 Gy, and 3.62 Gy, respectively, but equivalent parameters in ICBT plan were 5.26 Gy, 3.72 Gy, and 2.61 Gy, with p value ≤ 0.0001. In both the plans, D2cc of the bladder, rectum, and sigmoid were 4.59 Gy, 3.98 Gy, 2.77 Gy, and 4.46 Gy, 3.90 Gy, 2.67 Gy, respectively, with no statistical significance. Free-hand brachytherapy (IC + IS) achieves a statistically significant better dose distribution to high-risk clinical target volume (HR-CTV) comparing with ICBT technique with similar dose to organs at risk.

Image-guided high-dose-rate brachytherapy as the method of choice in medically inoperable early-stage endometrial cancer patients

PurposeAbout 3–9% of patients with endometrial cancer are unable to undergo surgery due to medical comorbidities, including morbid obesity, or age-related frailty syndrome. An alternative curative option is irradiation. The aim of this prospective study was to evaluate clinical outcomes of high-dose-rate intracavitary brachytherapy (HDR-ICBT) treatment in such patients. Materials and methodsSeventy-eight patients with FIGO stage I-II endometrial cancer disqualified from surgery were treated with HDR-ICBT with 45–52,5 Gy prescribed to high-risk clinical target volume (HR-CTV) in 5–9 fractions given once a week. All fractions were planned using computed tomography (CT) scans. ResultsThe median follow-up time was 67 months. Median age was 79 years (range: 42–93 years). Median body mass index (BMI) was 39,1 kg/m2 (range: 24,2–68 kg/m2). We observed no statistically significant impact of BMI ≥ 40 on overall survival (OS) or prgression free survival (PFS). The 3- and 5-year OS for the whole population were 69% and 55%, respectively. The impact of high risk features (FIGO II, grade 3 or type 2 cancer) on OS was significant (p = 0,049). The 5-year cumulative incidence of local failure, distant metastases and non-cancer death were 12,9% [95% CI: 5,4%–20,5%], 6,4% [95% CI: 0,9%–11,9%], 33,1% [95% CI: 22,3%–43,9%], respectively. The 5-year risk of cancer and non-cancer death were 9% (95% CI: 3%–16%) and 36% (95% CI: 25%–47%), respectively. We observed G1 vaginal apex stenosis only. ConclusionsCT-guided HDR-ICBT is a feasible and safe management of FIGO stage I endometrial cancer in obese and elderly patients. The survival outcome of the treated group is influenced more by associated comorbidities than by the progression of endometrial cancer.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study

PURPOSETo evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. MATERIAL AND METHODSTwenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D2cc of bladder, rectum, and sigmoid were 80, 70, and 70 Gy, respectively. Equivalent dose in 2-Gy fractions calculations used α/β = 10 Gy for high-risk clinical target volume (CTVHR) D90 and α/β = 3 Gy for organs at risks (OARs). As a planning study, dose distribution rescaling was conducted to deliver as much dose to CTVHR D90 as possible within the dose constraint limitation for OARs when IGABT was performed for four, three, and two fractions in both groups. RESULTSThe median CTVHR D90 was >80 Gy in the non-HGI group and >85 Gy in the HGI group for virtual two and three fractions. Rectum D2cc was significantly lower in the HGI group for three fractions (p < 0.01). CONCLUSIONSIn the HGI group, adequate dose delivery to CTVHR could be achieved with a reduced IGABT fraction number while meeting the dose constraints of OARs.

Phase 2 Clinical Trial of Simultaneous Boost Intensity Modulated Radiation Therapy With 3 Dose Gradients in Patients With Stage I-II Nasal Type Natural Killer/T-Cell Lymphoma: Long-Term Outcomes of Survival and Quality of Life

The aim of this study was to investigate the treatment results and long-term quality of life in patients with early-stage extranodal natural killer/T-cell lymphoma who were prospectively treated with simultaneous boost intensity modulated radiation therapy (SIB-IMRT) with 3 dose gradients. Sixty patients with stage I-II nasal cavity natural killer/T-cell lymphoma (NKTCL) and Waldeyer's ring NKTCL were enrolled in a single-arm, prospective, phase 2 clinical trial from August 2011 to April 2015. All patients were treated with definitive radiation therapy combined with short-course induction chemotherapy. A newly designed SIB-IMRT scheme was uniformly adopted, with 54.6 Gy for the gross tumor volume (GTV) of the primary tumor and GTV of the positive lymph nodes, 50.7 Gy for the high-risk clinical target volume (CTV), and 45.5 Gy for the low-risk CTV, all delivered in 26 daily fractions. Before SIB-IMRT, L-asparaginase-based induction chemotherapy was used in 95.0% (57/60) of patients. With a median follow-up time of 95.8 months, the 5-year locoregional recurrence-free survival, progression-free survival, and overall survival rates were 83.3%, 81.7%, and 88.3%, respectively. Dosimetric analysis in the first 21 patients showed satisfying conformality for planning target volume of GTV, high-risk CTV, and low-risk CTV, while the organs at risk were well protected. The results of long-term quality-of-life investigations in patients without progression were favorable, and nasal discomfort was the most common symptom. No grade 3 or 4 acute or late toxicities were observed. The scheme of target volume delineation and dose setting that we designed has favorable clinical effects with mild side effects in treating patients with stage I-II nasal cavity NKTCL and Waldeyer's ring NKTCL.