High-risk Clinical Target Volume D90 Research Articles

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Dosimetric Analysis of Computed Tomography-Based Brachytherapy Planning in Carcinoma Cervix

Background The standard of care for locally advanced cervical cancer is concurrent chemoradiation followed by intracavitary brachytherapy (BT). BT forms an integral part of management as it improves local control and overall survival. In recent times, image-guided BT (IGBT) has been recommended as the standard of care. Computed tomography (CT) scan-based BT is a cost-effective and easily available modality for IGBT. The aim of the study was to do a dosimetric analysis of CT scan-based BT for patients with cervical cancer. Methods This was a retrospective study and included patients with cervical cancer treated with radical chemoradiation followed by BT. CT scan was done before every fraction after applicator placement, and CT-based planning was done for all fractions. Clinical details were abstracted from the case records, and dosimetric details were collected from the treatment planning systems. Total equivalent dose in 2 Gy per fraction (EQD2) was calculated for external beam radiation therapy and BT target volumes and organs at risk (OARs). Results This study included 50 patients. The mean age was 45 years. The majority of the cases were stage III. The mean high-risk clinical target volume (HRCTV) for the 1st, 2nd, and 3rd fraction was 53.1, 52.1, and 51.3 mL, respectively. Mean D90 HRCTV (dose received by 90% of the HRCTV) dose was 81.4 Gy (EQD2 10 Gy) and D2cc was 75.8 Gy (EQD2 3 Gy) for the rectum and sigmoid and 86.2 Gy (EQD2 3 Gy) for the bladder. Conclusion CT-based BT is a reasonable option in high-volume and low-resource settings where the availability of magnetic resonance imaging is limited. CT-based BT at every fraction can ensure proper applicator placement and aid in optimizing the dose to the target volumes and OARs.

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.

Clinical outcome after high dose rate intracavitary brachytherapy with traditional point 'A' dose prescription in locally advanced carcinoma of uterine cervix: dosimetric analysis from the perspective of computed tomography imaging-based 3-dimensional treatment planning.

To analyze tumour response and toxicity with respect to cumulative radiotherapy dose to target and organs at risk (OARs) with computed tomography (CT)-based image guided adaptive brachytherapy planning for locally advanced carcinoma cervix. Patients were treated with two-dimensional concurrent chemoradiotherapy to whole pelvis followed by intracavitary brachytherapy (ICBT) with dose prescription to point 'A'. CT image-based delineation of high-risk clinical target volume (HR-CTV), urinary bladder, rectum and sigmoid colon was done with generation of dose-volume histogram (DVH) data and optimization of doses to target and OARs. Follow up assessments were done for response of disease and toxicity with generation of data for statistical analysis. One hundred thirty-six patients were enrolled in the study. Delineated volume of HR-CTV ranged from 20.9 to 37.1 mL, with median value of 30.2 mL. The equivalent dose in 2 Gy per fraction (EQD2) for point 'A' ranged from 71.31 to 79.75 Gy with median value of 75.1 Gy and EQD2 HR-CTV D90 ranged from 71.9 to 89.7 Gy with median value of 85.1 Gy. 69.2% of patients showed complete response and after median follow-up of 25 months, 50 patients remained disease free, of whom, 74.0% had received ≥85 Gy to HR-CTV D90 versus 26.0% receiving <85 Gy to HR-CTV D90. s Amidst the unavailability of magnetic resonance imaging facilities in low middle income countries, incorporation of CT-image based treatment planning into routine practice for ICBT provides the scope to delineate volumes of target and OARs and to generate DVH data, which can prove to be a better surrogate for disease response and toxicity.

Single Institute Experience with MRI-Guided Adaptive Brachytherapy for Locally Advanced Cervix Cancer: Long Term Outcomes and Toxicity Analysis

We report over 10 years' experience of MRI-guided adaptive brachytherapy (MRIGABT) in locally advanced cervix cancer (LACC). A total of 162 patients with LACC FIGO stage IB-IVB were treated at our institute between 2010 and 2020. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m², 5 cycles, 1 day per cycle, 45-50.4 Gy external beam radiotherapy (EBRT) in 1·8-2 Gy fractions, followed by MRIGABT. Target volume definition and dose reporting for MRIGABT was according to GEC-ESTRO recommendations. MRIGABT dose prescription was according to our institutional practice. Overall survival (OS) and disease-free survival (DFS) were the primary endpoints. Kaplan-Meier estimates were calculated for OS and DFS at 2, 5 and 10-years. Organ-specific late toxicity grade ≥3 (≥G3) (CTCAEv5.0) was reported, alongside rates of bowel fistula, stricture, and perforation. Using logistic regression, we explored the relationship between EQD2 D2cc bladder and ≥G3 genitourinary (GU) toxicity. We compared patient proportions developing ≥ G3 GU toxicity in those who received EQD2 ≥85 Gy versus <85 Gy. We examined the following predictors of ≥G3 gastrointestinal (GI) toxicity: EQD2 dose (≥65 Gy versus <65 Gy), pre-existing bowel conditions, nodal boost, and extended field EBRT. Median follow up was 4.7 years (IQR 3.3-7.1 years). Median EBRT dose was 50.4 Gy (IQR 50.4-50.4 Gy); 91% received chemotherapy. Median high-risk clinical target volume (HRCTV) was 23.6 cm3 (IQR 16.6-31.3 cm3). Median doses were as follows; D90 HRCTV 88.9 Gy EQD210 (IQR 84.1-91.3 Gy), median D2cc bladder 81.6 (IQR 76.9-85.7 Gy), rectum 62.2 (IQR 57.9-65.3 Gy), sigmoid 67.4 (IQR 60.8-71.1 Gy), and bowel 55 (IQR 49.9-63.2 Gy), (all EQD23). The 2, 5 and-10-year OS were 98%, 80% and 75%. The 2, 5 and 10-year DFS were 98%, 75% and 60%. Late toxicity ≥G3 was 9% GU, 6% GI and 3% vaginal. There was a significant relationship between EQD2 and ≥G3 GU toxicity (OR: 1.11, 95% CI: 1.01-1.25; P = 0.04). When comparing those who received EQD2≥ 85Gy versus <85Gy, higher doses were associated with a greater proportion of ≥G3 GU toxicity (13% vs 6%). No significant predictors of ≥ G3 GI toxicity were observed. We observed excellent LC and OS. A significant relationship was found between EQD2 >85 Gy and bladder toxicity, although ≥G3 toxicity was low. We did not identify predictors of bowel toxicity. New predictors of bowel toxicity are required. Mean EBRT dose, D1.0 cc rectum, sigmoid and bowel are being investigated further.

Attention-Gated Deep-Learning–Based Automatic Digitization of Interstitial Needles in High-Dose-Rate Brachytherapy for Cervical Cancer

Deep learning can be used to automatically digitize interstitial needles in high-dose-rate (HDR) brachytherapy for patients with cervical cancer. The aim of this study was to design a novel attention-gated deep-learning model, which may further improve the accuracy of and better differentiate needles. Seventeen patients with cervical cancer with 56 computed tomography-based interstitial HDR brachytherapy plans from the local hospital were retrospectively chosen with the local institutional review board's approval. Among them, 50 plans were randomly selected as the training set and the rest as the validation set. Spatial and channel attention gates (AGs) were added to 3-dimensional convolutional neural networks (CNNs) to highlight needle features and suppress irrelevant regions; this was supposed to facilitate convergence and improve accuracy of automatic needle digitization. Subsequently, the automatically digitized needles were exported to the Oncentra treatment planning system (Elekta Solutions AB, Stockholm, Sweden) for dose evaluation. The geometric and dosimetric accuracy of automatic needle digitization was compared among 3 methods: (1) clinically approved plans with manual needle digitization (ground truth); (2) the conventional deep-learning (CNN) method; and (3) the attention-added deep-learning (CNN+AG) method, in terms of the Dice similarity coefficient (DSC), tip and shaft positioning errors, dose distribution in the high-risk clinical target volume (HR-CTV), organs at risk, and so on. The attention-gated CNN model was superior to CNN without AGs, with a greater DSC (approximately 94% for CNN+AG vs 89% for CNN). The needle tip and shaft errors of the CNN+AG method (1.1 mm and 1.8 mm, respectively) were also much smaller than those of the CNN method (2.0 mm and 3.3 mm, respectively). Finally, the dose difference for the HR-CTV D90 using the CNN+AG method was much more accurate than that using CNN (0.4% and 1.7%, respectively). The attention-added deep-learning model was successfully implemented for automatic needle digitization in HDR brachytherapy, with clinically acceptable geometric and dosimetric accuracy. Compared with conventional deep-learning neural networks, attention-gated deep learning may have superior performance and great clinical potential.

Retrospective analysis of local recurrence pattern by computed tomography image-guided intracavitary and interstitial brachytherapy for locally advanced cervical cancer in a single Japanese institution

PURPOSEThe purpose of this study was to investigate the treatment results with focus on local control (LC) by computed tomography (CT)-guided intracavity brachytherapy and interstitial brachytherapy (ICBT/ISBT) for locally advanced cervical cancer (LACC). METHODS AND MATERIALSPatients with LACC undergoing ICBT/ISBT at least once in our institution between January 2017 and June 2019 were analyzed retrospectively. The primary endpoint was local control (LC), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and late toxicities. Differences between patient subgroups for prognostic factors in LC, PFS, and OS were analyzed using the log-rank test. The recurrence patterns of LC were also investigated. RESULTSForty-four patients were included in the present study. The median high-risk clinical target volume (HR-CTV) at the initial brachytherapy was 48.2 cc. The median total dose of HR-CTV D90 (EQD2) was 70.7 Gy. The median followup period was 39.4 months. The 3-year LC, PFS and OS rates in all patients were 88.2%, 56.6%, and 65.4% (95% CI 50.3–78.0%), respectively. Corpus invasion and large HR-CTV (70 cc or more) were significant prognostic factors in LC, PFS, and OS. Marginal recurrences at the fundus of the uterus were detected in 3 of 5 patients in whom local recurrence was observed. Late toxicities of Grade 3 or higher were detected in 3 patients (6.8%). CONCLUSIONSFavorable LC was achieved by performing CT-guided ICBT/ISBT for LACC. The brachytherapy strategy for patients with corpus invasion or large HR-CTV may need to be reconsidered.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. The study included 167 patients (T1+2=108, T3+4=59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6months (interquartile range, 20-43.2). The maximum rectal D2 (75Gy)/bladder D2 (90Gy) constraints were deviated by 6%/10% and 10%/5% for T1+2 and T3+4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1+2 and 10%/2% for T3+4. The 2-year local progression-free survival was 89% for T1+2 and 82% for T3+4. For T1+2, the 2-year local progression-free survival for the high-risk clinical target volume D90≥68Gy (indicated by receiver operating characteristic analysis; area under the curve=0.711) was 92% versus 67% for <68Gy (log-rank; P=0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P=0.0006). For T3+4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82cm3 (area under the curve=0.67) and 43% for ≥82cm3 (P=0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P=0.0024). Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1+2 disease.

Dosimetric impact of applicator displacement on three-dimensional image-guided high-dose-rate brachytherapy treatments for cervical cancer.

To determine the dosimetric impact of brachytherapy applicator displacement during intracavitary (IC) and combined intracavitary/interstitial (IC/IS) high-dose-rate brachytherapy in the treatment of cervical cancer. Data from 27 consecutively treated patients undergoing IC or IC/IS high-dose-rate brachytherapy with tandem and ovoid-based applicators at a single academic medical center were analyzed. Virtual applicator displacements (a single shift of whole applicator with tandem/ovoid/associated needles) of 0 (clinical position), 2, 5, 7, and 10 mm in the inferior direction were modeled on treatment planning CT or MRI scans, with maintaining the same dwell times. Radiation dose to target volumes (D90 of high-risk clinical target volume) and organs at risk (OARs) (D0.1cc, D1cc, and D2cc of bladder, rectum, and sigmoid) were calculated for each virtual applicator shift, and significance of displacements was assessed using general linear model and Kruskal-Wallis test. Mean dose to high-risk clinical target volume (HR-CTV) D90 was 95.7%, 88.9%, 84.6%, and 77.1% of the prescribed dose in clinical position with displacements of 2, 5, 7, and 10 mm, respectively. Rectal D2cc significantly increased by 28% and 44% at displacement of 7 mm and 10 mm, respectively. IC/IS cases showed relatively greater dosimetric differences than IC cases, with HR-CTV D90 doses of 94.4%, 85.8%, 80.4%, and 72.4% at virtual displacements of 2, 5, 7, and 10 mm, respectively. Applicator displacements of 5 mm or greater result in statistically significant and clinically meaningful decreases in radiation dose to HR-CTV during 3-dimensional high-dose-rate brachytherapy treatment planning, with corresponding increase in radiation dose to the rectum. IC/IS applicator displacements lead to relatively greater differences than those of IC applicators.

Hydrogel spacer injection to the meso-sigmoid to protect the sigmoid colon in cervical cancer brachytherapy: A technical report.

The use of a hydrogel spacer inserted into recto-vaginal fossa is a valuable strategy to mitigate radiation exposure to the rectum during radiation therapy for female pelvic malignancies. However, when the sigmoid colon is in proximity to the cervix, radiation exposure to the sigmoid colon cannot be adequately mitigated with a hydrogel spacer injected into the recto-vaginal fossa. Here, we presented a case, in which a hydrogel spacer was injected into the meso-sigmoid to protect the sigmoid colon. A 73-year-old female diagnosed with T3b stage IIIC2r uterine cervical cancer (FIGO 2018) underwent high-dose-rate interstitial brachytherapy consisting of 24 Gy in 4 fractions, following concurrent chemoradiotherapy with external beam radiation therapy of 50 Gy in 25 fractions of whole pelvic radiation therapy. In the initial brachytherapy, the sigmoid colon was in close contact with the uterine cervix. In the second brachytherapy, attempts to create a space between the sigmoid colon and uterine cervix using injected artificial ascites were unsuccessful due to rapid absorption of fluid. In the third and fourth brachytherapy fractions, 5 mL of hydrogel was injected into the meso-sigmoid through a pouch of Douglas under trans-rectal ultrasonography guidance. Dose ratio of sigmoid colon D2cc and high-risk clinical target volume (HR-CTV) D90 of each brachytherapy were evaluated. Dose ratio of the sigmoid colon D2cc to HR-CTV D90 was 1.03, 0.43, 0.56, and 0.47 in each respective brachytherapy session, indicating dose escalation to HR-CTV whilst achieving acceptable sigmoid dose with hydrogel spacer injected into the meso-sigmoid. The dose ratio of the sigmoid colon to HR-CTV D90 was decreased by introducing a hydrogel spacer into the meso-sigmoid. In cases where the sigmoid colon is in proximity to the cervical tumor, this novel technique can be considered to achieve better clinical outcomes.

Dosimetric comparison of rectal dose-reductive techniques in intra-cavitary brachytherapy for cervical cancer: A retrospective analysis.

Rectal complications in radiotherapy for cervical cancer can highly affect quality of life and correlate with rectal dose. Vaginal gauze packing (VP) and rectal retraction (RR) are widely used for rectal dose reduction in high-dose-rate brachytherapy. We aimed to perform a dosimetric comparison of these two methods for three-dimensional image-guided adaptive brachytherapy. We retrospectively examined 50 patients with cervical cancer treated with definitive radiotherapy, including intra-cavitary brachytherapy, performed with VP and RR. We extracted two fractions for each patient: one fraction with VP and the next fraction with RR, and then compared dose-volume parameters. In total, 50 fractions each were analyzed in VP and RR groups. Dose to 90% (D90) of high-risk clinical target volume (HR-CTV), and minimum dose to most exposed 2.0 cm3 of other organs at risk (D2cm3) for the rectum and bladder were determined from planning computed tomography. There were no significant differences between VP and RR in D90 of HR-CTV (mean: 7.479 Gy and 7.652 Gy, respectively, p = 0.172). The D2cm3 values for the rectum (mean: 4.234 Gy vs. 4.627 Gy, p = 0.008) and bladder (mean: 5.959 Gy vs. 6.690 Gy, p < 0.001) were significantly lower with VP compared with RR. VP reduced the dose to the rectum and bladder when compared with RR without impairing the dose to CTV.

Trans-rectal ultrasound-guided hybrid intra-cavitary and interstitial brachytherapy in carcinoma cervix: A feasibility study from a tertiary cancer center in India.

To report the feasibility of performing hybrid intra-cavitary and interstitial (IC/IS) brachytherapy in patients with carcinoma cervix under trans-rectal ultrasound (TRUS) guidance. All patients who received an external beam radiotherapy (EBRT) dose of 50 Gy in 25 fractions with weekly chemotherapy, followed by a brachytherapy boost (21 Gy in 3 fractions) were prospectively included for analysis. IC/IS brachytherapy was performed using Fletcher style tandem and ovoid applicator with interstitial component under TRUS guidance. Parameters of implant quality analyzed included ability to insert tandem, ratio of needles loaded to the number of needles inserted, and incidence of uterine or organ at risk (OARs) perforation. Dosimetric parameters evaluated were dose to point A*, TRAK, D90 high-risk clinical target volume (HR-CTV), and D2cc to OARs (bladder, rectum, and sigmoid). Width and thickness of the target was compared between TRUS (TRUSw and TRUSt) and MRI (MRIw and MRIt). Twenty carcinoma cervix patients treated with IC/IS brachytherapy were included for analysis. The mean HR-CTV volume was 36 cc. The median number of needles used were 6 (range, 2-10 needles). None of the patients had uterine perforation. Two patients had bowel and bladder perforation. The mean D90 HR-CTV and D98 HR-CTV were 87.3 Gy and 82 Gy EQD2, respectively. The mean D2cc to the bladder, rectum, and sigmoid were 80 Gy, 70 Gy, and 64 Gy EQD2, respectively. The mean dose to point A* was 70.4 Gy EQD2. The mean TRAK was 0.40. The mean TRUSw (±SD) and MRIw (±SD) were 4.58 cm (±0.44) and 4.49 cm (±0.50), respectively. The mean TRUSt (±SD) and MRIt (±SD) were 2.7 cm (±0.59) and 2.62 cm (±0.59), respectively. On statistical analysis, there was a significant correlation between TRUSw and MRIw (r = 0.93), and TRUSt and MRIt (r = 0.98). TRUS-guided IC/IS brachytherapy is feasible and provides adequate coverage of the target, with acceptable doses to OARs.

Clinical outcomes of single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy for locally advanced cervical cancer: A multi-institution initial experience.

The aim of the study was to evaluate the safety and clinical outcomes of single application multi-fractionated computed tomography (CT)-guided interstitial high-dose-rate brachytherapy given in four fractions in locally advanced cervical cancer. Patients with locally advanced cervical cancer stage IIB-IVA treated definitively with external radiation ± weekly cisplatin, followed by single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy in four fractions were included. Dosimetry data, clinical response, and toxicity records were reviewed. Between January 2018 and December 2022, twenty-two patients were included. Clinical stage distribution was as follows: IIB - 13.6%, IIIB - 27.3%, IIIC - 22.7%, and IVA - 36.4%. Mean high-risk clinical target volume (HR-CTV) was 66.19 ±32.69 cm3, and HR-CTV D90 dose was 86.8 ±1.7 Gy. 2 cc doses to bladder, rectum, and sigmoid were 84.6 ±2.8 Gy, 71.5 ±2.4 Gy, and 65.6 ±4.0 Gy, respectively. Mean overall treatment time was 66 ±21 days. With a median follow-up of 11.5 months (range, 5-44 months), median survival and local control were not achieved. One-year local control rate, one-year progression-free survival, and one-year overall survival were 82%, 66%, and 78%, respectively. Univariate analysis showed overall treatment time to be the only variable associated with all oncologic outcomes. For acute toxicity, grade 3 toxicity in four patients and grade 4 toxicity of infection in one patient were observed. For late toxicity, grade 3 gastrointestinal toxicity was noted in two patients. Initial results suggest that single application multi-fractionated CT-guided interstitial brachytherapy given in four fractions in locally advanced cervical cancer seems to be feasible and safe, but additional evidence is needed to generate more validated conclusions.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator-guided intensity modulated radiotherapy boost in patients with bulky cervical tumour.

To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). A retrospective cohort study. Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China. Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited. This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6and 5Gy per fraction for five fractions, respectively. Mean HR-CTV was 65.8 ± 23.6ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6Gy and 78.1 ± 2.5Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3and 56.7 ± 8.7Gy, respectively. Median follow-up was 85 months (47.9-124.2months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

GSOR10 Presentation Time: 9:45 AM: Positron Emission Tomography (PET) versus Computed Tomography (CT)-Guided Intracavitary Brachytherapy for Locally Advanced Cervical Cancer: A Randomised Study

<h3>Purpose</h3> This study compared early clinical outcomes in locally advanced cervical cancer (LACC) treated with PET-CT guided intracavitary brachytherapy (ICBT) versus 3D CT guided ICBT after external beam radiation therapy (EBRT). <h3>Materials and Methods</h3> From September 2019 to April 2021, 50 patients with newly diagnosed LACC (FIGO stage IIB to IIIB) who received EBRT (50.4Gy in 28 fractions over 5.5 weeks) with concurrent weekly chemotherapy were randomized into two arms: PET/CT- guided ICBT arm (25 patients) and CT- guided ICBT arm (25 patients). High-risk clinical target volume (HRCTV) in PET-CT arm included cervix along with FDG avid lesion and in CT arm included cervix along with residual disease based on CT scan findings. The prescribed dose of ICRT was 7.0 Gy X 3 fractions (once a week fraction). Rectum, bladder, and sigmoid colon were contoured as organs at risk in both arms. Local control, overall survival, and dosimetry comparison between two arms were evaluated. Common Terminology Criteria for Adverse Events v.4.03 (CTCAE v4.03) was used for reporting early toxicity. <h3>Results</h3> Clinical characteristics like age, stage etc. were comparable in the two arms. The 2- year local control rate was 79.1% in PET-CT arm and 72.7% in CT arm (p-value, 0.3). The 2-year overall survival was 89% in CT arm and 82.9% in PET-CT arm (p-value, 0.6). The mean dose to HRCTV D90 and HRCTV D95 in PET CT arm was 87.7Gy (s=6.1Gy) and 83.04Gy (s=5.5Gy) and in CT arm was 85.6Gy (s=6.4Gy) and 80.6Gy (s=5.7Gy) (p-value, 0.13).The mean dose to bladder, rectum and sigmoid colon in PET-CT arm were 80.3Gy (s=8.2Gy), 70Gy (s=6.1Gy) and 66.2Gy (s=7.4Gy) and in CT arm were 79 Gy (s=6.9Gy), 70.2Gy (s=7.2Gy) and 64.9Gy (s=6.3Gy), (p-value:0.58, 0.88 and 0.55). No Grade III/IV OAR toxicity were reported in both arms. <h3>Conclusion</h3> Though the limited sample size, the results of our randomized study show that PET-CT guided ICBT is feasible in patients with LACC. The clinical outcome (overall survival, local control, and OAR toxicity) and dosimetry parameters were comparable in both arms. Based on marginally better local control in the PET-CT arm, though not statistically significant, we suggest further studies with a larger sample size to evaluate the role of PET-CT in LACC.

Outcomes of 3D MRI Based HDR Brachytherapy with Hybrid Multichannel Vaginal Cylinder Applicator and Freehand Needles for Treatment of Vaginal Disease

<h3>Purpose/Objective(s)</h3> Multichannel vaginal cylinder (MCVC) is unable to cover residual vaginal cancer >7 mm thick or with supra-vaginal extension. Freehand needles inserted directly into areas of disease can extend isodose lines to allow for better coverage of disease if clinically indicated. We report outcomes of use of MCVC with freehand needles at our institution. <h3>Materials/Methods</h3> All patients with malignancies involving vagina treated from 2014-2021 with HDR BT at our institution with MCVC with freehand needles were identified. Clinical characteristics including primary malignancy, initial stage, date of diagnosis and recurrence (if applicable), prior RT, use of EBRT, and BT dose and fractionation were collected. Number of freehand needles used per fraction, 3D imaging used for planning, high-risk clinical target volume (HR-CTV) at each fraction, dose to 2cc (D2cc) of organs at risk, and HR-CTV D90 were recorded. Initial response based on examination and imaging and overall local control outcomes were recorded. Local failure was defined as time to recurrence either within HR-CTV or marginal failure, calculated from date of last BT fraction, with censorship at date of last follow-up. Local control was analyzed via Kaplan-Meier method. <h3>Results</h3> 33 patients were identified with median follow-up 1.9 years (IQR 1.0-2.9 years). 19 patients (57.6%) had primary endometrial cancer with vaginal recurrence/disease. Remaining patients had primary vaginal cancer or involvement secondary to other primaries. 8 patients had recurrent disease after previous course of RT. 24 patients received EBRT with median dose of 45 Gy in 25 fractions, with remaining patients treated with BT alone. BT prescription dose ranged from 20-36 Gy in 3-7 fractions, with a total of 168 BT fractions delivered. Median number of freehand needles utilized was 3, with freehand needles utilized in 157/168 total fractions. MRI-based plan was done for at least 1 fraction in 30 patients (90.9%). Median HR-CTV at time of BT was 19.7cc. Median D2cc to the bladder, rectum, and sigmoid were 56.4 Gy, 55.7 Gy, and 45.4 Gy, respectively. Median D90 to the HR-CTV for pts treated with EBRT plus BT was 76.7 Gy and for BT alone was 48.8 Gy. 29 patients (87.9%) had complete local response to BT on initial examination and/or follow-up imaging. 1 and 2-year local control rates for those who did not have prior RT was 89.5% and 89.5%, respectively. 1 and 2-year local control rates for those who had previous RT was 58.3% and 29.2%, respectively. 1 patient had vaginal laceration requiring surgical repair and 1 patient with disease progression developed small bowel obstruction 1 month after BT, with no additional acute grade 3+ toxicities identified. <h3>Conclusion</h3> Our approach with MCVC plus freehand needles with MRI-based planning was feasible and safe. Initial local response is excellent, with acceptable local control rates and low rate of serious acute toxicities. Multi-institutional experiences are needed to further validate this approach for treatment of vaginal disease.

A feasibility study of a modified treatment strategy combined external beam radiation therapy and brachytherapy for cervical cancer.

PurposeTo evaluate the feasibility of a modified treatment strategy combined external beam radiation therapy (EBRT) and brachytherapy (BT) for cervical cancer through a dosimetry analysis.Material and methodsThis study retrospectively selected 12 cervical cancer patients treated with the conventional treatment strategy, which consisted of 45─50 Gy/25 fractions of EBRT using volumetric‐modulated arc therapy (VMAT) and image‐guided BT with a fraction dose of 5─7 Gy. The modified treatment strategy decreased the central EBRT dose while increasing the number of BT fractions. New target volumes were additionally contoured, and new VMAT EBRT plans were generated for the modified treatment strategy. The dosimetric parameters for evaluation included the doses to the most irradiated 2 cc (D2cc) of the organs at risk (OARs) and doses to at least 90% (D90) of the gross tumor volume (GTV) and high‐risk clinical target volume (HR‐CTV). The total doses to OARs and targets obtained by adding the equivalent doses in 2 Gy fraction (EQD2) from the EBRT and BT plans were used for quantitative comparison between the modified and conventional treatment strategies.ResultsComparison to the conventional treatment strategy, the modified treatment strategy resulted in a higher bladder D2cc, a slightly lower rectal D2cc and a similar HR‐CTV D90, all with no significant differences (p > 0.05). The GTV D90 of the modified treatment strategy was significantly higher than that of the conventional treatment strategy (p < 0.01).ConclusionThe modified treatment strategy can significantly increase the BT dose while remaining the total doses to the bladder and rectum basically unchanged, demonstrating its feasibility and promising prospect in clinical use.

Clinical Outcomes of MRI-Guided Adaptive Brachytherapy for Each Fraction in Locally Advanced Cervical Cancer: A Single Institution Experience

PurposeThis study aims to evaluate clinical outcomes of MRI-guided adaptive brachytherapy (MR-IGABT) for each brachytherapy fraction in patients with locally advanced cervical cancer (LACC).Methods and MaterialsA retrospective analysis was performed on 97 consecutive patients with LACC treated with 44.0–50.4 Gy external beam radiotherapy (EBRT) ± concurrent platinum-containing chemotherapy followed by 4 × 7 Gy MR-IGABT between September 2014 and April 2019. Intracavitary (IC)/interstitial (IS)/hybrid intracavitary and interstitial (IC/IS) brachytherapy was used in MR-IGABT. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Clinical outcomes including overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), local control (LC), and treatment-related toxicity evaluated by the RTOG criteria were analyzed. Kaplan–Meier and univariable and multivariable Cox regression analyses were used to analyze the prognostic factor.ResultsMedian follow-up was 21.1 months. Median dose to 90% (D90) of the high-risk clinical target volume (HR-CTV) was 91.7 Gy (range 76.7~107.2 Gy). Two-year OS, CSS, PFS, and LC were 83.5%, 84.1%, 71.1%, and 94.8%, respectively. Four patients (4.1%) suffered from grade 3 late gastrointestinal radiation toxicity, and no other grade 3 or greater radiation toxicity occurred. Initial HR-CTV was an independent factor of OS (p = 0.001, HR = 1.018/cm3), PFS (p = 0.012, HR = 1.012/cm3), and LC (p = 0.011, HR = 1.028/cm3). The HR-CTV D90 (p = 0.044, HR = 0.923/Gy) was an independent factor of PFS. Age was an independent factor of LC (p = 0.010, HR = 1.111/year).ConclusionFor patients with LACC, MR-IGABT was effective and safe. It showed favorable LC, OS, and minimal toxicity. Moreover, initial HR-CTV, HR-CTV D90, and age were significant prognostic factors.

Optimizing the IPSA Conditions to Improve the Treatment Plan Quality in Brachytherapy for Cervical Cancer.

Recent prevalent use of three-dimensional image-guided brachytherapy (3D brachytherapy) has dramatically improved the treatment outcomes of cervical cancer. Inverse planning simulated annealing (IPSA) is one of the commonly used algorithms in 3D brachytherapy, but different conditions may affect the treatment plan quality. In this study, we compared HRCTV (high-risk clinical target volume) D90 (dose prescription) and HRCTV D95 D2cc (dose received by 2.0cc) of the rectum, bladder, and sigmoid in 30 patients with cervical cancer under four IPSA conditions. The HRCTV D90 (mean ± SD cGy) was 607.32 ± 37.86, 599.01 ± 23.62, 598.67 ± 13.07, and 596.45 ± 10.94 in four groups, respectively. The HRCTV D95 was 558.19 ± 38.51, 558.17 ± 25.72, 557.03 ± 16.12, and 555.26 ± 12.78, respectively. The sigmoid D2cc was 282.96 ± 44.84, 273.14 ± 60.69, 268.94 ± 62.32, and 292.69 ± 52.44. HRCTV D90, HRCTV D95, and sigmoid D2cc were not statistically different among the four groups (p > 0.05). However, the target fitness in group one, especially at the cervix, was poor. The rectum D2cc was 351.49 ± 32.90, 361.49 ± 28.09, 370.82 ± 24.44, and 375.33 ± 30.90. The rectum D2cc in group one was the lower than that in group three and group four (p < 0.05). The bladder D2cc was 423.59 ± 31.39, 380.75 ± 37.25, 383.27 ± 32.55, and 385.22 ± 25.79. The bladder D2cc in group one was higher than the other groups (p < 0.05). The maximum rectum limit dose (400cGy) is lower than the bladder (500cGy), and HRCTV is a whole in the IPSA algorithm; these result in the insufficiency or even absence of cervix dose that first need to meet in clinics. In conclusion, IPSA condition optimization can improve the quality of treatment plan in 3D brachytherapy and make it closer to clinical practice.

Inter-Fractional Variations in Volume and Radiation Dose to the Organs at Risk, High-Risk Clinical Target Volume and Implication of Image-Guided Adaptive Planning During Intracavitary Brachytherapy of Carcinoma Cervix.

BackgroundGeometrical and anatomical variations occur during the brachytherapy of carcinoma cervix and dose optimization is necessary for every fraction of high‑dose rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the cervix. A single planned treatment is usually delivered for multiple fractions without consideration of inter-fractional applicator positioning variations and organ motion, which may lead to substantial differences between the planned and delivered doses. Aim and objectivesThis study was aimed at evaluating the inter-fractional variation in volume and radiation dose to organs at risk during ICBT for cervical cancer. Furthermore, the doses to high-risk clinical target volume (HRCTV) and the role of adaptive planning in ICBT were assessed.Materials and methodsTwenty-two patients with carcinoma of the cervix Stage IB2-IVA receiving ICBT were enrolled in the study. All the patients were treated with ICBT four fractions in two applications. For the first application, magnetic resonance imaging-based planning was done, and for the next three fractions, computed tomography (CT) scans were done before every treatment fraction. The CT images were contoured and replanned by keeping the First (I) fraction of each application as the reference. Dose-volume histograms (DVH) were generated, and details of D2cc (DVH on a volume of 2cc) of bladder, rectum, and sigmoid colon (organs at risk-OAR) and D90 HRCTV (dose covering 90%) were documented.ResultsIn patients receiving ICBT, variations in OAR D2cc ranged from 1.5 to 2.5Gy for the bladder (p- 0.001), from 2.0 to 3.2Gy (p-0.005) for the rectum and from 1.5 to 3.5Gy for the sigmoid colon (p 0.103). The p-value was significant for D2cc when compared with the OAR volume for the bladder and rectum in both applications, whereas it was not significant for the sigmoid colon. The percentage change in HRCTV coverage was 7% in the first application and by 16% in the second application because of adaptive planning.ConclusionSignificant variations in doses received by D2cc of the bladder and rectum as well as significant improvement in HRCTV coverage between the fractions were observed because of replanning. Hence, image-guided HDR-ICBT should be incorporated with adaptive planning when delivering in multiple fractions.