CTV D90 Research Articles

Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities

BackgroundThe management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma.MethodsThe study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan–Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5.ResultsDuring a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1–2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1–2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients.Conclusions3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Dosimetric Analysis of Local Failure Outcomes and Vertebral Compression Fracture Risk in Single-Fraction Spine Stereotactic Radiosurgery for Metastatic Sarcoma

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and their inherent radioresistance. We sought to analyze dosimetric parameters impacting local failure and vertebral compression fracture outcomes in a homogenously treated cohort of patients with SSM treated with single-fraction spine stereotactic radiosurgery (SSRS). A retrospective review was conducted on a cohort of patients with SSM treated with definitive SSRS at a single tertiary institution. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to local failure (LF). The log-rank test was utilized to examine group differences. Patients were censored at time of last follow-up or death. Cox proportionate hazards modeling was used to determine hazard ratios (HR) and their respective 95% confidence intervals (CI). A total of 66 patients with 96 lesions underwent SSRS for SSM. Median follow-up was 17 months (IQR 8-28). Median age was 55 years (IQR 41-63). The most common histological subtype was leiomyosarcoma (41%) followed by liposarcoma (9%). 81 lesions received 24 Gy to the GTV, 12 received 18 Gy and 3 received 16 Gy. Median GTV and CTV volume was 13.6cc (IQR 5-27) and 51.6cc (IQR 30-80) respectively. 27% of patients had Bilsky 1b or greater disease. 16 of 96 lesions demonstrated progression representing a crude local failure rate of 17% with median time to failure of 8 months (IQR 5-18). The 1-year actuarial progression free survival (PFS) was 89% with a median PFS of 13 months (IQR 16-63). Median overall survival (OS) was 15 months (IQR 8-28) from SSRS. 8% of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). Every 1 Gy increase in GTV minimum dose (DMin) across the range (5.8-25cc) was associated with a reduced risk of local failure (HR = 0.875 [95% CI 0.787-0.974], p = 0.01). Stratifying thresholds for GTV DMin, a local control benefit was seen as low as 12 Gy and higher (HR = 0.329 [95% CI 0.11-0.97, p = 0.044) with a significantly greater magnitude benefit seen at 14 Gy (HR = 0.267 [95% CI 0.09-0.77, p = 0.014) and above 15 Gy (HR = 0.091 [95% CI 0.03-0.41], p = 0.0018). There were no other queried variables besides GTV Dmin associated with local control including: GTV: volume, mean, Dmax, D90, CTV: volume, Dmin, Dmean, Dmax, or D90. There was an increased risk of VCF with increasing CTV DMean (HR = 2.4 [95% CI 1.4-4.1], p = 0.002) and CTV D90 (HR = 2.2 [95% CI 1.2-4.0], p = 0.01); however, no association with GTV parameters. This study represents one of the most homogenously treated and the largest cohorts of patients with sarcoma spinal metastases treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. Increasing GTV minimum dose is significantly associated with superior local control with no corresponding increased risk of VCF.

Automatic planning for head and neck seed implant brachytherapy based on deep convolutional neural network dose engine.

Seed implant brachytherapy (SIBT) is an effective treatment modality for head and neck (H&N) cancers; however, current clinical planning requires manual setting of needle paths and utilizes inaccurate dose calculation algorithms. This study aims to develop an accurate and efficient deep convolutional neural network dose engine (DCNN-DE) and an automatic SIBT planning method for H&N SIBT. A cohort of 25 H&N patients who received SIBT was utilized to develop and validate the methods. The DCNN-DE was developed based on 3D-unet model. It takes single seed dose distribution from a modified TG-43 method, the CT image and a novel inter-seed shadow map (ISSM) as inputs, and predicts the dose map of accuracy close to the one from Monte Carlo simulations (MCS). The ISSM was proposed to better handle inter-seed attenuation. The accuracy and efficacy of the DCNN-DE were validated by comparing with other methods taking MCS dose as reference. For SIBT planning, a novel strategy inspired by clinical practice was proposed to automatically generate parallel or non-parallel potential needle paths that avoid puncturing bone and critical organs. A heuristic-based optimization method was developed to optimize the seed positions to meet clinical prescription requirements. The proposed planning method was validated by re-planning the 25 cases and comparing with clinical plans. The absolute percentage error in the TG-43 calculation for CTV V100 and D90 was reduced from 5.4% and 13.2% to 0.4% and 1.1% with DCNN-DE, an accuracy improvement of 93% and 92%, respectively. The proposed planning method could automatically obtain a plan in 2.5±1.5 min. The generated plans were judged clinically acceptable with dose distribution comparable with those of the clinical plans. The proposed method can generate clinically acceptable plans quickly with high accuracy in dose evaluation, and thus has a high potential for clinical use in SIBT.

Clinical outcomes using a 3D printed tandem-needle-template and the EMBRACE-II planning aims for image guided adaptive brachytherapy in locally advanced cervical cancer

Background Extensive local disease or narrow vagina may compromise brachytherapy (BT) in patients with cervical cancer. This is the first study to analyze long-term outcomes of using 3D printed vaginal tandem-needle templates (3DP TNT) for transvaginal insertion of needles in parallel (P) or parallel and oblique (P&O) direction to the tandem. Material and methods All patients treated with BT using 3DP TNT from 2015-2020 were included. Decision to use a 3DP TNT and preplanning were made after 4-5 weeks of external beam radiotherapy, based on gynecological examination and MRI with a tandem-ring applicator in situ. The TNT was 3D-printed in house consisting of a circular template with P&O holes for guidance of plastic needles and a shaft fitting the uterine tandem. Thus, the radioactive source was never in direct contact with the 3DP TNT. The TNT was 3D printed in a standard or personalized configuration. Planning aims were based on the Embrace II protocol. Results 101 patients (median age of 63 years) were included: 49 with P needles only and 52 with P&O needles. Personalized TNT was used in 19 patients in the P&O group. Performance status (WHO) was > 0 in 48%. FIGO2018 stage III-IV was present in 77%. T-score at diagnosis and BT was 9.1 and 6.3 respectively, with a significantly higher T-score in the P&O compared to P group. The mean high-risk CTV D90 was 93 Gy with no significant difference between the two groups. Three-year local control rates were 85%, 95%, 75% for the overall, P- and P&O group respectively and 68%, 80% and 56% for cancer specific survival. Grade ≥3 treatment related complications were observed in 10 (10%) patients. Conclusions 3DP TNT for BT in cervical cancer provides successful management of very extensive local disease and/or unfavorable anatomy with the possibility for treatment individualization.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators

PURPOSESurface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALSPlanning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3–5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTSTen patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7–40.6), mean CTV D0.1cc 49.2 Gy (range 45.6–53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0–1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONSSMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

Automated treatment planning framework for brachytherapy of cervical cancer using 3D dose predictions

Objective. To lay the foundation for automated knowledge-based brachytherapy treatment planning using 3D dose estimations, we describe an optimization framework to convert brachytherapy dose distributions directly into dwell times (DTs). Approach. A dose rate kernel was produced by exporting 3D dose for one dwell position from the treatment planning system and normalizing by DT. By translating and rotating this kernel to each dwell position, scaling by DT and summing over all dwell positions, dose was computed (D calc). We used a Python-coded COBYLA optimizer to iteratively determine the DTs that minimize the mean squared error between D calc and reference dose D ref, computed using voxels with D ref 80%–120% of prescription. As validation of the optimization, we showed that the optimizer replicates clinical plans when D ref = clinical dose in 40 patients treated with tandem-and-ovoid (T&O) or tandem-and-ring (T&R) and 0–3 needles. Then we demonstrated automated planning in 10 T&O using D ref = dose predicted from a convolutional neural network developed in past work. Validation and automated plans were compared to clinical plans using mean absolute differences () over all voxels (xn = Dose, N = #voxels) and DTs (xn = DT, N = #dwell positions), mean differences (MD) in organ D 2cc and high-risk CTV D90 over all patients (where positive indicates higher clinical dose), and mean Dice similarity coefficients (DSC) for 100% isodose contours. Main results. Validation plans agreed well with clinical plans (MADdose = 1.1%, MADDT = 4 s or 0.8% of total plan time, D 2cc MD = −0.2% to 0.2% and D90 MD = −0.6%, DSC = 0.99). For automated plans, MADdose = 6.5% and MADDT = 10.3 s (2.1%). The slightly higher clinical metrics in automated plans (D 2cc MD = −3.8% to 1.3% and D90 MD = −5.1%) were due to higher neural network dose predictions. The overall shape of the automated dose distributions were similar to clinical doses (DSC = 0.91). Significance. Automated planning with 3D dose predictions could provide significant time savings and standardize treatment planning across practitioners, regardless of experience.

Radiobiological and dosimetric comparison of 60Co versus 192Ir high-dose-rate intracavitary-interstitial brachytherapy for cervical cancer

BackgroundHigh-dose-rate (HDR) intracavitary-interstitial brachytherapy (IC-ISBT) is an effective treatment for bulky, middle, and advanced cervical cancer. In this study, we compared the differences between 60Co and 192Ir HDR IC-ISBT plans in terms of radiobiological and dosimetric parameters, providing a reference for clinical workers in brachytherapy.MethodsA total of 30 patients with cervical cancer receiving HDR IC-ISBT were included in this study, and IC-ISBT plans for each individual were designed with both 60Co and 192Ir at a prescribed dose of CTV D90 = 6 Gy while keeping the dose to OARs as low as possible. Physical dose and dose–volume parameters of CTV and OARs were extracted from TPS. The EQD2, EUBED, EUD, TCP, and NTCP were calculated using corresponding formulas. The differences between the 60Co and 192Ir IC-ISBT plans were compared using the paired t-test.ResultsIn each patient's 60Co and 192Ir IC-ISBT plan, the average physical dose and EQD2 of 60Co were lower than those of 192Ir, and there were statistically significant differences in D2cc and D1cc for the OARs (p < 0.05); there were statistically significant differences in D0.1 cc for the bladder (p < 0.05) and no significant differences in D0.1 cc for the rectum or intestines (p > 0.05). The EUBED ratio (60Co/192Ir) at the CTV was mostly close to 1 when neither 60Co or 192Ir passed their half-lives or when both passed two half-lives, and the difference between them was not significant; at the OARs, the mean value of 60Co was lower than that of 192Ir. There was no statistical difference between 60Co and 192Ir in the EUD (93.93 versus 93.92 Gy, p > 0.05) and TCP (97.07% versus 97.08%, p > 0.05) of the tumors. The mean NTCP value of 60Co was lower than that of 192Ir.ConclusionsConsidering the CTV and OARs, the dosimetric parameters of 60Co and 192Ir are comparable. Compared with 192Ir, the use of 60Co for HDR IC-ISBT can ensure a similar tumor control probability while providing better protection to the OARs. In addition, 60Co has obvious economic advantages and can be promoted as a good alternative to 192Ir.

PO43 Presentation Time: 4:45 PM: Reduced Duration Intracavitary Brachytherapy in Cervix Malignancies: A Comparative Analysis from Single Institute

<h3>Purpose</h3> The on-going pandemic has impacted the use of anesthesia and the operating room frequency thereby affecting the brachytherapy treatment in various institutions due to the COVID-19 protocols. This has led to single applications of Intracavitary brachytherapy (ICRT) being used to deliver entire treatment boost in cervix cancer. We present our dosimetric and early clinical outcomes comparing traditional weekly three-fractions ICRT with single application/ two-applications ICRT <h3>Materials and Methods</h3> In this retrospective analysis conducted in our department, a total of 39 cases, treated between January 2021 to January 2022 were evaluated for the study. Of these, 15 cases were treated with the traditional once a week applicator insertion for 3 fractions and 24 cases underwent lesser application - 20 cases underwent 2 insertions and 4 cases single insertion (all receiving total 3 fractions of 7Gy each). The dosimetric parameters were compared including CTV D90 and D95 along with rectum, sigmoid and bladder D2cc, 1cc and 0.1cc respectively. The acute toxicity assessment was done using the RTOG scale. The follow-up was undertaken as per the institutional protocol and Mann-Whitney U-test were applied to compare the cohorts. <h3>Results</h3> With a median follow-up of 6 months, the median CTV was D90%: 81.2 vs. 80.9 Gy and the median CTV volume was 44.3 vs 42.9 cc respectively. The 0.1 cm³ and 2 cm³ to bladder, rectum, and sigmoid were 105.6 vs 104.2 Gy and 85.5 vs 85.9Gy, 89.4Gy vs 88.7Gy and 69.1 vs 67.8Gy, and 84.7 vs 84.1Gy and 71.7 vs 69.9Gy, respectively suggesting no significant difference in the dosimetric outcomes with the two forms of applications. The less than three applications had a shorter overall treatment time with median OTT of 43 days vs. 55 days (p = 0.02). On completion of treatment and 6 months follow-up, local control was achieved in all patients. There was no significant difference in the acute toxicities in terms of cystitis and proctitis in both forms of the application. <h3>Conclusion</h3> The single application/ twice application ICRT procedure showed similar outcomes as the traditional three-week duration treatment in terms of dosimetric outcomes and acute toxicities and ultimately leading to shortened overall treatment time. It also helped reduce the anesthesia burden and various resources associated with the procedure.

Four-fraction ultra-accelerated minimal breast irradiation in early breast cancer: The initial feasibility results of an institutional experience

To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Change in Image-Guided Planning Strategies Over Time Impacts Global Outcomes for Intracavitary Cervical Cancer Brachytherapy

Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional non-volumetric (NV) dosimetry system to three-dimensional (3D) CT and/or MRI-based planning techniques. The purpose of this study is to retrospectively evaluate the relative improvements in image-guided planning strategies over time with regards to dosimetry, survival, and acute toxicity to address the hypothesis that modern image-guidance improves outcomes because of accurate target definition.Ninety-five locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiation and high dose rate (HDR) BT from 2009-2016 at a single academic institution were retrospectively divided into three BT planning groups: point-A based NV dosimetry using CT imaging (2008 - 2011, n = 37), CT-based volumetric dosimetry (2012 - 2014, n = 33), and MRI-based volumetric dosimetry (2015 - 2016, n = 25). To compare the dosimetry data of the 3 cohorts, the NV cohort had organs at risk (OAR) and high-risk clinical target volumes (HR_CTV) contoured. Overall survival (OS), progression free survival (PFS), and local control (LC) at 5 years were plotted using Kaplan-Meier curves for the 3 cohorts. To identify potential predictor variables (age, FIGO stage, HR CTV volume, HR_CTV D90 (dose to 90% of the HR CTV) and image planning technique) on outcomes, we used the univariate (UVA) and multivariate (MVA) cox proportional-hazards model, with significant hazard ratios (HZ) reported. Finally, acute grade 3-4 toxicities for all patients were compared using a 2-sided Pearson χ2 test.For all patients, the mean BT HR CTV D90 was significantly lower for MRI (P = 0.015) and CT (P < 0.001) compared to NV (point A prescriptions were higher for the NV cohort by physician choice), with no significant difference between MRI and CT (P = 0.231). However, for patients with larger tumors (HR CTV ≥ 30 cc), the mean HR CTV D90 was higher for CT (41.6 Gy, P = 0.473) and MRI (41.6 Gy, P = 0.256) based-planning compared to that of NV (38.2 Gy). Both MRI and CT had significantly less D2cc to bowel (P < 0.001) and sigmoid (P < 0.001) compared to NV-based planning. Interestingly, CT had significantly less D2cc to bowel compared to MRI-based planning (P = 0.002). On MVA, age (< 60 vs ≥ 60 yrs) was significant for worse 5-year OS (HZ: 2.48) and LC (HZ: 5.25); MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and LC (HZ: 0.16), while the CT cohort was only significant for improved LC (HZ: 0.29). There was no significant difference in acute grades 3-4 toxicities, but MRI did trend towards improved acute grade 3-4 gastrointestinal toxicity compared to NV (P = 0.055).CT and MRI-based 3D planning had significantly less D2cc to bowel and sigmoid. MRI-based planning had significant improvement in 5-year OS, PFS, and LC compared to NV on MVA, while CT-based 3D planning had improved LC. Modern image-guidance in this time-based series improves global patient outcomes in LACC.P. D'Cunha: None. Y. Gonzalez: None. C.R. Nwachukwu: None. B.A. Hrycushko: None. P.M. Medin: None. T. Banks: Develop/vet educational website content; AAPM.A. Owrangi: None. X. Jia: None. K.V. Albuquerque: Research Grant; Astra Zeneca. Honoraria; ACR, ARRT. Travel Expenses; ACR, ARRT, ASCO.

Risk factors for venous thromboembolism induced by prolonged bed rest during interstitial brachytherapy for gynecological cancer: a retrospective study

BackgroundScreening and management of venous thromboembolism (VTE) after surgery is important in preventing sublethal VTE. However, the risk factors for VTE during interstitial brachytherapy (ISBT) remain unknown, and appropriate screening and management strategies are yet to be established. Therefore, this study aimed to evaluate the risk factors for VTE resulting from requisite bed rest during ISBT for gynecologic cancers.MethodsWe retrospectively analyzed 47 patients. For patients without definitive preceding radiotherapy, whole pelvic irradiation (30–50 Gy) followed by ISBT of 12–30 Gy/2–5 fx/1–3 days was administered to CTV D90. For patients with preceding radiotherapy, 36–42 Gy/6–7 fx/3–4 days was delivered by ISBT alone. The supine position was required during ISBT. D-dimer (DD) was measured at initial presentation, 1 week before ISBT, pre-ISBT, on the day of, and the day following needle removal. Patients were divided into three groups according to the risk of VTE and were managed accordingly; Group 1: DD was not detected (negative) before ISBT, Group 2: VTE was not detected on venous ultrasound imaging, although DD was positive before ISBT, and Group 3: VTE was detected (positive) before ISBT. An intermittent pneumatic compression device was used during ISBT; for the patients without VTE before ISBT. Heparin or oral anticoagulants were administered to patients with VTE before ISBT.ResultsOverall, the median values of DD pre-ISBT, on the day of, and on the day following needle removal were 1.0 (0.4–5.8), 1.1 (0.5–88.9), and 1.5 (0.7–40.6) μg/mL, respectively. After ISBT, no patients had deep vein thrombosis (DVT) in groups 1 and 2. In group 3, 7 of 14 patients experienced worsening of VTE but remained asymptomatic. In univariate analysis, DVT diagnosed before ISBT, Caprini score ≥ 7, and difference in DD values between pre-ISBT and the day of or the day following needle removal ≥ 1 were associated with the incidence or worsening of VTE.ConclusionDD should be measured before and after ISBT to detect the incidence or worsening of VTE in patients with DVT. The Caprini score may help in the prediction of VTE during or after ISBT.

Dosimetric Modeling of Intracavitary versus Combined Intracavitary/Interstitial Applicators During High Dose Rate Brachytherapy for Cervical Cancer

With increased adoption of image guided adaptive brachytherapy (IGABT) for definitive treatment of cervical cancer, combined intracavitary/interstitial (IC/IS) brachytherapy applicators are increasingly utilized as a means of dose escalation while minimizing exposure to organs at risk (OAR) structures compared to traditional intracavitary (IC) applicators. Aside from high risk CTV volume, little data exists to guide clinicians as to relative OAR dose reductions that might be predicted for a given patient with use of combined IC/IS vs IC applicators and tumor/target volume characteristics that correlate with greatest benefit. We performed pair-wise comparisons of IGABT treatment plans modeled with IC and IC/IS applicators to determine relative dose reductions to bladder, rectum, and sigmoid. In addition, we hypothesized that CTV asymmetry would be associated with a relatively greater degree of OAR dose reduction with use of an IC/IS applicator. Treatment planning MRI or CT images for fifteen consecutive patients treated with IC or IC/IS brachytherapy applicators as part of definitive therapy for FIGO 2018 stage IB3 to IIIC cervical cancer at a tertiary care academic medical center were obtained. For each dataset, high dose rate brachytherapy treatment plans were generated for both IC and IC/IS brachytherapy applicators using a treatment planning software. When interstitial needles were not placed at the time of applicator insertion, needle/dwell positions were modeled based on ovoid position and patient anatomy. Treatment plans were generated to minimize dose to the D2 cc volume of OAR contours while reaching an equivalent dose to the D90 of the high-risk CTV. OAR (bladder, rectum, and sigmoid colon), CTV, and GTV volumes, consistent with GEC-ESTRO guidelines, were obtained from previously administered treatment plans and were not modified. As a surrogate for target volume asymmetry, the ratio of maximum antero/posterior to lateral CTV dimension (AP:L ratio), was calculated for each patient. Paired t-tests were used to identify significant differences between IC and IC/IS treatment plans with respect to OAR doses, while Spearman correlation tests were used to assess correlations between OAR sparing and CTV AP:L ratios. Mean volumes for GTV and CTV were 7.4 (1.1 to 19.4) and 29.7 (10.4 to 52.3) cubic centimeters. Mean doses to D2 cc volumes were 15.9% lower for bladder (p<0.01); 15.3% lower for rectum(p<0.01); and 10.0% lower for sigmoid (p<0.01) with IC/IS plans. The CTV AP:L ratio demonstrated a significant inverse correlation with D2cc dose reduction for bladder (p<0.05), rectum (p<0.05), and sigmoid (p<0.05). For an equivalent prescribed radiation dose, IC/IS applicators are associated with significant reductions in bladder, rectal, and sigmoid D2cc doses. CTV asymmetry, as measured by AP:L ratio, is associated with relatively greater dose reductions to bladder, rectum, and sigmoid with use of IC/IS applicators.

Looking Beyond D90: A Novel Way of Correlating Brachytherapy Quality With Local Control in Cervix Cancer

The current formalism for reporting and adding the effects of BT and external beam (EB) RT doses are based on a single metric, D90 to HR-CTV and its EQD2. Previously published work however, has demonstrated that BED(D90) is unable to distinguish between plans that are optimized differently or created with different applicator systems. In comparison, EUBED and gBEUD, which both integrate voxel level BED, are better at discerning these important differences. We sought to measure local control in women being treated with radiotherapy for locally advanced cervix cancer and assess its correlation with EUBED and gBEUD over the whole volume of HR-CTV compared to the traditional, single point metrics D90. 163 women with FIGO 2018 IB3-IIIC2 cervical cancer from 3 institutions were included. All women received EBRT ± chemotherapy and 3-5 fractions of intracavitary brachytherapy. The median follow-up for all women was 59.5 months (range 0-87 months). At this time 6.1% have had local recurrences, 12.2% distant recurrences, 1.2% both local and distant. Data was extracted from TPS and dosimetric and radiobiological quantities computed. EUBED and gBEUD were calculated for each fraction. EUBED uses an extra parameter α (range 0.05-0.5Gy-1) with smaller values typically associated with radioresistant tumors. Similarly, gBEUD uses a parameter a which allows a variable emphasis on hot/cold spots (range –5,5). Distributions were compared using the 2-sample Kolmogorov-Smirnoff test at 5% significance. Distributions of all dosimetric quantities were compared among institutions, starting with CTV size and D90. D90 did not distinguish between patient populations with different outcomes. EUBED integrates biological effect over a volume in a manner very similar with gBEUD for negative a. Such exponents are typically used in relation with local control emphasizing ‘cold spots.’ Interestingly, a large ‘hot’ volume is present in all T&O and T&R applications and some practitioners even emphasize contiguity of 150% or 200% isodoses in their plans. gBEUD for positive values [3.5] proved to be the only metric that successfully predicted local recurrence. Based on these findings, gBEUD should be included routinely to the set of parameters used to evaluate implants. This is particularly important now, when based on increased use of MRI and of hybrid devices one has the ability to create dose distributions which are significant departures from the classical pear.Tabled 1Abstract 3063; TableInstitutionABCHR-CTV Volume (cm3)41.6±15.031.9±14.936.2±21.0D90 (%PD)101.5±11.7112.5±24.3117.2±10.5 Open table in a new tab

Clinical Outcomes of Distal Vaginal and Vulvar Cancer Treated with Image-Guided Brachytherapy

The primary aim of this study is to evaluate treatment outcomes with image guided brachytherapy (IGBT) for distal vaginal and vulvar cancers in the modern era of image guidance. Women treated for distal vaginal or vulvar malignancies utilizing IGBT between 2012 and 2019 were retrospectively reviewed. All patients were treated with a combination of external beam radiation therapy (EBRT) and IGBT. EQD2 values were calculated for the bladder, rectum and urethra. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. Eighteen patients were included in the final analysis. Twelve patients (66.7%) had primary disease of the distal vagina or vulva, most commonly squamous cell carcinoma of the vagina (N = 5, 41.7%). Six had recurrent disease, most commonly recurrent endometrial carcinoma (N = 5; 83.3%). Of patients with primary disease, 8 (66.7%) were FIGO stage II, 3 (25%) were stage III and one (8.3%) was stage IV. Six patients (33.3%) had lymph node involvement at the time of presentation. All patients received EBRT to a median dose of 45 Gy in 25 fractions. Fifteen to 27.5 Gy was then given in 3 to 5 fractions for IGBT. IGBT was performed on 14 patients (77.8%) with a Syed applicator,3 (16.7%) with a Capri applicator and 1 (5.6%) with a custom multichannel applicator. MRI-guidance was used for treatment planning in 15 patients (83.3%) and CT-guidance was used for the remaining 3 (16.7%). Mean follow up was 20.6 months. Mean dose to the high-risk CTV D90 was 72.4 Gy. Mean D2cc for the rectum, bladder and urethra were 50 Gy, 50.6 Gy and 62.9 Gy, respectively. Five patients (27.8%) had a recurrence of any type. Three patients (16.7%) had local recurrence, 1 patient (5.6%) had distant recurrence only and 1 patient (5.6%) had simultaneous regional and distant recurrence. Twelve (66.7%) patients had G2 or higher toxicity and 9 (50%) had G3 toxicity. No G4 or higher toxicities were observed. G2 or higher acute toxicities included: 1 (5.6%) G2 cystitis, 3 (16.7%) G2 proctitis, 1 (5.6%) G3 vaginal stenosis, 8 (44.4%) G2-3 dermatitis, 1 (5.6%) G3 vaginal infection and 5 (27.8%) G2-3 vaginal pain. G2 or higher chronic toxicities included: 2 (11.8%) G2 proctitis, 2 (11.8%) G3 vaginal stenosis, 1 (5.9%) G2 dermatitis, 2 (11.8%) G2 vaginal necrosis, 2 (11.8%) G3 vaginal necrosis, 6 (35.3%) grade 2-3 vaginal pain and 1 (5.9%) G2 urethral necrosis. Definitive radiation therapy in the form of EBRT and IGBT has a tolerable acute and chronic toxicity profile while providing meaningful locoregional control for women with distal vaginal and vulvar cancers.

The Incidence of Venous Thromboembolism Induced by Prolonged Bed Rest during Interstitial Brachytherapy for Gynecological Cancer

To evaluate the incidence and worsening of venous thromboembolism (VTE) caused by long duration of bed rest through interstitial brachytherapy (ISBT) for gynecologic cancer. We retrospectively analyzed 47 patients treated with ISBT between June 2017 and December 2019. For the patients without definitive preceding radiotherapy, whole pelvic irradiation (30-50 Gy) followed by ISBT of 12-30 Gy/ 2-5 fx/ 1-3 days was administered to CTV D90. For the patients with preceding radiotherapy, 36-42 Gy/ 6-7 fx/ 3-4 days was delivered by ISBT alone. D-dimer was measured four times as follows: at first presentation, pre-ISBT, on the day and the next day of needle removal. If D-dimer exceeded upper limit of normal range before ISBT, venous ultrasound imaging (VUI) and/or contrast enhanced CT were performed. In the management of VTE, the patients were divided into 3 groups. Group 1: D-dimer was negative before ISBT. Intermittent pneumatic compression device (IPCD) was used during keeping supine position, and VUI or CT was performed, if D-dimer exceeded standard value in during or after ISBT. Group 2: VTE was not detected in VUI or CT, although D-dimer was positive before ISBT. IPCD was used, and VUI or CT was performed, if D-dimer during or after BT exceeded positive value of pre-ISBT. Group 3: VTE was detected before ISBT. VUI or CT was performed, if D-dimer during or after ISBT exceeded the value of pre-ISBT. For the patients diagnosed with deep-vein thrombosis (DVT) at first consultation, VUI was principally performed at pre-ISBT. In the VUI at pre-ISBT, heparinization was performed for the patients with acute or subacute DVT, and oral anticoagulant was interrupted 2 days before ISBT for the patients with chronic DVT. Median age of the patients was 61. Thirty-seven patients had cervical cancer, seven endometrial cancers, and 2 other histology. Patients of FIGO III, IVA, vaginal recurrence after hysterectomy, local recurrence after chemoradiation were 18, 15, 11, 3, respectively. Median dose of ISBT was 24 Gy/ 4 fx/ 2 days. Group 1, 2 and 3 included 18, 15 and 14, respectively. In group 3, 8 patients were diagnosed with DVT at first presentation, and 6 at pre-ISBT. Eight of 14 patients received heparinization. For all patients, median value of D-dimer at pre-ISBT, the day and the next day of needle removal were 1.0 μg/ml (0.4-5.8), 1.1 (0.5-88.9), and 1.5 (0.7-40.6), respectively. During or after ISBT, VUI was performed in 7, 5 and 10 patients with Group 1, 2 and 3, respectively. In group 1 and 2, there was no case of DVT. In 9 of 14 patients (group 3), DVT was getting worse and/or pulmonary embolism occurred. In univariate analysis, DVT diagnosed before ISBT was associated with the incidence or worsening of VTE (p < 0.01). D-dimer should be measured before and after ISBT to detect the incidence or worsening of VTE for the patients with DVT diagnosed before ISBT.

Application value of individualized 3D-printed vaginal template for cervical cancer brachytherapy

Objective To introduce the workflow of individualized 3D-printed intracavitary/interstitial vaginal template design. Dosimetric parameters and operation safety were investigated to evaluate the performance of 3D-printed template and freehand implantation. Methods Forty patients previously treated with intracavitary/interstitial Ir-192 HDR brachytherapy were enrolled in this study. All patients were randomly divided into the treatment (n=20) and control groups (n=20). In the treatment group, twenty patients were treated with individualized 3D-printed template. CT-based preplan was carried out to determine the needle implantation cannels. Template with customized shape and implantation cannels was then produced by a 3D printer. Finally, the template was inserted under CT guidance. In the control group, twenty patients received freehand implantation. Needle insertion was decided empirically without the preplan process. Results The difference of D90 for high risk CTV was found to be minor, while the D2cm3 in the rectum, bladder and sigmoid was significantly improved in the treatment group. Meanwhile, the high dose region and conformal index were also improved in the treatment group. A total of 273 needles were inserted and one (0.3%) not-used needle was found. No normal tissues were penetrated during needle insertion in the treatment group. In the control group, a total of 203 needles were inserted and 4(2.0%) not-used needles were observed, and normal tissue penetration occurred in 3(1.5%) needle insertion. Conclusions The individualized 3D-printed template implantation approach has advantages in terms of dosimetry and safety compared with freehand implantation. The actual treatment can achieve the dosimetric design requirements of the preplan. Key words: 3D printing; Cervical neoplamsm/brachytherapy; Dosimetry

High dose rate interstitial brachytherapy for early stage lip cancer using customized dental spacer.

The present study aimed to report the efficacy and toxicity of our high-dose-rate (HDR) brachytherapy for early stage lip cancer (LC) using customized dental spacers. A retrospective analysis was performed among six patients with early stage LC treated with HDR interstitial brachytherapy between April 2015 and August 2019 using customized dental spacers. The total treatment dose was 49 Gy/7 fractions or 54 Gy/9 fractions. The median follow-up duration for the patients was 13 (range: 2–52) months. All patients completed the entire brachytherapy protocol safely and have experienced no local recurrence thus far. The CTV D100 and D90 values per fraction were median 100 (range: 98.3–100) % prescribed dose (PD) and median 133.4 (range: 129.3–138.9) % PD, respectively. The D2cc and D0.1cc values per fraction for the mandible were median 1.07 (range, 0.79–1.88) Gy and median 1.65 (range: 1.21–2.83) Gy, D2cc and D0.1cc values per fraction for oral cavity were median 1.48 (range, 1.31–1.72) Gy and median 2.73 (range: 1.79–2.88) Gy, respectively. Acute toxicities encountered were mucositis and lip edema limited to the irradiated area; none of them was beyond grade 2 and all were resolved within 1–2 months after treatment. We did not observe any late grade 2 adverse events or worse. This study shows that the adverse effects of HDR brachytherapy for early stage LC can be minimized using a dental spacer. Cooperation with the dentistry department is essential to make spacers that are individually customized for each patient.

The Physical Dose Difference of Three Types of Implantation on the CTV and Lungs in Interstitial Brachytherapy

Purpose: To study the difference of physical dose of target volume and lungs among actual irregular arrangement multi-needle interstitial brachytherapy plan (AIBP), virtual regular arrangement multi-needle interstitial brachytherapy plan (VRBP) and virtual single needle center point interstitial brachytherapy plan (VSBP). Methods: According to the inclusion criteria: the CTV shape was approximately spherical and multiply needles arrangement was irregular. Thirteen lung cancer patients underwent interstitial brachytherapy were collected. Based on the thirteen CT data sets, the AIBP, VRBP and VSBP were respectively designed, then we collected the dose metrics involving: the minimum dosage received by 95% of the CTV (D95), D90, D80, D50 and D30; the percentage of lung volume receiving a dose of ≥ 5 Gy (V5), V20, V30 and the mean lung dose (MLD); D50 of heart; the maximum dose (Dmax) of spinal cord and the Dmax of ribs. The differences were tested by the two-sample paired (Wilcoxon) signed rank test, a P value less than 0.05 was considered statistically significant. Result: The differences of D95, D90, D80, D50 and D30 of CTV, D50 of heart, Dmax of spinal and Dmax of ribs were not statistical significant (P>0.05) and the V5, V20, V30 and MLD of lungs and ipsilateral lung were statistical significant (P 0.05) except for D30 of CTV (P<0.05) between AIBP and VRBP. Conclusion: In interstitial brachytherapy for lung tumor, the arrangement of implantation needles could influenced the dose distribution in target and lungs. If the CTV shape could be approximately considered to be a spherical and a regular arrangement of multiply needles was difficult to achieve; the lung dose of the AIBP might have no obvious advantage over the VSBP and the VSBP should be worth a try.

Comparative analysis of image-guided adaptive interstitial brachytherapy and intensity-modulated arc therapy versus conventional treatment techniques in cervical cancer using biological dose summation.

PurposeTo compare image-guided adaptive interstitial brachytherapy (BT) and intensity-modulated arc therapy (IMAT) with conventional treatment techniques in cervical cancer using an alternative biological dose summation method.Material and methodsInitially, 21 interstitial BT and IMAT plans of patients with cervical cancer were included and additional plans were created (inverse optimized interstitial, optimized intracavitary, non-optimized intracavitary BT plans, and conformal external beam radiotherapy [EBRT]). The most exposed volume of critical organs in BT were identified manually on EBRT CT images. Biological total doses (EQD2) were calculated and compared between each combination of BT and EBRT plans. This method was compared with uniform dose conception (UDC) in IMAT and conformal EBRT plans.ResultsThe D90 of high-risk CTV and D2 of bladder and sigmoid were different in BT techniques only: p = 0.0149, < 0.001, < 0.001, respectively. The most advantageous values were obtained in the interstitial treatment plans and inverse optimized interstitial plans did not differ dosimetrically from these, while optimized intracavitary plans resulted in worse dose-volume parameters, and the worst of all were intracavitary plans without optimization. The D2 of rectum was significantly lower with IMAT than with conformal EBRT plans (p = 0.037) and showed the same trend in BT plans as the other parameters (p < 0.001). The UDC dose summation method overestimated D2 of bladder, rectum, and sigmoid (p < 0.001 for all).ConclusionsAlthough optimization improves the quality of conventional BT plans, interstitial plans produce significantly higher dose coverage of high-risk clinical target volume (HR-CTV) and lower doses to organs at risk (OARs). IMAT plans decrease the dose to the rectum. UDC overestimates OARs doses.

Intrapatient Dosimetric Variability Between Two Adjustable Brachytherapy Applicators for Cervical Cancer: Tandem/Ovoid vs. Tandem/Split-Ring

The choice of intracavitary applicator for high-dose rate brachytherapy for cervical cancer has dosimetric implications for target coverage as well as toxicity. Prior analyses have compared rigid (tandem/ring) and adjustable applicators, however there is a deficiency of data clarifying the differences and indications among tandem/ovoid (TO) and the increasingly-used tandem/split-ring (TSR) applicator. To our knowledge, our institution is the first to analyze intrapatient spatial and dosimetric variability between adjustable TO and TSR applicators. Between 2010 and 2017, 108 patients with cervical cancer were treated with a brachytherapy boost (median 28 Gy in 4 fractions) with two insertions under general anesthesia one week apart, after pelvic external beam radiotherapy to 45-50.4 Gy. Sixteen of these patients were treated with both TO and TSR applicators. CT-based high-risk CTVs were delineated according to GEC-ESTRO guidelines. Doses to ICRU points A, B, P, organs at risk (OAR) including bladder, rectum, vagina, and D2cc of OAR were compared. Spatial characteristics of the 100% isodose distribution and physical geometry of the applicators were analyzed as well (craniocaudal, anterior-posterior, and horizontal left-right dimensions). Target coverage was evaluated by comparing the CTV volume, D90 (Gy) and V100 (%) between insertions. Paired two-tailed T-tests were used, and significance was assessed at p<0.05. Across the 32 insertions studied, there were no statistically significant differences in CTV volume, D90, V100, or dose to points A, B, P, rectum and bladder between the two applicators. TO applicators had a significantly lower dose delivered to the left and right vaginal mucosae than TSR applicators (left mean 8.1 vs. 13.3 Gy, p<0.01; right mean 7.67 vs. 12.5 Gy, p<0.01). TO applicators also yielded a larger maximum craniocaudal dimension of the 100% isodose distribution (mean 8.2 vs. 6.8cm, p<0.01). TSR applicators, however, yielded a wider horizontal max dimension of the 100% isodose distribution (mean 7.8 vs. 6.7cm, p<0.01) and a correspondingly wider horizontal colpostat separation (mean 5.4 vs. 3.7 cm, p<0.01). Because this analysis evaluates both TO and TSR applicators in the same patients, it provides the unique advantage of contrasting dosimetry and target coverage while controlling for tumor and pelvic anatomy. Our study demonstrates that TO applicators consistently yield lower vaginal mucosal doses compared to TSR, likely reflective of the generally larger ovoid caps, without significantly different dose to the rectum or bladder. Although tumor coverage was equivalent, differences in dose distribution persist, such as greater horizontal width with TSR and improved craniocaudal coverage with TO, which may guide selection between the two devices.