Rectum D2cc Research Articles

A comparison of treatment planning techniques for low-dose-rate (LDR) prostate brachytherapy

PurposeThe purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients. Methods and MaterialsTreatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V100 (%), prostate V150 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), urethra D30 (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans. ResultsProstate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V100 (%) values and significantly lower rectum D0.1cc (Gy), urethra D10 (%), and urethra D30 (%) values, and loose seed MRI-based plans showed significantly lower prostate V100 (%), prostate D90 (Gy), rectum D0.1cc (Gy), rectum D2cc (Gy), urethra D10 (%), and urethra D30 (%) values. ConclusionsTRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds.

Dosimetric Evaluation of Electronic Brachytherapy for Postsurgical Vaginal Cuff Irradiation in Endometrial Cancer

We evaluated dosimetric parameters associated with acute toxicity in women with endometrial cancer treated with electronic brachytherapy (EBT) to the vaginal cuff. This dosimetric study included women with endometrial cancer treated with EBT following surgery. The EBT system uses a miniature low-energy (50-kV peak) X-ray source with a single-channel vaginal cylinder applicator to deliver radiation to the vaginal target along a specified length of the cylinder. EBT was delivered either as monotherapy or as a sequential boost following completion of pelvic external beam radiation (EBRT). EBT was delivered using either a 2.5 cm, 3.0 cm, or 3.5 cm diameter vaginal cylinder. EBT was generally delivered to 4 cm treatment length, prescribed as 7 Gy to 5 mm depth x 3 fractions in the monotherapy group or 6 Gy to vaginal surface x 3 fractions in the boost group. Dosimetric evaluation of EBT plans included measurement of maximum vaginal mucosal surface dose, minimum dose in the most irradiated 2 cc volume (D2cc) of bladder, rectum, and bowel structures. Patients were followed by their treating physician to evaluate treatment response and toxicity. EBT plans were evaluated in 50 consecutive patients treated between 2017-2019. Median time to completion of EBT was 1.3 weeks (range, 0.3-2.3 weeks). Dosimetric treatment parameters were as follows (mean, standard deviation): maximum mucosal dose relative to prescription dose (156.6%, 35.3%), bladder D2cc (3.8 Gy, 1.3 Gy), rectum D2cc (4.4 Gy, 1.6 Gy), bowel D2cc (1.6 Gy, 1.2 Gy). At a median follow-up of 1.6 months (range, 0.4-4.1 months), 9 (18%) patients presented with acute grade 1 GI toxicity, 7 (14%) presented with acute grade 1 GU toxicity, and 7 (14%) presented with acute grade 1-2 GYN toxicity. On univariate analysis, smaller EBT cylinder diameter size (p<0.01), but not maximum vaginal mucosal surface dose (p = 0.11) was associated with vaginal stenosis. There was no significant association between bowel or rectum D2cc with GI toxicity, and bladder D2cc with GU toxicity. EBT is an alternative form of vaginal brachytherapy designed to reduce radiation safety shielding requirements, potentially improving patient access to brachytherapy. EBT dose to organs at risk and vaginal surface mucosa appear comparable to those generated on high dose rate source-based brachytherapy systems. Smaller EBT cylinder diameter was associated with vaginal stenosis. Further evaluation is warranted to characterize late toxicity and tumor control outcomes.

Integrated Intraoperative MRI-Guided Brachytherapy for Cervical Cancer: An Institutional Experience of Treatment Workflow, Planning and Patient Toxicities

MRI planning for cervical cancer brachytherapy is associated with reduced toxicity and improved outcomes compared to historical techniques. MRI brachytherapy, however, is resource-intensive, which poses challenges in workflow and efficiency. Currently, most MRI planning protocols involve performing the brachytherapy insertion followed by patient recovery before obtaining MRI images with the patient awake. As this conventional process is lengthy and can cause patient discomfort, the goal of this study is to report the experience of an integrated MRI-based intraoperative brachytherapy program. Patients undergoing intraoperative MRI-guided brachytherapy for cervical cancer from an institutional registry trial between 2018 and 2019 were reviewed. All had intracavitary and/or interstitial brachytherapy insertion, MRI-imaging /planning, treatment delivery and applicator removal all under general anesthesia (GA). Patient, cancer and treatment-related data were abstracted. Brachytherapy specific data included applicator characteristics, dose aims, target prescriptions and organs-at-risk (OAR) doses. Pain was scored using a Likert scale from 1-10 at recovery, and at scheduled times prior to discharge. Procedure and anesthetic related toxicities at recovery and first follow-up were reviewed. Thirty-four patients with stage IBI - IIIA cervical cancers were available for analysis in this novel intraoperative program. Median age was 62 (range, 31 - 80). Eighteen patients were treated with interstitial needles for at least 1 insertion (15 hybrid, 3 perineal). The median number of needles used for fractions (Fx) 1, 2, 3 and 4 were 4, 5, 4 and 4 for hybrid applicators and 21, 21, 20 for perineal templates (3 fractions) respectively. For interstitial patients, average times for insertion (Ins), MRI imaging (MRI), planning/treatment (PlanTx) were respectively 61 +/- 14 mins, 42 +/- 8 mins, 98 +/-24 mins. Total treatment time under GA was 200 +/- 35 mins. For intracavitary patients, Ins, MRI, PlanTx times were respectively 52 +/- 14 mins, 40 +/- 10 mins, 80 +/- 17 mins, with total treatment time under GA being 172 +/- 25 mins. Mean CTVHR D90, rectum D2cc and bladder D2cc doses were 93.7.1 Gy (80.2 - 111.1), 57.9 Gy (49.7 - 67.9) and 74.9 Gy (58.7 - 86.2) respectively. There were no observed anesthetic complications, and all patients were discharged the same day. Mean pain scores post-anesthesia for interstitial patients were 0.75 (0-2), 0.95 (0 - 3.75), 0.9 (0 - 4.62) and 2.3 (0-5.4) for each consecutive fraction. For intracavitary mean pain was 0.81 (0 - 4.5), 0.59 (0 - 3.3), 0.48 (0 - 4.4) and 0.94 (0 - 4). Intraoperative MRI-based brachytherapy planning and treatment is feasible and well-tolerated with minimal pain. Interstitial procedures tended to be longer than intracavitary, but no anesthetic complications were seen. Prospective evaluation of patient toxicities, outcomes and experience is needed to evaluate this technique further.

Role of Ultrasound Guided Tandem Placement in Intracavitary Brachytherapy for Cervical Cancer Management – A Randomized, Open Label Study From an Indian Experience

Tandem placement within the uterine cavity can be a tedious affair in Intracavitary brachytherapy and blind insertion of the tandem may result in suboptimal tandem placement or uterine perforation and reduce the control rate of the tumor locally. Although routine real time ultrasound guided tandem placement has shown better results, it is seldom practiced. Ultrasound (US) is a simple imaging modality that is readily available in most departments and allows real-time visualization of applicators. We present our study with aim to evaluate the role of routine real-time intraoperative trans-abdominal ultrasound guided tandem placement in terms of decreased complication rates, improved implant geometry and increased operator efficiency. A total of 62 patients were randomized and assessed prospectively at our institution who underwent intracavitary brachytherapy for various stages of cervix cancer between October 2019 to March 2020 with 31 patients undergoing US guided tandem placement versus 31 patients who did not undergo the same. A total of 124 applications were analyzed and Cervical dilation, tandem selection and subsequent insertion were guided by trans-abdominal ultrasound with confirmation of the final placement of the applicator on US followed by CT imaging for treatment planning. Thereafter, the perforation rates and the applicator suitability for patient anatomy were assessed. Role of intervention in case of perforation, the time taken for the application, complications following the perforation were also assessed. The rate of perforation in the US assistance arm was 3% applications versus 12% in the non-US assistance arm. The cervical os could be easily identified visually, which was then confirmed with ultrasound guidance. The length of the uterine canal changed in 25 patients during the subsequent brachytherapy application with help of US assistance. Visualization of patient anatomy during the procedure aided the selection of suitable tandem length and angle in 39 of cases and resulted in optimal applicator selection and placement. The average insertion time was 19 minutes versus 27 minutes favoring US assistance (p = 0.012). The need for the assistance from radiology and gynecologic oncology for identification of the uterine cavity was not required in any of the cases suggesting excellent feasibility of US use. The bladder d2cc (EQD2) was 71.4Gy vs 74.8Gy (p = 0.034) and Rectum d2cc was 74.9Gy vs 77.8Gy (p = 0.023) favoring the US assisted arm. The study emphasizes on the routine use of US assistance to improve optimal applicator selection and proper applicator geometry and thereby, reduce the reinsertion and perforation rates. US assistance also helps reduce the procedure time and out-of-department referrals. It is an accurate, fast, easily available, and cost-effective method.

Evaluation Of MR Only Trans-Perineal Interstitial Gynecological HDR Brachytherapy Workflow Using MR-Line Marker And MR Template

There is a growing interest in using MR-only trans-perineal gynecological interstitial brachytherapy because it offers excellent soft-tissue contrast due to MR imaging while reducing the resources required for planning and uncertainty due to registration with CT. The purpose of this work is to evaluate the variation in MR-only workflow in comparison to CT guided approach in gynecological trans-perineal interstitial high dose rate (HDR) brachytherapy. An in-house MR-line marker was designed and created to provide positive contrast on T1W MR images for delineating 6F interstitial catheters (Elekta), replacing the need for CT. A marker plate filled with contrast was affixed to the trans-perineal template, providing a clear reference plane for planning on T1W MR images. Ten patients diagnosed with locally advanced cervical cancer treated with HDR brachytherapy were retrospectively evaluated. An MR-only workflow was developed that used the positive contrast from the MR-markers on T1W images in conjunction with negative contrast on T2W images, to robustly and accurately delineate the interstitial catheters. Inter-observer variability in delineated catheter paths and time required to delineate the catheters were evaluated for 3 therapists and 2 medical physicists. A dosimetric comparison of the plans in the MR-only workflow was made with those in CT based workflow. The contrast in the MR-line marker was stable over time. MR-line markers were visible on planning T1-3D MR images but the complementary information from co-registered T2-3D images were needed at some anatomical locations where the background signal was comparable to that of the markers. MR-template helped to make quality assurance of reconstructed catheter lengths and hence to locate the first dwell point reliably. More than about 97% of catheter reconstruction variations were within 2mm. There were no statistical differences in gross tumor volume (GTV) D98 and High-risk clinical target volume (HR-CTV) D90 and the organs at risk (Bladder, sigmoid, rectum and bowel) D2cc between MR-only and hybrid CT/MR workflow. The average catheter reconstruction time was 51 ± 10 minutes across all ten patients for all observers. The results of this study show that the MR-only workflow is feasible. The use of MR markers enabled accurate and reproducible delineation of the catheters. Furthermore, it was also demonstrated that an MR-only workflow is dosimetrically equivalent to a CT based approach.

Evaluating Clinical Outcomes in 3D vs. 2D Vaginal Brachytherapy

Vaginal brachytherapy (VB) for early stage endometrial cancer (EC) has technologically evolved with the incorporation of 3D imaging into treatment planning. When our institution transitioned from phantom-based 2D template planning to 3D CT-based planning, we implemented selective optimization of standard dwell times for cases with bowel adhered to the vaginal apex. Our hypothesis was that optimizing 3D plans with unfavorable bowel dosimetry would result in no detriment to local control and potentially improve treatment tolerability. We reviewed records of patients with stage I-II EC treated with VB at our institution from 1/2017-6/2019 (3D group). We compared patient, tumor, and treatment characteristics to a historic cohort treated at our institution between 2011-2015 (2D group). Patients had minimum 6 months follow-up. Patients with stage III-IV disease, prior or concurrent pelvic radiation, or synchronous pelvic primary were excluded. Recurrence-free survival (RFS), local control, and treatment tolerability (any acute toxicity recorded prospectively on treatment) were analyzed. Statistical analyses were performed in Stata and included Chi-square and Wilcoxon Rank Sum tests to compare between-group characteristics and Cox proportional hazards analysis to assess RFS. A total of 403 patients were included (n = 99/3D and n = 304/2D). The 3D vs. 2D groups were similar in age, weight, gravidity, cylinder sizes, histology, and chemotherapy, though differed in race (p = 0.004) and % stage IA/IB/II (p = 0.022). VB dose was similar, with majority receiving either 18Gy/3 fractions (46% vs. 46%) or 21Gy/3 fractions (40% vs. 38%) to 5mm depth. In the 3D cohort, however, the proportion of vagina treated was less (3D median 50%, IQ range 43-56% vs. 2D median 60%, IQ range 50-67%; p<0.001). and standard dwell times were decreased to improve bowel dosimetry in 21%. Median follow-up times were 524 and 903 days in the 3D and 2D groups, respectively. There was no significant difference in RFS (HR 0.48, 95% CI 0.19-1.22, p = 0.122). Vaginal recurrence occurred in 1 and 2 patients, respectively, with recurrence distal to treated mucosa in all cases. There were no significant differences between groups in rates of acute GI (14.1% vs. 10.9%, p = 0.376), GU (8.1% vs. 11.2%, p = 0.380), or vaginal (20.2% vs. 19.4%, p = 0.827) toxicities. All toxicities were mild (grade 1-2). In the 3D patients, there were no significant differences (p>0.05) in bowel, rectal, or bladder Dmax or D2cc values between those with vs. without symptoms on treatment. 3D vs. 2D planning maintained excellent local control despite selectively reducing the volume of prescription isodose overlapping with bowel. Treatment tolerability was favorable in both groups with no benefit observed in the short term, however, longer follow-up is needed to compare late outcomes.

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.

A novel minimally invasive dynamic-shield, intensity-modulated brachytherapy system for the treatment of cervical cancer.

To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2%±0.3% (P<0.001) and 6.7%±0.5% (P<0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7%±0.6% (P<0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D98 by 1.5%±0.2% (P=0.034) and decreasing sigmoid D2cc by 1.9%±0.4% (P=0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT. Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.

Strict bladder filling and rectal emptying during prostate SBRT: Does it make a dosimetric or clinical difference?

BackgroundTo evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences.MethodsEighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses.ResultsBladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = − 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (− 3.6 ± 9.6%; P < 0.01) and D2cc (− 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (− 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities.ConclusionsDespite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

Dose-averaged linear energy transfer per se does not correlate with late rectal complications in carbon-ion radiotherapy

Background and purposeSeveral studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT. Materials and methodsOverall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible “clinical dose”), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. ResultsNine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D2cc was ≥60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se. ConclusionWe demonstrated that severe rectal toxicities were related to the rectal D2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se.

Paracervical blocks facilitate timely brachytherapy amidst COVID-19

PurposeThe COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT). Methods and MaterialsThis technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment. Results18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D2cc for rectum and bladder were 64.8 (58.6–70.2) Gy and 84.1 (70.9–89.4) Gy, respectively. Median (IQR) CTV high-risk D90 was 88.0 (85.6–89.8) Gy. ConclusionsIn a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.

Techniques for and uncertainties of MRI-based reconstruction of titanium tandem and ring brachytherapy applicators

PurposeEliminating patient computed tomography (CT) scans for tandem and ring (T&R) brachytherapy can reduce overall procedure time and eliminates imaging dose. However, reconstructing titanium applicators in magnetic resonance imaging (MRI) is challenging. We evaluated the uncertainty of different applicator reconstruction workflows in MR-guided brachytherapy, and assessed the clinical impact of reconstruction uncertainties. Methods and materialsTitanium MRI-compatible T&Rs with aqueous gel in the buildup cap were reconstructed on CTs and MRIs to assess the uncertainties of four different workflows. Reconstruction was performed using (1) proton density–weighted MRIs with solid applicator from a library, (2) applicator-only reference CT fused with MRIs, (3) T2-weighted (T2W) MRIs following GEC-ESTRO guidelines, and (4) patient CTs fused with patient MRIs with in situ applicators. We evaluated dwell positions and plan quality differences using high-risk clinical target volume coverage, and EQD2 D2cc of rectum, sigmoid, bladder, and small bowel. ResultsThe 2σ uncertainty for dwell positions for each workflow were (1) 2.7 mm for both ring and tandem, (2) 1.4 mm ring and 0.8 mm tandem, (3) 0.2 mm ring and 0.8 mm tandem, and (4) 1.9 mm ring and 0.4 mm tandem. Reconstruction uncertainties resulted in dose variations within acceptable levels (below 10%) except for (1) which resulted in larger dose to the rectum (20%). Dose uncertainties were similar between reference CT and patient CT. ConclusionsReconstruction with a reference CT results in similar uncertainty to a patient CT. T2W MRI plans have acceptable uncertainty levels for the applicator reconstruction and resulting dose distributions.

Development of an indigenous low-cost multichannel cylinder applicator for vaginal tumors

PurposeThe purpose of this study was to report our experience regarding the development of a low-cost multichannel vaginal cylinder applicator for superficial and recurrent vaginal tumors. Methods and MaterialsThe applicator mold was created by applying heated wax sheets in layers around a plastic tube. Interstitial stainless-steel needles were placed at equal distance around the mold surface to create multiple channels for treatment. Two plans were created using CT images for a patient with a recurrent tumor over the posterior vaginal wall for comparing single-channel and multichannel cylinder dosimetry. The doses received by the target (high risk clinical target volume) and organs at risk (OARs) were computed using dose–volume histograms. ResultsThere was no significant difference in terms of the prescribed dose delivered to high risk clinical target volume between the two plans. The volume of the target receiving 150 and 200 percent (V150 and V200) dose was higher in the multichannel cylinder plan than the single-channel cylinder plan. In terms of doses to the OARs, there was no significant difference between the rectum doses (D2cc rectum). There was a significant reduction in the dose to the bladder (D2cc bladder), urethra (D0.1cc urethra), and uninvolved vagina (D2cc uninvolved vagina). ConclusionsMultichannel vaginal cylinders reduce doses to the OARs as compared with the single-channel vaginal cylinder in superficial vaginal lesions limited to the wall of the vagina. Their use is limited by the cost of the applicator. Our low-cost multichannel vaginal cylinder can be used as a reliable alternative in such situations.

A knowledge-based organ dose prediction tool for brachytherapy treatment planning of patients with cervical cancer

PurposeThe purpose of this study is to explore knowledge-based organ-at-risk dose estimation for intracavitary brachytherapy planning for cervical cancer. Using established external-beam knowledge-based dose-volume histogram (DVH) estimation methods, we sought to predict bladder, rectum, and sigmoid D2cc for tandem and ovoid treatments. Methods and materialsA total of 136 patients with loco-regionally advanced cervical cancer treated with 456 (356:100 training:validation ratio) CT-based tandem and ovoid brachytherapy fractions were analyzed. Single fraction prescription doses were 5.5–8 Gy with dose criteria for the high-risk clinical target volume, bladder, rectum, and sigmoid. DVH estimations were obtained by subdividing training set organs-at-risk into high-risk clinical target volume boundary distance subvolumes and computing cohort-averaged differential DVHs. Full DVH estimation was then performed on the training and validation sets. Model performance was quantified by ΔD2cc = D2cc(actual)-D2cc(predicted) (mean and standard deviation). ΔD2cc between training and validation sets were compared with a Student's t test (p < 0.01 significant). Categorical variables (physician, fraction-number, total fractions, and case complexity) that might explain model variance were examined using an analysis of variance test (Bonferroni-corrected p < 0.01 threshold). ResultsTraining set deviations were bladder ΔD2cc = −0.04 ± 0.61 Gy, rectum ΔD2cc = 0.02 ± 0.57 Gy, and sigmoid ΔD2cc = −0.05 ± 0.52 Gy. Model predictions on validation set did not statistically differ: bladder ΔD2cc = −0.02 ± 0.46 Gy (p = 0.80), rectum ΔD2cc = −0.007 ± 0.47 Gy (p = 0.53), and sigmoid ΔD2cc = −0.07 ± 0.47 Gy (p = 0.70). The only significant categorical variable was the attending physician for bladder and rectum ΔD2cc. ConclusionA simple boundary distance-driven knowledge-based DVH estimation exhibited promising results in predicting critical brachytherapy dose metrics. Future work will examine the utility of these predictions for quality control and automated brachytherapy planning.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2–6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9–105.9), 77.7 Gy EQD2 (range, 56.9–99.1), 68.0 Gy EQD2 (range, 48.6–90.7) and 62.0 Gy EQD2 (range, 39.6–83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Conventional vs machine learning–based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial

PurposeThe purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. Materials and Methods41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. Results21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D90%, V100%, rectum V100, or rectum D1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). ConclusionsA machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.

Automated applicator digitization for high-dose-rate cervix brachytherapy using image thresholding and density-based clustering

PurposeThe purpose of the study was to develop and evaluate an automated digitization algorithm for high-dose-rate cervix brachytherapy, with the goal of reducing the duration of treatment planning, staff resources, variability, and potential for human error. MethodsAn automated digitization algorithm was developed and retrospectively evaluated using treatment planning data from 10 patients with cervix cancer who were treated with a titanium tandem and ovoids applicator set. Applicators were segmented, without human interaction, by thresholding CT images to isolate high-density voxels and assigning the voxels to applicator and nonapplicator structures using HDBSCAN, a density-based linkage clustering algorithm. The applicator contours were determined from the centroid of the clustered voxels on each image slice and written to a treatment plan file. Automated contours were evaluated against manual digitization using distance and dosimetric metrics. ResultsA close agreement between automatic and manual digitization was observed. The mean magnitude of contour disagreement for 10 patients equaled 0.3 mm. Hausdorff distances were ≤1.0 mm. The applicator tip coordinates had submillimeter agreement. The median and mean dose volume histogram parameter differences were less than or equal to 1% for high-risk clinical target volume D90, high-risk clinical target volume D95, bladder D2cc, rectum D2cc, large bowel D2cc, and small bowel D2cc. The average execution time for the automated algorithm was less than 30 s. ConclusionThe digitization of titanium tandem and ovoids applicators for high-dose-rate brachytherapy treatment planning can be automated using straightforward thresholding and clustering algorithms. The adoption of automated digitization is expected to improve the consistency of treatment plans and reduce the duration of treatment planning.

Does Use of Bowel Prep Improve HDR Cervix Implant Dosimetry?

Cervical cancer (CC) brachytherapy (BT) has evolved from Point A to volumetric MRI-based prescriptions. At our institution, in transitioning to MRI-guided BT, an inpatient (IP) rather than outpatient (OP) paradigm was adopted due to resource considerations. The IP regimen mandated a pre-procedure bowel prep (BP) to improve logistics and comfort; the OP regimen did not. We hypothesized that use of BP may theoretically displace rectum and sigmoid walls away from the applicators and thereby improve BT dosimetry. We included locally advanced CC patients treated with HDR intra-cavitary BT over a 5-year period. Earlier patients were treated with 4-5 individually planned OP fractions (5-7Gy), with prescription to point A. Later patients were treated IP, generally in 4 fractions (6.8-7Gy) from two individually planned implant insertions, with MRI performed with applicator in situ. Most (98%) fractions were done with tandem and ring. Data collected from each individually planned fraction included % D2cc rectum, % D2cc sigmoid, treated volume (defined as the volume in cc covered by the 100% prescription isodose), and use of BP. Per-patient cumulative doses (EQD2, Gy) to the rectum and sigmoid were recorded. Median values were compared with the Wilcoxon Rank Sum test. Univariable and multivariable linear regression was performed to assess impact of BP. Statistical analyses were performed in Stata. Data from 140 individually planned fractions (66 OP, 74 IP) from 53 patients were analyzed. The median OP vs IP fractional %D2cc rectum and %D2cc sigmoid were 44.2% vs 24.7% (p<0.001) and 57.4% vs 50.8% (p=0.007). The resulting median cumulative D2cc values for OP vs IP rectum and sigmoid were 58.1 Gy vs 50.3 Gy (p<0.001) and 64 Gy vs 62 Gy (p=0.51). Median treated volume for all fractions was 51.0cc (IQ: 41.8-64.4). OP vs IP median treated volume was 58.2cc (IQ: 48.9-70.4) and 45.6cc (IQ: 35.7-53.0), respectively (p<0.001). On univariable analyses, both IP treatment with BP, and smaller treated volume, were associated with significantly lower %D2cc rectum and %D2cc sigmoid. On multivariable analyses, IP treatment with BP (Coef -0.15, CI -0.19 to -0.11, P<0.001) and smaller treated volume (Coef 0.06, CI 0.02 to 0.11, P=0.002) both remained significantly associated with lower %D2cc rectum, but only treated volume remained significant for %D2cc sigmoid (Coef 0.12, CI 0.05 to 0.17, p<0.001); IP treatment with BP did not (Coef -0.02, CI -0.08 to 0.04, p=0.4). On sensitivity analysis, IP treatment with BP resulted in significantly lower %D2cc rectum for both smaller (<51cc) (Coef -0.19, CI -0.24 to -0.14, P<0.001) and larger (≥51cc) (Coef -0.12, CI -0.17 to -0.05, P=0.001) treated volumes. The transition from point A to MRI-guided BT was associated with improved dosimetry. Further, we observed an independent association between IP treatment with BP and reduced rectal D2cc for both larger and smaller volume tumors.

Three Dimensional Printed Individual Template Based 192ir High-Dose Rate Interstitial Brachytherapy for Central Recurrent Gynecologic Cancer: A Phase II Clinical Trial

To evaluate the feasibility, safety, and accuracy of three-dimensional (3D)-printed individual template (3D-PIT) based with HDR interstitial brachytherapy (HDR-IB) for pelvic central recurrent gynecologic cancer (CR-GYN). 32 patients diagnosed CR-GYN in our institution were received 192Ir HDR-IB. 3D-PIT technique was carried out for all these patients in our center. They underwent procedure that firstly simulation; then preplan; thirdly 3D template design and printing and fourthly interstitial 192Ir HDR brachytherapy operation. There are two types of individual 3D-PIT designed. Type I: transvaginal template/applicator, and Type II: transvaginal combined transperineal template. The prescription dose to GTV was 10-36Gy, 5-6Gy/fraction, 2-6f. Dose parameters were D90, D100, V100, conformal index, external index and homogeneity index of the target volume, and the dose received by 2cm3 of normal tissue of organs at risk (rectum, bladder, and intestine) were recorded. We compared the dose parameters of the treatment plan with the preplan. The short-term efficacy was evaluated by RECIST v1.1, and the adverse event was evaluated by CTCAE V4.0. In total 32 patients, 205 needles were inserted for 153 applications, The mean V100, D100, and D90 per fraction were 88.9%±9.8%,3.45Gy±0.54Gy, and 5.79 Gy±0.32Gy respectively; the mean D2cc of rectum, bladder and colon per fraction were 3.14Gy±0.23Gy, 3.76Gy±0.72Gy and 2.47Gy±0.34Gy respectively. The mean CI, EI, and HI were 0.59±0.12, 0.31±0.16, and 0.47±0.22. Dosimetry parameters comparison between preplan and treatment plan of 20/32 patients with Type II 3D-PIT based HDR-IB show that there were no statistically significant (P > 0.05) difference in GTV volume, V100, D100, D90, CI and HI. Treatment plan EI was lower than preplan, and the difference was statistically significant (P = 0.022). Median follow up time was 10 months (3–28 months). No severe complications of procedures occurred. Grade 3 or 4 late toxicities (fistula ) were observed in 3 patients (9%). The local response rate (CR + PR) was 84.4% (27/32) one month later completion of treatment. In addition, the median TTP was 15.4 months (95% CI 11.3- 19.6ms), 1 year and 2 year local control rate were 51.7% and 51.7%. 3D-PIT based with CT-simulator for HDR-IB for central r-GYN has good dosimetry parameters consistently, was clinically feasible and efficient, and complications did not increased significantly.

MRI-Guided Brachytherapy PLAN Optimization with Three Versus FOUR Fraction Treatment for Locally Advanced Cervical Cancer

MRI-guided brachytherapy (MRgBT) has become the standard treatment for locally advanced cervical cancer. The ability to optimize target and organ-at-risk (OAR) doses with three-dimensional image-based planning has improved toxicity profiles and local control. MRgBT, however is considerably more resource-intensive than the classical 2D planning and most of the available data on MRgBT has been based on a four fraction protocol of 7 Gy per fraction (7x4). A potential alternative to minimize resource utilization is a three fraction regimen of 8 Gy per fraction (8x3). However, there is limited data on MRgBT using the 8x3 protocol. The ability of this higher dose per fraction treatment to meet EMBRACE II planning aims has not been extensively studied. This study aims to compare optimized 8x3 vs 7x4 plan dosimetry. Ten patients with locally advanced cervical cancer (FIGO IB2 – IVA) treated at a single institution between July 2018 and January 2019 were included in this planning study. Clinical plans that were optimized and treated using a prescription 7x4 and the EMBRACE II planning aims (CTVHR D90% 90-95 Gy, rectum D2cm3 < 65 Gy and bladder D2cm3 < 80 Gy) were retrieved. Plans were then scaled to 8x3 and adjusted using graphical optimization. Three scenarios were evaluated: (1) The CTVHR D90% EQD2 dose was adjusted to be equivalent to the 7x4 plans; while limiting doses to organs at risk. Bladder and rectum D2cm3 doses and GTV D98% doses were recorded. (2) The bladder D2cc EQD2 dose was adjusted to be equivalent to the 7x4 plans (3) The rectal D2cc EQD2 dose was adjusted to be equivalent to the 7x4 plans. An a/b of 10 was used for the tumor bioequivalent dose calculations and an a/b of 3 for the OAR calculations. Doses were compared using Mann-Whitney-Wilcoxon. The median GTVres and CTVHR volumes were 13.42 cc (1.02 – 92.2) and 32.5 cc (10.99 – 120.4). For the 7x4 plans optimized for clinical treatment, median CTVHR D90%, rectum and bladder D2cm3 EQD2 doses were 93.7 Gy (87.4 – 104.4), 58 Gy (51.3 – 83.7) and 77.7 Gy (72.2 – 89.1). For scenario 1, where CTVHR D90% was made equivalent , median rectum and bladder D2cm3 were 58.5 Gy (51.3 – 84.6 ) and 77.1 Gy (73.1 – 90.0), respectively, with no significant differences compared to the 7x4 plans (P=1.0, P=0.85). Median GTVres D98% for 8x3 plans vs 7x4 was 105.1 Gy (84.5 – 150) vs 110.2 Gy (86.4 - 144.4), P = 0.63. When bladder and rectum in 8x3 were set equal to 7x4 plans (scenarios 1 & 2), there was no significant difference in CTVHR D90% doses (P=0.63, P=0.91) or GTVres D98% (P=0.53, P=0.53) . In this study, planning optimization with the 8x3 fraction protocol yields similar EQD2 doses for CTVHR D90%, bladder and rectum D2cm3 when compared with the 7x4 fraction protocol. The EQD2 GTV D98% is marginally lower for 8x3 when compared to 7x4; however, remains clinically acceptable. Further evaluation in a large cohort of patients is underway.