On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Endoluminal and Interstitial Brachytherapy for the Treatment of Gastrointestinal Malignancies: a Systematic Review.

Radiation therapy is an integral component in the multimodality management of many gastrointestinal (GI) cancers at all stages of clinical presentation. With recent advances in technology and radiation delivery, external beam radiation therapy (EBRT) can be delivered with reduced toxicity. However, despite these advances, EBRT doses are still limited by the presence of radiosensitive serial structures near clinical targets in the GI tract. Relative to EBRT techniques, brachytherapy techniques have a lower integral dose and more rapid fall-off, allowing for high-dose delivery with little normal tissue exposure. Given the unique characteristics of brachytherapy, it is an attractive strategy to treat GI malignancies. This review addresses the application of both high-dose rate brachytherapy (HDRBT) and low-dose rate brachytherapy (LDRBT) to multiple GI malignancies for both definitive and palliative management.

Dosimetric comparison of Acuros XB with collapsed cone convolution/superposition and anisotropic analytic algorithm for stereotactic ablative radiotherapy of thoracic spinal metastases.

The aim of this study is to compare the recent Eclipse Acuros XB (AXB) dose calculation engine with the Pinnacle collapsed cone convolution/superposition (CCC) dose calculation algorithm and the Eclipse anisotropic analytic algorithm (AAA) for stereotactic ablative radiotherapy (SAbR) treatment planning of thoracic spinal (T-spine) metastases using IMRT and VMAT delivery techniques. The three commissioned dose engines (CCC, AAA, and AXB) were validated with ion chamber and EBT2 film measurements utilizing a heterogeneous slab-geometry water phantom and an anthropomorphic phantom. Step-and-shoot IMRT and VMAT treatment plans were developed and optimized for eight patients in Pinnacle, following our institutional SAbR protocol for spinal metastases. The CCC algorithm, with heterogeneity corrections, was used for dose calculations. These plans were then exported to Eclipse and recalculated using the AAA and AXB dose calculation algorithms. Various dosimetric parameters calculated with CCC and AAA were compared to that of the AXB calculations. In regions receiving above 50% of prescription dose, the calculated CCC mean dose is 3.1%-4.1% higher than that of AXB calculations for IMRT plans and 2.8%-3.5% higher for VMAT plans, while the calculated AAA mean dose is 1.5%-2.4% lower for IMRT and 1.2%-1.6% lower for VMAT. Statistically significant differences (p < 0.05) were observed for most GTV and PTV indices between the CCC and AXB calculations for IMRT and VMAT, while differences between the AAA and AXB calculations were not statistically significant. For T-spine SAbR treatment planning, the CCC calculations give a statistically significant overestimation of target dose compared to AXB. AAA underestimates target dose with no statistical significance compared to AXB. Further study is needed to determine the clinical impact of these findings.

Optimizing Online Adaptation Timing in the Treatment of Locally Advanced Cervical Cancer.

PURPOSE: Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared. MATERIALS AND METHODS: A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test. RESULTS: Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART. CONCLUSIONS: This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume.

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening-a prospective vaginal length and dose correlation.

PURPOSE: Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). MATERIALS AND METHODS: Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. RESULTS: The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. CONCLUSION: Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

The accuracy of artificial intelligence deformed nodal structures in cervical online cone-beam-based adaptive radiotherapy.

Background and Purpose: Online cone-beam-based adaptive radiotherapy (ART) adjusts for anatomical changes during external beam radiotherapy. However, limited cone-beam image quality complicates nodal contouring. Despite this challenge, artificial-intelligence guided deformation (AID) can auto-generate nodal contours. Our study investigated the optimal use of such contours in cervical online cone-beam-based ART. Materials and Methods: From 136 adaptive fractions across 21 cervical cancer patients with nodal disease, we extracted 649 clinically-delivered and AID clinical target volume (CTV) lymph node boost structures. We assessed geometric alignment between AID and clinical CTVs via dice similarity coefficient, and 95% Hausdorff distance, and geometric coverage of clinical CTVs by AID planning target volumes by false positive dice. Coverage of clinical CTVs by AID contour-based plans was evaluated using D100, D95, V100%, and V95%. Results: Between AID and clinical CTVs, the median dice similarity coefficient was 0.66 and the median 95 % Hausdorff distance was 4.0 mm. The median false positive dice of clinical CTV coverage by AID planning target volumes was 0. The median D100 was 1.00, the median D95 was 1.01, the median V100% was 1.00, and the median V95% was 1.00. Increased nodal volume, fraction number, and daily adaptation were associated with reduced clinical CTV coverage by AID-based plans. Conclusion: In one of the first reports on pelvic nodal ART, AID-based plans could adequately cover nodal targets. However, physician review is required due to performance variation. Greater attention is needed for larger, daily-adapted nodes further into treatment.

Intramedullary brachytherapy for the treatment of long bone metastatic disease: A case report.

Case: A 56-year-old woman with metastatic melanoma and femoral lesions with impending pathologic fracture was indicated for intramedullary brachytherapy (IMBT) and intramedullary nail. Conclusions: IMBT + intramedullary nail is a new technique for the treatment of long bone metastases. IMBT maximizes radiation to the tumor and minimizes radiation to surrounding tissues. It allows the patient to resume systemic treatment expediently. Our cadaver model and patient were both treated for femoral metastases; however, this technique allows for the treatment of any long bone. This is a safe technique that minimizes treatment time compared with other standard radiation regimens.

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

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

Organ sparing treatment for penile cancer using a 3D-printed high-dose-rate brachytherapy applicator.

PURPOSE: We present a case study of the treatment of localized squamous cell carcinoma on the glans penis with a custom-fabricated high-dose-rate (HDR) brachytherapy applicator. METHODS AND MATERIALS: A cylindrically shaped applicator was fabricated with eight embedded channels suitable for standard plastic brachytherapy catheters. An additional custom silicone bolus/sleeve was designed to be used with the 3D-printed applicator to provide an additional offset from the source to skin to reduce the surface dose and for patient comfort. RESULTS: The patient (recurrent cT1a penile cancer) underwent CT simulation, and the brachytherapy plan was created with a nominal prescription dose of 40 Gy in 10 fractions given bidaily to the surface, and 35 Gy at 5 mm depth. Dose coverage to the clinical target volume was 94% (D90). Most fractions were treated with only 5-10 min of setup time. Follow up visits up to 1 year showed no evidence of disease with no significant changes in urinary and sexual function and limited cosmetic detriment to the patient. CONCLUSIONS: Patient-specific organ-sparing HDR plesiotherapy using 3D printing technology can provide reliable and reproducible patient setup and may be effective in achieving disease control for superficial penile cancer, although preserving patient quality of life.

Feasibility of eradication of breast cancer cells remaining in postlumpectomy cavity and draining lymph nodes following intracavitary injection of radioactive immunoliposomes.

Most diagnosed early stage breast cancer cases are treated by lumpectomy and adjuvant radiation therapy, which significantly decreases the locoregional recurrence but causes inevitable toxicity to normal tissue. By using a technique of preparing liposomes carrying technetium-99m ((99m)Tc), rhenium-186 ((186)Re), or rhenium-188 ((188)Re) radionuclides, as well as chemotherapeutic agents, or their combination, for cancer therapy with real time image-monitoring of pharmacokinetics and prediction of therapy effect, this study investigated the potential of a novel targeted focal radiotherapy with low systemic toxicity using radioactive immunoliposomes to treat both the surgical cavity and draining lymph nodes in a rat breast cancer xenograft positive surgical margin model. Immunoliposomes modified with either panitumumab (anti-EGFR) or bevacizumab (anti-VEGF) were remote loaded with (99m)Tc diagnostic radionuclide, and injected into the surgical cavity of female nude rats with positive margins postlumpectomy. Locoregional retention and systemic distribution of (99m)Tc-immunoliposomes were investigated by nuclear imaging, stereofluorescent microscopic imaging, and gamma counting. Histopathological examination of excised draining lymph nodes was performed. The locoregional retention of (99m)Tc-immunoliposomes in each animal was influenced by the physiological characteristics of the surgical site of individual animals. Panitumumab- and bevacizumab-liposome groups had higher intracavitary retention compared with the control liposome groups. Draining lymph node uptake was influenced by both the intracavitary radioactivity retention level and metastasis status. The panitumumab-liposome group had higher accumulation on the residual tumor surface and in the metastatic lymph nodes. Radioactive liposomes that were cleared from the cavity were metabolized quickly and accumulated at low levels in vital organs. Therapeutic radionuclide-carrying specifically targeted panitumumab- and bevacizumab-liposomes have increased potential compared to non-antibody targeted liposomes for postlumpectomy focal therapy to eradicate remaining breast cancer cells inside the cavity and draining lymph nodes with low systemic toxicity.

Change in image-guided planning strategies over time impacts oncologic and survival outcomes for intracavitary cervical cancer brachytherapy.

PURPOSE: Intracavitary cervical brachytherapy (BT) has transitioned from a two-dimensional nonvolumetric (NV) dosimetry system to three-dimensional computed tomography (CT) and/or magnetic resonance imaging (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 toxicity. METHODS AND MATERIALS: A single site retrospective review of 95 locally advanced cervical cancer patients treated with concurrent chemoradiation and high dose rate BT from 2009 to 2016 were divided into three BT planning groups: point-A based NV dosimetry using CT imaging (n = 37), CT-based volumetric dosimetry (n = 33), and MRI-based volumetric dosimetry (n = 25). Overall survival (OS), progression free survival (PFS), and pelvic control (PC) at 5 years were plotted using Kaplan-Meier curves. Univariate and multivariate (MVA) cox proportional-hazards models calculated hazard-ratios (HZ). Finally, acute and late grade 3-4 toxicities were compared between the cohorts. RESULTS: Both MRI and CT had significantly less D2cc to bowel (p < 0.001) and sigmoid (p < 0.001) compared to NV-based planning. On MVA, age (<60 vs. ≥60 years) was significant for worse 5-year OS (HZ: 2.48) and PC (HZ: 5.25). MRI, with NV as the reference, had significantly improved 5-year OS (HZ: 0.26), PFS (HZ: 0.34) and PC (HZ: 0.16). There was no significant difference in grade ≥3 toxicities between the cohorts. CONCLUSIONS: 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.

Brachial Plexus Tolerance to Single-Session SABR in a Pig Model.

PURPOSE: The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. METHODS AND MATERIALS: Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. RESULTS: Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. CONCLUSIONS: The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

Volumetric Modulated Arc Therapy Enabled Total Body Irradiation (VMAT-TBI): Six-year Clinical Experience and Treatment Outcomes.

Total body irradiation is an important part of the conditioning regimens frequently used to prepare patients for allogeneic hematopoietic stem cell transplantation (SCT). Volumetric-modulated arc therapy enabled total body irradiation (VMAT-TBI), an alternative to conventional TBI (cTBI), is a novel radiotherapy treatment technique that has been implemented and investigated in our institution. The purpose of this study is to (1) report our six-year clinical experience in terms of treatment planning strategy and delivery time and (2) evaluate the clinical outcomes and toxicities in our cohort of patients treated with VMAT-TBI. This is a retrospective single center study. Forty-four patients at our institution received VMAT-TBI and chemotherapy conditioning followed by allogeneic SCT between 2014 and 2020. Thirty-two patients (73%) received standard-dose TBI (12-13.2 Gy in 6-8 fractions twice daily), whereas 12 (27%) received low-dose TBI (2-4 Gy in one fraction). Treatment planning, delivery, and treatment outcome data including overall survival (OS), relapse-free survival (RFS), and toxicities were analyzed. The developed VMAT-TBI planning strategy consistently generated plans satisfying our dose constraints, with planning target volume coverage >90%, mean lung dose ∼50% to 75% of prescription dose, and minimal hotspots in critical organs. Most of the treatment deliveries were <100 minutes (range 33-147, mean 72). The median follow-up was 26 months. At the last follow-up, 34 of 44 (77%) of patients were alive, with 1- and 2-year OS of 90% and 79% and RFS of 88% and 71%, respectively. The most common grade 3+ toxicities observed were mucositis (31 patients [71%]) and nephrotoxicity (6 patients [13%]), both of which were deemed multifactorial in cause. Four patients (9%) in standard-dose cohort developed grade 3+ pneumonitis, with 3 cases in the setting of documented respiratory infection and only 1 (2%) deemed likely related to radiation alone. VMAT-TBI provides a safe alternative to cTBI. The dose modulation capability of VMAT-TBI may lead to new treatment strategies, such as simultaneous boost and further critical organ sparing, for better malignant cell eradication, immune suppression, and lower toxicities.

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: effects of nonuniform intratumoral dose distribution.

PURPOSE: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. METHODS: 99mTc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186Re/ 18Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. RESULTS: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for 186Re/188Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. CONCLUSIONS: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.

Effects From Nonuniform Dose Distribution in the Spinal Nerves of Pigs: Analysis of Normal Tissue Complication Probability Models.

PURPOSE: Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig. METHODS AND MATERIALS: Common phenomenological and semimechanistic NTCP models were fit using the maximum likelihood estimate method to dose-response data from spinal nerve irradiation studies in pigs. Statistical analysis was used to compare how well each model fit the data. Model parameters were then applied to a previously published dose distribution used for spinal cord irradiation in rats under the assumption of a similar dose-response. RESULTS: The Lyman-Kutcher-Burman model, relative seriality, and critical volume model fit the spinal nerve data equally well, but the mean dose logistic and relative seriality models gave the best fit after penalizing for the number of model parameters. The minimum dose logistic regression model was the only model showing a lack of fit. When extrapolated to a 0.5-cm simulated square-wave-like dose distribution, the serial behaving models showed negligible increase in dose-response curve. The Lyman-Kutcher-Burman model and relative seriality models showed significant shifting of NTCP curves due to parallel behaving parameters. The critical volume model gave the closest match to the rat data. CONCLUSIONS: Several phenomenological and semimechanistic models were observed to adequately describe the increase in the radiation tolerance of the spinal nerves when changing the irradiated length from 1.5 to 0.5 cm. Contrary to common perception, model parameters suggest parallel behaving tissue architecture. Under the assumption that the spinal nerve response to radiation is similar to that of the spinal cord, only the critical volume model was robust when extrapolating to outcome data from a 0.5-cm square-wave-like dose distribution, as was delivered in rodent spinal cord irradiation research.

Simultaneous needle catheter selection and dwell time optimization for preplanning of high-dose-rate brachytherapy of prostate cancer.

PURPOSE: Needle catheter positions critically affect the quality of treatment plans in prostate cancer high-dose-rate (HDR) brachytherapy. The current standard needle positioning approach is based on human intuition, which cannot guarantee a high-quality plan. This study proposed a method to simultaneously select needle catheter positions and determine dwell time for preplanning of HDR brachytherapy of prostate cancer. METHODS: We formulated the needle catheter selection problem and inverse dwell time optimization problem in a unified framework. In addition to the dose objectives of the planning target volume (PTV) and organs at risk (OARs), the objective function incorporated a group-sparsity term with a needle-specific adaptive weighting scheme to generate high-quality plans with the minimal number of needle catheters. The optimization problem was solved by a fast-iterative shrinkage-thresholding algorithm. For validation purposes, we tested the proposed algorithm on 10 patient cases previously treated at our institution and compared the resulting plans with plans generated using needle catheters selected manually. RESULTS: Compared to the plan with manually selected needle catheters, when normalizing both plans to the same PTV coverage V 100% = 95%, the plans generated by the proposed algorithm reduced median V 125% from 65% to 64%, but increased median V 150% from 35% to 38%, and V 200% from 14% to 16%. All planning objectives were met. All clinically important dosimetric parameters of OARs were reduced. D 1cc of bladder and rectum were reduced from 8.57 Gy to 8.50 Gy and from 7.24 Gy to 6.80 Gy, respectively. D max of urethra was reduced from 15.85 Gy to 15.77 Gy. The median number of selected needle catheters was reduced by two. The computational time for solving the proposed optimization problem was ∼90 s using MATLAB. CONCLUSION: The proposed algorithm was able to generate plans for prostate cancer HDR brachytherapy preplanning with increased median conformity index (0.73-0.77) and slightly lower median homogeneity index (0.64-0.62) with the number of selected needles reduced by two compared to the manual needle selection approach.

Upfront radiotherapy with brachytherapy for medically inoperable and unresectable patients with high-risk endometrial cancer.

OBJECTIVES: Comprehensive surgery with adjuvant therapy is standard of care for high-risk endometrial cancers, whereas upfront radiotherapy with brachytherapy is indicated for inoperable/unresectable patients, irrespective of risk. We evaluated outcomes for inoperable/unresectable patients with high-risk endometrial cancer (HREC: stage III and/or grade 3) and low-risk endometrial cancer (LREC: stage I/II and grade 1/2) treated with upfront radiotherapy. METHODS: Twenty-nine patients with inoperable/unresectable endometrial cancer were treated with upfront radiotherapy at an academic medical center from 2012 to 2019. Cancer-specific survival (CSS), overall survival (OS), and recurrence rates between patients with HREC and LREC were compared. RESULTS: Median follow-up was 17.0 months (range 3.7-54.0). Twenty cancers were stage I + II and nine were stage III. Twenty-one cancers were grade 1 + 2 and eight were grade 3. Thirteen patients (45%) had HREC. Twenty-five patients received radiotherapy/chemoradiotherapy for primary treatment, while 4 patients received chemoradiotherapy before surgery. All patients underwent high dose rate brachytherapy (HDR) with 7 receiving HDR alone and 22 receiving external beam radiation and HDR. Two-year CSS was 100% for both HREC and LREC patients (log-rank p = 0.32). There was no OS difference between HREC and LREC patients (2-year: 73% vs. 77%; log-rank p = 0.33). Four HREC and 1 LREC patients recurred with one local recurrence in each group. There were no acute grade ≥3 and two late grade ≥3 gastrointestinal/genitourinary toxicities. CONCLUSIONS: Upfront radiotherapy for inoperable/unresectable HREC patients was well tolerated with high local control and CSS rates. Upfront radiotherapy with brachytherapy remains important even for high-risk inoperable and unresectable endometrial cancer patients.

Low-cost 3D print-based phantom fabrication to facilitate interstitial prostate brachytherapy training program.

PURPOSE: The purpose of this study was to manufacture a realistic and inexpensive prostate phantom to support training programs for ultrasound-based interstitial prostate brachytherapy. METHODS AND MATERIALS: Five phantom material combinations were tested and evaluated for material characteristics; Ecoflex 00-30 silicone, emulsion silicone with 20% or 50% mineral oil, and regular or supersoft polyvinyl chloride (PVC). A prostate phantom which includes an anatomic simulated prostate, urethra, seminal vesicles, rectum, and normal surrounding tissue was created with 3D-printed molds using 20% emulsion silicone and regular and supersoft PVC materials based on speed of sound testing. Needle artifact retention was evaluated at weekly intervals. RESULTS: Speed of sound testing demonstrated PVC to have the closest ultrasound characteristics of the materials tested to that of soft tissue. Several molds were created with 3D-printed PLA directly or cast on 3D-printed PLA with high heat resistant silicone. The prostate phantom fabrication workflow was developed, including a method to produce dummy seeds for low-dose-rate brachytherapy practice. A complete phantom may be fabricated in 1.5-2 h, and the material cost for each phantom was approximated at $23.98. CONCLUSIONS: A low-cost and reusable phantom was developed based on 3D-printed molds for casting. The proposed educational prostate phantom is an ideal cost-effective platform to develop and build confidence in fundamental brachytherapy procedural skills in addition to actual patient caseloads.

Existence of a Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy.

PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed. RESULTS: Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal. CONCLUSIONS: A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model.

A machine-learning-based prediction model of fistula formation after interstitial brachytherapy for locally advanced gynecological malignancies.

PURPOSE: External beam radiotherapy combined with interstitial brachytherapy is commonly used to treat patients with bulky, advanced gynecologic cancer. However, the high radiation dose needed to control the tumor may result in fistula development. There is a clinical need to identify patients at high risk for fistula formation such that treatment may be managed to prevent this toxic side effect. This work aims to develop a fistula prediction model framework using machine learning based on patient, tumor, and treatment features. METHODS AND MATERIALS: This retrospective study included 35 patients treated at our institution using interstitial brachytherapy for various gynecological malignancies. Five patients developed rectovaginal fistula and two developed both rectovaginal and vesicovaginal fistula. For each patient, 31 clinical features of multiple data types were collected to develop a fistula prediction framework. A nonlinear support vector machine was used to build the prediction model. Sequential backward feature selection and sequential floating backward feature selection methods were used to determine optimal feature sets. To overcome data imbalance issues, the synthetic minority oversampling technique was used to generate synthetic fistula cases for model training. RESULTS: Seven mixed data features were selected by both sequential backward selection and sequential floating backward selection methods. Our prediction model using these features achieved a high prediction accuracy, that is, 0.904 area under the curve, 97.1% sensitivity, and 88.5% specificity. CONCLUSIONS: A machine-learning-based prediction model of fistula formation has been developed for patients with advanced gynecological malignancies treated using interstitial brachytherapy. This model may be clinically impactful pending refinement and validation in a larger series.