The role of radiation therapy in the management of liver cancers, both primary and metastatic, has changed drastically over the past several decades. Although conventional radiation was limited by ...technology, the advent of advanced image-guided radiotherapy and the rise in evidence for and popularity of stereotactic body radiotherapy have expanded the indications for radiation in these two distinct disease types. Magnetic resonance imaging–guided radiation therapy, daily online adaptive radiotherapy, and proton radiotherapy are some of many modern radiotherapy techniques that allow for increasingly efficacious treatment of intrahepatic disease while simultaneously allowing for increased normal tissue sparing, including sparing of the normal liver and the radiosensitive luminal gastrointestinal tract. Modern radiation therapy should be considered along with approaches such as surgical resection and radiofrequency ablation for the management of liver cancers of diverse histologies. Herein we describe the use of modern radiotherapy in two example settings, colorectal liver metastases and intrahepatic cholangiocarcinoma, and how external beam radiotherapy provides options within multidisciplinary discussions to elect optimal patient-specific treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Online adaptive stereotactic radiotherapy allows for improved target and organ at risk (OAR) delineation and inter-fraction motion management via daily adaptive planning. The use of adaptive SBRT for ...the treatment of pancreatic cancer (performed until now using only MRI or CT on rails-guided adaptive radiotherapy), has yielded promising outcomes. Herein we describe the first reported case of cone beam CT-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of pancreatic cancer.
A 61-year-old female with metastatic pancreatic cancer presented for durable palliation of a symptomatic primary pancreatic mass. She was prescribed 35 Gy/5 fractions utilizing CT-STAR. The patient was simulated utilizing an end-exhale CT with intravenous and oral bowel contrast. Both initial as well as daily adapted plans were created adhering to a strict isotoxicity approach in which coverage was sacrificed to meet critical luminal gastrointestinal OAR hard constraints. Kilovoltage cone beam CTs were acquired on each day of treatment and the radiation oncologist edited OAR contours to reflect the patient's anatomy-of-the-day. The initial and adapted plan were compared using dose volume histogram objectives, and the superior plan was delivered. Use of the initial treatment plan would have resulted in nine critical OAR hard constraint violations. The adapted plans achieved hard constraints in all five fractions for all four critical luminal gastrointestinal structures.
We report the successful treatment of a patient with pancreatic cancer treated with CT-STAR. Prior to this treatment, the delivery of ablative adaptive radiotherapy for pancreatic cancer was limited to clinics with MR-guided and CT-on-rails adaptive SBRT technology and workflows. CT-STAR is a promising modality with which to deliver stereotactic adaptive radiotherapy for pancreatic cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abiraterone is an important agent in the treatment of advanced prostate cancer. Early changes in prostate-specific antigen while on abiraterone in patients with metastatic castrate-resistant prostate ...cancer potentially have financial and health implications for patients. Limited data is available on early prostate-specific antigen change and subsequent survival given phase III trials did not measure prostate-specific antigen changes before 12 weeks.
A single-center retrospective study was performed. Metastatic castrate-resistant prostate cancer patients treated with abiraterone (without prior enzalutamide) at Tulane Cancer Center were reviewed with a focus on early prostate-specific antigen decline and relationship to overall survival.
A total of 110 patients were analyzed for prostate-specific antigen response of ≥ 30 and > 50% at 4, 8, and 12 weeks. A prostate-specific antigen response of either > 30% or > 50% at 4, 8, or 12 weeks was associated with improved overall survival at all time points except > 50% decline at 8 weeks. Multivariate analysis indicated, for all time points, that early prostate-specific antigen declines were predictive of overall survival. The neutrophil to lymphocyte ratio and docetaxel pretreatment also were predictive in many, but not all, of the multivariate analyses.
A > 30% or > 50% prostate-specific antigen decline at 4, 8, or 12 weeks provides important information regarding subsequent overall survival for patients with metastatic castrate-resistant prostate cancer. While these data require validation with a large, multi-institutional trial, they can provide physicians with information regarding prognosis and the timing of expected outcomes. These data affirms the notion that prostate-specific antigen responses as early as 4 weeks after abiraterone initiation can be used to inform both patients and physicians about metastatic castrate-resistant prostate cancer outcomes after initiating treatment with this important but costly therapeutic choice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•CT-STAR met all constraints in 98% of fractions.•Simulated treatment with non-adapted plans would have yielded 94 OAR violations.•100% of non-adapted plans generated had ≥1 OAR hard constraint ...violation.•Median time per fraction was 36.28 minutes (27.57–55.86).•CT-STAR is a feasible modality for ablating locally advanced pancreatic cancer.
We conducted a prospective, in silico imaging clinical trial to evaluate the feasibility and potential dosimetric benefits of computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of locally advanced pancreatic cancer (LAPC).
Eight patients with LAPC received five additional CBCTs on the ETHOS system before or after their standard of care radiotherapy treatment. Initial plans were created based on their initial simulation anatomy (PI) and emulated adaptive plans were created based on their anatomy-of-the-day (PA). The prescription was 50 Gy/5 fractions. Plans were created under a strict isotoxicity approach, in which organ-at-risk (OAR) constraints were prioritized over planning target volume coverage. The PI was evaluated on the patient’s anatomy-of-the-day, compared to the daily PA, and the superior plan was selected. Feasibility was defined as successful completion of the workflow in compliance with strict OAR constraints in ≥80% of fractions.
CT-STAR was feasible in silico for LAPC and improved OAR and/or target dosimetry in 100% of fractions. Use of the PI based on the patient’s anatomy-of-the-day would have yielded a total of 94 OAR constraint violations and ≥1 hard constraint violation in 40/40 fractions. In contrast, 39/40 PA met all OAR constraints. In one fraction, the PA minimally exceeded the large bowel constraint, although dosimetrically improved compared to the PI. Total workflow time per fraction was 36.28 minutes (27.57–55.86).
CT-STAR for the treatment of LAPC cancer proved feasible and was dosimetrically superior to non-adapted CT-stereotactic body radiotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of radiotherapy in the management of primary and metastatic liver malignancies has expanded in recent years due to advances such as IGRT and SBRT. MRI-guided radiotherapy (MRgRT) has arisen ...as an excellent option for the management of hepatocellular carcinoma, cholangiocarcinoma, and liver metastases due to the ability to combine improved hepatic imaging with conformal treatment planning paradigms like adaptive radiotherapy and advanced motion management techniques. Herein we review the data for MRgRT for liver malignancies, as well as describe workflow and technical considerations for the 2 commercially available MRgRT delivery platforms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We successfully implemented an APRT for CBCT-guided adaptive contouring.•We hypothesized APRT led contouring would reduce adaptive contouring times.•183 adaptive sessions were reviewed, 136 APRT led ...and 47 non-APRT led.•Average APRT led contouring time was 8 min vs. 20 min for non-APRT led.•The APRT statistically significantly improved contouring and total workflow times.
We successfully implemented an APRT specializing in CBCT-guided online adaptive contouring. These data show statistical improvements in contouring time with APRT-led vs non-APRT led ART contouring, suggesting that an APRT specifically trained to manage the ART process may reduce physician workload and patient treatment time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Developed knowledge-based tools for robust adaptive radiotherapy (ART) planning for stereotactic pancreatic ART.•Population-based conifdence intervals determined for daily adaptive variations.•This ...tool was able to identify adaptive plans with large deviations or planning errors.•This technology can be used as an ART clinical trial QA tool and improve overall ART quality at an institution.
We aimed to develop knowledge-based tools for robust adaptive radiotherapy (ART) planning to determine on-table adaptive DVH metric variations or planning process errors for stereotactic pancreatic ART. We developed volume-based dosimetric identifiers to identify deviations of ART plans from simulation plans.
Two patient cohorts who were treated on MR-Linac for pancreas cancer were included in this retrospective study; a training cohort and a validation cohort. All patients received 50 Gy in 5 fractions. PTV-OPT was generated by subtracting the critical organs plus a 5 mm-margin from PTV. Several metrics that potentially can identify failure-modes were calculated including PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5%. The difference between each DVH metric in each adaptive plan with the DVH metric in simulation plan was calculated. The 95% confidence interval (CI) of the variations in each DVH metric was calculated for the patient training cohort. Variations in DVH metrics that exceeded the 95% CI for all fractions in training and validation cohort were flagged for retrospective investigation for root-cause analysis to determine their predictive power for identifying failure-modes.
The CIs for the PTV & PTV_OPT V95% and PTV & PTV_OPT D95%/D5% were ± 13%, ± 5%, ± 0.1, ± 0.03, respectively. We estimated the positive predictive value and negative predictive value of our method to be 77% and 89%, respectively, for the training cohort, and 80% for both in the validation cohort.
We developed dosimetric indicators for ART planning QA to identify population-based deviations or planning errors during online adaptive process for stereotactic pancreatic ART. This technology may be useful as an ART clinical trial QA tool and improve overall ART quality at an institution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and ...neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Herein we report the clinical and dosimetric experience for patients with metastases treated with palliative simulation-free radiation therapy (SFRT) at a single institution.
SFRT was performed at a ...single institution. Multiple fractionation regimens were used. Diagnostic imaging was used for treatment planning. Patient characteristics as well as planning and treatment time points were collected. A matched cohort of patients with conventional computed tomography simulation radiation therapy (CTRT) was acquired to evaluate for differences in planning and treatment time. SFRT dosimetry was evaluated to determine the fidelity of SFRT. Descriptive statistics were calculated on all variables and statistical significance was evaluated using the Wilcoxon signed rank test and t test methods.
Thirty sessions of SFRT were performed and matched with 30 sessions of CTRT. Seventy percent of SFRT and 63% of CTRT treatments were single fraction. The median time to plan generation was 0.88 days (0.19-1.47) for SFRT and 1.90 days (0.39-5.23) for CTRT (P = .02). The total treatment time was 41 minutes (28-64) for SFRT and 30 minutes (21-45) for CTRT (P = .02). In the SFRT courses, the maximum and mean deviations in the actual delivered dose from the approved plans for the maximum dose were 4.1% and 0.07%, respectively. All deliveries were within a 5% threshold and deemed clinically acceptable.
Palliative SFRT is an emerging technique that allowed for a statistically significant lower time to plan generation and was dosimetrically acceptable. This benefit must be weighed against increased total treatment time for patients receiving SFRT compared with CTRT, and appropriate patient selection is critical.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
FIGO stage IVA cervical cancer is a unique diagnosis that conveys a poor prognosis. Despite the use of PET/CT for staging, concurrent chemotherapy, and image-guided brachytherapy, overall survival ...(OS) in these patients is low. Treatment requires aggressive use of radiotherapy and chemotherapy. We report results of a prospective observational cohort study for patients with de novo stage IVA cervical cancer treated at a single institution.
Patients with a new diagnosis of stage IVA cervical cancer treated at an academic institution between 1997 and 2020 were prospectively monitored. Staging was retroactively assigned using the 2018 FIGO staging system. All patients had a PET/CT prior to treatment and were treated with definitive intent radiotherapy with or without chemotherapy. The primary outcome of interest was OS. Secondary outcomes were local control, progression-free survival (PFS), and disease-specific survival (DSS).
32 patients with de novo stage IVA cervical cancer were treated with definitive intent radiotherapy. Median follow-up time was 4.27 years (1.31–10.35). 22/32 (69%) of patients received brachytherapy as a part of their definitive treatment, and 28/32 (88%) received chemotherapy concurrently with radiotherapy. 14/32 (44%) of patients had no evidence of disease at last follow-up. The 5-year local control, PFS, DFS, and OS estimates were 79%, 49%, 53%, and 48%, respectively. On multivariate analysis, complete metabolic response was associated with a statistically significant improvement in PFS (HR = 0.256, 95% CI = 0.078–0.836, p = 0.024) and OS (HR = 0.273, 95% CI 0.081–0.919).
These data demonstrate a robust OS in patients with stage IVA cervical cancer when treated with definitive chemoradiotherapy.
•Stage IVA cervical cancer is a disease with a classically poor prognosis.•32 patients with stage IVA disease treated with definitive chemoradiotherapy were prospectively observed.•69% of patients received brachytherapy, and 88% of patients received concurrent chemotherapy.•Overall survival was 48% at five years and 44% of patients had no evidence of disease at last follow-up.•Complete metabolic response was associated with an improved progression-free and overall survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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