Inter-fractional portability of deep learning models for lung target tracking on cine imaging acquired in MRI-guided radiotherapy.

MRI-guided radiotherapy systems enable beam gating by tracking the target on planar, two-dimensional cine images acquired during treatment. This study aims to evaluate how deep-learning (DL) models for target tracking that are trained on data from one fraction can be translated to subsequent fractions. Cine images were acquired for six patients treated on an MRI-guided radiotherapy platform (MRIdian, Viewray Inc.) with an onboard 0.35 T MRI scanner. Three DL models (U-net, attention U-net and nested U-net) for target tracking were trained using two training strategies: (1) uniform training using data obtained only from the first fraction with testing performed on data from subsequent fractions and (2) adaptive training in which training was updated each fraction by adding 20 samples from the current fraction with testing performed on the remaining images from that fraction. Tracking performance was compared between algorithms, models and training strategies by evaluating the Dice similarity coefficient (DSC) and 95% Hausdorff Distance (HD95) between automatically generated and manually specified contours. The mean DSC for all six patients in comparing manual contours and contours generated by the onboard algorithm (OBT) were 0.68 ± 0.16. Compared to OBT, the DSC values improved 17.0 - 19.3% for the three DL models with uniform training, and 24.7 - 25.7% for the models based on adaptive training. The HD95 values improved 50.6 - 54.5% for the models based on adaptive training. DL-based techniques achieved better tracking performance than the onboard, registration-based tracking approach. DL-based tracking performance improved when implementing an adaptive strategy that augments training data fraction-by-fraction.

Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer.

The optimal treatment paradigm for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below limits of detection by imaging) and benefit from systemic therapy. To risk-stratify and identify the patients most likely to benefit from locally consolidative RT, we performed a multi-institutional cohort study of 1487 patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). In total, 1880 liquid biopsies were performed and approximately 20% of patients (n = 309) had ctDNA measured prior to RT and after their diagnosis of oligometastatic disease. Patients with undetectable ctDNA (pathogenic or likely pathogenic variants in plasma using the Tempus xF assay) before RT had significantly improved progression-free survival (PFS) (P = 0.004) and overall survival (OS) (P = 0.030). ctDNA maximum variant allele frequency (VAF) pre-RT and ctDNA mutational burden pre-RT were both significantly inversely correlated with PFS (maximum VAF P = 0.008, mutational burden P = 0.003) and OS (maximum VAF P = 0.007, mutational burden P = 0.045). These findings were corroborated by multivariate Cox proportional hazards models that included eight additional clinical and genomic parameters. Overall, these data suggest that in patients with oligometastatic NSCLC, pre-RT ctDNA can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged PFS and OS. Similarly, ctDNA may be useful to identify undiagnosed micrometastatic disease where it may be appropriate to prioritize systemic therapies.

Prospective In Silico Evaluation of Cone-Beam Computed Tomography-Guided StereoTactic Adaptive Radiation Therapy (CT-STAR) for the Ablative Treatment of Ultracentral Thoracic Disease.

Purpose: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage. Methods and Materials: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico. Initial, nonadaptive plans (PI) were created based on simulation images and simulated adaptive plans (PA) were based on study CBCTs. 55 Gy/5 fractions was prescribed, with OAR constraint prioritization over PTV coverage under a strict isotoxicity approach. PI were applied to patients' anatomy of the day and compared with daily PA using dose-volume histogram metrics, with selection of superior plans for simulated delivery. Feasibility was defined as completion of the end-to-end adaptive workflow while meeting strict OAR constraints in ≥80% of fractions. CT-STAR was performed under time pressures to mimic clinical adaptive processes. Results: Seven patients were accrued, 6 with intraparenchymal tumors and 1 with a subcarinal lymph node. CT-STAR was feasible in 34 of 35 simulated fractions. In total, 32 dose constraint violations occurred when the PI was applied to anatomy-of-the-day across 22 of 35 fractions. These violations were resolved by the PA in all but one fraction, in which the proximal bronchial tree dose was still numerically improved through adaptation. The mean difference between the planning target volume and gross total volume V100% in the PI and the PA was -0.24% (-10.40 to 9.90) and -0.62% (-11.00 to 8.00), respectively. Mean end-to-end workflow time was 28.21 minutes (18.02-50.97). Conclusions: CT-STAR widened the dosimetric therapeutic index of ultracentral thorax SBRT compared with nonadaptive SBRT. A phase 1 protocol is underway to evaluate the safety of this paradigm for patients with ultracentral early-stage NSCLC.

Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer.

The optimal treatment for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease can experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below current limits of detection by imaging) that may benefit from further prioritization of systemic therapy. To better risk-stratify this population and identify the patients most likely to benefit from locally consolidative radiation therapy, we performed a multi-institutional cohort study of patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA). Among this real-world cohort of 1,487 patients undergoing analysis (using the Tempus xF assay), a total of 1,880 ctDNA liquid biopsies along with paired clinical data were obtained across various timepoints. Approximately 20% (n=309) of patients had ctDNA obtained prior to RT and after their diagnosis of oligometastatic disease. Samples were de-identified and analyzed for mutational burden and variant frequencies of detectable deleterious (or likely deleterious) mutations in plasma. Patients with undetectable ctDNA before RT had significantly improved progression-free survival and overall survival compared to patients with detectable ctDNA prior to RT. In patients that received RT, 598 pathogenic (or likely deleterious) variants were identified. ctDNA mutational burden pre-RT and ctDNA maximum variant allele frequency (VAF) pre-RT were both significantly inversely correlated with both progression-free (P = 0.0031 for mutational burden, P = 0.0084 for maximum VAF) and overall survival (P = 0.045 for mutational burden, P = 0.0073 for maximum VAF). Patients without detectable ctDNA prior to RT had significantly improved progression-free survival (P = 0.004) and overall survival (P = 0.03) compared to patients with detectable ctDNA prior to RT. These data suggest that in patients with oligometastatic NSCLC, pre-radiotherapy ctDNA analysis can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged progression-free and overall survival. Similarly, ctDNA may be useful to identify those patients with undiagnosed micrometastatic disease, in whom it may be appropriate to prioritize systemic therapy.

Simulated computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of locally advanced pancreatic cancer.

BACKGROUND AND PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: CT-STAR for the treatment of LAPC cancer proved feasible and was dosimetrically superior to non-adapted CT-stereotactic body radiotherapy.

Heart Sparing Radiotherapy Techniques in Breast Cancer: A Focus on Deep Inspiration Breath Hold.

Adjuvant radiation therapy is a critical component of breast cancer management. However, when breast cancer patients receive incidental radiation to the heart, there is an increased risk of cardiac disease and mortality. This is most common for patients with left-sided breast cancers and those receiving nodal irradiation as part of treatment. The overall risk of cardiac toxicity increases 4-16% with each Gray increase in mean heart radiation dose, with data suggesting that no lower limit exists which would eliminate cardiac risk entirely. Radiation techniques have improved over time, leading to lower cardiac radiation exposure than in the past. This decline is expected to reduce the incidence of radiation-induced heart dysfunction in patients. Deep inspiration breath hold (DIBH) is one such technique that was developed to reduce the risk of cardiac death and coronary events. DIBH is a non-invasive approach that capitalizes on the natural physiology of the respiratory cycle to increase the distance between the heart and the therapeutic target throughout the course of radiation therapy. DIBH has been shown to decrease the mean incidental radiation doses to the heart and left anterior descending coronary artery by approximately 20-70%. In this review, we summarize different techniques for DIBH and discuss recent data on this technique.

In Silico Trial of Computed Tomography-Guided Stereotactic Adaptive Radiation Therapy (CT-STAR) for the Treatment of Abdominal Oligometastases.

PURPOSE: We conducted a prospective, in silico clinical imaging study (NCT04008537) to evaluate the feasibility of cone beam computed tomography-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of abdominal oligometastases. We hypothesized that CT-STAR produces improved dosimetry compared with nonadapted CT-stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Eight patients receiving stereotactic body radiation therapy for abdominal oligometastatic disease received 5 additional kV cone beam CTs on the ETHOS system. These additional cone beam CTs were used for imaging during an emulator treatment session. Initial plans were created based on their simulation (PI) and emulated adaptive plans were based on anatomy-of-the-day. The prescription was 50 Gy out of 5 fractions. Organ-at-risk (OAR) constraints were prioritized over planning target volume coverage under a strict isotoxicity approach. The PI was applied to the patient's anatomy-of-the-day and compared with the reoptimized adaptive plans using dose-volume histogram metrics, with selection of the superior plan. Feasibility was defined as completion of the adaptive workflow and compliance with strict OAR constraints in ≥80% of fractions. Fractions were performed under time pressures by a physician and physicist to mimic the adaptive process. RESULTS: CT-STAR was feasible, with successful workflow completion in 38 out of 40 (95%) fractions. PI application to daily anatomy created OAR constraint violations in 30 out of 40 (75%) fractions. There were 8 stomach, 18 duodenum, 16 small bowel, and 11 large bowel PI OAR constraint violations. In contrast, OAR violations occurred in 2 out of 40 (5%) adaptive plans (both small bowel violations, both improved from the PI). CT-STAR also improved gross tumor volume V100 and D95 coverage in 25 out of 40 (63%) and 20 out of 40 (50%) fractions, respectively. Zero out of 40 (0%) fractions were deemed nonfeasible due to poor image quality and/or inability to delineate structures. Adaptation time per fraction was a median of 22.59 minutes (10.97-47.23). CONCLUSIONS: CT-STAR resolved OAR hard constraint violations and/or improved target coverage in silico compared with nonadapted CT-guided stereotactic body radiation therapy for the ablation of abdominal oligometastatic disease. Although limitations of this study include its small sample size and in silico design, the consistently high-quality cone beam CT images captured and comparable timing metrics to prior adaptive studies suggest that CT- STAR is a viable treatment paradigm for the ablation of abdominal oligometastatic disease. Clinical trials are in development to further evaluate CT-STAR in the clinic.

Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Chemotherapy With Nonoperative Intent of the Primary for Locoregional Complete Responders.

PURPOSE: Nonoperative management with short-course radiation therapy (SCRT) as a component of definitive therapy for oligometastatic rectal cancer has not been previously reported. This single-institution retrospective analysis evaluates treatment with SCRT in combination with chemotherapy (SCRT-CTX) with nonoperative intent for patients with a locoregional clinical complete response (cCR). METHODS AND MATERIALS: Thirty-six patients with newly diagnosed oligometastatic rectal cancer were treated with SCRT-CTX between January 1, 2018, and May 31, 2020. Digital rectal examination, endoscopy, and imaging (computed tomography or magnetic resonance imaging) were used to determine cCR. Medically operable patients without cCR underwent surgical resection of the primary rectal tumor. Patients with cCR who experienced a local failure received salvage surgery. Rates of hospitalization related to primary tumor disease and pelvic symptoms were reviewed. Overall survival (OS) and progression free survival were evaluated. RESULTS: Seventeen percent (6/36) of patients achieved cCR after SCRT-CTX. Eleven percent (4) of patients experienced a local failure. OS for all patients was 83% (71%-96%) at 12 months and 57% (41%-80%) at 24 months. Progression free survival for all patients was 56% (41%-74%) at 12 months and 10% (3.1%-35%) at 24 months. On multivariate analysis, having received more than 4 months of chemotherapy (hazard ratio = 0.21; 95% confidence interval, 0.06-0.71; P = .01) and definitive treatment of metastatic site (hazard ratio = 0.17; 95% confidence interval, 0.05-0.66; P = .01) predicted for improved OS. The number of patients requiring hospitalization due to obstruction (8/36, 22%), rectal bleeding (5/36, 14%), or need for permanent ostomy placement (5/36, 14%) was low, and there was a decrease in endorsement of obstructive symptoms and rectal bleeding after completion of SCRT-CTX. CONCLUSIONS: SCRT-CTX with nonoperative intent for patients with a locoregional cCR may be a reasonable treatment option for patients with newly diagnosed oligometastatic rectal adenocarcinoma and demonstrates excellent control of pelvic disease and symptoms. Increased duration of chemotherapy within the treatment paradigm may improve oncologic outcomes.

Stereotactic Radiation for Lung Cancer: A Practical Approach to Challenging Scenarios.

Stereotactic body radiation therapy (SBRT) is an effective and well-tolerated treatment for medically inoperable patients with early stage NSCLC. SBRT is a noninvasive treatment involving the delivery of ablative radiation doses with high precision in the course of a few treatments. Relative to conventionally fractionated radiation, SBRT achieves superior local control and survival. SBRT use has increased dramatically in the past 15 years and is currently considered the standard of care in cases of inoperable early stage NSCLC. It is being increasingly applied to more complex patient populations at higher risk of treatment-related toxicity. In these more complex patients, there is an increasing need to balance patient and treatment factors in selecting the optimal patients for SBRT. Here, we review several challenging clinical scenarios often encountered in thoracic multidisciplinary tumor boards.

Hyperbaric oxygen therapy for radiation-induced brachial plexopathy, a case report and literature review.

AIM: To report a case of radiation-induced brachial plexopathy (RIBP) with significant radiographic and clinical improvement after a course of hyperbaric oxygen (HBO). BACKGROUND: RIBP is a rare complication after radiotherapy to the neck and axilla. There are no standard treatment options, with empirical use pharmacotherapy being predominately used, which has had mixed results.HBO is efficacious for the treatment of other severe radiation-induced side effects, however, its benefit in RIBP has conflicting reports. CASE PRESENTATION: A 45-year-old male, with a 33 pack-year smoking history, presented with a 6-month history of a progressive left neck mass. The final diagnosis was unknown primary squamous cell carcinoma of the head and neck. He received intensity-modulated radiation therapy (IMRT) with 70 Gy prescribed to the gross tumor volume (PTV HR) and 56 Gy to the oropharynx, nasopharynx, and bilateral lymphatics (PTV SR) in 35 daily fractions with three cycles of concurrent cisplatin at 100 mg/m2.Fifteen months following therapy completion, the patient began to endorse symptoms of left brachial plexopathy. Decadron was prescribed for 2 weeks, trental and vitamin E for 6 months, and HBO. The patient returned for follow-up 2 months after completing 30 dives of HBO at 2.4 atmospheres for 2 hours per session. He reported pain resolution and full range of motion of his left arm. CONCLUSIONS: The best management strategy of RIBP is prevention by reducing total RT doses and close follow-up. However, when RIBP occurs, we recommend treatment with HBO therapy, steroids, trental, and vitamin E as tolerable.