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

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB)

Background: Stereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system. Method: This was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not. Results: A total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n = 44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n = 103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p < 0.001). The rate of complication was low and not statistically different between cohorts (p = 0.44). Conclusions: The FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked

CT-based online adaptive radiotherapy improves target coverage and organ at risk (OAR) avoidance in stereotactic body radiation therapy (SBRT) for prostate cancer

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. METHODS: Seven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student\u27s RESULTS: Seven patients completed 35 Fx\u27s of adaptive RT. Daily adaptation resulted in a statistically significant mean improvement in PTV V100 for all targets: [21.4 % ± 4.3 % for PTV 4000 (p \u3c 0.0001); 8.7 % ± 1.1 % for PTV 3625 (p \u3c 0.0001); and 11.5 % ± 3.1 % for PTV 2500 (p = 0.0013)]. Mean rectal D0.03 was significantly reduced by 38.8 cGy ± 5.95 cGy (p \u3c 0.0001) per fraction (194 cGy/5 fractions) compared to the initial plans. There was a modest increase in bladder dose of 10.9 cGy ± 4.93 cGy per fraction (p = 0.0424) for the adaptive plans. The adaptive plans met bladder constraints for every fraction. There were no statistically significant differences between sigmoid or bowel dose for adapted vs. initial plans. No patients experienced acute CTCAE grade ≥ 3 GI/GU adverse events (median F/U 9.5 months). All statistically significant differences were maintained in the presence and absence of rectal hydrogel spacer (p \u3c 0.05). CONCLUSIONS: CT-based online adaptive SBRT resulted in statistically significant and clinically meaningful improvements in PTV coverage and D0.03 cc dose to the rectum. A trial evaluating CT adaptive whole-pelvis prostate SBRT is underway

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 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 P 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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Pineal Region Glioblastoma, a Case Report and Literature Review

Introduction: Pineal region glioblastoma multiforme (GBM) is a rare disease entity with a generally poor prognosis. We present a case of a patient with an unresectable pineal region GBM treated with chemoradiation with favorable outcome.Case background: A 65-year-old patient who was presented with visual symptoms was found to have a pineal region tumor on imaging. A stereotactic biopsy showed a World Health Organization Grade IV GBM, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, isocitrate dehydrogenase 1 and 2 wild type. The patient was treated with radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide. Disease progression occurred at 58 weeks post-biopsy, which prompted the initiation of bevacizumab. The patient was alive and functioning well as of his last follow up, 166 weeks from the initial biopsy.Discussion: On our review of the literature, 24 cases of pineal region GBM have been reported. The median reported survival for these previously reported cases was 6 months (range, 2--24 months). This patient has the longest overall survival reported to date for a patient with this diagnosis. This is the first patient in the literature with pineal region GBM who has been reported to have MGMT promoter methylation.Concluding remarks: Although pineal region GBM is a rare disease entity with a gener- ally poor prognosis, long-term survival is achievable for select patients. MGMT promoter methylation may potentially have prognostic value. Favorable control of recurrent disease with the use of bevacizumab is possible

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB)

Abstract Background Stereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system. Method This was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not. Results A total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n-‰=-‰44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n-‰=-‰103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p-‰&lt;-‰0.001). The rate of complication was low and not statistically different between cohorts (p-‰=-‰0.44). Conclusions The FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked. Trial registration An exemption for this retrospective review was granted by the East Carolina University IRB under UMCIRB 15-001726