Comprehensive Bridging Radiotherapy for Limited Pre-CART Non-Hodgkin Lymphoma.

This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.

First Report of Chagas Disease Vector Species Triatoma sanguisuga (Hemiptera: Reduviidae) Infected with Trypanosoma cruzi in Delaware.

In July and October 2023, two live triatomine bugs were found inside a home in New Castle County, Delaware. The bugs were identified as Triatoma sanguisuga, the most widespread triatomine bug species in the United States. Triatoma sanguisuga is a competent vector of Trypanosoma cruzi, the causative agent of Chagas disease. The two specimens were tested via real-time PCR (qPCR) for infection with T. cruzi, and one of the specimens was positive. Despite T. sanguisuga being endemic to the area, attainment of accurate species identification and T. cruzi testing of the bugs required multiple calls to federal, state, private, and academic institutions over several months. This constitutes the first report of T. sanguisuga infected with T. cruzi in Delaware. In addition, this is the first published report of T. sanguisuga in New Castle County, the northernmost and most densely populated county in Delaware. New Castle County still conforms to the described geographic range of T. sanguisuga, which spans from Texas to the East Coast of the United States. The T. cruzi infection prevalence of the species has not been studied in the northeastern United States, but collections in southern states have found prevalences as high as 60%. The Delaware homeowner's lengthy pursuit of accurate information about the vector highlights the need for more research on this important disease vector in Delaware.

Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.

Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts. Methods: Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8-10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4-9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5-31.2) and CNS disease control rate was 92.0% (95% CI: 74.0-99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4-8.3) and median CNS TTP of 7.1 months (95% CI: 4.4-9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events. Conclusions: Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.

Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Prompt Pain Relief From Bone Metastases: The Virtual Simulation Program.

Purpose: Rapid pain relief for patients with bone metastases can be a challenge due to the lengthy and complex radiation therapy workflow. The purpose of this study was to evaluate the time (in days) between initial radiation oncology consultation and start of palliative radiation treatment after implementing an alternative virtual simulation palliative workflow. Methods and Materials: Patients meeting strict criteria were selected for virtual simulation, which included only those with painful bone metastases who were recommended palliative radiation therapy using standard anterior-posterior/posterior-anterior or opposed lateral fields. A recent (within 30 days) diagnostic computed tomography (CT) scan clearly visualizing the target volume was required for treatment planning. For comparison, a reference group of 40 consecutive patients with bone metastases who underwent in-person CT simulation before virtual simulation implementation was reviewed. Results: Forty-five patients were treated for painful bone metastases as part of the virtual simulation program from May 2021 to October 2022. Regarding travel distance, 23 patients lived locally (<50 miles from the treatment center) and 22 patients were distant (≥50 miles from the treatment center). Average time from consultation to treatment for all patients undergoing virtual simulation was 3.7 days, compared with 7.5 days for patients undergoing in-person CT simulation (3.8 days sooner, on average; P ≤ .001). Before full implementation of the virtual simulation program, 5 eligible patients participated in a virtual simulation pilot from April 2021 to May 2021, in which each patient was contoured and planned on both a pre-existing diagnostic CT scan and a standard CT simulation scan. For virtual simulation-based plans, the average V90, V95, and V99 were 99.99%, 99.87%, and 96.70%. No significant planning target volume (PTV) coverage difference was found on subsequent in-person CT simulation scans. Conclusions: The virtual simulation program decreased the time from consultation to start of treatment by more than 50% for patients recommended palliative radiation therapy for painful bone metastases. This benefit was most significant for outpatients traveling ≥50 miles for treatment. Virtual simulation-based planning can be considered for patients anxious to proceed with radiation therapy quickly or in underserved settings with limited transportation options to regional treatment centers.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. Design, Setting, and Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Main Outcomes and Measures: Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). Results: A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions and Relevance: In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Patterns of progression after immune checkpoint inhibitors for Hodgkin lymphoma: implications for radiation therapy.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs.

Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

How to know when little kidneys are in trouble: a review of current tools for diagnosing AKI in neonates.

Due to a plethora of risk factors, including prematurity, neonates are at risk for acute kidney injury (AKI) and, once established, AKI is associated with poor outcomes. The most widely used AKI biomarker is creatinine, despite research demonstrating creatinine to be a suboptimal tool for diagnosing neonatal AKI. This article uses an amalgamated case study to illustrate the inadequacies of creatinine for detection of preterm AKI and to present a range of novel AKI biomarkers relevant to the neonatal population. Clinical evaluation of novel AKI biomarkers is needed to improve precision and rapidity of AKI management in neonates.

Carbon Ion Radiotherapy: An Evidence-Based Review and Summary Recommendations of Clinical Outcomes for Skull-Base Chordomas and Chondrosarcomas.

Skull-base chordoma and chondrosarcoma are rare radioresistant tumors treated with surgical resection and/or radiotherapy. Because of the established dosimetric and biological benefits of heavy particle therapy, we performed a systematic and evidence-based review of the clinical outcomes of patients with skull-base chordoma and chondrosarcoma treated with carbon ion radiotherapy (CIRT). A literature review was performed using a MEDLINE search of all articles to date. We identified 227 studies as appropriate for review, and 24 were ultimately included. The published data illustrate that CIRT provides benchmark disease control outcomes for skull-base chordoma and chondrosarcoma, respectively, with acceptable toxicity. CIRT is an advanced treatment technique that may provide not only dosimetric benefits over conventional photon therapy but also biologic intensification to overcome mechanisms of radioresistance. Ongoing research is needed to define the magnitude of benefit, patient selection, and cost-effectiveness of CIRT compared to other forms of radiotherapy.

Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma. Design: This is a retrospective study with results reported in 2023. The median follow-up time was 43 months. Setting: Single tertiary care comprehensive cancer center. Participants: Under an approved Institutional Review Board protocol, the Palantir Foundry software system was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least one tumor marker measured at MD Anderson between 2016 and 2023. Results: A total of 1,338 patients with appendiceal adenocarcinoma were included, with a median age of 56.5 years. The majority of the patients had metastatic disease (80.7%). CEA was elevated in more than half of the patients tested (56%), while CA19-9 and CA125 were elevated in 34% and 27%, respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; 82% vs 95%, 84% vs 92%, and 69% vs 93% elevated vs normal for CEA, CA19-9, and CA125 respectively (all p<0.0001). Quantitative evaluation of tumor markers increased prognostic ability. Patients with highly elevated (top 10th percentile) CEA, CA19-9 or CA125 had markedly worse survival with 5-year survival rates of 59%, 64%, and 57%, respectively (HR vs. normal : 9.8, 6.0, 7.6, all p<0.0001). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease elevated CEA, CA19-9 or CA125 were all still associated worse survival (HR vs. normal : 3.4, 1.8, 3.9, p<0.0001 for CEA and CA125, p=0.0019 for CA19-9). Interestingly tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high relative to low-grade tumors (18.3 vs. 15.0, p=0.0009). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with a 11-fold increased risk of death in patients with all three tumor markers elevated relative to those with none elevated. Mutation in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions: These findings demonstrate the utility of measuring CEA, CA19-9, and CA125 in the management of appendiceal adenocarcinoma. Given their prognostic value, all three biomarkers should be included in the initial workup of patients diagnosed with appendiceal adenocarcinoma.

Optimising motor development in the hospitalised infant with CHD: factors contributing to early motor challenges and recommendations for assessment and intervention.

BACKGROUND: Neurodevelopmental challenges are the most prevalent comorbidity associated with a diagnosis of critical CHD, and there is a high incidence of gross and fine motor delays noted in early infancy. The frequency of motor delays in hospitalised infants with critical CHD requires close monitoring from developmental therapies (physical therapists, occupational therapists, and speech-language pathologists) to optimise motor development. Currently, minimal literature defines developmental therapists' role in caring for infants with critical CHD in intensive or acute care hospital units. PURPOSE: This article describes typical infant motor skill development, how the hospital environment and events surrounding early cardiac surgical interventions impact those skills, and how developmental therapists support motor skill acquisition in infants with critical CHD. Recommendations for healthcare professionals and those who provide medical or developmental support in promotion of optimal motor skill development in hospitalised infants with critical CHD are discussed. CONCLUSIONS: Infants with critical CHD requiring neonatal surgical intervention experience interrupted motor skill interactions and developmental trajectories. As part of the interdisciplinary team working in intensive and acute care settings, developmental therapists assess, guide motor intervention, promote optimal motor skill acquisition, and support the infant's overall development.

Impact of KRAS Mutations and Co-mutations on Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p<0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p=0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p<0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p=0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p=0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n=408).

Efficacy and Tolerability of ALK/MET Combinations in Patients With ALK-Rearranged Lung Cancer With Acquired MET Amplification: A Retrospective Analysis.

Introduction: MET amplification is a potentially actionable resistance mechanism in ALK-rearranged (ALK+) lung cancer. Studies describing treatment outcomes of this molecular subgroup are lacking. Methods: We assembled a cohort of patients with ALK+ lung cancer and acquired MET amplification (identified by tissue or plasma) who received regimens targeting both ALK and MET. Efficacy and safety were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 and Common Terminology Criteria for Adverse Events version 4.03, respectively. Results: A total of 12 patients were included in the series. MET amplification was detected after a median of 1.5 (range 1-5) lines of therapy. Four distinct regimens were implemented to address MET amplification: crizotinib (n = 2), lorlatinib plus crizotinib (n = 6), alectinib plus capmatinib (n = 3), and alectinib plus crizotinib (n = 1). Partial responses were observed in five (42%) of 12 patients, including patients who received crizotinib (n = one of two), lorlatinib plus crizotinib (n = three of six), and alectinib plus capmatinib (n = one of three). Primary progression was observed in four patients (33%). Grades 1 to 2 peripheral edema, occurring in seven (58%) patients, was found with both crizotinib and capmatinib. One patient required dose reduction of capmatinib plus alectinib for persistent grade 2 edema. Across the regimens, one patient discontinued therapy for toxicity, specifically neurocognitive toxicity from lorlatinib plus crizotinib. At progression on ALK+ MET therapy, potential resistance mechanisms included MET copy number changes and ALK kinase domain mutations. Conclusions: Combined ALK and MET inhibition is associated with moderate antitumor activity in patients with ALK+ NSCLC with concurrent MET amplification. Prospective studies are indicated to confirm activity and identify individuals most likely to benefit from the treatment.

Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.

PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.

Integrated Radiology, Pathology, and Pharmacy Program to Accelerate Access to Osimertinib.

PURPOSE: Targeted therapy yields superior outcomes relative to genotype-agnostic therapy for patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. Workflows that facilitate timely detection of EGFR mutations and early dispensation of osimertinib can improve management of this disease. METHODS: We developed an Integrated Radiology, Pathology, and Pharmacy Program to minimize delays in initiating osimertinib. The intervention consisted of parallel workflows coupling interventional radiology, surgical pathology, and analysis of nucleic acids from frozen tissue with early pharmacy engagement. We compared time to EGFR testing results and time to treatment for participating patients with those of historical cohorts. RESULTS: Between January 2020 and December 2021, 222 patients participated in the intervention. The median turnaround time from biopsy to EGFR results was 1 workday. Forty-nine (22%) tumors harbored EGFR exon 19 deletions or EGFR L858R. Thirty-one (63%) patients were prescribed osimertinib via the intervention. The median interval between osimertinib prescription and osimertinib dispensation was 3 days; dispensation occurred within 48 hours for 42% of patients. The median interval between biopsy and osimertinib dispensation was 5 days. Three patients received osimertinib within 24 hours of EGFR results. Compared with patients with EGFR-mutant non-small-cell lung cancer who were diagnosed through routine workflows, the intervention led to a significant reduction in median time between biopsy and EGFR results (1 v 7 days; P < .01) and median time to treatment initiation (5 v 23 days; P < .01). CONCLUSION: Combining radiology and pathology workflows with early parallel pharmacy engagement leads to a significant reduction in time to initiating osimertinib. Multidisciplinary integration programs are essential to maximize clinical utility of rapid testing.

Consolidative radiotherapy for residual fluorodeoxyglucose activity on day +30 post CAR T-cell therapy in non-Hodgkin lymphoma.

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.

Developmental care pathway for hospitalised infants with CHD: on behalf of the Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative.

Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, "Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease," includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.