Surveillance evaluations in patients with stage I, II, III, or resectable IV melanoma who were treated with curative intent: A systematic review.

PURPOSE: Appropriate surveillance of patients with melanoma treated with curative intent is vital to improve patient outcomes. A systematic review was conducted to capture locoregional recurrence and metastatic disease, and to evaluate the effectiveness of various surveillance strategies. METHODS: MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and National Cancer Institute Clinical Trials Database were searched. Randomized controlled trials (RCTs) and comparative studies reporting at least one patient-related outcome were included. Exclusion criteria included: published in non-English or recruited >20 % or an uncertain percentage of non-target patients without conducting a subgroup analysis for the target patients. This review was registered at PROSPERO (CRD42021246482). RESULTS: Among 17,978 publications from the literature search, one RCT and five non-randomized comparative studies were included and comprised 4016 patients. The aggregate evidence certainty was low for the RCT and very low for the comparative studies, as assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. For patients with stage IA-IIC melanoma, a reduced follow-up schedule with clinical follow-up strategies alone may be safe and cost-effective. For stage IIC-IIIC patients, at least two serial PET/CT or whole-body CT and brain MRI imaging within a median follow-up of 31.2 months may detect 50 % of recurrences that lead to additional management, such as surgery. PET/CT may have a higher positive predictive value and lower false positive rate compared with CT alone in detecting recurrence in stage I-III patients. CONCLUSION: Surveillance protocols should be based on individual risk of recurrence and established best practices when formulating follow-up strategies, as suggested by the studies reviewed. Future high-quality studies are needed to clarify the frequency of imaging follow-up strategies, especially in patients with high-risk stage II melanoma.

A cost-effective approach to measurements of fluorophore temperature sensitivity and temperature change with reasonable accuracy.

The demand for measuring fluorophore temperature sensitivity and temperature change in chemical or biological samples has spurred the search for effective methods. While infrared (IR) light-based thermal devices are popular, they are limited to surface temperature measurement. Fluorescence-based thermometry, which utilizes intensity, lifetime, polarization, and spectrum change, provides the temperature information directly from the samples and can have high temporal and spatial resolution. However, measuring fluorescence can be tricky and expensive. A cost-effective approach to achieving reasonable accuracy is highly desired. This study introduces such an approach, employing a light-emitting diode (LED) for fluorophore excitation and a laser diode (LD) for sample heating, with a phone camera recording fluorescence changes. A data processing method converts the video into digital data, processed through digital filters. Utilizing a small-volume cuvette enhances heating efficiency. This study serves as a practical guide for inexperienced individuals, including students, instructors, and researchers, facilitating entry into the field and navigating the complexities of fluorescence-based thermometry.

The Role of Adjuvant Radiotherapy for the Treatment of Resected High-Risk Stage III Cutaneous Melanoma in the Era of Modern Systemic Therapies.

Modern adjuvant systemic therapies (STs) have revolutionized the management of stage III melanoma. Currently, the role of adjuvant radiotherapy (RT) remains unclear. In this single-center retrospective study, patients with clinically detectable stage III melanoma with high-risk features for lymph node basin (LNB) recurrence and whose tumors were fully resected with complete lymphadenectomy (CLD) between 2010 and 2019 were assessed. We determined the cumulative incidence (CIF) of LNB recurrence and any disease recurrence or progression using competing risk analysis. A total of 108 patients were identified; the median age was 59 years (24-92), and 74 (69%) were men. A total of 51 (42%) received adjuvant RT, 22 (20%) received adjuvant ST, and 35 (32%) received no adjuvant therapy. The advent of ST changed clinical practice, with a significant increase in the use of adjuvant ST and a decrease in the use of RT when comparing practice patterns before and after 2015 (p < 0.001). The 3-year CIF of LNB recurrence was similar in patients treated with adjuvant RT (6.3%) and adjuvant ST (9.8%). The 3-year CIF of any disease recurrence or progression was lower in patients receiving adjuvant ST (24%) compared to those receiving adjuvant RT (52%) or no adjuvant therapy (55%, p = 0.06). Three-year overall survival (OS) was not significantly different in patients treated with ST compared to those not treated with any ST (p = 0.118). Despite ST replacing RT as the dominant adjuvant treatment modality, this change in practice has not resulted in increased LNB recurrence for patients at high risk of LNB recurrence following CLD.

Canadian Consensus Recommendations on the Management of Extensive-Stage Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC). The literature search included guidelines, systematic reviews, and randomized controlled trials. Regular meetings were held from September 2022 to March 2023 to discuss the available evidence to propose and agree upon specific recommendations. The panel addressed biomarkers and histological features that distinguish SCLC from non-SCLC and other neuroendocrine tumours. Evidence for initial and subsequent systemic therapies was reviewed with consideration for patient performance status, comorbidities, and the involvement and function of other organs. The resulting consensus recommendations herein will help clarify evidence-based management of ES-SCLC in routine practice, help clinician decision-making, and facilitate the best patient outcomes.

A Systematic Review of Idiopathic Secondary Stenosis Following Index Surgery for Craniosynostosis.

BACKGROUND: Primary craniosynostosis is a congenital craniofacial disorder in which cranial sutures prematurely close. Iatrogenic secondary stenosis is abnormal cranial suture closure caused by surgical manipulation of the suture. In contrast, idiopathic secondary stenosis develops in a suture that did not undergo surgical manipulation. The objective of this systematic review was to consolidate and characterize the incidence, classification, and management of idiopathic secondary stenosis in the literature. METHODS: Literature from PubMed, Web Of Science, and EMBASE from 1970 to March 2022 was reviewed. The following information was extracted for individual patients: incidence of idiopathic secondary stenosis, index primary craniosynostosis, primary surgical correction, presenting signs of secondary stenosis, management, and further complications. RESULTS: Seventeen articles detailing 1181 patients were included. Ninety-one developed idiopathic secondary stenosis (7.7%). Only 3 of these patients were syndromic. The most common index craniosynostosis was sagittal synostosis (83.5%). The most common suture undergoing idiopathic secondary stenosis was the coronal suture (91.2%). Patients presented at a median age of 24 months. The most common presenting sign was a radiologic finding (85.7%), although some patients presented with headache or head deformity. Only 2 patients, both syndromic, had complications following surgical correction of secondary stenosis. CONCLUSIONS: Idiopathic secondary stenosis is a rare, long-term complication following index surgical repair of craniosynostosis. It can occur following any surgical technique. It most commonly affects the coronal suture but can affect any of the sutures, including pansynostosis. Surgical correction is curative in nonsyndromic patients.

Multimodal Intervention Assessing the Appropriateness of Acid Suppression Therapy is Associated With Reduced Prescriptions at the Time of Discharge for Hospitalized Inpatients.

Background: Acid suppression therapy (AST), including proton pump inhibitors and histamine 2 receptor antagonists, are an overused class of medications. When used inappropriately, AST leads to polypharmacy, increased healthcare costs, and possible negative health consequences. Objective: To assess whether an intervention including prescriber education combined with a pharmacist-driven protocol was effective in reducing the percentage of patients who were discharged with inappropriate AST. Methods: This was a prospective pre-post study of adult patients who were prescribed AST before or during their admission to an internal medicine teaching service. All internal medicine resident physicians received education on appropriate AST prescribing. During the 4-week intervention period, dedicated pharmacists assessed the appropriateness of AST and made recommendations regarding deprescribing if no appropriate indication was identified. Results: During the study period, there were 14 166 admissions during which patients were prescribed AST. Out of the 1143 admissions during the intervention period, appropriateness of AST was assessed by a pharmacist for 163 patients. AST was determined to be inappropriate for 52.8% (n = 86) of patients and discontinuation or de-escalate of therapy occurred in 79.1% (n = 68) of these cases. The percentage of patients discharged on AST decreased from 42.5% before the intervention to 39.9% after the intervention (P = .007). Conclusion: This study suggests that a multimodal deprescribing intervention reduced prescriptions for AST without an appropriate indication at the time of discharge. To increase the efficiency of the pharmacist assessment several workflow improvements were identified. Further study is necessary to understand the long-term outcomes of this intervention.

The Potential Revolution of Cancer Treatment with CRISPR Technology.

Immuno-oncology (IO) and targeted therapies, such as small molecule inhibitors, have changed the landscape of cancer treatment and prognosis; however, durable responses have been difficult to achieve due to tumor heterogeneity, development of drug resistance, and adverse effects that limit dosing and prolonged drug use. To improve upon the current medicinal armamentarium, there is an urgent need for new ways to understand, reverse, and treat carcinogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 is a powerful and efficient tool for genome editing that has shown significant promise for developing new therapeutics. While CRISPR/Cas9 has been successfully used for pre-clinical cancer research, its use in the clinical setting is still in an early stage of development. The purpose of this review is to describe the CRISPR technology and to provide an overview of its current applications and future potential as cancer therapies.

Use of radiation therapy among patients with Extensive-stage Small-cell lung cancer receiving Immunotherapy: Canadian consensus recommendations.

OBJECTIVES: Thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) are commonly used in the management of extensive-stage small-cell lung cancer (ES-SCLC); however, Phase III trials of first-line immunotherapy often excluded these options. Guidance is needed regarding appropriate use of TRT, PCI, and magnetic resonance imaging (MRI) surveillance while new data are awaited. MATERIALS AND METHODS: In two web-based meetings, a pan-Canadian expert working group of five radiation oncologists and four medical oncologists addressed eight clinical questions regarding use of radiation therapy (RT) and MRI surveillance among patients with ES-SCLC receiving immunotherapy. A targeted literature review was conducted using PubMed and conference proceedings to identify recent (January 2019-April 2022) publications in this setting. Fifteen recommendations were developed; online voting was conducted to gauge agreement with each recommendation. RESULTS: After considering recently available evidence across lung cancer populations and clinical experience, the experts recommended that all patients with a response to chemo-immunotherapy, good performance status (PS), and limited metastases be considered for consolidation TRT (e.g., 30 Gy in 10 fractions). When considered appropriate after multidisciplinary team discussion, TRT can be initiated during maintenance immunotherapy. All patients who respond to concurrent chemo-immunotherapy should undergo restaging with brain MRI to guide decision-making regarding PCI versus MRI surveillance alone. MRI surveillance should be conducted for two years after response to initial therapy. PCI (e.g., 25 Gy in 10 fractions or 20 Gy in 5 fractions) can be considered for patients without central nervous system involvement who have a response to chemo-immunotherapy and good PS. Concurrent treatment with PCI and immunotherapy or with TRT, PCI, and immunotherapy is appropriate after completion of initial therapy. All recommendations were agreed upon unanimously. CONCLUSIONS: These consensus recommendations provide practical guidance regarding appropriate use of RT and immunotherapy in ES-SCLC while awaiting new clinical trial data.

Facial Dermal Filler Injection and Vaccination: A 12-Year Review of Adverse Event Reporting and Literature Review.

BACKGROUND: Following authorization of 2 COVID-19 vaccines in December 2020, media attention increased towards postvaccine adverse events (AEs) in patients with facial dermal filler injections. OBJECTIVES: The purpose of this study was to characterize vaccine-related facial dermal filler AEs by scrutinizing the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried from January 1, 2011 to January 28, 2023 for facial dermal filler medical device reports (MDRs) discussing vaccination-related AEs. A PubMed (National Institutes of Health, Bethesda, MD) literature review on dermal filler AEs was then conducted. Data were analyzed with descriptive statistics. RESULTS: Of 10,637 MDRs identified, 33 were included. There were 25 MDRs (75.8%) related to COVID-19 vaccination. Hyaluronic acid-based fillers were described in 31 MDRs (93.9%). AEs were mostly reported within days postinjection (n = 7, 21.2%), but ranged from immediately (n = 2, 6.1%) to months (n = 6, 18.2%) postinjection. Most AEs were reported postvaccine (n = 17, 51.5%) vs postfiller (n = 14, 42.4%). In 26 reports (78.8%), AEs occurred at the site of filler injection. Most MDRs described inflammation/swelling (n = 21, 28.0%). The literature review returned 302 articles, of which 14 were included. Only 1 article (7.1%) was published in a plastic surgery journal. CONCLUSIONS: Although the pandemic brought attention to COVID-19 vaccine-related facial dermal filler AEs, this study shows a low incidence compared with the millions of vaccine and filler injections administered. Reactions with non-COVID-19 vaccines were also documented. Increased awareness may help providers counsel patients undergoing vaccination and dermal filler implantation.

Implementation of an online and in-person addiction medicine course and its impact on medical students' knowledge on substance use disorders.

BACKGROUND: Substance use is a public health crisis that requires improved education on substance use disorders (SUDs) in medical school curriculum to ensure that the future generation of physicians is prepared to care for this growing patient population. OBJECTIVES: This study evaluates how the implementation of an online and in-person addiction medicine course impacted medical students' knowledge on SUD and caring for patients with SUD. METHODS: 86 third-year and fourth-year medical students participated in either an online or in-person elective course on addiction medicine. Students learned about SUDs through various modalities, such as online SUD modules, clinical encounters, movies, books, participation in support group meetings and learning evidence-based tools to screen or treat patients. To assess the impact of the course curriculum on students' knowledge in treating SUDs, a pre and post survey was administered and analyzed. RESULTS: After completing the SUD course, students showed significant improvement (P < 0.01) in caring for SUD patients. Specifically, they improved in the areas of: assessing a patient with SUD, comfort and knowledge in using motivational interviewing to affect behavior change in a patient with a SUD, and knowledge of community resources related to SUD. Students also showed a significant improvement (P < 0.01) in the number of unique SUDs (such as opioids or alcohol) they felt knowledgeable about and in the number of treatment modalities for unique SUDs. CONCLUSIONS: Implementation of an addiction medicine course that utilizes various teaching modalities can significantly improve medical students' fundamental knowledge on SUD.

3'-Deoxy-3'-(18F) Fluorothymidine Positron Emission Tomography/Computed Tomography in Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy: A Pilot Study.

Purpose: The primary objective was to compare 3'-deoxy-3'-(18F) fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) uptake in 3 cohorts of stereotactic body radiation therapy (SBRT) patients: (1) pre-SBRT, (2) stable post-SBRT lung fibrosis, and (3) suspicious or proven local recurrence post-SBRT. The secondary objectives were to optimize FLT-PET imaging by comparing FLT uptake in respiratory-gated (4-dimensional) versus nongated (3-dimensional) FLT-PET scans. Methods: Patients with early-stage non-small cell lung cancer planned or treated with SBRT at the institution with radiographic findings of fibrosis or recurrence were eligible for the study. All patients underwent imaging with FLT-PET/CT before SBRT in cohort 1 and at fibrosis or recurrence in cohort 2 and 3, respectively. The planned sample size was 20 patients in each cohort, with 60 patients total. FLT-PET standardized uptake value (SUV) variables including SUVmax, SUVmean, SUVpeak, SUV50, and SUV95 were compared among the 3 cohorts using the Kruskal-Wallis test. The correlation of respiratory-gated and nongated FLT-PET SUV variables was performed using the Spearman correlation coefficient. Results: Forty-one patients were recruited for the study (20 in cohort 1, 16 in cohort 2, and 5 in cohort 3) between 2015 and 2019. The majority received a diagnosis of stage I lung cancer (86%), and the most common prescription was 48 Gy in 4 fractions (59%). Respiratory-gated FLT-PET was performed in 35 patients. The FLT SUV variables were well correlated between respiratory-gated and nongated scans (r = 0.8-1.0). The SUVpeak, SUVmean, and SUVmax were significantly lower in the fibrosis cohort compared with the recurrence and pretreatment cohorts. The SUV50 and SUV95 values in the recurrence cohort were statistically similar to the pretreatment cohort. Conclusions: FLT-PET/CT may be helpful in differentiating SBRT-related fibrosis from recurrence. Nongated FLT-PET/CT with reporting of SUVmax and SUV95 values is recommended.

Association of Pretreatment Hippocampal Volume With Neurocognitive Function in Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology/RTOG 0933.

Purpose: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. Methods and Materials: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test-Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. Results: Forty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm3 (range, 1.9-7.4 cm3), 2.8 cm3 (range, 0.9-4.0 cm3), and 2.7 cm3 (range, 1.0-3.7 cm3), respectively. The median total brain volume was 1343 cm3 (range, 1120.5-1738.8 cm3). For all measures of corrected HV, increasing HV was associated with higher baseline HVLT-R TR and DR scores (ρ: range, 0.35-0.40; P-value range, .009-.024) and 4-month TR and DR scores (ρ: range, 0.29-0.40; P-value range, .009-.04), with the exception of right HV and 4-month DR scores (ρ: 0.29; P = .059). There was no significant association between HV and NCF change between baseline and 4 months. Fourteen patients (33.3%) developed NCF deterioration per the primary endpoint of RTOG 0933. There was no significant difference in HV between patients with deteriorated and nondeteriorated NCF, although in all instances, patients with deteriorated NCF had numerically lower HV. Conclusions: Larger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF.

Reconstruction of GRACE Mass Change Time Series Using a Bayesian Framework.

Gravity Recovery and Climate Experiment and its Follow On (GRACE (-FO)) missions have resulted in a paradigm shift in understanding the temporal changes in the Earth's gravity field and its drivers. To provide continuous observations to the user community, missing monthly solutions within and between GRACE (-FO) missions (33 solutions) need to be imputed. Here, we modeled GRACE (-FO) data (196 solutions) between 04/2002-04/2021 to infer missing solutions and derive uncertainties in the existing and missing observations using Bayesian inference. First, we parametrized the GRACE (-FO) time series using an additive generative model comprising long-term variability (secular trend + interannual to decadal variations), annual, and semi-annual cycles. Informative priors for each component were used and Markov Chain Monte Carlo (MCMC) was applied to generate 2,000 samples for each component to quantify the posterior distributions. Second, we reconstructed the new data (229 solutions) by joining medians of posterior distributions of all components and adding back the residuals to secure the variability of the original data. Results show that the reconstructed solutions explain 99% of the variability of the original data at the basin scale and 78% at the one-degree grid scale. The results outperform other reconstructed data in terms of accuracy relative to land surface modeling. Our data-driven approach relies only on GRACE (-FO) observations and provides a total uncertainty over GRACE (-FO) data from the data-generation process perspective. Moreover, the predictive posterior distribution can be potentially used for "nowcasting" in GRACE (-FO) near-real-time applications (e.g., data assimilations), which minimize the current mission data latency (40-60 days).

Patient-Reported and Clinical Outcomes From 5-Fraction SBRT for Oligometastases: A Prospective Single-Institution Study.

PURPOSE: To describe the long-term outcomes of a 5-fraction normal tissue tolerance adapted strategy for the management of oligometastases (OM). METHODS AND MATERIALS: Patients with histologically confirmed solid tumors, ≤5 extracranial metastases, suitable for a definitive approach for all metastatic lesions, at least one lesion suitable for Stereotactic Body Radiotherapy (SBRT), Eastern Coooperative Oncology Group Performance Status ≤2 were eligible. Treatment intervention was a 5-fraction (25-55 Gy) normal tissue adapted dosing strategy. The primary outcome was cumulative local progression rate at 12 months. RESULTS: Between March 2013 and January 2018, 137 patients started SBRT. Median follow-up was 35.7 months. In addition, 107 (78%) patients had a solitary OM. The mean planning target volume D95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D95 was highest for lung lesions (48.7 [standard deviation, 4.7]; biological effective dose using an alpha/beta ratio of 10, 96.1) Gy but was <40 Gy for all other anatomic sites. Two grade 3 toxicities (gastrointestinal bleed) were observed with stomach D0.05 30.3 Gy and 30.4 Gy. The cumulative local progression rate at 12 of 36 months was 16.1% (95% CI, 10-22) and 38.3% (95% CI 30-46.7); overall survival was 90% and 37%, and progression free survival was 58% and 19%, respectively. Mean symptom burden (Edmonton Symptom Assessment Total Score) worsened in patients with progressive disease (+8.8) at 12 months and was paralleled by changes in mean European Organization for Research and Treatment Quality of Life Core Questionnaire Summary Score and Global Health Quality of Life Score. Systemic therapy was initiated in 55% of patients at an average of 12.7 (standard deviation 12.4) months. CONCLUSIONS: If long-term progression free survival is the primary goal of therapy, SBRT for OM achieved this in <20% of patients attributable to a high risk of distant failure. Favorable local progression free survival is accompanied by preservation of quality of life, avoidance of symptom progression and reduced need of antineoplastic therapies at 12 months. Information on symptom burden, quality of life, as well as pattern of antineoplastic therapy use after progressive disease is useful to support conversations between patients, families, and health care providers. Strategies to improve patient selection and reduce distant progression rate remain a priority for further study.

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer.

INTRODUCTION: In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. METHODS: A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. RESULTS: PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. CONCLUSION: PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care.

Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE): A Phase 3 Randomized Clinical Trial.

IMPORTANCE: Palliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear. OBJECTIVE: To examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT. DESIGN, SETTING, AND PARTICIPANTS: Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between June 24, 2016, and March 6, 2019. Data analysis was conducted from January 23, 2020, to October 22, 2021. Patients had up to 1 year of follow-up. Ninety patients at 6 tertiary academic cancer centers who had stage III/IV NSCLC and were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) were included. INTERVENTIONS: Patients were randomized (1:1) to standard RT (control arm) or ES-IMRT. Target coverage was compromised to ensure the maximum esophagus dose was no more than 80% of the RT prescription dose. MAIN OUTCOMES AND MEASURES: The primary outcome was esophageal quality of life (QOL) 2 weeks post-RT, measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy: Esophagus questionnaire. Higher esophageal cancer subscale scores correspond with improved QOL, with a 2- to 3-point change considered clinically meaningful. Secondary outcomes included overall survival, toxic events, and other QOL metrics. Intention-to-treat analysis was used. RESULTS: Between June 24, 2016, and March 6, 2019, 90 patients were randomized to standard RT or ES-IMRT (median age at randomization, 72.0 years [IQR, 65.6-80.3]; 50 [56%] were female). Thirty-six patients (40%) received 20 Gy and 54 (60%) received 30 Gy. For the primary end point, the mean (SD) 2-week ECS score was 50.5 (10.2) in the control arm (95% CI, 47.2-53.8) and 54.3 (7.6) in the ES-IMRT arm (95% CI, 51.9-56.7) (P = .06). Symptomatic RT-associated esophagitis occurred in 24% (n = 11) of patients in the control arm vs 2% (n = 1) in the ES-IMRT arm (P = .002). In a post hoc subgroup analysis based on the stratification factor, reduction in esophagitis was most evident in patients receiving 30 Gy (30% [n = 8] vs 0%; P = .004). Overall survival was similar with standard RT (median, 8.6; 95% CI, 5.7-15.6 months) and ES-IMRT (median, 8.7; 95% CI, 5.1-10.2 months) (P = .62). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, ES-IMRT did not significantly improve esophageal QOL but significantly reduced the incidence of symptomatic esophagitis. Because post hoc analysis found that reduced esophagitis was most evident in patients receiving 30 Gy of RT, these findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02752126.

SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines.

Proteinaceous cysteine residues act as privileged sensors of oxidative stress. As reactive oxygen and nitrogen species have been implicated in numerous pathophysiological processes, deciphering which cysteines are sensitive to oxidative modification and the specific nature of these modifications is essential to understanding protein and cellular function in health and disease. While established mass spectrometry-based proteomic platforms have improved our understanding of the redox proteome, the widespread adoption of these methods is often hindered by complex sample preparation workflows, prohibitive cost of isotopic labeling reagents, and requirements for custom data analysis workflows. Here, we present the SP3-Rox redox proteomics method that combines tailored low cost isotopically labeled capture reagents with SP3 sample cleanup to achieve high throughput and high coverage proteome-wide identification of redox-sensitive cysteines. By implementing a customized workflow in the free FragPipe computational pipeline, we achieve accurate MS1-based quantitation, including for peptides containing multiple cysteine residues. Application of the SP3-Rox method to cellular proteomes identified cysteines sensitive to the oxidative stressor GSNO and cysteine oxidation state changes that occur during T cell activation.

Factors Associated With Hospitalization Among Breast Cancer Patients With COVID-19: A Diverse Multi-Center Los Angeles Cohort Study.

BACKGROUND: The SARS-CoV-2 virus has infected and killed millions of people worldwide. Breast cancer is the most prevalent cancer in women and few studies have investigated the outcomes of patients with a history of breast cancer and COVID-19. We report the clinical outcomes of patients with invasive breast cancer who tested positive for SARS-CoV-2, including hospitalization and death, and evaluate demographic and cancer-related factors associated with these outcomes. PATIENTS: Patients with a history of invasive breast cancer and positive SARS-CoV-2 test from January 1 to December 31, 2020 at two large, academic Los Angeles health systems were included. METHODS: Retrospective chart review of the electronic medical record was performed. Data for demographic and cancer-related factors were manually abstracted. Relationships between outcomes and clinical variables were evaluated using Fisher's exact test and linear regression analysis. RESULTS: Among a total of 132 patients, 40 (30.3%) were hospitalized, while 11 (8.3%) required intensive care support, and 8 patients (6.1%) died. Older age and presence of one or more additional comorbidities were associated with hospitalization and death (P = .010, P = .003, P = .034, P < .001). Hispanic/Latinx ethnicity was associated with hospitalization (P = .047). Cancer treatment was not associated with hospitalization or death. CONCLUSION: In our diverse, multi-center, breast cancer cohort, Hispanic/Latinx ethnicity, older age and presence of other comorbidities were associated with worse outcomes from COVID-19. Breast cancer treatment, including surgery, radiation, systemic therapy, and endocrine therapy, was not associated with hospitalization in our cohort. Further studies are needed to explore the relationship between breast cancer and COVID-19 outcomes.

Indications for the Use of Proton Pump Inhibitors for Stress Ulcer Prophylaxis and Peptic Ulcer Bleeding in Hospitalized Patients.

Proton pump inhibitors are widely used throughout the world for the treatment of gastrointestinal disorders that are related to acid secretion, such as peptic ulcer disease and dyspepsia. Another common indication for proton pump inhibitors is stress ulcer prophylaxis. Proton pump inhibitors have proven efficacy for the treatment of acid-related gastrointestinal disorders, but there is concern that their use may be associated with the development of significant complications, such as fractures, Clostridium difficile infection, acute kidney injury, chronic kidney disease, and hypomagnesemia. Proton pump inhibitors are overused in the hospital setting, both for stress ulcer prophylaxis and gastrointestinal bleeding, and then they are often inappropriately continued after discharge from the hospital. This narrative review article outlines the evidence surrounding appropriate proton pump inhibitor use for stress ulcer prophylaxis and peptic ulcer bleeding.