Historical cosmetic talc consumption and incidence of mesothelioma in the United States.

Jointpoint Regression Software from the National Cancer Institute was used to model age-adjusted male and female pleural and peritoneal mesothelioma rates in the surveillance, epidemiology, and end results (SEER) 8, SEER 12, and SEER 22 cancer registries. Linear mixed models were then used to determine if there was a statistical association between U.S. cosmetic talc consumption and the 30-year lagged age-adjusted mesothelioma rates (1) over the reporting period for each registry and (2) for the periods of time identified by the jointpoint model where changes in the rate of mesothelioma occurred. Regardless of the SEER registry used, from the early-1980s through 2020, rates of peritoneal mesothelioma have remained steady or declined. Female pleural mesothelioma rates were unchanged from the early-1980s until 2017 when rates declined, while male rates peaked in the early 1990s and have since declined. Cosmetic talc consumption was not statistically associated with an increased rate of pleural or peritoneal mesothelioma in males or females, suggesting that the use of cosmetic talc products is not associated with the development of mesothelioma.

Self-reported occupational noise exposure and hearing protection device use among NHANES participants and the risk of hearing loss.

Occupational noise exposure continues to be a prevalent hazard in many industries. While the proliferation of noise dosimeters and wearable devices has made it easier to assess a worker's exposure to noise, many employees exposed to hazardous (i.e., >85 dBA) levels of noise may go their entire career without ever having their personal noise levels measured. In contrast to other occupational exposures, noise is easily perceived by the individual exposed, allowing them to develop subjective judgments regarding its characteristics. To determine whether such self-reported exposures to occupational noise are associated with hearing loss, this analysis used audiometric data and self-reported occupational exposure to loud noise from the National Health and Nutrition Examination Survey (NHANES), which has collected such data from 1999 to May 2020. Linear and logistic regressions models found a statistically significant association between self-reported noise exposure and worsened hearing at the 3, 4, 6, and 8 kHz hearing frequency as well as an elevated odds ratio for the development of hearing loss greater than 25 dB at the 2, 3, and 4 kHz audiometric frequencies. The results of this analysis suggest that in the absence of exposure measurements, workers are likely able to detect exposure to hazardous levels of noise. In these instances, additional measurements should be collected to determine if the workers should be enrolled in a hearing conservation program.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Vaccination of Adults With Cancer: ASCO Guideline.

PURPOSE: To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. RECOMMENDATIONS: The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell-depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine.Additional information is available at www.asco.org/supportive-care-guidelines.

Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review.

BACKGROUND: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.

Effectiveness of Colonoscopy Screening vs Sigmoidoscopy Screening in Colorectal Cancer.

Importance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking. Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy. Design, Setting, and Participants: This comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021. Intervention: Invitation to endoscopic screening. Main Outcomes and Measures: Primary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial. Results: This analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death. Conclusions and Relevance: The findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.

A Phase 2 Trial of Primary Tumor Stereotactic Body Radiation Therapy Boost Before Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor before the start of CRT to improve PTC. METHODS AND MATERIALS: Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1 year, and the hypothesis was that the 1-year PTC rate would be ≥90%. Secondary objectives included objective response rate, regional and distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional magnetic resonance imaging and blood-based miRNA analysis. RESULTS: The study enrolled 21 patients (10 men and 11 women); the median age was 62 years (range, 52-78). The median pretreatment primary tumor size was 5.0 cm (range, 1.0-8.3). The most common nonhematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 nonhematologic toxicity occurred (respiratory failure/radiation pneumonitis), and no grade 5 toxicities occurred. The objective response rate at 3 and 6 months was 72.7% and 80.0%, respectively, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control rates were 81.6% and 70.3%, respectively. Disease-free survival and overall survival at 2 years were 46.1% and 50.3%, respectively, and median survival was 37.8 months. Functional magnetic resonance imaging detected a mean relative decrease in blood oxygenation level-dependent signal of -87.1% (P = .05), and miR.142.3p was correlated with increased risk of grade ≥3 pulmonary toxicity (P = .01). CONCLUSIONS: Dose escalation to the primary tumor using upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. Functional magnetic resonance imaging suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p was correlated with pulmonary toxicity.

Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade.

INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade has changed the landscape of treatment for metastatic urothelial cancer, but single-agent cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade in metastatic urothelial cancer has been underexplored. A prior phase 2 trial of tremelimumab in PD-1/PD-L1-blockade naive patients with metastatic urothelial cancer revealed activity comparable to that observed with PD-1/PD-L1 blockade raising the hypothesis that these classes of immune checkpoint inhibitors might be non-cross-resistant. METHODS: The current phase 2 trial treated patients with PD-1/PD-L1 blockade-resistant metastatic urothelial cancer with single-agent tremelimumab (750 mg intravenously every 28 days for up to 7 cycles). The primary end point was objective response rate. RESULTS: Twenty-six patients were enrolled and 24 patients were evaluable for response. The objective response rate was 8.3%, composed of a total of two partial responses that lasted 10.9 and 24.0 months. Stable disease was observed in another 20.8% of patients, with a median duration of stable disease of 5.4 months. Diarrhea occurred in 15 patients (58%), elevated hepatic transaminases occurred in seven patients (27%), and adrenal insufficiency occurred in two patients (8%); one patient died after experiencing immune-related hepatitis. CONCLUSIONS: High dose CTLA-4 blockade in patients with PD-1/PD-L1-resistant metastatic urothelial cancer has modest activity and is associated with treatment-related toxicity similar to prior reports.

A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.

PURPOSE: Peposertib-an orally administered DNA-dependent protein kinase inhibitor-has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) and assessed its safety and efficacy in locally advanced rectal cancer. PATIENTS AND METHODS: Patients were treated for 5 to 5.5 weeks with 50- to 250-mg peposertib once daily, capecitabine 825 mg/m2 twice daily, and radiotherapy (RT), 5 days per week. Following clinical restaging (8 weeks after CRT completion), patients with clinical complete response (cCR) could opt for surveillance. Total mesorectal excision was recommended upon incomplete response (IR). RESULTS: Nineteen patients were treated with peposertib at doses of 50 mg (n = 1), 100 mg, 150 mg, and 250 mg (n = 6 each). Dose-limiting toxicities occurred in one out of five (100 mg), one out of six (150 mg), and three out of six (250 mg) evaluable patients. Peposertib ≤150 mg once daily was tolerable in combination with CRT. After 8 weeks of treatment with peposertib and CRT, the cCR was 15.8% (n = 3). Among the three patients with cCR, two underwent surgery and had residual tumors. Among the 16 patients with IR, seven underwent surgery and had residual tumors; five of the remaining nine patients opted for consolidative chemotherapy. The combined cCR/pathologic complete response (pCR) rate was 5.3% (n = 1, 100 mg cohort). CONCLUSIONS: Peposertib did not improve complete response rates at tolerable dose levels. The study was closed without declaring the MTD/RP2D.

Disparities in outcomes and access to therapy options in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) disproportionately impacts racial and ethnic minorities and patients with lower socioeconomic status. These social determinants of health (SDH) lead to disparities in access to care and outcomes. We aim to understand the relationship between SDH and survival and locoregional treatment options in HCC. METHODS: Using the National Cancer Database, we evaluated survival and access locoregional treatments including non-transplant surgery, liver transplant (LT), and liver-directed radiation therapy (LDRT) in patients with HCC diagnosed between 2004 and 2017. Variables including clinical stage, age, sex, race, income, rurality, year of diagnosis, facility type (FT), Charlson-Deyo score (CD), and insurance were evaluated. Cox proportional hazards multivariable regression and dominance analyses were used for analyses. RESULTS: In total, 140 340 patients were included. Worse survival was seen with advanced stage, older age, Black race, rurality, public insurance, treatment at a nonacademic center, and lower income. The top predictors for survival included stage, age, and income. Completion of non-transplant surgery was best predicted by stage, FT, and insurance type, whereas LT was predicted by age, year of diagnosis, and CD score. LDRT utilization was most associated with year of diagnosis, FT, and CD score. CONCLUSION: For patients with HCC, survival was predicted primarily by stage, age, and income. The primary sociodemographic factors associated with access to surgical treatments, in addition to FT, were insurance and income, highlighting the financial burdens of health care. Work is needed to address disparities in access to care, including improved insurance access, addressing financial inequities and financial toxicities of treatments, and equalizing care opportunities in community centers.

Precision Medicine in Urothelial Carcinoma: Current Markers to Guide Treatment and Promising Future Directions.

OPINION STATEMENT: The treatment landscape for urothelial cancer has changed dramatically in the last 10 years, with the approval of several new treatments. At the same time, profiling of individual tumors has become more commonplace with widespread availability of molecular testing and immunohistochemistry. For urothelial cancer, this has led to current guidelines recommending that molecular testing be obtained in the metastatic setting, and that it be considered in the setting of locally advanced disease. Between molecular testing and immunohistochemistry testing of tumors, the only current guideline-directed application of these tests is in the identification of FGFR3 or FGFR2 alterations for use of FGFR inhibitors. While additional recurrent molecular alterations linked to the pathogenesis of urothelial cancer have been identified, the ability to successfully "drug" the pathways association with such alterations remains limited. There has been extensive research into whether expression of particular proteins might inform specific treatment approaches such as the use of PD-L1 testing to guide immune checkpoint blockade. With the integration of antibody-drug conjugates into the treatment armamentarium for urothelial cancer, ongoing research is seeking to determine whether expression of the targets of these therapies, such as Nectin 4, Trop-2, or HER2, could help to guide treatment.

Expanded molecular detection of MPL codon p.W515 and p.S505N mutations in myeloproliferative neoplasms.

BACKGROUND: Patients negative for the JAK2 p.V617F somatic variant are frequently reflexed to testing for MPL exon 10 variants. Detection of these variants via multiplexed allele-specific PCR followed by fragment analysis has been previously published. The present study builds on this concept by improving the detection of the p.W515A variant, adding a second allele-specific primer to detect the p.W515R variant, and incorporating an improved primer for p.S505N detection. METHODS: The W515 amplification employs 5'-labeled allele-specific forward primers to detect p.W515K, p.W515L, p.W515R, and p.W515A. The p.S505N amplification includes an allele-specific reverse primer with a tail extension. Fragments were subject to capillary electrophoresis on an ABI 3500 Genetic Analyzer and analyzed using GeneMapper 6.0 (Thermo Fisher Scientific). RESULTS: Thirty MPL-negative and 13 MPL-positive samples previously tested by a reference laboratory were tested with the MPL LDT. Results were 100% concordant. The MPL LDT has a limit of detection of at least 5% VAF for the p.W515 variants and 10% VAF for the p.S505N variant. CONCLUSION: Current MPL assays are predominantly focused on p.W515L/K and p.S505N mutations. We have engineered an MPL test for detecting p.W515A/L/K/R and p.S505N variants, thereby increasing the diagnostic yield with little additional expense or technician time.

An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma.

This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies, as well as updated information from previous studies. Based on the 16 studies considered for chrysotile (<10% amphibole), we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma; it should be noted that smoking or previous or concurrent occupational exposure to amphiboles (if it existed) was not controlled for. NOAEL values ranged from 2.3-<11.5 f/cc-years to 1600-3200 f/cc-years for lung cancer and from 100-<400 f/cc-years to 800-1599 f/cc-years for mesothelioma. The range of best-estimate NOAELs was estimated to be 97-175 f/cc-years for lung cancer and 250-379 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased risk at any exposure level, while all but one of the six studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Only eight cases of peritoneal mesothelioma were reported in all studies on predominantly chrysotile-exposed cohorts combined. This analysis also proposed best-estimate amosite and crocidolite NOAELs for mesothelioma derived by the application of relative potency estimates to the best-estimate chrysotile NOAELs for mesothelioma and validated by epidemiology studies with exposure-response information. The best-estimate amosite and crocidolite NOAELs for mesothelioma were 2-5 f/cc-years and 0.6-1 f/cc-years, respectively. The rate of peritoneal mesothelioma in amosite- and crocidolite-exposed cohorts was between approximately 70- to 100-fold and several-hundred-fold higher than in chrysotile-exposed cohorts, respectively. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile, amosite, and crocidolite exposures.

Is Cell-Free DNA Testing in Hepatocellular Carcinoma Ready for Prime Time?

Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any prognostic or predictive value. Thus, current cfDNA testing cannot be relied upon for perioperative risk stratification (POR), including early detection of recurrence, long-term surveillance, predicting outcomes, and treatment response. Prior evidence on cfDNA mutation profiling (non-specific detection or gene panel testing) suggests that it can be a reliable tool for POR and prognostication, but it still requires significant improvements. cfDNA methylation changes or epigenetic markers have not been explored extensively, but early studies have shown potential for it to be a prognostic biomarker tool. The predictive value of cfDNA (mutations and EM) to assist treatment selection (systemic therapy, immune-checkpoint inhibitor vs. tyrosine kinase inhibitor) and to monitor response to systemic and locoregional therapies should be a future area of focus. We highlighted the unmet needs in the HCC management and the current role of cfDNA testing in HCC in addressing them.

Tolyporphins-Exotic Tetrapyrrole Pigments in a Cyanobacterium-A Review.

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium-microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known-each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open ß-pyrrole positions and two, one, or zero appended C-glycoside (or -OH or -OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.

Long-term Clinical Outcomes of Yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma: A 5-Year Institutional Experience.

RATIONALE AND OBJECTIVES: To examine the clinical outcomes of yttrium-90 (Y90) transarterial radioembolization (TARE) for primary hepatocellular carcinoma (HCC) through the evaluation of a 5-year institutional experience. MATERIALS AND METHODS: This retrospective study evaluated 88 consecutive patients with primary HCC receiving Y90 TARE treatment at an academic medical center from 2017 to 2021. Disease distribution was bilobar in 60.2% of patients with an average lesion diameter of 5.0 ± 3.4 cm and Barcelona Clinic Liver Cancer stage B or C in 77% of the participants. Clinical outcomes were elucidated by examination of complications, liver function tests, biochemical response, and radiographic response. Objective response ratio (ORR) and progression-free survival (PFS) were also calculated. RESULTS: The mean administered Y90 radiation dose was 127.8 ± 20.2 Gy. No significant complications or LFT elevations occurred post-therapy. Of the 73.9% of patients with α-fetoprotein-producing tumors, 67.8% experienced a complete or partial biochemical response 1 month post-treatment. The ORR was 83.3% on 6-month imaging and PFS was 9.6 ± 8.5 months. Functional outcomes (Eastern Cooperative Oncology Group) were maintained or improved in 79.6% and 76.1% of patients by 6 months and 1 year post-treatment, respectively. The mean survival was 14.7 ± 12.1 months. At 6 months post-treatment, 77.3% of patients were downstaged to or maintained Milan criteria, which was sustained for 74.4% and 70.0% of patients 1 year and 2 years after treatment, respectively. CONCLUSION: Y90-TARE is a safe and effective therapy for primary HCC. Enduring outcomes further act as a realistic bridge to liver transplantation, with a majority of patients maintaining Milan criteria and preserving their functional status long term.

Occupational exposure to cosmetic talc and mesothelioma in barbers, hairdressers, and cosmetologists: A systematic review of the epidemiology.

Inhalation exposure to cosmetic talc has generated much scientific debate regarding its potential as a risk factor for mesothelioma, a rare, but fatal cancer. Barbers, hairdressers, and cosmetologists have regularly used cosmetic talc-containing products, but the collective epidemiological evidence for mesothelioma in these occupations has yet to be described. As such, we conducted a systematic review of PubMed and the National Institute for Occupational Safety and Health's (NIOSH) Numbered Publications list to identify original epidemiological literature reporting measures of association between these occupations and incidence of or death from mesothelioma. Literature screening was performed independently twice, the results of which were summarized and tabulated and underwent a review for their accuracy. A total of 12 studies met our inclusion criteria, including three cohort, six case-control, and three proportionate mortality/registration studies. The data from these studies were collected in 13 European and North American countries, spanning more than 50 years. We supplemented this review with queries of occupational mortality databases that are managed by the Washington State Department of Health and NIOSH for 26 U.S. states. Most findings were null and if statistically significant, nearly all showed an inverse relationship, indicative of a protective effect of these occupations on mesothelioma risk. Overall, the epidemiological evidence does not support an increased risk of mesothelioma for these occupations. This research fills an important data gap on the etiology of mesothelioma in barbers, hairdressers, and cosmetologists, and provides a benchmark for those with comparatively less exposure, such as non-occupational users of similar cosmetic talc-containing products.

High-Throughput Screening of Streptavidin-Binding Proteins in Self-Assembled Solid Films for Directed Evolution of Materials.

Evolution has shaped the development of proteins with an incredible diversity of properties. Incorporating proteins into materials is desirable for applications including biosensing; however, high-throughput selection techniques for screening protein libraries in materials contexts is lacking. In this work, a high-throughput platform to assess the binding affinity for ordered sensing proteins was established. A library of fusion proteins, consisting of an elastin-like polypeptide block, one of 22 variants of rcSso7d, and a coiled-coil order-directing sequence, was generated. All selected variants had high binding in films, likely due to the similarity of the assay to magnetic bead sorting used for initial selection, while solution binding was more variable. From these results, both the assembly of the fusion proteins in their operating state and the functionality of the binding protein are key factors in the biosensing performance. Thus, the integration of directed evolution with assembled systems is necessary to the design of better materials.