Combined radiotherapy and hyperthermia is a well-established alternative to chemoradiotherapy for advanced stage cervical cancer patients with a contraindication for chemotherapy. Pre-clinical ...evidence suggests that the radiosensitizing effect of hyperthermia decreases substantially for time intervals between radiotherapy and hyperthermia as short as 1-2 h, but clinical evidence is limited. The purpose of this study is to determine the effect of the time interval between external beam radiotherapy (EBRT) and same-day hyperthermia on in-field recurrence rate, overall survival and late toxicity in women with advanced stage cervical cancer.
Patients with advanced stage cervical cancer who underwent a full-course of curative daily EBRT and (4-5) weekly hyperthermia sessions between 1999 and 2014 were included for retrospective analysis. The mean time interval between EBRT fractions and same-day hyperthermia was calculated for each patient; the median thereof was used to divide the cohort in a 'short' and 'long' time-interval group. Kaplan-Meier analysis and stepwise Cox regression were used to compare the in-field recurrence and overall survival. Finally, high-grade (≥3) late toxicity was compared across time-interval groups. DNA repair suppression is an important hyperthermia mechanism, DNA damage repair kinetics were therefore studied in patient biopsies to support clinical findings.
Included were 58 patients. The 3-year in field recurrence rate was 18% and 53% in the short (≤79.2 min) and long (>79.2 min) time-interval group, respectively (p = 0.021); the 5-year overall survival was 52% and 17% respectively (p = 0.015). Differences between time-interval groups remained significant for both in-field recurrence (HR = 7.7, p = 0.007) and overall survival (HR = 2.3, p = 0.012) in multivariable Cox regression. No difference in toxicity was observed (p = 1.00), with only 6 and 5 events in the short and long group, respectively. The majority of DNA damage was repaired within 2 h, potentially explaining a reduced effectiveness of hyperthermia for long time intervals.
A short time interval between EBRT and hyperthermia is associated with a lower risk of in-field recurrence and a better overall survival. There was no evidence for difference in late toxicity.
COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes ...in cerebral hemodynamics among healthcare-workers using PPE.
Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask.
A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone.
Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.
•Most N95 mask users develop de novo headache or worsening of pre-existing headache.•End-tidal carbon dioxide levels increase while donning N95 respirator mask.•Significant cerebral hemodynamic changes occur during donning of N95 mask.•Powered air-purifying respirator restores N95 mask induced cerebral hemodynamic changes.
Purpose
Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association ...of malignancies with IgG4-related ophthalmic disease (IgG4-ROD).
Design
Retrospective cohort study.
Methods
Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005–2019.
Findings
Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months’ follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5–17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5–87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies.
Conclusion
In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.
Cancer-Associated Mutations in Endometriosis without Cancer Anglesio, Michael S; Papadopoulos, Nickolas; Ayhan, Ayse ...
New England journal of medicine/The New England journal of medicine,
05/2017, Letnik:
376, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Genetic analysis of endometriotic lesions from 39 patients revealed mutations in cancer driver genes in 26%. In some patients, the same mutation was present in lesions from different sites. The role ...of mutations in cancer-associated genes in endometriosis needs further study.
Endometriosis is a relatively common disease, affecting up to 10% of women of reproductive age.
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Its incidence is as high as 50% among adolescents with pelvic pain.
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Clinical symptoms include dysmenorrhea, pelvic pain, and infertility.
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Endometriotic lesions are considered to be benign (nonmalignant or nonneoplastic), inflammatory, estrogen-dependent lesions that are characterized by the ectopic presence of normal-appearing, functional endometrial tissue composed of glands and stroma outside of the uterus.
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The disease is often associated with multiple lesions that can be distributed throughout the abdominal–pelvic peritoneum and visceral organs.
There are three anatomical subtypes of endometriosis: superficial . . .
Population-based cancer registries have treatment information for all patients making them an excellent resource for population-level monitoring. However, specific treatment details, such as drug ...names, are contained in a free-text format that is difficult to process and summarize. We assessed the accuracy and efficiency of a text-mining algorithm to identify systemic treatments for lung cancer from free-text fields in the California Cancer Registry.
The algorithm used Perl regular expressions in SAS 9.4 to search for treatments in 24,845 free-text records associated with 17,310 patients in California diagnosed with stage IV non-small cell lung cancer between 2012 and 2014. Our algorithm categorized treatments into six groups that align with National Comprehensive Cancer Network guidelines. We compared results to a manual review (gold standard) of the same records.
Percent agreement ranged from 91.1% to 99.4%. Ranges for other measures were 0.71-0.92 (Kappa), 74.3%-97.3% (sensitivity), 92.4%-99.8% (specificity), 60.4%-96.4% (positive predictive value), and 92.9%-99.9% (negative predictive value). The text-mining algorithm used one-sixth of the time required for manual review.
SAS-based text mining of free-text data can accurately detect systemic treatments administered to patients and save considerable time compared to manual review, maximizing the utility of the extant information in population-based cancer registries for comparative effectiveness research.
Selective denervation of sensory nerve branches to the wrist is a palliative surgical treatment option for patients with chronic wrist pain when preserving the range of motion and function is ...preferred. Treatment varies from partial isolated denervation of the posterior interosseous nerve to extensive ‘complete’ denervations. This study aimed to provide an overview of the literature regarding treatment outcomes in the domains of pain, grip strength, patient satisfaction and return to work. MEDLINE (PubMed), EMBASE and Cochrane databases were systematically searched and identified 993 studies, of which 12 were eligible for analysis. Denervation resulted in high ‘return to work’ rates (up to 94%), patient satisfaction (up to 92%), increased grip strength (7%–64%) and improved average pain scores (36%–92%). Treatment outcomes of both partial and complete denervations were favourable; however, variations in outcomes suggest the need for improving evidence regarding surgical technique and nerve identification.
Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy ...of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (
Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 27.7%) v 82 of 162 50.6%; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 3.8% v four of 162 2.5% patients), abdominal pain (three 2.3% v two 1.2% patients), anemia (zero v four 2.5% patients), and radiation hepatitis (two 1.5% v zero 0% patients). Fewer patients in the RE group (27 of 130 20.8%) than in the sorafenib group (57 of 162 35.2%) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.
Management of advanced-stage non-small cell lung cancer (NSCLC) has changed significantly over the past two decades with the development of numerous systemic treatments, including targeted therapies. ...However, a high proportion of advanced-stage patients are untreated. The role that health insurance plays in receipt of systemic treatments is unclear.
Using California Cancer Registry data (2012-2014), we developed multivariable Poisson regression models to assess the independent effect of health insurance type on systemic treatment utilization among patients with stage IV NSCLC. Systemic treatment information was manually abstracted from treatment text fields.
A total of 17,310 patients were evaluated. Patients with Medicaid/other public insurance were significantly less likely to receive any systemic treatments risk ratio (RR), 0.78; 95% confidence interval (CI), 0.75-0.82, bevacizumab combinations (RR, 0.57; 95% CI, 0.45-0.71), or tyrosine kinase inhibitors (RR, 0.70; 95% CI, 0.60-0.82) compared with the privately insured. Patients with Medicare or dual Medicare-Medicaid insurance were not significantly different from the privately insured in their likelihood of receiving systemic treatments.
Substantial disparities in the use of systemic treatments for stage IV NSCLC exist by source of health insurance in California. Patients with Medicaid/other public insurance were significantly less likely to receive systemic treatments compared with their privately insured counterparts.
Source of health insurance influences care received. Further research is warranted to better understand barriers to treatment that patients with Medicaid face.
Inactivation of tumour suppressor genes is central to the development of all common forms of human cancer. This inactivation often results from epigenetic silencing associated with hypermethylation ...rather than intragenic mutations. In human cells, the mechanisms underlying locus-specific or global methylation patterns remain unclear. The prototypic DNA methyltransferase, Dnmt1, accounts for most methylation in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line. This deletion reduced global DNA methylation by less than 3%. Surprisingly, however, genetic disruption of both DNMT1 and DNMT3b nearly eliminated methyltransferase activity, and reduced genomic DNA methylation by greater than 95%. These marked changes resulted in demethylation of repeated sequences, loss of insulin-like growth factor II (IGF2) imprinting, abrogation of silencing of the tumour suppressor gene p16INK4a, and growth suppression. Here we demonstrate that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and provide compelling evidence that such methylation is essential for optimal neoplastic proliferation.
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