Visualizing electrostatic gating effects in two-dimensional heterostructures.

The ability to directly monitor the states of electrons in modern field-effect devices-for example, imaging local changes in the electrical potential, Fermi level and band structure as a gate voltage is applied-could transform our understanding of the physics and function of a device. Here we show that micrometre-scale, angle-resolved photoemission spectroscopy1-3 (microARPES) applied to two-dimensional van der Waals heterostructures4 affords this ability. In two-terminal graphene devices, we observe a shift of the Fermi level across the Dirac point, with no detectable change in the dispersion, as a gate voltage is applied. In two-dimensional semiconductor devices, we see the conduction-band edge appear as electrons accumulate, thereby firmly establishing the energy and momentum of the edge. In the case of monolayer tungsten diselenide, we observe that the bandgap is renormalized downwards by several hundreds of millielectronvolts-approaching the exciton energy-as the electrostatic doping increases. Both optical spectroscopy and microARPES can be carried out on a single device, allowing definitive studies of the relationship between gate-controlled electronic and optical properties. The technique provides a powerful way to study not only fundamental semiconductor physics, but also intriguing phenomena such as topological transitions5 and many-body spectral reconstructions under electrical control.

Conduction Band Replicas in a 2D Moiré Semiconductor Heterobilayer.

Stacking monolayer semiconductors creates moiré patterns, leading to correlated and topological electronic phenomena, but measurements of the electronic structure underpinning these phenomena are scarce. Here, we investigate the properties of the conduction band in moiré heterobilayers of WS2/WSe2 using submicrometer angle-resolved photoemission spectroscopy with electrostatic gating. We find that at all twist angles the conduction band edge is the K-point valley of the WS2, with a band gap of 1.58 ± 0.03 eV. From the resolved conduction band dispersion, we deduce an effective mass of 0.15 ± 0.02 me. Additionally, we observe replicas of the conduction band displaced by reciprocal lattice vectors of the moiré superlattice. We argue that the replicas result from the moiré potential modifying the conduction band states rather than final-state diffraction. Interestingly, the replicas display an intensity pattern with reduced 3-fold symmetry, which we show implicates the pseudo vector potential associated with in-plane strain in moiré band formation.

Adjuvant and salvage radiotherapy after neoadjuvant therapy and radical prostatectomy for high-risk localized prostate cancer.

BACKGROUND: We sought to describe patterns of delivery of adjuvant (aRT) and salvage RT (sRT) in patients who underwent RP after receiving neoadjuvant androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC). METHODS: Two hundred eighteen patients treated on phase 2 neoadjuvant trials between 2006 and 2018 at two academic centers were evaluated. aRT and sRT were defined as receipt of RT with a PSA of ≤0.1 or >0.1 ng/mL, respectively. Primary outcomes were biochemical recurrence (BCR), defined as time from aRT/sRT to a PSA rising to >0.1 ng/mL, and metastasis-free survival (MFS) after RT. RESULTS: Twenty-three (11%) and 55 (25%) patients received aRT and sRT respectively. Median PSA at start of aRT and sRT was 0.01 and 0.16 ng/mL, and median duration from RP to RT was 5 and 14 months, respectively. All aRT patients had NCCN high-risk disease, 30% were pN1 and 43% had positive surgical margins; 52% had prostate bed RT. Fifty-one percent of sRT patients had biopsy Gleason 9-10, 29% were pT2 and 9% had positive surgical margins; 63% had RT to the prostate bed/pelvis. At a median follow-up of 5.3 and 3.0 years after aRT and sRT, 3-year freedom from BCR was 55% and 47%, and 3-year MFS was 56% and 53%, respectively. CONCLUSIONS: aRT was infrequently used in patients who received neoadjuvant ARPI before RP for HRLPC. Outcomes of aRT and sRT were similar but generally poor. Studies evaluating intensified systemic therapy approaches with postoperative RT in this high-risk population are needed.

Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

BACKGROUND: This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. METHODS: A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. RESULTS: The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p = .96) or grade 2 gastrointestinal (p = .75), genitourinary (p = .44), and sexual (p = .29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p = .03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p = .005). A nonsignificant trend (p = .09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. CONCLUSIONS: Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.

Insulin resistance during androgen deprivation therapy in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.

Factors associated with the melanoma diagnostic interval in Ontario, Canada: a population-based study.

BACKGROUND: Protracted times to diagnosis of cancer can lead to increased patient anxiety, and in some cases, disease progression and worse outcomes. This study assessed the time to diagnosis for melanoma, and its variability, according to patient-, disease-, and system-level factors. METHODS: This is a descriptive, cross-sectional study in Ontario, Canada from 2007-2019. We used administrative health data to measure the diagnostic interval (DI)-and its two subintervals-the primary care subinterval (PCI) and specialist care subinterval (SCI). Multivariable quantile regression was used. RESULTS: There were 33,371 melanoma patients. The median DI was 36 days (interquartile range [IQR]: 8-85 days), median PCI 22 days (IQR: 6-54 days), and median SCI 6 days (IQR: 1-42 days). Increasing comorbidity was associated with increasing DI. Residents in the most deprived neighbourhoods and those in rural areas experienced shorter DIs and PCIs, but no differences in SCI. There was substantial variation in the DI and SCI across health regions, but limited differences in the PCI. Finally, patients with a history of non-melanoma skin cancer, and those previously established with a dermatologist experienced significantly longer DI, PCI, and SCI. DISCUSSION: This study found variability in the melanoma DI, notably by system-level factors.

Implantable Hearing Devices in Ontario: A Population-Based Study of Access to Care and Access to Devices.

INTRODUCTION: The prevalence of hearing loss in Canada is high, with many patients requiring implantable hearing devices (IHDs) as treatment for their disease severity. Despite this need, many eligible patients do not pursue these interventions. The objective of this study was to examine rates of IHD based on geographic location to understand locoregional variation in access to care. STUDY DESIGN: This was a retrospective population-based cohort study. SETTING: All hospitals in the Canadian province of Ontario. METHODS: Of all patients with IHD between April 1, 1992, and March 31, 2021, cochlear implants (CIs) (4,720) and bone-anchored hearing aids (BAHA) (1,125) cohorts were constructed. Place of residence was categorized based on Local Health Integrated Network (LHIN). Summary statistics for place of surgical institution based on LHIN at first surgery, name of institution of first surgery and "as the crow flies" distance (in km) between place of residence and surgical institution were calculated. Rate of implantations was calculated for LHIN regions based on number of surgeries per 1,000,000 persons/years. RESULTS: Toronto Central, Central, Central East, and Champlain regions had >10% of patients undergoing BAHA and CI. 1,019 (90.6%) and 4,232 (89.7%) of patients receiving BAHA and CI, respectively, resided in urban/suburban regions and 94 patients (8.4%) and 436 (9.2%) resided in rural regions. The median distance between residential location and the institution was 46.4 km (interquartile range [IQR], 18.9-103.6) and 44.7 km (IQR, 15.7-96.9) for BAHA and CI, respectively. From 1992 to 2021, the number of CI and BAHA performed across Ontario increased by 17 folds and 6 folds, respectively. CONCLUSION: This large comprehensive population study provides longitudinal insight into the access to care of IHD based on geographic factors. Our findings of the present population-based study indicate an overall increase in access to devices with disproportionate access to care based on geographic locations. Further work is needed to characterize barriers to IHD access to align with demands.

Colonic cytomegalovirus DNA detection by polymerase chain reaction does not influence outcomes in inflammatory bowel disease and immunosuppressed cohorts.

BACKGROUND AND AIM: Cytomegalovirus (CMV) colitis is associated with negative outcomes in inflammatory bowel disease (IBD) and immunosuppressed cohorts and therefore requires timely recognition for appropriate management. We aimed to evaluate the diagnostic tools for CMV colitis and their associations with clinical outcomes. METHODS: A retrospective cohort study of patients in a metropolitan health service with colonic samples analysed for CMV between 2012 and 2022, stratified into IBD and non-IBD groups, was performed. The main outcome measures were the prevalence of positive and negative results for each CMV test, as well as need for colectomy, use of antiviral and hospital length of stay. RESULTS: Five hundred eighty-two biopsies from 418 patients were included; the median age was 36 years (interquartile range, 24-52 years) and 223 (53.3%) were men. Four hundred sixty-one (79.2%) biopsies were from patients with IBD and 121 (20.8%) were from those without IBD. There were similar proportions of positive CMV histology (IBD 5.9% and non-IBD 7.4%) and tissue CMV polymerase chain reaction (PCR) in the two groups (IBD 5.6% and non-IBD 5.0%), but within each group, results were discordant. Positive CMV histology was significantly associated with need for colectomy in the IBD group, while positive tissue CMV PCR was not. Positive CMV histology, and tissue and serum CMV PCR were all significantly associated with antiviral use. Positive serum CMV PCR was significantly associated with colectomy. CONCLUSIONS: Histopathology remains the most predictive tool in assessing CMV colitis, while qualitative tissue CMV PCR was found to have limited utility. Quantitative serum CMV PCR may be useful but requires further evaluation.

Acute toxicity comparison of magnetic resonance-guided adaptive versus fiducial or computed tomography-guided non-adaptive prostate stereotactic body radiotherapy: A systematic review and meta-analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is gaining wider adoption for prostate cancer management but there remain significant toxicity risks when delivering prostate SBRT with standard techniques. Magnetic resonance-guided daily adaptive SBRT (MRg-A-SBRT) offers technological advantages in precision of radiation dose delivery, but the toxicity profile associated with MRg-A-SBRT compared to more standardly used fiducial or computed tomography-guided non-adaptive prostate SBRT (CT-SBRT) remains unknown. METHODS: A meta-analysis to compare acute toxicity rates associated with MRg-A-SBRT and CT-SBRT for prostate cancer was performed in compliance with PRISMA guidelines. MEDLINE (PubMed) and Google Scholar were searched for prospective studies of prostate SBRT that were published between January 1, 2018 and August 31, 2022. Random effects and fixed effects models were used to estimate pooled toxicity rates, and meta-regression was performed to compare toxicity between MRg-A-SBRT and CT-SBRT study groups. RESULTS: Twenty-nine prospective studies were identified that met the inclusion criteria and included a total of 2547 patients. The pooled estimates for acute grade 2 or higher (G2+) genitourinary (GU) and gastrointestinal (GI) toxicity for MRg-A-SBRT were 16% (95% confidence interval [CI], 10%-24%) and 4% (95% CI, 2%-7%) and for CT-SBRT they were 28% (95% CI, 23%-33%) and 9% (95% CI, 6%-12%), respectively. On meta-regression, the odds ratios for acute G2+ GU and GI toxicities comparing MRg-A-SBRT and CT-SBRT were 0.56 (95% CI, 0.33-0.97, p = .04) and 0.40 (95% CI, 0.17-0.96, p = .04), respectively. CONCLUSION: MRg-A-SBRT is associated with a significantly reduced risk of acute G2+ GU or GI toxicity compared to CT-SBRT. Longer follow-up will be needed to evaluate late toxicity and disease control outcomes. PLAIN LANGUAGE SUMMARY: Magnetic resonance imaging-guided daily adaptive prostate stereotactic radiation (MRg-A-SBRT) is a treatment that may allow for delivery of prostate radiation more precisely than other radiotherapy techniques, but it is unknown whether this reduces side effects compared to standardly used computed tomography-guided SBRT (CT-SBRT). In this systematic review and meta-analysis combining data from 29 clinical trials including 2547 patients, it was found that the risk of short-term urinary side effects was reduced by 44% and the risk of short-term bowel side effects was reduced by 60% with MRg-A-SBRT compared to CT-SBRT.

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy.

BACKGROUND: Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy. METHODS: In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer. RESULTS: With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7-19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort. CONCLUSIONS: Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

Colon Cancer Disparities in Stage at Presentation and Time to Surgery for Asian Americans, Native Hawaiians, and Pacific Islanders: A Study with Disaggregated Ethnic Groups.

BACKGROUND: Vast differences in barriers to care exist among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) groups and may manifest as disparities in stage at presentation and access to treatment. Thus, we characterized AANHPI patients with stage 0-IV colon cancer and examined differences in (1) stage at presentation and (2) time to surgery relative to white patients. PATIENTS AND METHODS: We assessed all patients in the National Cancer Database (NCDB) with stage 0-IV colon cancer from 2004 to 2016 who identified as white, Chinese, Japanese, Filipino, Native Hawaiian, Korean, Vietnamese, Laotian, Hmong, Kampuchean, Thai, Asian Indian or Pakistani, and Pacific Islander. Multivariable ordinal logistic regression defined adjusted odds ratios (AORs), with 95% confidence intervals (CI), of (1) patients presenting with advanced stage colon cancer and (2) patients with stage 0-III colon cancer receiving surgery at ≥ 60 days versus 30-59 days versus < 30 days postdiagnosis, adjusting for sociodemographic/clinical factors. RESULTS: Among 694,876 patients, Japanese [AOR 1.08 (95% CI 1.01-1.15), p < 0.05], Filipino [AOR 1.17 (95% CI 1.09-1.25), p < 0.001], Korean [AOR 1.09 (95% CI 1.01-1.18), p < 0.05], Laotian [AOR 1.51 (95% CI 1.17-1.95), p < 0.01], Kampuchean [AOR 1.33 (95% CI 1.04-1.70), p < 0.01], Thai [AOR 1.60 (95% CI 1.22-2.10), p = 0.001], and Pacific Islander [AOR 1.41 (95% CI 1.20-1.67), p < 0.001] patients were more likely to present with more advanced colon cancer compared with white patients. Chinese [AOR 1.27 (95% CI 1.17-1.38), p < 0.001], Japanese [AOR 1.23 (95% CI 1.10-1.37], p < 0.001], Filipino [AOR 1.36 (95% CI 1.22-1.52), p < 0.001], Korean [AOR 1.16 (95% CI 1.02-1.32), p < 0.05], and Vietnamese [AOR 1.55 (95% CI 1.36-1.77), p < 0.001] patients were more likely to experience greater time to surgery than white patients. Disparities persisted when comparing among AANHPI subgroups. CONCLUSIONS: Our findings reveal key disparities in stage at presentation and time to surgery by race/ethnicity among AANHPI subgroups. Heterogeneity upon disaggregation underscores the importance of examining and addressing access barriers and clinical disparities.

MR-guided prostate SBRT in prostate cancer patients with low-volume metastatic disease.

BACKGROUND: Recent data have found an overall survival benefit from prostate-directed radiotherapy in patients with low-volume metastatic prostate cancer. Prostate SBRT is an attractive treatment in this setting and may be optimised with MR-guided adaptive treatment. Here, we share our institutional experience delivering stereotactic MR-guided adaptive prostate SBRT (SMART) for patients with low-volume metastatic disease. METHODS: We reviewed patients with low-volume metastatic disease who received prostate SMART from October 2019 to December 2021 on a 0.35T MR-Linac. The cohort included 14 patients. Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed using CTCAE v 5.0. Progression was defined as a change in systemic or hormonal therapy regimen as a result of PSA rise or disease progression. RESULTS: The median follow-up time was 29 months. Seven patients had hormone sensitive prostate cancer and 7 had castrate resistant prostate cancer (CRPC). 13 patients received 36.25 Gy in 5 fractions and one patient received 33 Gy in 5 fractions. At the time of last follow-up, 11 patients had not experienced progression and three patients, all with CRPC, had experienced progression. No patients developed local progression in the prostate after SMART. One patient experienced acute grade 2 urinary toxicity (7%) and no patients experienced acute grade 2 GI toxicity (0%). No grade 3 + acute toxicities were observed. CONCLUSIONS: Prostate SMART was found to be well tolerated and all patients had local control of disease within the prostate at the time of last follow-up. Prostate SMART may represent a low-risk and well-tolerated approach for delivering prostate-directed radiotherapy for patients with limited metastatic disease.

Hearing Loss and Dementia: A Population-Based Cohort Study.

INTRODUCTION: Hearing loss (HL) is considered a potentially modifiable risk factor for dementia. We aimed to examine the relationship between HL and incident dementia diagnosis in a province-wide population-based cohort study with matched controls. METHODS: Administrative healthcare databases were linked to generate a cohort of patients who were aged ≥40 years at their first claimed hearing amplification devices (HAD) between April 2007 and March 2016 through the Assistive Devices Program (ADP) (257,285 with claims and 1,005,010 controls). The main outcome was incident dementia diagnosis, ascertained using validated algorithms. Dementia incidence was compared between cases and controls using Cox regression. Patient, disease, and other risk factors were examined. RESULTS: Dementia incidence rates (per 1,000 person-years) were 19.51 (95% confidence interval [CI]: 19.26-19.77) and 14.15 (95% CI: 14.04-14.26) for the ADP claimants and matched controls, respectively. In adjusted analyses, risk of dementia was higher in ADP claimants compared with controls (hazard ratio [HR]: 1.10 [95% CI: 1.09-1.12, p < 0.001]). Subgroup analyses showed a dose-response gradient, with risk of dementia higher among patients with bilateral HADs (HR: 1.12 [95% CI: 1.10-1.14, p < 0.001]), and an exposure-response gradient, with increasing risk over time from April 2007-March 2010 (HR: 1.03 [95% CI: 1.01-1.06, p = 0.014]), April 2010-March 2013 (HR: 1.12 [95% CI: 1.09-1.15, p < 0.001]), and April 2013-March 2016 (HR: 1.19 [95% CI: 1.16-1.23, p < 0.001]). CONCLUSION: In this population-based study, adults with HL had an increased risk of being diagnosed with dementia. Given the implications of HL on dementia risk, understanding the effect of hearing interventions merits further investigation.

Second malignancy probabilities in patients with prostate cancer treated with whole pelvis radiation therapy versus prostate only radiation therapy.

BACKGROUND: Whole pelvic radiation therapy (WPRT) may improve outcomes compared with prostate only radiation therapy (PORT) in some subsets of men with prostate cancer, as in the POP-RT trial. However, there is concern about increased risk of adverse effects with WPRT, including the development of radiation-induced second malignancies (SM). Given the rarity of SM, little is known about relative rates of SM between WPRT and PORT. METHODS: A retrospective cohort analysis was performed of men with nonmetastatic, node-negative prostate cancer with at least 60 months of follow-up using a national database. SM probabilities were compared in men receiving either WPRT or PORT using multivariable logistic models adjusting for clinical and sociodemographic factors. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up were also conducted. RESULTS: Of 50,237 patients in the study, 39,338 (78.4%) received PORT, and 10,899 (21.7%) received WPRT. Median follow-up was 106.2 months (interquartile range 82.32-132.25). Crude probabilities of SM were 9.16% for WPRT and 8.88% for PORT. The adjusted odds ratio (AOR) for development of SM with PORT versus WPRT was 1.046 (95% confidence interval 0.968-1.130). Temporal sensitivity analyses by stratifying by year of diagnosis and follow-up length also did not demonstrate any significant difference in rates of SM between WPRT and PORT using AORs with WPRT as the referent. CONCLUSIONS: Retrospective analysis of over 50,000 patients did not demonstrate an association between WPRT and an increased probability of SM compared to PORT. Given the findings of POP-RT, the use of WPRT may become widespread for certain subsets of men. Thus, our findings could help guide how we counsel patients deciding between WPRT and PORT and suggest the need for prospective assessment of SM risk with WPRT and PORT.

A population-based validation study of the 8th edition UICC/AJCC TNM staging system for cutaneous melanoma.

BACKGROUND: The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets. METHODS: This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan-Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression. RESULTS: In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively. CONCLUSION: TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7.

Shared burden: the association between cancer diagnosis, financial toxicity, and healthcare cost-related coping mechanisms by family members of non-elderly patients in the USA.

PURPOSE: There has been little research on the healthcare cost-related coping mechanisms of families of patients with cancer. Therefore, we assessed the association between a cancer diagnosis and the healthcare cost-related coping mechanisms of participant family members through their decision to forego or delay seeking medical care, one of the manifestations of financial toxicity. METHODS: Using data from the National Health Interview Survey (NHIS) between 2000 and 2018, sample weight-adjusted prevalence was calculated and multivariable logistic regressions defined adjusted odds ratios (aORs) for participant family members who needed but did not get medical care or who delayed seeking medical care due to cost in the past 12 months, adjusting for relevant sociodemographic covariates, including participant history of cancer (yes vs. no) and participant age (18-45 vs. 46-64 years old). The analysis of family members foregoing or delaying medical care was repeated using a cancer diagnosis * age interaction term. RESULTS: Participants with cancer were more likely than those without a history of cancer to report family members delaying (19.63% vs. 16.31%, P < 0.001) or foregoing (14.53% vs. 12.35%, P = 0.001) medical care. Participants with cancer in the 18 to 45 years old age range were more likely to report family members delaying (pinteraction = 0.028) or foregoing (pinteraction < 0.001) medical care. Other factors associated with cost-related coping mechanisms undertaken by the participants' family members included female sex, non-married status, poorer health status, lack of health insurance coverage, and lower household income. CONCLUSION: A cancer diagnosis may be associated with familial healthcare cost-related coping mechanisms, one of the manifestations of financial toxicity. This is seen through delayed/omitted medical care of family members of people with a history of cancer, an association that may be stronger among young adult cancer survivors. These findings underscore the need to further explore how financial toxicity associated with a cancer diagnosis can affect patients' family members and to design interventions to mitigate healthcare cost-related coping mechanisms.

Safety, satisfaction and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

BACKGROUND: Infliximab remains a mainstay for the treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and healthcare providers. AIMS: To assess the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. METHODS: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions: over 30 min if receiving a standard dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. RESULTS: Fifty-two patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with a standard dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild and self-limiting. None required drug cessation. Patient satisfaction was improved with shortened infusion time as compared with the patients' previous experiences (P = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (±4.9) to 7.9 mg/L (±4.1) (P = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per patient per year for standard and dose-intensified infliximab respectively. CONCLUSION: Accelerated infliximab infusions for standard and dose-intensified regimens seem to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations.

Identification and engagement of naturally occurring retirement communities to support healthy aging in Canada: A set of methods for replication.

BACKGROUND: Naturally occurring retirement communities (NORCs), unplanned communities with a high proportion of older adult residents, offer a model to support older adults to age well in place. The aim of this paper is to provide a comprehensive description of the methods used to identify and engage NORCs appropriate for the development of supportive service programming in Canada. METHODS: Three steps were used to identify and select NORCs in which to develop supportive service programming including: 1) identification of potential NORCs using Canadian Census Dissemination Areas, the Ontario Marginalization Index and Google Maps, 2) engagement of property owner/manager to determine the availability of common space for communal programming and willingness of the owner to support programming and, 3) engagement of older adult residents within the NORC to co-design programming. RESULTS: Four cities in the south-east, south-central, and south-west of Ontario, Canada were identified to develop NORCs with supportive service programming. Using the methods described, six NORCs were identified, landlords and older adult residents were engaged, and programs initiated between April 2018 and March 2019. The sites included two private high-rise apartments, a city-owned low-rise subsidized apartment complex, two multi-building private high-rise complexes and a mobile home community. An average of 35 (min 20, max 78) older adult members were engaged in an average of 20.5 unique activity sessions at each site per month. On average, social (54%) and physical activities (30%) were more common than nutritional (10%) and knowledge-sharing (8%). CONCLUSIONS: The increased prevalence of unplanned, geographically-bound NORCs creates an opportunity for governments, social and health service providers and policy makers to support healthy aging in their communities. Our experience with the creation of six new NORCs with supportive service programming provides a tested set of methods that can be applied in other communities.

Field-Dependent Band Structure Measurements in Two-Dimensional Heterostructures.

In electronic and optoelectronic devices made from van der Waals heterostructures, electric fields can induce substantial band structure changes which are crucial to device operation but cannot usually be directly measured. Here, we use spatially resolved angle-resolved photoemission spectroscopy to monitor changes in band alignment of the component layers, corresponding to band structure changes of the composite heterostructure system, that are produced by electrostatic gating. Our devices comprise graphene on a monolayer semiconductor, WSe2 or MoSe2, atop a boron nitride dielectric and a graphite gate. Applying a gate voltage creates an electric field that shifts the semiconductor bands relative to those in the graphene by up to 0.2 eV. The results can be understood in simple terms by assuming that the materials do not hybridize.

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis.

BACKGROUND: The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. METHODS: For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R2 weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R2 was 0·7 or greater. FINDINGS: 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R2 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R2 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R2 0·28 [0·0045-0·65]), and local failure (R2 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R2 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R2 0·78 [0·59-0·89]) correlated strongly. INTERPRETATION: Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. FUNDING: Prostate Cancer Foundation and National Institutes of Health.