Clinical and economic outcomes of pharmacological stress tests in patients with a history of COVID-19.

BACKGROUND: Despite millions of COVID-19 cases in the United States, it remains unknown whether a history of COVID-19 infection impacts the safety of pharmacologic myocardial perfusion imaging stress testing (pharmacologic MPI). HYPOTHESIS: The aim of this study was to assess if a prior COVID-19 infection was associated with a higher risk of complications during and following pharmacologic MPI testing. METHODS: This retrospective cohort analysis included 179 803 adults (≥18 years) from the PharMetrics® Plus claims database who underwent pharmacologic MPI between March 1, 2020 and February 28, 2021. Patients with a history of COVID-19 infection (COVID-19 group) were compared with propensity-score matched no-COVID-19 history group for reversal agent use, 30-day resource use, and post-MPI cardiac events/procedures. RESULTS: The most commonly used stress agent was regadenoson (91.7%). The COVID-19 group (n = 6372; 3.5%) had slightly higher: reversal agent use (difference 1.13% [95% confidence interval [CI]: 0.33, 1.92]), all-cause costs (difference USD $128 [95% CI: $73-$181]), and office visits (81.5% vs. 77.0%) than the no-COVID-19 group. Prior COVID-19 infection did not appear to impact subsequent cardiac events/procedures. CONCLUSIONS: COVID-19 history was associated with slightly higher reversal agent use, all-cause costs, and office visits after pharmacologic MPI; however, the differences were not clinically meaningful. Concerns for use of stress agents in patients with prior COVID-19 do not appear to be warranted.

Secondary invasive fungal infection in hospitalised patients with COVID-19 in the United States.

BACKGROUND: Invasive fungal infections (IFIs) have been identified as a complication in patients with Coronavirus disease 2019 (COVID-19). To date, there are few US studies examining the excess humanistic and economic burden of IFIs on hospitalised COVID-19 patients. OBJECTIVES: This study investigated the incidence, risk factors, clinical and economic burden of IFIs in patients hospitalised with COVID-19 in the United States. PATIENTS/METHODS: Data from adult patients hospitalised with COVID-19 during 01 April 2020-31 March 2021 were extracted retrospectively from the Premier Healthcare Database. IFI was defined either by diagnosis or microbiology findings plus systemic antifungal use. Disease burden attributable to IFI was estimated using time-dependent propensity score matching. RESULTS: Overall, 515,391 COVID-19 patients were included (male 51.7%, median age: 66 years); IFI incidence was 0.35/1000 patient-days. Most patients did not have traditional host factors for IFI such as hematologic malignancies; COVID-19 treatments including mechanical ventilation and systemic corticosteroid use were identified as risk factors. Excess mortality attributable to IFI was estimated at 18.4%, and attributable excess hospital costs were $16,100. CONCLUSIONS: Invasive fungal infection incidence was lower than previously reported, possibly due to a conservative definition of IFI. Typical COVID-19 treatments were among the risk factors identified. Furthermore, diagnosis of IFIs in COVID-19 patients may be complicated because of the several non-specific shared symptoms, leading to underestimation of the true incidence rate. The healthcare burden of IFIs was significant among COVID-19 patients, including higher mortality and greater cost.

Real-World Treatment Patterns and Outcomes Among Patients with Basal Cell Carcinoma Following First-Line Hedgehog Inhibitor Discontinuation.

INTRODUCTION: Until recently, patients discontinuing first-line (1L) hedgehog inhibitors (HHIs) for basal cell carcinoma (BCC) had few subsequent treatment options. The objective of this study was to describe the treatment journey and prognosis of patients discontinuing 1L HHI for BCC. METHODS: This was a retrospective cohort study of patients with BCC who discontinued 1L HHI treatment in The US Oncology Network between 1 January 2012 and 1 January 2019 (with follow-up until 1 May 2020). Two cohorts were identified: patients who initiated a second-line (2L) treatment (2L initiators), and patients with 1L progression or toxicity without pathology-confirmed complete response who did not initiate 2L treatment (2L non-initiators). Patient demographics, treatment characteristics, and outcomes are reported for each cohort. RESULTS: Among 115 patients with BCC who received 1L HHI treatment, 63.5% (n = 73/115) discontinued 1L HHIs. Of those, 50.7% (n = 37/73) discontinued because of documented toxicity or progression, without evidence of a complete response. We identified 4 patients who initiated 2L systemic treatment (median age 68.7 years, 100.0% female) and 15 patients who were eligible for the 2L non-initiator cohort (median age 80.2 years, 20.0% female). Median 1L HHI duration was 6.8 months (range 1.9-20.6 months) for the 2L non-initiator cohort and 8.6 months (range 6.8-42.2 months) for 2L initiators. At the end of follow-up, among 2L non-initiators (median follow-up duration 9.7 months), 40.0% were lost to follow-up, 33.3% had died, 20.0% continued observation, and 6.7% transitioned to an academic medical center or hospital; among 2L initiators (median follow-up duration 6.3 months), 50.0% were lost to follow-up, 25.0% had died, and 25.0% continued observation. CONCLUSIONS: Following 1L HHI discontinuation, lack of standardized care and suboptimal outcomes were observed, including limited receipt of 2L treatment. Further studies are necessary to evaluate the impact of newer BCC treatment options.

Treatment patterns and outcomes for patients with newly diagnosed glioblastoma multiforme: a retrospective cohort study.

Aim: Investigate real-world outcomes and healthcare utilization of patients with glioblastoma multiforme (GBM) related to O6-methylguanine DNA methyltransferase (MGMT) promoter testing and methylation. Patients & methods: US Oncology Network data were analyzed for patients receiving first-line (1L) treatment for GBM. Results: Most patients received 1L radiation with temozolomide. Unadjusted median overall survival (OS) was higher in tested versus untested (median:18.1 vs 11.8 months) and in methylated versus unmethylated (median: 25.5 vs 12.4 months). Untested status, unmethylated MGMT and older age were associated with reduced OS and longer 1L treatment with increased OS. Similar findings were observed for progression-free survival. Utilization was similar between cohorts. Conclusion: In community oncology practices, MGMT methylation and testing were predictive of better survival in GBM.

Lay abstract We studied the characteristics and survival of patients with newly diagnosed glioblastoma multiforme (GBM) in community-based oncology practices. These patients had received temozolomide and radiotherapy with surgery, which is the standard of care for GBM. We were interested in how patient survival was related to methylation of the O⁶-methylguanine DNA methyltransferase (MGMT) promoter. The study showed that patients with methylated versus unmethylated MGMT GBM survived longer. However, patients who were tested for methylation, whether MGMT was methylated or not, also survived longer. This may be because patients who get tested also get better care in general.

Clinical outcomes among unresectable, locally advanced, and metastatic cutaneous squamous cell carcinoma patients treated with systemic therapy.

Prior studies of conventional chemotherapy or epidermal growth factor receptor inhibitors for advanced (ie, locally advanced cutaneous squamous cell carcinoma [laCSCC] or metastatic [mCSCC]) cutaneous squamous cell cancer enrolled ≤ 40 patients. This retrospective, observational study assessed real-world treatment patterns and clinical outcomes in patients with unresectable laCSCC or mCSCC using electronic health records of patients who initiated first-line (1L) systemic treatment from 1 January 2008 to 31 December 2015, with follow-up to 30 September 2017. The median duration of follow-up from 1L treatment was 10.1 months (range 0.03-67.6 months). Duration of therapy (DOT) and overall survival (OS) were assessed using Kaplan-Meier analysis. Response rate was calculated as the proportion of patients who achieved physician-assessed-response. Eighty-two patients were identified (17 laCSCC and 65 mCSCC). Median age at 1L treatment initiation was 75 years; 85% were male, 88% had an Eastern Cooperative Oncology Group performance status of 1, and 84% had received radiotherapy. The most common 1L regimens were carboplatin + paclitaxel (27%) and cetuximab monotherapy (24%). The median 1L DOT was 4.1 months for laCSCC and 2.3 months for mCSCC. The physician-assessed response rate for 1L therapy was 17.6% for laCSCC, and 18.5% for mCSCC. The median OS from 1L treatment initiation was 16.2 months for laCSCC, and 15.3 months for mCSCC. Only 24 patients (29%) received second-line therapy. This is the largest retrospective data set regarding patients with advanced CSCC treated with anticancer systemic therapy prior to approval of the anti-programmed cell death-1 antibody, cemiplimab. Efficacy was low in both laCSCC and mCSCC. These data provide historic benchmarks for outcomes in patients with advanced CSCC prior to Food and Drug Administration approval of cemiplimab-rwlc.

Meta-Analysis of Local Invasive Breast Cancer Recurrence After Electron Intraoperative Radiotherapy.

BACKGROUND: Electron intraoperative radiotherapy (IORT) can be used during breast conserving surgery to treat early-stage invasive breast cancer. Using data from current clinical and observational studies, this study aimed to assess the impact of single-fraction electron IORT on local recurrence rates. METHODS: Studies on single-fraction electron IORT during breast conserving surgery were identified through a search of PubMed and Google Scholar, as well as through secondary referencing. Local recurrence rate was the main outcome of interest. A meta-analysis of proportions using a binomial distribution to model the within-study variability and a random effects model was conducted to estimate a pooled local recurrence rate. To estimate a 5-year recurrence rate, a single-sample Poisson-normal model was applied to model the probability of events occurring during a fixed period (60 months). RESULTS: The study identified 13 publications. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% confidence interval CI 0.00-0.06%) for the studies with a follow-up period shorter than 5 years, 0.03% per person-month (95% CI 0.02-0.06%) for studies with a follow-up period of 5 years or longer, and 0.02% per person-month (95% CI 0.01-0.04%) overall. Based on this model, the predicted 5-year local recurrence rate was 2.7% (range 1.9-3.7%). CONCLUSIONS: According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month, with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT for low-risk patients.

Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis (BRCR-D-16-00033).

BACKGROUND: Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer incorporating the degree of family history. METHODS: We created a microsimulation model for women with first-degree, second-degree, and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or ER-negative breast cancer at the ages of 40, 50, 60, and 70. The model incorporated a 10-year posttreatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate quality-adjusted life expectancy for the clinical strategies CPM and no CPM. RESULTS: CPM showed minimal improvement on quality-adjusted life expectancy among women age 50-60 with no or a unilateral first-degree or second-degree family history (decreasing from 0.31 to -0.06 quality-adjusted life-years (QALYs)) and was unfavorable for most subgroups of women age 70 with stage III breast cancer regardless of degree of family history (range -0.08 to -0.02 QALYs). Sensitivity analysis showed that the highest predicted benefit of CPM assuming 95 % risk reduction in CBC was 0.57 QALYs for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer. CONCLUSIONS: Women age 40 with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For most subgroups of women, CPM has a minimal to no effect on quality-adjusted life expectancy, irrespective of family history of breast cancer.

Overtreatment and Cost-Effectiveness of the See-and-Treat Strategy for Managing Cervical Precancer.

BACKGROUND: See-and-treat using loop electrosurgical excision procedure (LEEP) has been recommended as an alternative in managing high-grade cervical squamous intraepithelial lesions, but existing literature lacks evidence of the strategy's cost-effectiveness. We evaluated the overtreatment and cost-effectiveness of the see-and-treat strategy compared with usual care. METHODS: We modeled a hypothetical cohort of 40-year-old females who had not been screened for cervical cancer and followed them through their lifetimes using a Markov model. From a U.S. health-system perspective, the analysis was conducted in 2012 dollars and measured effectiveness in quality-adjusted life-years (QALY). We estimated incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $50,000/QALY. The robustness of the see-and-treat strategy's cost-effectiveness and its overtreatment rates were further examined in various sensitivity analyses. RESULTS: In the base-case, the see-and-treat strategy yielded an ICER of $70,774/QALY compared with usual care. For most scenarios in the deterministic sensitivity analysis, this strategy had ICERs larger than $50,000/QALY, and its cost-effectiveness was sensitive to the disutility of LEEP treatment and biopsy-directed treatment adherence under usual care. Probabilistic sensitivity analysis showed that the see-and-treat strategy had a 50.1% chance to be cost-effective. It had an average overtreatment rate of 7.1% and a 78.8% chance to have its overtreatment rate lower than the 10% threshold. CONCLUSION: The see-and-treat strategy induced an acceptable overtreatment rate. Its cost-effectiveness, compared with usual care, was indiscriminating at the chosen willingness-to-pay threshold but much improved when the threshold increased. IMPACT: The see-and-treat strategy was reasonable for particular settings, that is, those with low treatment adherence. Cancer Epidemiol Biomarkers Prev; 25(5); 807-14. ©2016 AACR.

Disparities in cervical cancer survival among Asian-American women.

PURPOSE: We compared overall survival and influencing factors between Asian-American women as a whole and by subgroup with white women with cervical cancer. METHODS: Cervical cancer data were from the Surveillance, Epidemiology, and End Results registry; socioeconomic information was from the Area Health Resource File. We used standard tests to compare characteristics between groups; the Kaplan-Meier method with log-rank test to assess overall survival and compare it between groups; and Cox proportional hazards models to determine the effect of race and other covariates on overall survival (with and/or without age stratification). RESULTS: Being 3.3 years older than white women at diagnosis (P < .001), Asian-American women were more likely to be in a spousal relationship, had more progressive disease, and were better off socioeconomically. Women of Filipino, Japanese, and Korean origin had similar clinical characteristics compared to white women. Asian-American women had higher 36- and 60-month survival rates (P = .004 and P = .013, respectively), higher overall survival rates (P = .049), and longer overall survival durations after adjusting for age and other covariates (hazard ratio = 0.77, 95% confidence interval: 0.68-0.86). Overall survival differed across age strata between the two racial groups. With the exception of women of Japanese or Korean origin, Asian-American women grouped by geographic origin had better overall survival than white women. CONCLUSIONS: Although Asian-American women, except those of Japanese or Korean origin, had better overall survival than white women, their older age at cervical cancer diagnosis suggests that they have less access to screening programs.

An alternative approach for estimating the accuracy of colposcopy in detecting cervical precancer.

INTRODUCTION: Since colposcopy helps to detect cervical cancer in its precancerous stages, as new strategies and technologies are developed for the clinical management of cervical neoplasia, precisely determining the accuracy of colposcopy is important for characterizing its continued role. Our objective was to employ a more precise methodology to estimate of the accuracy of colposcopy to better reflect clinical practice. STUDY DESIGN: For each patient, we compared the worst histology result among colposcopically positive sites to the worst histology result among all sites biopsied, thereby more accurately determining the number of patients that would have been underdiagnosed by colposcopy than previously estimated. MATERIALS AND METHODS: We utilized data from a clinical trial in which 850 diagnostic patients had been enrolled. Seven hundred and ninety-eight of the 850 patients had been examined by colposcopy, and biopsy samples were taken at colposcopically normal and abnormal sites. Our endpoints of interest were the percentages of patients underdiagnosed, and sensitivity and specificity of colposcopy. RESULTS: With the threshold of low-grade squamous intraepithelial lesions for positive colposcopy and histology diagnoses, the sensitivity of colposcopy decreased from our previous assessment of 87.0% to 74.0%, while specificity remained the same. The drop in sensitivity was the result of histologically positive sites that were diagnosed as negative by colposcopy. Thus, 28.4% of the 798 patients in this diagnostic group would have had their condition underdiagnosed by colposcopy in the clinic. CONCLUSIONS: In utilizing biopsies at multiple sites of the cervix, we present a more precise methodology for determining the accuracy of colposcopy. The true accuracy of colposcopy is lower than previously estimated. Nevertheless, our results reinforce previous conclusions that colposcopy has an important role in the diagnosis of cervical precancer.

Better contralateral breast cancer risk estimation and alternative options to contralateral prophylactic mastectomy.

The incidence of contralateral prophylactic mastectomy (CPM) has increased among women with breast cancer, despite uncertain survival benefit and a declining incidence of contralateral breast cancer (CBC). Patient-related reasons for undergoing CPM include an overestimation of the risk of CBC, increased cancer worry, and a desire to improve survival. We summarize the existing literature on CBC risk and outcomes and the clinical benefit of CPM among women with unilateral breast cancer who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast. Published studies were retrieved from the MEDLINE database with the keywords "contralateral breast cancer" and "contralateral prophylactic mastectomy". These include observational studies, clinical trials, survival analyses, and decision models examining the risk of CBC, the clinical and psychosocial effects of CPM, and other treatment strategies to reduce CBC risk. Studies that have evaluated CBC risk estimate it to be approximately 0.5% annually on average. Patient-related factors associated with an increased risk of CBC include carriers of BRCA1/2 mutations, young age at breast cancer, and strong family history of breast cancer in the absence of a BRCA1/2 mutation. Although CPM reduces the risk of CBC by approximately 94%, it may not provide a significant gain in overall survival and there is conflicting evidence that it improves disease-free survival among women with breast cancer regardless of estrogen receptor (ER) status. Therefore, alternative strategies such as the use of tamoxifen or aromatase inhibitors, which reduce the risk of CBC by approximately 50%, should be encouraged for eligible women with ER-positive breast cancers. Future research is needed to evaluate the impact of decision and educational tools that can be used for personalized counseling of patients regarding their CBC risk, the uncertain role of CPM, and alternative CBC risk reduction strategies.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings.

Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training.

Inverse decision theory with applications to screening and diagnosis of cervical intraepithelial neoplasia.

OBJECTIVE: Medical decision makers would like to use decision theory to determine optimal treatment strategies for patients, but this requires priors, likelihoods, and losses. It can be very difficult to specify a loss or utility function in a medical setting, especially when considering both patient health outcomes and economic costs. These issues led to the development of Inverse Decision Theory (IDT), which involves determining the set of losses under which a given decision rule is optimal. METHODS: We apply IDT to the current standard of care for the diagnosis and treatment of precancerous lesions to the cervix, using a Bayesian approach to estimate the probabilities associated with diagnostic tests and make inferences about the region of optimality. There are two ways in which Inverse Decision Theory can be useful: (i) if the decision rule of interest is optimal, then we obtain information about the losses for the optimal treatment strategy, and (ii) if the decision rule of interest is not optimal, then we characterize the losses under which it would be optimal, and assess whether or not it contains reasonable values of the losses. RESULTS: This paper introduces important clinical results: in particular, we find that the current standard of care for cervical precancer is probably not optimal, and a new decision rule which requires a confirmatory biopsy for all patients with a positive Pap smear test result is better. CONCLUSION: We have developed a very general and flexible approach for evaluating treatment strategies that could prove useful in a variety of medical applications.