Guideline concordant care for patients with locally advanced cervical cancer by disaggregated Asian American and Native Hawaiian/Pacific Islander groups: A National Cancer Database Analysis.

OBJECTIVE: Despite the within-group heterogeneity, Asian American (AA) and Native Hawaiian and Pacific Islander (NH/PI) patients are often grouped together. We compared the patterns of guideline-concordant care for locally advanced cervical cancer for disaggregated AA and NH/PI patients. METHODS: Patients with stage II-IVA cervical cancer between 2004 and 2020 were identified from the National Cancer Database. AA patients were disaggregated as East Asian (EA), South Asian (SA), and Southeast Asian (SEA). NH/PI patients were classified as a distinct racial subgroup. The primary outcome was the proportion undergoing guideline-concordant care, defined by radiation therapy with concurrent chemotherapy, brachytherapy, and completion of treatment within eight weeks. RESULTS: Of 48,116 patients, 2107 (4%) were AA and 171 (<1%) were NH/PI. Of the AA patients, 36% were SEA, 31% were EA, 12% were SA, and 21% could not be further disaggregated due to missing or unknown data. NH/PI patients were more likely to be diagnosed at an early age (53% NH/PI vs. 30% AA, p < 0.001) and have higher rates of comorbidities (18% NH/PI vs. 14% AA, p < 0.001). Within the AA subgroups, only 82% of SEA patients received concurrent chemotherapy compared to 91% of SA patients (p = 0.026). SA patients had the longest median OS (158 months) within the AA subgroups compared to SEA patients (113 months, p < 0.001). CONCLUSION: Disparities exist in the receipt of standard of care treatment for cervical cancer by racial and ethnic subgroups. It is imperative to disaggregate race and ethnicity data to understand potential differences in care and tailor interventions to achieve health equity.

The Value of Gastric Cancer Staging by Endoscopic Ultrasonography Features in the Diagnosis of Gastroenterology.

This research was aimed at exploring the application value of endoscopic ultrasonography (EUS) in the diagnosis of gastric cancer staging and the correlation between staging and clinical features of gastric cancer. A total of 72 patients with gastric cancer were selected and randomly divided into two groups. The patients in the pathological group underwent postoperative pathological examination, while those in the EUS group received preoperative EUS examination. The results showed that the staging accuracy of EUS was 73.33% for T1, 78.57% for T2, 27% for T3, and 100% for T4, compared with the pathological staging. The accuracy of N- and N+ was 42.5% and 82.3% in EUS, respectively, and the total accuracy was 55.7%. There was no considerable difference in the accuracy of T staging between early gastric cancer and advanced gastric cancer (P > 0.05), but there was a considerable difference in N staging (P < 0.05). Lymph node metastasis affected the accuracy of N staging (P < 0.05). The number and location of metastatic lymph nodes did not affect the judgment of metastatic lymph nodes (P > 0.05). In addition, the proportion of understaging and overstaging was greatly different among different lesion sizes and histological types of gastric cancer (P < 0.05). To sum up, the accuracy of EUS for T and N staging of gastric cancer needed to be improved. The location of gastric cancer lesions affected the accuracy of T staging, while the depth of invasion and lymph node metastasis affected the accuracy of N staging.

Computed Tomography Image Features under Deep Learning Algorithm Applied in Staging Diagnosis of Bladder Cancer and Detection on Ceramide Glycosylation.

The research is aimed at investigating computed tomography (CT) image based on deep learning algorithm and the application value of ceramide glycosylation in diagnosing bladder cancer. The images of ordinary CT detection were improved. In this study, 60 bladder cancer patients were selected and performed with ordinary CT detection, and the detection results were processed by CT based on deep learning algorithms and compared with pathological diagnosis. In addition, Western Blot technology was used to detect the expression of glucose ceramide synthase (GCS) in the cell membrane of tumor tissues and normal tissues of bladder. The comparison results found that, in simple CT clinical staging, the coincidence rates of T1 stage, T2a stage, T2b stage, T3 stage, and T4 stage were 28.56%, 62.51%, 78.94%, 84.61%, and 74.99%, respectively; and the total coincidence rate of CT clinical staging was 63.32%, which was greatly different from the clinical staging of pathological diagnosis (P < 0.05). In the clinical staging of algorithm-based CT test results, the coincidence rates of T1 stage and T2a stage were 50.01% and 91.65%, respectively; and those of T2b stage, T3 stage, and T4 stage were 100.00%; and the total coincidence rate was 96.69%, which was not obviously different from the clinical staging of pathological diagnosis (P > 0.05). Therefore, it could be concluded that the algorithm-based CT detection results were more accurate, and the use of CT scans based on deep learning algorithms in the preoperative staging and clinical treatment of bladder cancer showed reliable guiding significance and clinical value. In addition, it was found that the expression level of GCS in normal bladder tissues was much lower than that in bladder cancer tissues. This indicated that the changes in GCS were closely related to the development and prognosis of bladder cancer. Therefore, it was believed that GCS may be an effective target for the treatment of bladder cancer in the future, and further research was needed for specific conditions.

Preoperative MRI PI-RADS scores are associated with prostate cancer upstaging on surgical pathology.

INTRODUCTION: Prostate Imaging Reporting and Data System (PI-RADS) scores can help identify clinically significant prostate cancer and improve patient selection for prostate biopsies. However, the role of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear. The purpose of this study was to evaluate the association of PI-RADS scores with prostate cancer upstaging. Upstaging on final pathology harbors a higher risk for biochemical recurrence with important implications for additional treatments, morbidity, and mortality. METHODS: All patients from a single high-volume institution who underwent a prostate multiparametric magnetic resonance imaging and radical prostatectomy between 2016 and 2020 were included in this retrospective analysis. Univariable and multivariable analyses were conducted to investigate potential associations with upstaging events, defined by pT3, pT4, or N1 on final pathology. A logistic regression model was constructed for the prediction of upstaging events based on PI-RADS score, prostate-specific antigen density (PSA-D), and biopsy Gleason grade groups. We built receiver operative characteristic (ROC) curves to measure the area under the curve of different predictive models. RESULTS: Two hundred and ninety-four patients were included in the final analysis. Upstaging events occurred in 137 (46.5%) of patients. On univariable analysis, patients who were upstaged on final pathology had significantly higher PI-RADS scores (odds ratio [OR] 2.34 95% confidence interval [CI] 1.64-3.40, p < 0.001) but similar PSA-D (OR 2.70 95% 0.94-8.43, p = 0.188) compared with patients who remained pT1 or pT2 on final pathology. On multivariable analysis, PI-RADS remained independently significantly associated with upstaging, suggesting it is an independent risk predictor for upstaging. Lymph node metastasis only occurred in patients with PI-RADS 4 or 5 lesions (n = 15). Our model using PSA-D, biopsy Gleason grade, and PI-RADS had a predictive AUC of 0.69 for upstaging events, an improvement from 0.59 using biopsy Gleason grade alone. CONCLUSION: PI-RADS scores are independent predictors for upstaging events and may play an important role in forecasting biochemical recurrence and lymph node metastasis. Modern nomograms should be updated to include PI-RADS to predict lymph node metastases and the likelihood of biochemical recurrence more accurately.

How socioeconomic and clinical factors impact prostate-cancer-specific and other-cause mortality in prostate cancer stratified by clinical stage: Competing-risk analysis.

BACKGROUND: The aim of this study was to analyze the causes of death and risk factors of prostate-cancer-specific mortality (PCSM) and other-cause mortality (OCM) at different clinical stages using data from the Surveillance, Epidemiology, and End Results database. METHODS: The characteristics and cause-specific death classifications of males with prostate cancer (PCa) were extracted. Multivariate competing-risk regression analysis was used to identify significant predictors and quantify the cumulative incidence of PCSM and OCM at different clinical stages. RESULTS: Of the 244,433 PCa patients who were included, 19,274 died from 7356 PCSM, and 11,918 from OCM. The proportion of PCSM gradually increased from 2010 to 2016. The risk factors for PCSM in the localized PCa stage included older age, not being married, living in a county with higher poverty rates, and higher PSA levels and Gleason scores. Meanwhile, Medicaid and lower education levels were the additional risk factors of OCM. The risk factors for PCSM in the regional PCa stage included older age, not being married, Medicaid, living in a county with higher poverty rates, and higher PSA levels and Gleason scores. Meanwhile, the income level did not affect OCM risk. The risk factors for PCSM in the distant metastatic PCa stage included a separated/divorced/widowed marital status, Medicaid, and higher PSA levels and Gleason scores. Meanwhile, older age, an unmarried or separated/divorced/widowed marital status, and higher PSA levels were risk factors for OCM. In addition, receiving both surgery and radiation was worse than just receiving surgery for PCa specific survival in localized and regional PCa patients. CONCLUSION: Some pretreatment and treatment factors may influence OCM that are not identical to those for PCSM at the corresponding stage. Decision-makers and managers should fully consider OCM to maximize treatment benefits for PCa.

BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update.

There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.

Revisiting the AJCC staging system of adrenocortical carcinoma.

OBJECTIVE: To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS: Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS: A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS: There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Identification of 5 Hub Genes Related to the Early Diagnosis, Tumour Stage, and Poor Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.

BACKGROUND: The majority of primary liver cancers in adults worldwide are hepatocellular carcinomas (HCCs, or hepatomas). Thus, a deep understanding of the underlying mechanisms for the pathogenesis and carcinogenesis of HCC at the molecular level could facilitate the development of novel early diagnostic and therapeutic treatments to improve the approaches and prognosis for HCC patients. Our study elucidates the underlying molecular mechanisms of HBV-HCC development and progression and identifies important genes related to the early diagnosis, tumour stage, and poor outcomes of HCC. METHODS: GSE55092 and GSE121248 gene expression profiling data were downloaded from the Gene Expression Omnibus (GEO) database. There were 119 HCC samples and 128 nontumour tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). Volcano plots and Venn diagrams were drawn by using the ggplot2 package in R. A heat map was generated by using Heatmapper. By using the clusterProfiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, KM survival curves and ROC curves were generated to validate hub gene expression. RESULTS: By GO enrichment analysis, 694 DEGs were enriched in the following GO terms: organic acid catabolic process, carboxylic acid catabolic process, carboxylic acid biosynthetic process, collagen-containing extracellular matrix, blood microparticle, condensed chromosome kinetochore, arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. In the KEGG pathway enrichment analysis, DEGs were enriched in arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. By PPI network construction and analysis of hub genes, we selected the top 10 genes, including CDK1, CCNB2, CDC20, BUB1, BUB1B, CCNB1, NDC80, CENPF, MAD2L1, and NUF2. By using TCGA and THPA databases, we found five genes, CDK1, CDC20, CCNB1, CENPF, and MAD2L1, that were related to the early diagnosis, tumour stage, and poor outcomes of HBV-HCC. CONCLUSIONS: Five abnormally expressed hub genes of HBV-HCC are informative for early diagnosis, tumour stage determination, and poor outcome prediction.

National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis.

BACKGROUND: In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. METHODS: In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. FINDINGS: 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (ß=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (ß=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. INTERPRETATION: Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. FUNDING: None.

Contemporary treatment patterns and survival of cervical cancer patients in Ethiopia.

BACKGROUND: Cervical cancer is the second commonly diagnosed cancer and the second leading cause of cancer death in women in Ethiopia, with rates among the highest worldwide. However, there are limited data on cervical cancer treatment patterns and survival in the country. Herein, we examine treatment patterns and survival of cervical cancer patients treated in Tikur Anbessa Hospital Radiotherapy Center (TAHRC), the only hospital with radiotherapy facility in the country. METHODS: Women with histologically verified cervical cancer who were seen in 2014 (January 1, 2014 to December 31, 2014) at TAHRC were included. Information about clinical characteristics and treatments were extracted from the patients' medical record files. The information on vital status was obtained from medical chart and through telephone calls. RESULT: Among 242 patients included in the study, the median age at diagnosis was 48 years. The median waiting time for radiotherapy was 5.6 months (range 2 to 9 months). Stage migration occurred in 13% of patients while waiting for radiotherapy. Consequently, the proportion of patients with stage III or IV disease increased from 66% at first consultation to 74% at the initiation of radiotherapy. Among 151 patients treated with curative intent, only 34 (22.5%) of the patients received concurrent chemotherapy while the reaming patients received radiotherapy alone. The 5-year overall survival rate was 28.4% (20.5% in the worst-case scenario). As expected, survival was lower in patients with advanced stage at initiation of radiotherapy and in those treated as palliative care. CONCLUSION: The survival of cervical cancer patients remains low in Ethiopia because of late presentation and delay in receipt of radiotherapy, leading to stage migration in substantial proportion of the cases. Concerted and coordinated multisectoral efforts are needed to promote early presentation of cervical cancer and to shorten the unacceptable, long waiting time for radiotherapy.

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

INTRODUCTION: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation. METHODS: Retrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1-2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition). RESULTS: High-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35). CONCLUSIONS: Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation.

DNA 5-hydroxymethylcytosine in pediatric central nervous system tumors may impact tumor classification and is a positive prognostic marker.

BACKGROUND: Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG loci. RESULTS: Linear mixed effects models adjusted for age and sex tested the CpG-specific differences in 5hmC between tumor and non-tumor samples, as well as between tumor subtypes. Results from model-based clustering of tumors was used to test the relation of cluster membership with patient survival through multivariable Cox proportional hazards regression. We also assessed the robustness of multiple epigenetic CNS tumor classification methods to 5mC-specific data in both pediatric and adult CNS tumors. Compared to non-tumor samples, tumors were hypohydroxymethylated across the epigenome and tumor 5hmC localized to regulatory elements crucial to cell identity, including transcription factor binding sites and super-enhancers. Differentially hydroxymethylated loci among tumor subtypes tended to be hypermethylated and disproportionally found in CTCF binding sites and genes related to posttranscriptional RNA regulation, such as DICER1. Model-based clustering results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results suggest 5mC-specific data from OxBS-treated samples impacts methylation-based tumor classification systems giving new opportunities for further refinement of classifiers for both pediatric and adult tumors. CONCLUSIONS: We identified that 5hmC localizes to super-enhancers, and genes commonly implicated in pediatric CNS tumors were differentially hypohydroxymethylated. We demonstrated that distinguishing methylation and hydroxymethylation is critical in identifying tumor-related epigenetic changes. These results have implications for patient prognostication, considerations of epigenetic therapy in CNS tumors, and for emerging molecular neuropathology classification approaches.

Detection of Human Papillomavirus in Papillary Thyroid Carcinoma and its Association with Tumor Staging and Pathologic Features.

Background: The role of human papillomavirus (HPV), as a common infection, has been evaluated in many cancers such as the cervix and squamous cell carcinoma of the head and neck. To the best of our knowledge, for the first time, the association of HPV with papillary thyroid carcinoma (PTC) and its pathologic features are investigated. Methods: A retrospective cross-sectional study was conducted from May 2014 to January 2018 in several hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Thyroid tissue specimens of patients diagnosed with PTC (n=82) and benign thyroid nodules (n=77) were collected using the consecutive sampling method. The presence of HPV in PTC, adjacent normal tissue, and benign thyroid nodules was evaluated using the polymerase chain reaction (PCR) method. The frequency of HPV positivity in PTC tissues was compared with benign thyroid nodules and adjacent normal tissue. Association of pathologic features of PTC with HPV positivity was also investigated. Data were analyzed using SPSS version 21.0, and P values less than 0.05 were considered statistically significant. Results: HPV PCR positivity was observed in 3.8% of benign thyroid nodules and 13.4% of PTC samples but in none of the adjacent normal tissues. After adjustment for age and sex, the prevalence of HPV PCR positivity in the PTC tissues was significantly more than the benign thyroid nodules (P=0.015). The prevalence was also significantly higher than the adjacent normal tissues (P<0.001). Conclusion: There was a significant association between PTC and HPV positivity. Further studies are required to determine the cause and effect of the association between these two conditions.

Phase-Specific and Lifetime Costs of Multiple Myeloma Among Older Adults in the US.

Importance: Health care costs associated with diagnosis and care among older adults with multiple myeloma (MM) are substantial, with cost of care and the factors involved differing across various phases of the disease care continuum, yet little is known about cost of care attributable to MM from a Medicare perspective. Objective: To estimate incremental phase-specific and lifetime costs and cost drivers among older adults with MM enrolled in fee-for-service Medicare. Design, Setting, and Participants: A retrospective cohort study was conducted using population-based registry data from the 2007-2015 Surveillance, Epidemiology, and End Results database linked with 2006-2016 Medicare administrative claims data. Data analysis included 4533 patients with newly diagnosed MM and 4533 matched noncancer Medicare beneficiaries from a 5% sample of Medicare to assess incremental MM lifetime and phase-specific costs (prediagnosis, initial care, continuing care, and terminal care) and factors associated with phase-specific incremental MM costs. The study was conducted from June 1, 2019, to April 30, 2021. Main Outcomes and Measures: Incremental MM costs were calculated for the disease lifetime and the following 4 phases of care: prediagnosis, initial, continuing care, and terminal. Results: Of the 4533 patients with MM included in the study, 2374 were women (52.4%), 3418 (75.4%) were White, and mean (SD) age was 75.8 (6.8) years (2313 [51.0%] aged ≥75 years). The characteristics of the control group were similar; however, mean (SD) age was 74.2 (8.8) years (2839 [62.6%] aged ≤74 years). Mean adjusted incremental MM lifetime costs were $184 495 (95% CI, $183 099-$185 968). Mean per member per month phase-specific incremental MM costs were estimated to be $1244 (95% CI, $1216-$1272) for the prediagnosis phase, $11 181 (95% CI, $11 052-$11 309) for the initial phase, $5634 (95% CI, $5577-$5694) for the continuing care phase, and $6280 (95% CI, $6248-$6314) for the terminal phase. Although inpatient and outpatient costs were estimated as the major cost drivers for the prediagnosis (inpatient, 55.8%; outpatient, 40.2%), initial care (inpatient, 38.1%; outpatient, 35.5%), and terminal (inpatient, 33.0%; outpatient, 34.6%) care phases, prescription drugs (44.9%) were the largest cost drivers in the continuing care phase. Conclusions and Relevance: The findings of this study suggest that there is substantial burden to Medicare associated with diagnosis and care among older adults with MM, and the cost of care and cost drivers vary across different phases of the cancer care continuum. The study findings might aid policy discussions regarding MM care and coverage and help further the development of alternative payment models for MM, accounting for differential costs across various phases of the disease continuum and their drivers.

Evaluation of Insurance Coverage and Cancer Stage at Diagnosis Among Low-Income Adults With Renal Cell Carcinoma After Passage of the Patient Protection and Affordable Care Act.

Importance: The association of the Patient Protection and Affordable Care Act (ACA) with insurance status and cancer stage at diagnosis among patients with renal cell carcinoma (RCC) is unknown. Objective: To test the hypothesis that the ACA may be associated with increased access to care through expansion of insurance, which may vary based on income. Design, Setting, and Participants: This retrospective cohort analysis included patients diagnosed with RCC from January 1, 2010, to December 31, 2016, in the National Cancer Database. Data were analyzed from July 1 to December 31, 2020. The periods from 2010 to 2013 and from 2014 to 2016 were defined as pre- and post-ACA implementation, respectively. Patients were categorized as living in a Medicaid expansion state or not. Exposures: Implementation of the ACA. Main Outcomes and Measures: The absolute percentage change (APC) of insurance coverage was calculated before and after ACA implementation in expansion and nonexpansion states. Secondary outcomes included change in stage at diagnosis, difference in the rate of insurance change, and change in localized disease between expansion and nonexpansion states. Adjusted difference-in-difference modeling was performed. Results: The cohort included 78 099 patients (64.7% male and 35.3% female; mean [SD] age, 54.66 [6.46] years), of whom 21.2% had low, 46.2% had middle, and 32.6% had high incomes. After ACA implementation, expansion states had a lower proportion of uninsured patients (adjusted difference-in-difference, -1.14% [95% CI, -1.98% to -1.41%]; P = .005). This occurred to the greatest degree among low-income patients through the acquisition of Medicaid (APC, 11.0% [95% CI, 8.6%-13.3%]; P < .001). Implementation of the ACA was also associated with an increase in detection of stage I and II disease (APC, 4.0% [95% CI, 1.6%-6.3%]; P = .001) among low-income patients in expansion states. Conclusions and Relevance: Among patients with RCC, ACA implementation was associated with an increase in insurance coverage status in both expansion and nonexpansion states for all income groups, but to a greater degree in expansion states. The proportion of patients with localized disease increased among low-income patients in both states. These data suggest that ACA implementation is associated with earlier RCC detection among lower-income patients.

Medical costs according to the stages of colorectal cancer: an analysis of health insurance claims in Hachioji, Japan.

BACKGROUND: Although the effect of the early detection of colorectal cancer (CRC) on medical costs needs to be clarified, there are few reports on the actual medical costs of CRC patients in Japan. We aimed to identify medical costs according to CRC stage, using health insurance claims. METHODS: This observational study included CRC patients who had received specific treatment for CRC, which was defined by the procedure code and the claim computer processing system code associated with the treatment of CRC. CRC patients who underwent endoscopic or radical surgical treatment were defined as the curable group and those with palliative treatment, including palliative chemotherapy, as the non-curable group. Total medical costs and medical costs of specific treatments for CRC for 3 years were measured using the claims held by Hachioji City from May 2014 to July 2019. RESULTS: This study included 442 patients in the curable group, including 267 patients who underwent endoscopic treatment, and 175 patients who underwent radical surgical treatment, and 161 patients in the non-curable group. The mean (standard deviation) total medical costs in the curable and non-curable groups were 2,130 (2,494) and 8,279 (5,600) thousand Japanese Yen (JPY), respectively. The mean (standard deviation) medical costs for the specific treatment of CRC in the curable and non-curable groups were 408 (352) and 3,685 (3,479) thousand JPY, respectively. CONCLUSIONS: We clarified the actual medical costs of CRC in curable and non-curable groups. These results suggest the effect of early detection of CRC in reducing medical costs.

Lymphovascular invasion as a criterion for adjuvant chemotherapy for FIGO stage I-IIa clear cell carcinoma, mucinous, low grade serous and low grade endometrioid ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on overall survival (OS) and recurrence-free survival (RFS) in patients managed for stage I-IIa clear cell carcinoma, mucinous, low-grade serous and low-grade endometrioid ovarian cancer MATERIAL AND METHODS: Retrospective multicentre study of the research group FRANCOGYN between January 2001 and December 2018. All patients managed for stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer and for whom the presence of histological slides for the review of LVSI was available, were included. Patient's characteristics with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A cox analysis for OS and RFS analysis were performed in all population. RESULTS: Over the study period, 133 patients were included in the thirteen institutions. Among them, 12 patients had LVSI (9%). LVSI was an independent predictive factor for poorer Overall and recurrence free survivals. LVSI affected OS (p < 0.001) and RFS (p = 0.0007), CONCLUSION: The presence of LVSI in stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer has an impact on OS and RFS and should put them at high risk and consider the option of adjuvant chemotherapy.

The Will Rogers phenomenon, breast cancer and race.

BACKGROUND: The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients' group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP. METHODS: This is a retrospective analysis of 300 BC women (2007-2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes. RESULTS: Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging (p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). A total of Whites (45.05% vs. 47.85%) Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged. With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004). CONCLUSION: The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.

Inverse correlation between PD-L1 expression and LGR5 expression in tumor budding of stage II/III colorectal cancer.

We investigated the expression of LGR5, the most robust and reliable known cancer stem cell (CSC) marker of colorectal cancer, and PD-L1 in tumor budding (TB), as well as clinicopathological features. Tissue microarrays (TMAs) were generated from TB samples from 32 stage II/III colorectal adenocarcinoma patients, and LGR5 expression in TMAs was evaluated by RNAscope, an extremely sensitive RNA in situ hybridization technique. LGR5 expression was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (P = 0.0256). In the PD-L1-positive group, the tumor-infiltrating lymphocytes (TILs) score tended to be higher while the TNM stage was lower compared with the PD-L1 negative group (P = 0.0822 and P = 0.0765, respectively). There was no significant difference in Overall Survival between the PD-L1-positive and PD-L1-negative groups (log-rank test, P = 0.8218). This study showed that PD-L1-positive patients are a unique population with low LGR5 expression, and that LGR5-positive cells may be a promising therapeutic target in PD-L1-negative patients.