Higher Stage Disease Research Articles

Evaluation of a Deep Learning–Derived Quantitative Retinopathy of Prematurity Severity Scale

To evaluate the clinical usefulness of a quantitative deep learning-derived vascular severity score for retinopathy of prematurity (ROP) by assessing its correlation with clinical ROP diagnosis and by measuring clinician agreement in applying a novel scale. Analysis of existing database of posterior pole fundus images and corresponding ophthalmoscopic examinations using 2 methods of assigning a quantitative scale to vascular severity. Images were from clinical examinations of patients in the Imaging and Informatics in ROP Consortium. Four ophthalmologists and 1 study coordinator evaluated vascular severity on a scale from 1 to9. A quantitative vascular severity score (1-9) was applied to each image using a deep learning algorithm. A database of 499 images was developed for assessment of interobserver agreement. Distribution of deep learning-derived vascular severity scores with the clinical assessment of zone (I, II, or III), stage (0, 1, 2, or 3), and extent (<3 clock hours, 3-6 clock hours, and >6 clock hours) of stage 3 evaluated using multivariate linear regression and weighted κ values and Pearson correlation coefficients for interobserver agreement on a 1-to-9 vascular severity scale. For deep learning analysis, a total of 6344 clinical examinations were analyzed. A higher deep learning-derived vascular severity score was associated with more posterior disease, higher disease stage, and higher extent of stage 3 disease (P < 0.001 for all). For a given ROP stage, the vascular severity score was higher in zone I than zones II or III (P < 0.001). Multivariate regression found zone, stage, and extent all were associated independently with the severity score (P < 0.001 for all). For interobserver agreement, the mean ± standard deviation weighted κ value was 0.67 ± 0.06, and the Pearson correlation coefficient ± standard deviation was 0.88 ± 0.04 on the use of a 1-to-9 vascular severity scale. A vascular severity scale for ROP seems feasible for clinical adoption; corresponds with zone, stage, extent of stage 3, and plus disease; and facilitates the use of objective technology such as deep learning to improve the consistency of ROP diagnosis.

Characteristics of Radiation-Associated Bladder Cancer Compared To Primary Bladder Cancer

Radiation-associated muscle-invasive bladder cancer (RA-MIBC) has been suggested to represent a more aggressive disease variant compared to primary (non-radiation associated) MIBC. We sought to characterize the presentation, patterns of care, and outcomes of RA-MIBC compared to primary MIBC. We identified 60,117 patients diagnosed with non-metastatic or metastatic MIBC between 1988 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database and stratified patients based on whether radiation had been administered to a pelvic primary prior to the development of bladder cancer. We used logistic regression to compare rates of chemotherapy, surgery, or radiation for patients with RA-MIBC compared to primary MIBC. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC. There were 1,093 patients with RA-MIBC and 59,024 patients with primary MIBC. Patients with RA-MIBC were older compared to patients with primary MIBC (mean age 77.4 years vs 72.4 years, p < 0.001) and more likely to be male (86.8% vs 73.3%, p<0.001). RA-MIBCs were more likely to be high-grade (57.5% vs 47.6%, p<0.001) more likely to have T4 disease at diagnosis (21.0% vs 17.3%, p<0.001), and less likely to be node-positive (4.2% vs 8.1%, p < 0.001). In terms of treatment, primary MIBC patients with non-metastatic disease were more likely to undergo radiation (14.0% vs 3.1%, p<0.001) as well as radiation with cystectomy (1.9% vs 0.8%, p<0.001) compared to those with RA-MIBC. Median survival was significantly shorter for patients with RA-MIBC (13 mo. vs 19 mo.; p<0.001). RA-MIBCs tend to present with higher grade and higher stage disease and are less likely to receive curative treatment. Even when adjusting for stage, grade, and receipt of treatment, patients with RA-MIBC have worse survival compared to those with primary MIBC. These findings raise the possibility that RA-MIBC represents a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand biological differences between RA-MIBC and primary MIBC and develop improved therapeutics for radiation-associated cancers.

Invasive mucinous adenocarcinoma of the lung: Serial CT findings, clinical features, and treatment and survival outcomes.

BackgroundInvasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma that can appear as airspace opacities on computed tomography (CT). In daily practice, we have occasionally encountered spontaneous regression of airspace opacities (SRAs) without treatment on serial CTs in patients with IMAs, which has not previously been described in the literature. Here, we describe serial CT findings with emphasis on SRAs in relation to clinicopathological features and treatment outcomes in patients with IMAs.MethodsA total of 46 patients with pathologically‐confirmed IMAs of the lung from January 2013 to June 2018 were included. Serial CT scans were reviewed and the patients were classified into SRA and no‐SRA groups according to the presence of SRA. Radiological features, clinicopathological characteristics, and treatment outcomes were compared between the SRA and no‐SRA groups.ResultsA total of 32 patients were included in the no‐SRA group and 14 patients in the SRA group. IMAs in the SRA group were mostly pneumonic (P < 0.001), larger (P < 0.001), multifocal (P = 0.001), and showed higher stage (P < 0.001) on initial CT. Of seven patients who died during follow‐up, six were from the SRA group (P < 0.001). Mean overall survival for all IMAs was 86.6 months (range, 0–110 months), and the SRA group showed significantly worse overall survival (P < 0.001).ConclusionsIMAs of the lung showing SRAs on serial CTs are larger and multifocal, and tend to be pneumonic in type on initial CT. Patients present at a higher stage of disease, with higher mortality rate and reduced overall survival.Key pointsSignificant findings of the study Invasive mucinous adenocarcinomas (IMAs) of the lung can show spontaneous regression of airspace opacities (SRAs) on serial CTs, without being correlated to the administration of anticancer drugs. IMAs that showed SRAs demonstrated reduced overall survival in patients. What this study adds When airspace opacities show regression on CT, IMA should still be included in the differential diagnosis. A more careful application of RECIST 1.1 is needed in the assessment of tumor response of IMAs.

Epstein-Barr Virus Expression in Classic Hodgkin Lymphoma in an Indian Cohort and its Association with Clinical and Histomorphological Parameters.

Epstein Barr virus (EBV) associated Hodgkin lymphoma (HL) has been defined as cases with clonal EBV infection, EBV genome and gene products in the Reed Sternberg cells. We evaluated the prevalence and clinico-pathological association of EBV in North Indian HL patients. Eighty-eight cases of histologically confirmed classic HL were evaluated for EBV by both IHC expression of LMP1 and real time PCR on formalin fixed lymph node tissue. The expression pattern was analyzed for any association with clinical and histomorphological parameters. Nodular sclerosis subtype was seen in 79.5% patients and mixed cellularity was seen in the remaining patients. Ninety percent of the cases were positive for EBV. The detection rate of EBV by IHC was higher. The EBV positive cases presented with higher disease stage (p < 0.05). The presence of histomorphological features like granuloma formation (5/5), atypical lymphocytes (8/8), histiocyte clusters (26/28), large area of necrosis (11/12), less prominent inflammatory response (25/27) was associated with EBV positivity (p > 0.05). In our study population a high proportion of HL cases showed positivity for EBV indicating a pathogenic role. The positivity was independent of age, gender and histological subtype. Further evaluation of EBV positivity in modulation of tumor immunity may provide insights into variable treatment outcome in EBV positive cases.

Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With "Single-cell" Growth Reveals 2 Distinct Types, One With "Plasmacytoid" Features.

Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic "plasmacytoid" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the "single-cell" Gleason pattern 5 prostatic adenocarcinoma contains 2 distinct subtypes. Somatic CDH1 alterations may play a role in the development of the "plasmacytoid" pattern characterized by monomorphic cytology with concomitant E-cadherin loss and aberrant p120 catenin expression.

Thyroid Disease and Active Smoking May Be Associated with More Severe Hidradenitis Suppurativa: Data from a Prospective Cross Sectional Single-Center Study

Introduction: Hidradenitis suppurativa (HS) is an obscure disease presenting with painful, deep-seated nodules and abscess formation in body areas rich in apocrine glands. Several factors, including thyroid disease and active smoking, have been reported to be associated with HS, but it remains unclear if such associations are related to clinical HS severity. The aim of this prospective cross-sectional study is to investigate the association between active smoking and thyroid disease and HS, as well as to determine if these associations are related to HS severity. Methods: Eligible were all patients seen in our HS outpatient clinic between September 2018 and February 2020. Data regarding demographic characteristics, clinical disease severity, comorbidities, and treatment modalities were registered. Descriptive statistics of demographic and disease characteristics was conducted. In order to evaluate the association between the disease stage and certain variables of interest, ordered logistic regression was performed. Results: A total of 290 patients were included in the study. Of these, 48.9% were males, and 51.1% females. The patients had a mean age of 37.3 years. A total of 42.4% of the patients were at Hurley stage I, 43.1% at stage II, and 14.5% at stage III. According to the IHS4 score system, 30.7% of the patients had mild, 50.3% moderate, and 19.0% severe disease. The median duration of disease was 10 years. Among the patients, 56.5% were active smokers, and 55.5% patients reported that stress triggers the disease’s flares. Univariable analyses demonstrated that among the various covariates, active smoking and thyroid disease were associated with a higher stage of disease. Conclusion: We conclude that thyroid disease and active smoking may be associated with more severe HS.

Rates and Patterns of Recurrences and Survival Outcomes after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

There have been concerns about higher incidence of local and retroperitoneal recurrences after robot-assisted radical cystectomy compared to open radical cystectomy. We report and detail relapses following robot-assisted radical cystectomy using a multinational database. A retrospective review of the International Robotic Cystectomy Consortium was performed. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Relapse rates and patterns were analyzed. Kaplan-Meier curves were used to depict relapse-free, local recurrence-free, distant metastasis-free and overall survival. Kaplan-Meier curves were further stratified by disease stage, lymph node status and margins. Multivariate stepwise Cox regression models were used to identify variables associated with relapse-free, local recurrence-free, distant metastasis-free and overall survival. Of 2,107 patients 521 (25%) experienced disease relapse. Mean age (SD) was 68±10 years with a median followup of 26 (IQR 11-55) months for the study cohort. Local recurrences were observed in 11% and distant metastases in 18%. Early oncologic failure (within 3 months) occurred in 4% of patients. The most common sites of local recurrence and distant metastasis were the pelvis (5%) and lungs (6%)/extrapelvic lymph nodes (5%), respectively. Abdominal wall/port site metastasis occurred in 1.2% and peritoneal carcinomatosis in 1.2%. Five-year relapse-free, local recurrence-free, distant metastasis-free and overall survival was 66%, 84%, 74% and 60%, respectively. Patients with higher disease stage, positive lymph nodes and positive soft tissue surgical margins demonstrated worse relapse-free, local recurrence-free, distant metastasis-free and overall survival (log rank p <0.01 for all comparisons). Multivariate regression models identified that node positive status and disease stage (pT3 or greater) were significantly associated with relapse-free, local recurrence-free, distant metastasis-free and overall survival (p <0.01). Disease stage remains the main variable associated with disease relapse and survival following radical cystectomy. Robot-assisted radical cystectomy was not associated with different patterns or higher relapse rates compared to historic open radical cystectomy data.

Brachytherapy vs external beam therapy among NSCLC patients undergoing limited surgical resection.

To compare brachytherapy to external beam radiation therapy (EBRT) with respect to overall survival (OS) and disease-specific survival (DSS) among NSCLC patients undergoing limited surgical resection. All cases of T1-4 N0 M0 NSCLC undergoing limited resection and either brachytherapy or EBRT diagnosed between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test and Fisher's exact analysis were used to analyze categorical variables while Student's t-test was used to analyze continuous variables. Univariate analysis to assess for differences in survival with respect to covariates was performed with the log-rank test. Multivariable analysis was performed with Cox proportional hazards regression models among the entire cohort and after sub-stratification by T stage. Among 543 patients, 471 underwent EBRT and 72 underwent brachytherapy. Brachytherapy demonstrated improved OS and DSS on univariate analysis as compared to EBRT (p < 0.05). Cox regression also demonstrated improved OS and DSS with brachytherapy (HR 0.604; 95% CI [0.380; 0.961] and HR 0.524; 95% CI [0.303; 0.908], respectively). Sub-cohort analysis demonstrated significant improvement in survival only among patients with T1 disease with similar survival between brachytherapy and EBRT among higher stage disease. Patients undergoing brachytherapy for T1-T4, N0, M0 NSCLC demonstrated at least similar survival as compared to those undergoing EBRT among patients undergoing limited resection. Improved survival was demonstrated among patients with T1 disease.

Prognostic significance of multi-positive invasive histopathology in oral cancer.

Oral squamous cell carcinoma (OSCC) is a lethal and deforming disease of rising incidence. With poor 5-year survival rates associated with higher stage disease, there is a need in clinical practice for reliable prognostic determinants to consolidate treatment planning and coordinate therapeutic approaches to improve long-term clinical outcomes for patients. A retrospective clinicopathological review of 467 OSCC patients with documented clinical outcome and treated in Hong Kong over a 19-year period was undertaken to investigate the potential prognostic role of 4 specific histopathological features of invasive tumour behaviour: perineural invasion (PNI), bone invasion (BNI), lymphovascular invasion (LVI) and extra-nodal extension (ENE) in metastatic neck disease. Histopathological data for PNI, BNI, LVI and ENE, and stratified as zero, one, two, three or four positives, were available for 279 patients. A trend for decreased disease-free status was seen with increasing numbers of positive histopathological features, although this was not statistically significant (P=.1076). The time to onset of further disease (loco-regional recurrence and/or distant metastasis) was statistically significant, however, with progressive disease presenting most rapidly with increasing numbers of positive invasive parameters (P=.000152). PNI, BNI, LVI and ENE, especially when found in combination, show promise as prognostic markers of poor clinical outcome following OSCC treatment. Further, multi-centre prospective studies are required to confirm the predictive value of multi-positive histopathological features in clinical practice and to help improve individualised treatment planning.

HOXC9 overexpression is associated with gastric cancer progression and a prognostic marker for poor survival in gastric cancer patients.

As a member of the homeobox family, HOXC9 is overexpressed in several malignant tumors and may be regarded as a biomarker for prognostic evaluation. However, the expression pattern and prognostic significance of HOXC9 in gastric cancer have not been detailedly studied. HOXC9 mRNA expression difference in normal tissues and gastric cancer tissues were investigated using RT-PCR, and immunohistochemistry was used to analyze HOXC9 protein expression in precancerous lesions and gastric cancer at different stages, and its clinicopathological characteristics and survival were statistically tested. Compared to the normal gastric mucosa tissues, the expression levels of HOXC9 mRNA in the human gastric cancer tissues were significantly higher. HOXC9 protein levels of gastric cancer were obviously higher than that in other noncancerous tissues (P < 0.001). Positive expression of HOXC9 was associated with tumor size (P = 0.036), lymphatic invasion (P = 0.001), depth of invasion (P < 0.001), lymph-node metastasis (P < 0.001), and higher stage disease (P < 0.001). Furthermore, Kaplan-Meier survival curves showed that HOXC9 expression is inversely correlated with both disease-specific and disease-free 5year survival of patients with gastric cancer (P < 0.001 for both). Strikingly, our multivariate Cox regression analysis revealed that HOXC9 expression was an independent poor prognostic factor in gastric cancer (P < 0.05). HOXC9 expression was observed in a subset of patients with gastric cancer and was associated with an unfavorable prognosis. As well as being a new prognostic indicator, HOXC9 protein could be a useful marker for early diagnosis.

Molecular Assays to Determine Optimal Duration of Adjuvant Endocrine Therapy in Breast Cancer.

Hormone receptor (HR) positive breast cancer has a high propensity for late recurrences that might be prevented with longer durations of endocrine therapy (ET). However, trials evaluating extended adjuvant ET have produced somewhat conflicting results. Additionally, ET is associated with not only day to day side effects that can impact quality of life, but more detrimental effects that can cause significant morbidity. Although patients with higher stage disease are at greater risk of late recurrences, even patients with stage 1 disease have a significant risk of recurrence after 5years. Current guidelines recommend extending therapy for patients with node-positive disease, but recommendations for patients with node-negative disease are less clear. This has led to the development of various genomic tests to aid oncologists in further individualizing their approach when it comes to deciding which subpopulation of patients with HR-positive breast cancer may benefit from extending their endocrine therapy beyond 5years. There are several assays that are prognostic of recurrences years 6 to 10 following diagnosis. Additionally, the breast cancer index has been shown to be predictive of extended ET in patients who have completed 5years of tamoxifen. None of the available assays are, to date, predictive of recurrence after 10years. Genomic testing is not appropriate for all patients, especially if the results will not predict the choice of further treatment. Ultimately, genomic testing should help facilitate shared decision making between the patient and oncologist.

Oncologic outcomes of radical nephroureterectomy (RNU).

Radical nephroureterectomy is the mainstay of surgical treatment for upper tract urothelial carcinoma (UTUC), a disease which comprises approximately 5% of urothelial malignancies. Minimally-invasive and nephron-sparing interventions have been explored, although thus far have not shown comparable oncologic outcomes except in a relatively narrow set of patients. Due to the relative rarity of the disease, it has taken decades and multi-disciplinary efforts to sufficiently identify prognostic factors of oncologic outcomes. Despite these efforts, however, oncologic outcomes of nephroureterectomy have remained remarkably stable over the past 30 years. New techniques, such as laparoscopic and robotic surgery, have been applied to this procedure. High level evidence regarding equivalent oncologic outcomes is lacking and open surgery remains the standard of care for high-stage disease, although there is a role for laparoscopic and robotic nephroureterectomy. The importance of bladder cuff removal in improving oncologic outcomes has been broadly accepted, although there is no consensus as to the most oncologically appropriate technique. There does appear to be evidence that endoscopic techniques confer worse oncologic control. The role of lymphadenectomy remains controversial, although there is evidence that increased nodal yield could have oncologic benefit. Given disease heterogeneity and varied technical approaches to the procedure, no consensus standardized template has been identified. There is level 1 evidence for the use of intravesical chemotherapy peri-operatively and that this intervention can improve the risk of intravesical recurrence. Advances in systemic neoadjuvant and adjuvant chemotherapy have yielded promising results and are likely to become standard of care for patients without contraindications. Immunotherapy and targeted biologic agents are also likely to improve the surgical efficacy of radical nephroureterectomy as well. Ultimately, more high level evidence is needed to identify successful surgical and medical approaches to UTUC and multi-institutional collaboration is critical to this progress.

A combined histo-score based on tumor differentiation and lymphocytic infiltrate is a robust prognostic marker for mobile tongue cancer

We wanted to evaluate the prognostic value of common histopathological variables in a large cohort of patients with cancer in the mobile tongue as such information can be important for treatment stratification of the individual patient, especially for patients with low-stage disease. In addition, we wanted to investigate whether an alternative scoring model with fewer options would compromise the prognostic value. One hundred fifty patients with oral tongue squamous cell carcinomas that were treated in curative intent and with available HE-stained tumor sections were included. We reclassified all tumors and performed univariate and multivariate survival analyses of histopathological and clinical variables. For the complete cohort, lymph node status, grade of differentiation, perineural infiltration, and lymphocytic infiltration were independent prognosticators. In the low-stage disease group, independent prognostic factors were tumor size, grade of differentiation, and lymphocytic infiltrate. For patients with low-stage disease, a histo-score combining the scores for tumor differentiation and lymphocytic infiltrate identified a group of patients with particularly low survival, as patients with moderately or poorly differentiated tumors and little lymphocytic infiltrate had a less favorable 5-year survival outcome than patients in the high-stage disease group. This study shows that a histo-score combining tumor differentiation and lymphocytic infiltration should be given special consideration in treatment planning. Our results also illustrate that many variables can be scored with fewer options than previously suggested to increase their reproducibility, and still maintain their prognostic value.

Open vs laparoscopic adrenalectomy for localized adrenocortical carcinoma.

The purpose of the study was to compare the long-term outcomes of patients with localized adrenocortical carcinoma (ACC) subjected to open vs laparoscopic surgery. Retrospective study. This retrospective study included 46 patients with the ACC ENSAT stage I-stage III of whom 23 underwent open surgery (OA group), whereas 23 were subjected to laparoscopic adrenalectomy (LA group). The main outcomes analysed in the study were differences between the OA and LA groups in recurrence-free survival (RFS) and overall survival (OS). Patients in OA group had larger tumours (120 [70-250] mm vs 75 [26-110] mm; P<.001), higher Ki-67 index (16 [1-65] % vs 10 [1-25] %; P=.04) and higher disease stage (P=.01) compared with the patients in the LA group. The median duration of follow-up for patients underwent OA and LA was 51 (12-174) and 53 (5-127) months, respectively. Eight patients (5 OA and 3 LA) experienced recurrent disease, whereas six patients (3 OA and 3 LA) died during follow-up. No differences in RFS and OS were found between patients who underwent open or laparoscopic surgery. The study demonstrated that in patients with localized ACC and without invasion of extra-adrenal tissues, LA is a plausible treatment option in terms of RFS and OS. However, our results are limited to referral centres with large experience in the management of patients with ACC and may not necessarily apply to nonspecialized centres.

Progressive Memory Circuit Impairments along with Alzheimer's Disease Neuropathology Spread: Evidence from in vivo Neuroimaging.

During the progression of Alzheimer's disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A - T-; Group 1: CN, A + T-; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.

Abstract B084: Factors associated with longer time to surgical treatment in melanoma

Abstract Background: Timely treatment for melanoma may affect survival, and characterizing predictors of treatment delay may inform intervention strategies. Objective: To determine patient-, provider-, and facility-level characteristics associated with a delay to treatment in melanoma. Methods: The National Cancer Database was used to examine factors associated with an increased interval between diagnosis and definitive surgical treatment among 205,665 patients with Stage I, II, or III cutaneous melanoma between 2004 and 2015 using multivariable Cox proportional hazards modeling. Results: The data demonstrated that the direction of the association between age at diagnosis and timing of surgery differed depending on insurance status. Among 115,461 privately insured patients, delay in surgical treatment was associated with older age (HR 0.85 in 70+ years, p &amp;lt;0.0001; HR 0.97 in 50-70 years, p &amp;lt;0.0001). By contrast, in 90,204 patients without private insurance, the association with age was weaker and in the opposite direction (HR 1.09 in 70+ years, p &amp;lt;0.0001; HR 1.09 in 50-70 years, p &amp;lt;0.0001). After adjustment for important patient and disease characteristics, other factors significantly associated with a longer time from diagnosis to surgery included non-white race, higher comorbidity burden, thicker tumor, higher disease stage, and head or neck melanoma location. Conclusion: Melanoma patients experience disparities in timely receipt of surgery. Identifying groups at risk of delay reveals who would benefit most from patient navigation or care-coordination programs. Public health intervention is warranted to address specific roadblocks contributing to surgical delay to improve care for all patients with melanoma. Citation Format: Marissa L.H. Baranowski, Howa Yeung, Suephy C. Chen, Theresa W. Gillespie, Michael Goodman. Factors associated with longer time to surgical treatment in melanoma [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B084.

Abstract D113: Socioeconomic disparities underlie outcomes in patients with pancreatic neuroendocrine tumors

Abstract Background Disparities are known to underlie outcomes in pancreatic ductal adenocarcinoma (PDAC). Pancreatic neuroendocrine tumors (PNET) represent a rare yet deadly form of pancreatic cancer. Health disparities have not been well described in this patient population. We hypothesize that given the significant health disparities in PDAC, cancer health disparities exist in patients with PNETs. Methods Patients treated for PNETs were identified in a National Cancer Database (NCDB) Patient User File for the years 2004-2015. Kaplan-Meier analysis was performed to assess survival. Cox proportional hazards models were used to assess the effect of clinical and socioeconomic factors on survival. Results Review of the NCDB found 19,752 reported cases of PNETs. Of those, 15,589 (78.9%) were non-Hispanic white (NHW), 2,462 (12.5%) were black (B), and 1,710 (8.6%) were Hispanic, white (H). On univariate analysis, greater age, male sex, higher Charlson comorbidity score, higher disease stage, lack of insurance, decreased median household income in area of residence, and no surgery were associated with worse survival (p&amp;lt; 0.05). While not statistically significant and unlike pancreatic adenocarcinoma, black patients had greater median survival (89.6 months; 95% CI 77.9-101.196) compared to NHW (76.4 months; 95% CI 72.9-79.8) and H (80.1 months; 95%CI 70.7-89.5) patients. On multivariate analysis, the same factors from the univariate analysis were associated with worsened survival (p&amp;lt; 0.05). Sub-analyses of patients who received surgery and those who did not again showed no significant difference in survival based on race. Conclusion While insurance status, median income in area of residence, and sex were associated with clinical outcomes in PNETs, race was not a contributing factor. This is in contrast to literature in PDAC which has demonstrated that black patients have worse survival. The reasons for this difference are unclear, but may biologically driven. It is important to understand disparities from different types of pancreatic tumors. Further work to understand biologic contributions to health inequities are needed. Citation Format: Patrick W Underwood, Andrea N Riner, Michael U Maduka, Sushanth Reddy, J. Bart Rose, Jose G Trevino. Socioeconomic disparities underlie outcomes in patients with pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D113.

Investigating potential disparities in clinical trial eligibility, offers and enrollment at an NCI-designated comprehensive cancer center.

e19076 Background: Although many prior studies have demonstrated the existence of disparities in cancer clinical trial enrollment, few studies have explored clinical trial eligibility criteria and offers as potential drivers of disparities in enrollment. Methods: We identified patients age 18-96 with gastrointestinal (GI) cancers who were seen as new patients at the University of Michigan in 2016. Primary outcomes were: 1) Eligibility for; 2) Offer of; and 3) Enrollment in, a clinical trial. All 28 clinical trials available in 2016 for patients with GI cancers were considered. We assessed individual patient eligibility for any trial by exhaustive review of the electronic medical record (EMR). We determined trial offers and patient enrollment in a trial by EMR review, including notes by clinicians and research coordinators. Independent variables included clinical and non-clinical patient-related factors (such as age, race, and gender) as well as provider-related factors. We assessed associations between patient- and provider-related factors and our primary outcomes, using multivariable regression. Results: Of 827 patients, 40% were female, 18% were age ≥75, 7% were Black, and 2% were Asian. 155 (19%) patients were potentially eligible for an open clinical trial. Among patients potentially eligible for a trial, 83 (54%) had documentation of a trial being offered and 46 (30%) enrolled. After adjustment, age &lt; 75, lower Charlson comorbidity index, not having a second primary cancer, hepatobiliary primary, and higher disease stage were associated with a higher odds of clinical trial eligibility (all P &lt; 0.05). Having ≥1 child, lower Charlson comorbidity index, hepatobiliary primary, and higher disease stage were associated with a higher odds of being offered a clinical trial (all P &lt; 0.05). Hepatobiliary primary and higher disease stage were associated with a higher odds of enrollment (all P &lt; 0.05). Conclusions: We found that patients age 75 or over were less likely to be eligible for a clinical trial, but did not find significant disparities in eligibility by other non-clinical factors such as gender and race. Only 54% of patients potentially eligible for a trial had documentation of a trial being offered; this varied by number of children, but not by any other non-clinical factors. We found no significant associations between non-clinical factors and enrollment. Future work is needed to ensure that eligibility criteria for clinical trials reflect the overall patient population, and that trials are offered to eligible patients.

Clinical characters of somatic DNA damage repair (DDR) gene mutations in Chinese NSCLC patients.

e13665 Background: Chinese NSCLC patients displayed unique genetic profile. NSCLC patients with DNA damage repair gene mutations showed distinct clinical appearance as well as superior response to immunotherapy. This study aims to disclose distribution of DNA damage mutations as well as their clinical characters in Chinese NSCLC patients. Methods: One hundred and ten patients with pathologically confirmed NSCLC were consecutively recruited from 2016-2018 in our center. Genomic DNA was captured and sequenced for 508 cancer related genes by BGI-seq 500. Raw data was processed followed by variant calling via in-house developed pipeline. Results: 89 (of 110) patients with median age of 55 years old (33-74 years) were included into final analysis due to complete follow-up as well as sufficient FFPE tissue for successful genomic profiling. Among them, 12 patients were squamous NSCLC, 72 patients were non-squamous NSCLC. Among 89 patients, 22 patients (24.7%) carried 36 mutations in 21 DDR genes (BRCA2 n = 6, BAP1 n = 3, ARID1A n = 2, ATM n = 2, ATR n = 2, BLM n = 2, FANCF n = 2, PARP1 n = 2,BARD1 n = 1,BRCA1 n = 1,CHEK2 n = 1, FANCD2 n = 1,FANCE n = 1,FANCG n = 1,FANCM N = 1,NBN n = 1,PARP3 n = 1,POLQ n = 1,RAD50 n = 1,RAD51C n = 1), most of them belongs to homologous recombination repair pathway (n = 19, 21.34%).8 patients carried compound mutations in DDR genes. No difference was found in age of initial diagnosis between DDR mutated and DDR wild type patients. While, ever smokers (RR (95%CI): 2.12 (1.37-3.20),P = 0.003), squamous NSCLC (RR(95%CI):4.47 (1.62-12.03), P = 0.006), male (RR (95%CI): 1.77(1.23-2.44),P = 0.006) displayed significantly higher prevalence of DDR gene mutations. Only one stage I patient carried DDR mutation(P = 0.008). Conclusions: In this study, mutation spectrum of DDR genes was proposed in Chinese NSCLC patients. DDR gene mutations more possibly occurred in male, higher disease stage as well as in squamous NSCLC and smokers. These findings show potential relevance to disease prognosis which needs further investigation.

Local Stage Dependent Necessity of Radiation Therapy in Rhabdoid Tumors of the Kidney (RTK)

Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhood kidney tumors. In this study, we analyze the evidence for RT in regard to risk factors, including tumor stage. This study analyzed 58 patients with RTK from Austria, Switzerland, and Germany treated in the framework of 4 consecutive, prospective renal/rhabdoid tumor studies from 1991 to 2014. All treatment protocols included multimodality treatment, including high-intensity chemotherapy, surgery, and RT. Local stage distribution was not applicable, I, II, and III in 1, 6, 11, and 40, respectively. Twenty-nine (50%) patients had stage IV disease at diagnosis. Thirty-seven patients (64%) achieved complete remission, and 49% (18/37) relapsed. Thirty-four patients (60%) patients had progressive disease and died, 17 had local disease, 10 had combined disease, and 7 had distant disease; 2 treatment-related deaths were reported (3%). Twenty-one patients received RT during first-line treatment, 18 of them to all involved sites. Eight of the 34 cases of progressive disease occurred in irradiated patients. The local failure rate of treated patients with local stage II or III disease was 29% (6/18) in patients irradiated to all sites compared with 68% (15/22) in nonirradiated patients. One of 6 stage I patients received RT, and 1 patient experienced distant relapse (2-year progression-free and overall survival both 83% ± 15%). Progression-free survival for local stage II and III disease treated with RT, adjusted for early relapse or treatment abandonment, was 67% ± 11%, compared with 15% ± 7% without RT (P < .0001). The 68% local failure rate in nonirradiated patients underlines the importance of local treatment. Our experience supports the use of RT for local control in higher stage disease. In contrast, no local relapse in 6 local stage I patients, including 5 nonirradiated patients, suggests omission of RT in this favorable subset of usually infant patients with RTK.