Diagnosis Of Metastatic Cancer Research Articles

B7-H3 expression by immunohistochemistry as a negative prognostic biomarker in colorectal carcinoma (CRC) in a racially diverse population.

e15127 Background: In CRC, utility of immunotherapy (IT) remains limited to persons with microsatellite instability–high (MSI-H) status. Immunotyping of CRC patients is critical towards further establishing IT's potential. Both incidence and survival rates for CRC in the United States vary between races due to multiple factors including genetic heterogeneity. In this study, we have profiled tumor samples in a racially diverse population for the expression of four different members of the B7 family of immune check point regulators. Methods: Tissue microarray (TMA) was generated from 208 CRC patients. Formalin fixed paraffin embedded (FFPE) tissues were utilized for immunohistochemistry (IHC) post- antigen retrieval. Antibodies specific for IHC staining were used for B7-H3 (D9M2L), PD-L1(E1L3N), B7-H4/B7x(D1M81) and HHLA2(566.1). Each specimen was scored for percent staining of tumor tissue (4 quartile groups) and for intensity (1-4x), and then an overall score (1-16) was calculated. The clinical outcome of interest was overall survival (OS), measured as time from diagnosis of metastatic cancer to death. Analysis for differences in OS was by log rank test, while differences between mean staining was by t test. Race was designated as non-Hispanic white (NHW, n = 41), non-Hispanic black (NHB, n = 84), Hispanic (n = 75), and others (8). Results: B7-H3 protein expression showed strong cytoplasmic distribution. NHB patients had a mean lower expression than NHW patients (0.19 vs 0.41, p = 0.02). Correspondingly, NHB patients had a worse OS than NHW patients (606 vs 759 days). No discernible differences were found in Hispanic patients. PD-L1 showed membranous distribution with 17% expression without significant difference among patients of different racial origin. HHLA2 was more widely expressed with about 35% staining but without statistical significance. B7-H4/B7x failed to show any expression. Conclusions: Expression of B7H3 varies among patients with differential racial backgrounds. It has the potential to be a prognostic biomarker and may be a reason for worse outcome among NHB patients in our population. Other B7 immune checkpoint markers failed to show clinical relevance.

TP4 REAL-WORLD TREATMENT PATTERNS FOR PATIENTS WITH METASTATIC HEAD AND NECK SQUAMOUS CELL CARCINOMA (MHNSCC) TREATED WITH IMMUNO-ONCOLOGY (IO) THERAPY

The treatment landscape for mHNSCC expanded with the approval of IO therapies. This study describes real-world treatment patterns in mHNSCC. Adults (age ≥18) who initiated IO (nivolumab or pembrolizumab) between 2/1/2016-11/30/2017 were identified in the IQVIA Real-World Data Adjudicated Claims–USTM database; first date of IO was the index date. Patients had ≥2 HNSCC diagnoses (≥30 days apart), ≥12 (up to 24) months of pre-index, ≥30 days of post-index, and ≥1 pre-index metastatic cancer diagnosis. Treatment patterns before and after IO initiation were described. 416 patients were identified (mean age 59 years, 78% male, 80% had ≥2 metastases in pre-index period). About 51%, 25%, and 9% of patients had 1, 2, or ≥3 treatment regimens prior to IO, respectively (median pre-index duration: 24 months). The most commonly observed initial, second, and third regimens before IO initiation were chemotherapy from one therapeutic class (e.g., platinum-based/taxane) (43%, 26%, 40%, respectively) or two therapeutic classes in combination (25%, 28%, 29%, respectively). Median durations of the pre-index regimens ranged from 2.5-3.3 months. 404 (97%) patients initiated IO as monotherapy and 12 (3%) initiated IO combined with other systemic treatments. The median duration of the index IO regimen was 3 months. 118 (28%) patients had subsequent regimens. The most common were single-class chemotherapy (n=33, 28%) and IO monotherapy (n=27, 23%), among which 22 patients restarted the index IO, 3 switched from pembrolizumab to nivolumab, and 2 switched from nivolumab to pembrolizumab. In real-world practice, most mHNSCC patients received ≥1 treatment regimen before IO, frequently chemotherapy from one therapeutic class, and the most common IO regimen initiated was monotherapy. Approximately one-fourth of patients with a subsequent regimen restarted their index IO or switched to another IO monotherapy. Future studies on IO treatment patterns and outcomes with longer follow-up are recommended.

Application of a Neural Network Whole Transcriptome–Based Pan-Cancer Method for Diagnosis of Primary and Metastatic Cancers

A molecular diagnostic method that incorporates information about the transcriptional status of all genes across multiple tissue types can strengthen confidence in cancer diagnosis. To determine the practical use of a whole transcriptome-based pan-cancer method in diagnosing primary and metastatic cancers and resolving complex diagnoses. This cross-sectional diagnostic study assessed Supervised Cancer Origin Prediction Using Expression (SCOPE), a machine learning method using whole-transcriptome RNA sequencing data. Training was performed on publicly available primary cancer data sets, including The Cancer Genome Atlas. Testing was performed retrospectively on untreated primary cancers and treated metastases from volunteer adult patients at BC Cancer in Vancouver, British Columbia, from January 1, 2013, to March 31, 2016, and testing spanned 10 822 samples and 66 output classes representing untreated primary cancers (n = 40) and adjacent normal tissues (n = 26). SCOPE's performance was demonstrated on 211 untreated primary mesothelioma cancers and 201 treatment-resistant metastatic cancers. Finally, SCOPE was used to identify the putative site of origin in 15 cases with initial presentation as cancers with unknown primary of origin. A total of 10 688 adult patient samples representing 40 untreated primary tumor types and 26 adjacent-normal tissues were used for training. Demographic data were not available for all data sets. Among the training data set, 5157 of 10 244 (50.3%) were male and the mean (SD) age was 58.9 (14.5) years. Testing was performed on 211 patients with untreated primary mesothelioma (173 [82.0%] male; mean [SD] age, 64.5 [11.3] years); 201 patients with treatment-resistant cancers (141 [70.1%] female; mean [SD] age, 55.6 [12.9] years); and 15 patients with cancers of unknown primary of origin; among the treatment-resistant cancers, 168 were metastatic, and 33 were the primary presentation. An accuracy rate of 99% was obtained for primary epithelioid mesotheliomas tested (125 of 126). The remaining 85 mesotheliomas had a mixed etiology (sarcomatoid mesotheliomas) and were correctly identified as a mixture of their primary components, with potential implications in resolving subtypes and incidences of mixed histology. SCOPE achieved an overall mean (SD) accuracy rate of 86% (11%) and F1 score of 0.79 (0.12) on the 201 treatment-resistant cancers and matched 12 of 15 of the putative diagnoses for cancers with indeterminate diagnosis from conventional pathology. These results suggest that machine learning approaches incorporating multiple tumor profiles can more accurately identify the cancerous state and discriminate it from normal cells. SCOPE uses the whole transcriptomes from normal and tumor tissues, and results of this study suggest that it performs well for rare cancer types, primary cancers, treatment-resistant metastatic cancers, and cancers of unknown primary of origin. Genes most relevant in SCOPE's decision making were examined, and several are known biological markers of respective cancers. SCOPE may be applied as an orthogonal diagnostic method in cases where the site of origin of a cancer is unknown, or when standard pathology assessment is inconclusive.

Early mortality of stage IV non-small cell lung cancer in the United States

Background: Early mortality is a major deterrent to oncologic management, often preventing delivery of therapy or leading to administration of treatment that offers limited benefit from aggressive interventions. Due to more recent progress in therapeutic options for stage IV non-small cell lung cancer (NSCLC) patients, identifying those at high risk of early mortality (within 30 days) could have implications for treatment selection. Because early mortality following diagnosis of metastatic non-small cell lung cancer (NSCLC) is not well-characterized, this investigation evaluated national trends and predictors thereof.Material and methods: The National Cancer Database was queried for cases of pathologically confirmed metastatic NSCLC with complete vital status and clinical information, diagnosed between 2006 and 2014. Multivariable logistic regression ascertained factors associated with 30-day mortality.Results: Of 346,681 patients, 45,861 (13%) experienced early mortality over the past decade, which remained relatively constant over time. Predictors of early mortality included advancing age (>65 years), male gender, Caucasian race, non-private insurance, lower income, greater comorbidities, residence in metropolitan and/or lesser-educated areas, treatment at community centers, patients with no prior history of cancer and regional differences (p < .01 for all). Early mortality was highest in patients older than 80 years with multiple comorbidities (29%). The majority of patients (71%) who died within 30 days did not receive any therapy.Conclusions: A fair proportion of NSCLC patients experience early mortality, which has not decreased over time. The majority of patients with early mortality do not receive treatment. Prognostic factors for early mortality should be considered during initial evaluation and subsequent follow-up of these patients. Doing so may impact systemic treatment selection by medical oncologists, management of (oligo)metastatic disease by radiation and surgical oncologists and cost-effective administration of these therapies in the stage IV NSCLC population.

Multicentre analysis of intensity of care at the end-of-life in patients with advanced cancer, combining health administrative data with hospital records: variations in practice call for routine quality evaluation

BackgroundAccessible indicators of aggressiveness of care at the end-of-life are useful to monitor implementation of early integrated palliative care practice. To determine the intensity of end-of-life care from exhaustive data combining administrative databases and hospital clinical records, to evaluate its variability across hospital facilities and associations with timely introduction of palliative care (PC).MethodsFor this study designed as a decedent series nested in multicentre cohort of advanced cancer patients, we selected 997 decedents from a cohort of patients hospitalised in 2009–2010, with a diagnosis of metastatic cancer in 3 academic medical centres and 2 comprehensive cancer centres in the Paris area. Hospital data was combined with nationwide mortality databases. Complete data were collected and checked from clinical records, including first referral to PC, chemotherapy within 14 days of death, ≥1 intensive care unit (ICU) admission, ≥2 emergency department visits (ED), and ≥ 2 hospitalizations, all within 30 days of death.ResultsOverall (min-max) indicator values as reported by facility providing care rather than the place of death, were: 16% (8–25%) patients received chemotherapy within 14 days of death, 16% (6–32%) had ≥2 admissions to acute care, 6% (0–15%) had ≥2 emergency visits and 18% (4–35%) had ≥1 intensive care unit admission(s). Only 53% of these patients met the PC team, and the median (min-max) time between the first intervention of the PC team and death was 41 (17–112) days. The introduction of PC > 30 days before death was independently associated with lower intensity of care.ConclusionsAggressiveness of end-of-life cancer care is highly variable across centres. This validates the use of indicators to monitor integrated PC in oncology. Disseminating a quality audit-feedback cycle should contribute to a shared view of appropriate end-of-life care objectives, and foster action for improvement among care providers.

The effect of a treatment delay on outcome in metastatic renal cell carcinoma

ObjectivesTo investigate if a first-line treatment delay (TD) can negatively affect the outcomes of patients affected by metastatic renal cancer. Patients and methodsPatients with a diagnosis of metastatic renal cancer who were ineligible for active surveillance were included in the sample. A TD was defined as the time from the diagnosis of metastatic disease to the start of first-line therapy with tyrosine kinase inhibitors. ResultsA total of 835 patients were assessed and 635 were included in the final analysis. The median TD was 6.3 weeks. No significant differences were found in baseline characteristics between patients experiencing a TD below/equal to or above the median value, with the exceptions being the rate of bone metastases (25.3% vs. 35.9%) and advanced disease at diagnosis (34.7% vs. 54.9%). In patients who had received a previous nephrectomy for localized disease, the TD was 5.3 compared to 8.0 weeks for those with metastatic disease at diagnosis (P = 0.001). Among this latter group, 68.7% had received a cytoreductive nephrectomy. In patients with a TD below/equal to and above the median value, the median progression-free survival was 10.3 and 11.2 months, respectively (hazard ratio = 1.03; 95% confidence intervals, 0.86–1.22; P = 0.78); the median overall survival was 27.3 and 28.2 months, respectively (hazard ratio = 1.04; 95% confidence intervals, 0.86–1.27; P = 0.68). The lack of differences was confirmed when adjusted for prognostic factors and baseline characteristics. ConclusionsThis study reports that patients with bone metastases and advanced disease at diagnosis have a significant probability of experiencing delayed first-line therapy of more than 6 weeks from the time of diagnosis. However, a TD does not significantly affect outcomes and survival.

Using a Dedicated Interventional Pulmonology Practice Decreases Wait Time Before Treatment Initiation for New Lung Cancer Diagnoses

While there is significant mortality and morbidity with lung cancer, early stage diagnoses carry a better prognosis. As lung cancer screening programs increase with more pulmonary nodules detected, expediting definitive treatment initiation for newly diagnosed patients is imperative. The objective of our analysis was to determine if the use of a dedicated interventional pulmonology practice decreases time delay from new diagnosis of lung cancer or metastatic disease to the chest to treatment initiation. Retrospective chart analysis was done of 87 consecutive patients with a new diagnosis of primary lung cancer or metastatic cancer to the chest from our interventional pulmonology procedures. Demographic information and time intervals from abnormal imaging to procedure and to treatment initiation were recorded. Patients were older (mean age 69) and former or current smokers (72%). A median of 27 days (1-127days) passed from our diagnostic biopsy to treatment initiation. A median of 53 total days (2-449days) passed from abnormal imaging to definitive treatment. Endobronchial ultrasound-guided transbronchial needle aspiration was the most commonly used diagnostic procedure (59%), with non-small cell lung cancer the majority diagnosis (64%). For surgical patients, all biopsy-negative lymph nodes from our procedures were cancer-free at surgical excision. Compared to prior reports from international and United States cohorts, obtaining a tissue biopsy diagnosis through a gatekeeper interventional pulmonology practice decreases median delay from abnormal imaging to treatment initiation. This finding has the potential to positively impact patient outcomes and requires further evaluation.

The Immunoreactivity of Uroplakin III in Urothelial Carcinoma of Urinary Bladder and Other Non-Urothelial Carcinoma

The aim of present study is evaluate the sensitivity and specificity of uroplakin III marker in the urothelial cancer patients, and to show whether there is association this marker with their clinicopathological parameters. This study is a retrospective (70 cases) of whom diagnosis as urothelial carcinoma of urinary bladder (male 41 and female 29) with added normal urothelial tissue and breast tissue were taken as control group. 41 nonurothelial carcinoma are also involved. All paraffin blocks which diagnosed as urothelial carcinoma were supported the diagnosis by pathologist. The all research materials are applied according to protocol from, Bio SB, Inc. Uroplakin III immunoreactivity assessment is depend on staining intensity and the positive percentage tumor cells. The age group between 64–75 years old reveals highest positive value 18 (42.9%). Uroplakin III expressions sensitivity is 44.3%, and it has higher positive percentage in low grade 20 (47.6%) in comparison with high grade 11(39.3%) but without significant difference (p = 0.492). Ta-1 and T2 Tumor stage show 26 (46.4%) and 5(35.7%) positive uroplakin III staining respectively, with no statistical association between them (p = 0.47). The all non-urothelial carcinoma show negative result (100% specificity). expression of uroplakin III with mild sensitivity and high specificity, it is regarded as good marker (even with mild sensitivity) for differentiation between primary urothelial carcinoma from other urological cancers in same site, and it can be useful for diagnosis of unkown metastatic cancer because of high specificity of uroplakin III.

Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells.

Isolation of circulating tumor cells (CTCs) from blood provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancer. The roles and clinical values of CTCs are under intensive investigation, yet most studies are limited by technical challenges in the comprehensive enrichment of intact and viable CTCs with minimal white blood cell (WBC) contamination. Here, we report a novel method based on contrast of cell magnetization in biocompatible ferrofluids (a colloidal magnetic nanoparticle suspension), termed as integrated ferrohydrodynamic cell separation (iFCS), that enriches CTCs in a tumor antigen-independent and cell size variation-inclusive manner, achieves a high throughput (12 mL h-1), high recovery rate (99.08% at down to ∼10 cells per mL spike ratio), and low WBC contamination (533 cells for every one milliliter blood processed) and is biocompatible. This method will enable large cohort research to define the clinical and diagnostic value of CTC subtypes.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018)

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Exploratory analysis of using supervised machine learning in [18F] FDG PET/CT images to predict treatment response in patients with metastatic and recurrent Brest tumors

Aim: Despite grate progress in treatments, breast cancer is still the most common invasive cancer and the most cause of cancer related death in women. Treatment could be improved and perhaps standardized if more reliable markers for tumour progression and poor prognosis could be developed. The aim of this study was to evaluate whether patient-based machine learning (ML) driven analysis of 2-deoxy-2-(18F) fluoro-D-glucose PET/CT ([18F] FDG-PET/CT) is feasible to predict for treatment response and overall survival (OS) in patients with ENT tumours. Materials and methods: In total 136 patients with the diagnosis of metastatic and recurrent breast cancer (ductal/Lobular), who had a positive [18F] FDG- PET/CT scan between 12/2008 and 12/2015 were included in this analysis. Up to five malignant lesions were delineated on the PET images using semi-automatic VOIs, which were summed up to one total tumour volume, followed by feature extraction. Clinical data such as age, tumour grade, OS, course of treatment, response and P53, HER2, ER (oestrogen receptor) and PR (progesterone receptor) status were collected. ML approaches were utilized to identify relevant textural features on PET/CT and patient features and their relative weights for survival and response prediction. The established models were validated in a Monte Carlo (MC) cross-validation scheme, as presented in Papp et al. The individual datasets for these ML executions was selected from the given MC subset by bootstrapping. Results: Median OS was 20.0 months (range: 0-89 mo). 46 patients received chemotherapy (8 patients received surgical resection after chemotherpy), 34 resections, 37 radiations and 23 hormonotherapy; response rates were 21/46, 18/35, 15/37 and 9/23 for the four treatment groups respectively. A treatment-based subgroup analysis yielded the best results with sensitivity (SNS) of 0.76, specificity (SPC) of 0.68 and an area under the curve (AUC) of 0.72 predicting for response and SNS of 0.7, SPC of 0.8 and AUC of 0.8 predicting for tumour grade after chemotherapy. For the whole cohort prediction of OS, response and grade showed values of 0.8, 0.6 and 0.6, 0.5, 0.6 and 0.7, 0.6, 0.6 and 0.7 for SNS, SPC and AUC respectively. Conclusion: These results demonstrate that textural and joint fusion features from PET-CT obtained by supervised ML are a valuable option for predicting OS, response and tumour grade in breast tumours.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer

BackgroundAnisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review.Case presentationThe case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin.ConclusionThe present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

Prognosis in Advanced Colon Cancer

This study evaluated the natural history of advanced colon cancer and determined prognosis after discontinuation of chemotherapy and introduction of palliative care for such patients. We also sought to determine if there are prognostic factors that predict survival in advanced colon cancer. A prospective enrollment of patients with a diagnosis of metastatic colon cancer into a database captured data on over 500 colon cancer patients who had undergone at least two episodes of treatment with chemotherapy, radiation therapy or secondary surgery for their condition. They were followed until death and an average length of survival was determined. The quartiles of survival were calculated and clinical and laboratory criteria were compared to see if prognostic factors could be identified that predicted the quartile of survival. The mean survival for patients with advanced colon cancer after discontinuation of either chemotherapy or radiation therapy was months. Several predictors of the poorest prognosis were identified, including small bowel obstruction, significant ascites requiring repeat paracentesis, bilirubin elevation, creatinine elevation, and hepatic encephalopathy. Prognosis of patients with colon cancer who discontinue treatments is poor. Survival can be predicted by clinical and laboratory characteristics easily identified by practitioners.

Spinal Cord Injury From Spinal Tumors: Prevalence, Management, and Outcomes

With the aging population in the United States, it can be anticipated that the prevalence of spinal cord injuries (SCIs) and cancer will increase. Primary or metastatic spine tumors sit at a unique intersection of these 2 realms. Our objective was to evaluate the prevalence, outcomes, and complications after the management of SCI arising from spinal tumors. In the present retrospective evaluation, all patients with SCI and a diagnosis of primary or metastatic spinal cancer who had been admitted to the inpatient rehabilitation unit at a level 1 trauma center from January 2003 to January 2014 were evaluated. The demographic data (age, sex, race/ethnicity), tumor characteristics, American Spinal Injury Association score, and complications were evaluated. A total of 757 SCI entries were identified, and 685 unique patients met our inclusion criteria. Of those, 81 had SCIs due to spinal tumors (11.8% of all SCIs and 19.2% of nontraumatic SCIs). Most tumors were located in the thoracic region (65.4%) and were primary central nervous system in origin (21.0%), including meningioma (7.4%), schwannoma (3.7%), and ependymoma (2.5%). The next most common origins of the spinal tumors were metastases from the lung (17.3%), prostate (9.9%), kidney (8.6%), lymphoma (7.4%), and multiple myeloma (7.4%). Of these patients, 76.5% underwent surgical management, with a complications rate of 61.3%. The overall mortality rate at the latest follow-up examination was 63.0%. SCI associated with spinal tumor is often managed surgically and associated with high rates of complications. The present study has demonstrated longer survival rates compared with the existing data.

Automated Survival Prediction in Metastatic Cancer Patients Using High-Dimensional Electronic Medical Record Data.

Oncologists use patients' life expectancy to guide decisions and may benefit from a tool that accurately predicts prognosis. Existing prognostic models generally use only a few predictor variables. We used an electronic medical record dataset to train a prognostic model for patients with metastatic cancer. The model was trained and tested using 12 588 patients treated for metastatic cancer in the Stanford Health Care system from 2008 to 2017. Data sources included provider note text, labs, vital signs, procedures, medication orders, and diagnosis codes. Patients were divided randomly into a training set used to fit the model coefficients and a test set used to evaluate model performance (80%/20% split). A regularized Cox model with 4126 predictor variables was used. A landmarking approach was used due to the multiple observations per patient, with t0 set to the time of metastatic cancer diagnosis. Performance was also evaluated using 399 palliative radiation courses in test set patients. The C-index for overall survival was 0.786 in the test set (averaged across landmark times). For palliative radiation courses, the C-index was 0.745 (95% confidence interval [CI] = 0.715 to 0.775) compared with 0.635 (95% CI = 0.601 to 0.669) for a published model using performance status, primary tumor site, and treated site (two-sided P < .001). Our model's predictions were well-calibrated. The model showed high predictive performance, which will need to be validated using external data. Because it is fully automated, the model can be used to examine providers' practice patterns and could be deployed in a decision support tool to help improve quality of care.

1512O - Automated survival prediction in metastatic cancer patients using high-dimensional electronic medical record data

Background: Oncologists use patients’ life expectancy to guide medical decisions and may benefit from a tool that provides accurate, unbiased assessments of prognosis. Existing prognostic models generally use only a few predictor variables. We used a large electronic medical record dataset to train a prognostic model for patients with metastatic cancer. Methods: The model was trained and tested using data from 12,588 patients treated for metastatic cancer in the Stanford Health Care system from 2008-2017. Data sources included provider note text, labs, vital signs, procedures, medication orders, and diagnosis codes. Patients were divided randomly into training and test sets (80%/20% split). A regularized Cox proportional hazards model with 4,126 predictor variables was fit to the training set and evaluated on the test set. A landmarking approach was used due to the multiple observations per patient, with t0 set to the time of metastatic cancer diagnosis. Performance was also evaluated using 399 palliative radiation courses in test set patients. An existing published model that uses performance status, primary tumor site, and treated site was used as a baseline [Chow, JCO 2008:20;26(36)]. Results: From the first visit after metastatic cancer diagnosis, median follow-up was 14.5 months and median overall survival was 20.9 months. Patients were seen for 384,402 daily visits. The prognostic model’s C-index for overall survival was 0.79 in the test set (averaged across landmark times). For palliative radiation courses, the C-index was 0.75 (95% CI 0.72-0.78), compared to 0.64 (95% CI 0.60-0.67) for an existing published model (p < 0.001).Table: 1512OPredicted vs actual survival for 2,518 test set patients at landmark time t0 (first visit after diagnosis of metastatic cancer)Predicted median survival in monthsActual median survival in months (95% CI)0-3 (n = 106)1.3 (0.9-2.0)3.1-6 (n = 172)3.7 (2.5-5.2)6.1-12 (n = 382)6.7 (5.6-7.9)>12 (n = 1858)35.7 (31.8-39.1) Open table in a new tab Conclusions: The model showed high predictive performance, which was significantly better than that of an existing model. Because it is fully automated, the model can be used to examine providers’ practice patterns and could deployed in a decision support tool to help improve quality of care. Legal entity responsible for the study: Michael Gensheimer. Funding: National Institutes of Health. Disclosure: M.F. Gensheimer: Research funding: Varian Medical Systems, Philips Healthcare. E. Cho: Employee of Genentech. D. Rubin: Research funding: Philips Healthcare. D.T. Chang: Research funding, honoraria: Varian Medical Systems; Stock ownership: ViewRay. All other authors have declared no conflicts of interest.

LOW YIELD OF CYTOLOGY FOR DIAGNOSIS OF MALIGNANT PLEURAL EFFUSION RELATED TO SQUAMOUS CELL LUNG CANCER

SESSION TITLE: Lung Cancer SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Malignant pleural effusion (MPE) is an ominous development of metastatic cancer that portends a dire prognosis. Some effusions are challenging to diagnose with pleural fluid cytology alone and necessitate pleural biopsy. The aim of this study was to assess the yield of pleural fluid cytology for diagnosis of malignancy secondary to metastatic squamous cell lung cancer as compared to bronchogenic adenocarcinoma. METHODS: We performed a retrospective review of patients with non-small cell lung cancer (NSCLC) who developed pleural effusions to evaluate the diagnostic yield of pleural fluid cytology from serial thoracentesis and pleural biopsy. With institutional review board approval (IRB Pro00091556) we identified MPE cases by reviewing referrals for tunneled pleural catheter placement or pleuroscopy in addition to screening cytopathology reports. RESULTS: Among 36 NSCLC patients with MPE, the initial diagnostic sensitivity of first thoracentesis to diagnose MPE was 66.7%, which improved to 71.4% with second thoracentesis, and 88.2% with pleural biopsy. Yield of pleural fluid cytology for diagnosis of malignancy was 11.1% vs. 85.2 % for squamous cell vs. adenocarcinoma (chi-square test p-value <0.0001). The diagnostic yield of pleural biopsy via pleuroscopy for squamous cell vs. adenocarcinoma was 66.7% vs. 92.9% (chi-square test p-value =0.52). 94.1% of all malignant effusions from NSCLC were classified as exudative by Light’s criteria. CONCLUSIONS: Yield of pleural fluid cytology for diagnosis of metastatic squamous cell lung cancer is low compared to bronchogenic adenocarcinoma. CLINICAL IMPLICATIONS: Clinicians should be aware of the low diagnostic sensitivity of pleural fluid cytology in patients with squamous cell lung cancer. These patients should be referred for pleural biopsy to confirm the diagnosis of an exudative effusion even when pleural fluid cytology is unrevealing. DISCLOSURES: Advisory Committee Member relationship with Leica Biosystems Please note: $5001 - $20000 Added 03/02/2018 by Rajesh Dash, source=Web Response, value=Travel Board Member relationship with College of American Pathologists Please note: $5001 - $20000 Added 03/02/2018 by Rajesh Dash, source=Web Response, value=Travel No relevant relationships by Kevin Davidson, source=Web Response No relevant relationships by Kamran Mahmood, source=Web Response

Hypertensive Emergency Leading to Diagnosis of Metastatic Pancreatic Cancer

Pancreatic cancer (PC) is associated with poor survival rate. The overall 5-year survival is less than 5%. We report a case of a patient who presented with uncontrolled blood pressure and acute kidney injury. By following a systematic approach, she was diagnosed with metastatic PC. A 63-y.o. female with PMH of HTN and hypothyroidism presented with frontal headache and blurry vision for 2 days. Patient was previously in her usual state of health. On arrival to ER, her physical exam was normal except for blood pressure of 219/105 that improved with IV labetalol and remained stable afterwards. Her blood work was normal except for acute kidney injury with creatinine of 3.8 mg/dL. Work up including CT head and MRI brain was negative. Due to elevated creatinine, US abdomen was done that showed significant bilateral hydronephrosis, more on the right side. CT abdomen confirmed bilateral hydroureteronephrosis, pyelocaliectasis without evidence of an obstructing renal stone and a 7.3 x 4.7 cm soft tissue mass within the splenic hilum with mild pancreatic ductal dilatation (IMG1). Patient underwent bilateral nephrostomy tubes with subsequent improvement of her creatinine to 1.2 mg/dL. MRI abdomen with and without contrast was then done to clarify CT findings, showing a 10.5 x 6.3 cm mass in the tail of the pancreas that abuts the splenic hilum and left kidney (IMG2). Malignant process was suspected so patient underwent EUS that showed a mass in the pancreatic body and pancreatic tail with endosonographic appearance consistent with adenocarcinoma that was staged T3 N0 Mx by endosonographic criteria. Cytology confirmed adenocarcimoa of the pancreas. CT chest was done to complete staging showing multiple bilateral lung nodules. CA19-9 was > 700,000 (N <34 U/mL). PC is an aggressive disease and ranks fourth in cancer-related mortality in USA. Because of the delayed presentation of definitive signs and symptoms of PC and the anatomic location of the pancreas, pancreatic tumors are rarely detected early, typically in an advanced stage by the time of presentation. This case is unique as a systematic approach to a patient presenting with hypertensive emergency, led to diagnosis of metastatic PC. It also highlights the rare initial presentation of PC with acute kidney injury secondary to bilateral hydronephrosis. Proposed mechanism of hydronephrosis is bilateral ureteral metastasis from PC that is exceedingly rare and only few cases are reported in the literature.1239_A.tif Figure 1: CT abdomen without contrast Yellow arrows outlining splenic hilar mass Red arrows pointing at hydronephrosis1239_B.tif Figure 2: MRI revealing splenic hilar mass of pancreatic origin

ACQUIRED ICHTHYOSIS: A RARE PRESENTATION OF LUNG CANCER

SESSION TITLE: Lung Cancer 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Acquired ichthyosis (AI) is a skin condition characterized by dry, rough and scaling skin, often described as “fish scale skin”. AI can be either congenital or acquired and can be associated with malignancies, lupus, chronic liver disease, kidney disease, malnutrition, AIDS and certain medications. Cancers associated with AI include but are not limited to: Hodgkin's lymphoma, lung and breast adenocarcinoma. Although AI is associated with underlying malignancy, this skin finding is not always recognized and is often treated independently and thus, a diagnostic evaluation for an underlying malignancy is not always performed. CASE PRESENTATION: A 54-year-old Caucasian male, who is an 80 pack year smoker and type 2 diabetic, presented to the ER with dizziness and syncope. He reported shoulder pain from falling, anorexia and unintentional weight loss. He had no shortness of breath, cough, hemoptysis, night sweats or fatigue. On exam, he was cachectic with severe dry, rough scaling skin especially to the palms and plantar surfaces (Figure1&2). He reported that this skin finding had been present for 2 months. CT of the head showed: a right frontal mass and a second heterogeneous mass within the cerebellum. So, a chest x-ray was obtained to evaluate for a possible primary neoplasm and showed a left peri-hilar mass. CT chest was subsequently completed and showed a left lower lobe mass with mediastinal lymphadenopathy, which CT guided biopsy later confirmed as small cell undifferentiated carcinoma. Podiatry was consulted for his skin findings which were believed to be paraneoplastic acquired ichthyosis and keratolytic therapy with 40% urea cream was ordered. Oncology was consulted and palliative radiation for brain metastasis and chemotherapy were started. Unfortunately, the patient died 4 months after his diagnosis was made. DISCUSSION: Lung cancer is associated with multiple paraneoplastic phenomena, including AI. Early recognition of cancer is very important especially in fast growing small cell lung cancers. As shown in this case, AI presented 2 months before the diagnosis of cancer was confirmed. This diagnosis could have been made earlier if a thorough evaluation by a dermatologist or a podiatrist was obtained. Furthermore review of the current literature and case reports on AI are very limited. Therefore, a high index of suspicion in the appropriate clinical scenario is warranted and can make a difference in the early diagnosis and treatment of associated malignancy. Unfortunately, for our patient his diagnosis of AI was made simultaneously with his diagnosis of metastatic lung cancer and so he lost an opportunity for earlier diagnosis. CONCLUSIONS: Paraneoplastic syndromes might be the first red flag observed with the presentation of cancer. Therefore, it is crucial that rare manifestation such as AI be recognized and investigated to rule underlying malignancy. Reference #1: Okulicz JF, Schwartz RA. Hereditary and acquired ichthyosis vulgaris. Int J Dermatol 2003; 42:95–8. Reference #2: Penven K, Verneuil L, Dompmartin A, Louvet S, Leroy D. An association of paraneoplastic syndromes in a patient. Ann Dermatol Venereol. 2002; 129(8-9):1042-5. Reference #3: Patel N, Spencer LA, English JC, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol 2006; 55:647. DISCLOSURES: No relevant relationships by Haytham Adada, source=Web Response No relevant relationships by Mahmoud Amarna, source=Web Response No relevant relationships by Camelia Chirculescu, source=Web Response No relevant relationships by AHMAD HAMMAD, source=Web Response No relevant relationships by Leisa Walker, source=Web Response

Metastatic Gastric Adenocarcinoma Diagnosed Following Spontaneous Bacterial Peritonitis: A Rare Complication of Malignant Ascites

Spontaneous bacterial peritonitis (SBP) complicating malignant ascites without evidence of liver disease or portal hypertension is a rare clinical presentation. We report a case of non-cirrhotic SBP leading to a new diagnosis of metastatic gastric cancer. A 51-year-old male presented with a one-month history of diffuse abdominal pain, early satiety, nausea and non-bloody, non-bilious emesis. On exam, the patient's abdomen was notably distended and diffusely tender to palpation. Admission laboratory data were significant for a mild leukocytosis of 12,700 WBC/mm3 with a neutrophilic predominance of 83% and mild anemia of 13.1 g/dl. Liver function tests showed a serum total bilirubin of 0.5 mg/dl, aspartate aminotransferase of 28 U/L, alanine aminotransferase of 16 U/L, protein of 6.7 g/dl, and albumin of 3.8 g/dl. Computed tomography of the abdomen and pelvis revealed new large volume abdominal ascites without radiological evidence of cirrhosis, portal vein thrombosis, or portal hypertension. A diagnostic paracentesis revealed 2843 WBC/ mm3, 40% neutrophils, 25% lymphocytes, fluid protein of 4.8 g/dl, and fluid albumin of 2.9 g/dl with a serum ascites albumin gradient (SAAG) of 0.9 g/dl. The patient was started on ceftriaxone for five days. Fluid culture remained negative, but repeat fluid studies showed 1475 WBC/mm3 with 25% neutrophils indicating ceftriaxone treated SBP. Upper endoscopy revealed a 10 mm, oozing, cratered gastric ulceration with surrounding congested mucosa. Biopsies later confirmed undifferentiated gastric adenocarcinoma. In addition, ascitic fluid cytology was positive for metastatic signet ring cells. SBP is an established diagnosis that has been known to complicate at least 8-10% of the cirrhotic patient population. However, spontaneous infection of ascites fluid in malignancy has not been well-described in the literature. Other cases of SBP complicating malignant ascites reported were in patients with hepatic involvement of their primary malignancies. One other case of SBP complicating gastric cancer without liver disease has been reported in the literature; this patient had hematemesis with severe anemia thought to result in bowel ischemia and bacterial gut translocation. Our patient did not report a history of gastrointestinal bleed and had a stable hemoglobin on presentation. In conclusion, this patient's diagnostic course represents a unique presentation of a rare complication of malignant ascites in gastric cancer.2681_A Figure 1. Computed tomography of abdomen revealing diffuse abdominal ascites2681_B Figure 2. Upper endoscopy revealing ulceration with surrounding congested mucosa of the greater curvature of the gastric body