Primary Tumor Types in Positive Serous Fluid Cytology in Patients Under Age 18, A-Single Institution Experience

The use of ex vivo drug sensitivity testing to predict drug activity in individual patients has been actively explored for almost 50 years without delivering a generally useful predictive capability. However, extended failure should not be an indicator of futility. This is especially true in cancer research, where ultimate success is often preceded by less successful attempts. For example, both immune- and genetic-based targeted therapies for cancer underwent numerous failed attempts before biological understanding, improved targets, and optimized drug development matured to facilitate an arsenal of transformational drugs. Similarly, directly assessing drug sensitivity of primary tumor biopsies—and the use of this information to help direct therapeutic approaches—has a long history with a definitive learning curve. In this review, we survey the history of ex vivo testing and the current state of the art for this field. We present an update on methodologies and approaches, describe the use of these technologies to test cutting-edge drug classes, and describe an increasingly nuanced understanding of tumor types and models for which this strategy is most likely to succeed. We consider the relative strengths and weaknesses of predicting drug activity across the broad biological context of cancer patients and tumor types. This includes an analysis of the potential for ex vivo drug sensitivity testing to accurately predict drug activity within each of the biological hallmarks of cancer pathogenesis. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Risk of Malignancy of Pelvic and Peritoneal Fluid Cytology with Histological Correlation Using the International System for Reporting Serous Fluid Cytopathology: Experience of a Large Healthcare System

Journal of the American Society of Cytopathology ◽

10.1016/j.jasc.2021.07.023 ◽

2021 ◽

Vol 10 (5) ◽

pp. S20

Author(s):

Deepika Savant ◽

Karen Chau ◽

Sujata Sajjan ◽

Hector Chavarria ◽

Nidhi Kataria ◽

...

Keyword(s):

Healthcare System ◽

Peritoneal Fluid ◽

International System ◽

Serous Fluid ◽

Risk Of Malignancy ◽

Fluid Cytology

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Effusion cytology of a mucinous borderline ovarian tumour: Pitfall or controversy? A case report with insight into the newly proposed International System for Reporting Serous Fluid Cytology

Cytopathology ◽

10.1111/cyt.12926 ◽

2020 ◽

Author(s):

Rubina Razack ◽

Mokoena Martins Mohosho ◽

Pieter Barnardt ◽

Pawel Tomasz Schubert

Keyword(s):

Case Report ◽

International System ◽

Ovarian Tumour ◽

Serous Fluid ◽

Borderline Ovarian Tumour ◽

Insight Into ◽

Fluid Cytology

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Role of CD68 immunohistochemistry in categorizing benign nonmesothelial cell population and refining “atypical” category in serous fluid cytology

Diagnostic Cytopathology ◽

10.1002/dc.24541 ◽

2020 ◽

Vol 48 (12) ◽

pp. 1199-1204

Author(s):

Omid Savari ◽

Sarmad Jassim ◽

Hector Ferrer ◽

Stephen J. Ganocy ◽

Santhi Ganesan

Keyword(s):

Cell Population ◽

Serous Fluid ◽

Fluid Cytology

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Differential Patterns of Bone Turnover in Relation to Bone Pain and Disease Extent in Bone in Cancer Patients with Skeletal Metastases

Clinical Chemistry ◽

10.1093/clinchem/45.8.1240 ◽

1999 ◽

Vol 45 (8) ◽

pp. 1240-1247 ◽

Cited By ~ 80

Author(s):

Alfredo Berruti ◽

Luigi Dogliotti ◽

Gabriella Gorzegno ◽

Mirella Torta ◽

Marco Tampellini ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Bone Turnover ◽

Urinary Excretion ◽

Bone Metastases ◽

Primary Tumor ◽

Bone Pain ◽

Bone Alkaline Phosphatase ◽

Skeletal Metastases ◽

Disease Extent ◽

Tumor Types

Abstract Background: The alteration of the bone microenvironment as a consequence of skeletal metastases is poorly understood. The aim of this study was to search for patterns of bone markers in relation to primary tumor type, bone pain, and number of sites involved in patients with bone metastases. Methods: We studied 323 patients with bone metastases from various primary malignancies. We sequentially measured the serum concentrations of bone alkaline phosphatase [by an electrophoretic technique (BALP)], carboxy-terminal telopeptide of type I collagen (ICTP), calcium (CaS), intact parathyroid hormone (PTH), and the fasting urinary excretion of calcium (Ca:Cr). Immunoradiometric serum bone alkaline phosphatase (I-BALP) and urinary excretion of deoxypyridinoline (DPYD) were also assessed in the 175 cases. Data were analyzed as a function of bone pain (assessed by a validated pain questionnaire), the number of radiographically confirmed sites of bone involvement, and the most frequent primary tumor types: breast cancer (BC; 124 patients), prostate cancer (PC; 90 patients), and non-small cell lung cancer (LC; 49 patients). Results: Serum BALP and I-BALP correlated with the number of radiologically identified blastic bone lesions. BALP and I-BALP were more frequently increased in PC (72% for both measurements) than in BC (50% and 60%, respectively) or LC (3% and 5%, respectively; P <0.001 for BALP and P = 0.001 for I-BALP). ICTP and DPYD values did not differ among PC, BC, and LC, but they did show a direct relationship with the disease extent in bone (P <0.001). CaS and Ca:Cr did not vary significantly according to the bone tumor burden. Bone pain directly correlated with ICTP (P <0.001), DPYD (P = 0.002), CaS (P <0.002), and Ca:Cr (P = 0.001), whereas the relationship was inverse for serum PTH (P = 0.002). When patients were stratified according to the primary tumor, ICTP correlated with the bone pain in all subsets (P <0.005, <0.005, and <0.001 for BC, PC, and LC, respectively), as did CaS and Ca:Cr in LC patients (P = 0.01 and 0.02, respectively) but not in PC and BC patients. Conclusions: The patterns of bone turnover markers differ among the primary tumor types. Both resorption and formation markers reflect the number of radiographically identified sites of bone metastases, whereas resorption markers and serum calcium but not formation markers correlate with bone pain.

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FAK expression as a prognostic marker in colorectal cancer: A single institution study of 298 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.623 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 623-623 ◽

Cited By ~ 2

Author(s):

Lindy Davis ◽

Felicia Lenzo ◽

Lourdes Ylagan ◽

Angela Omilian ◽

Kristopher Attwood ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Internal Control ◽

Primary Tumor ◽

Expression Patterns ◽

Tumor Stage ◽

Therapeutic Window ◽

Single Institution ◽

Normal Colon ◽

Primary Tumors

623 Background: Focal adhesion kinase (FAK) is an attractive therapeutic target in solid cancers, but there is no method for patient selection based on FAK expression nor biomarker for therapeutic response. Previous FAK expression studies were not standardized and showed varying correlations. This single-institution study aims to define FAK expression patterns in colorectal cancer (CRC) and correlate with patient outcomes and expression in other solid cancers. Methods: We analyzed 635 samples from 298 patients (pt) with CRC using tissue microarrays (TMAs) stained for FAK and scored 0-3 by a single pathologist. The TMAs contained samples of 298 primary tumors with 290 matching normal tissue and 47 matching metastases. As an internal control, we examined FAK and outcomes in 135 breast cancer pt and 145 melanoma pt. FAK expression and pt outcomes were evaluated using Kruskal-Wallis exact and Wilcoxon signed-rank tests. Results: FAK expression correlated with aggressive phenotype in CRC primaries. Matching normal colon had lower FAK than primaries (Mean FAK 0.61 vs 1.87, p < 0.001). Higher primary tumor FAK was associated with higher tumor stage; the 88 T1-2 primaries had a mean FAK 1.54, compared to FAK 2.06 in the 99 T3-4 tumors (p < 0.001). There was no difference in FAK among Stage II-IV pt, nor between mean FAK in the primaries (1.87) versus metastases (1.73). When FAK was dichotomized as high vs low (high = FAK > 2), high primary tumor FAK was associated with shorter overall survival (OS). Median OS was 91 months (95% CI 73-130) in high FAK (n = 122 pt) vs 155 months (95% CI 124-196) in low FAK (n = 176 pt), p = 0.007. The OS rates at 5 and 10 years in high FAK were 65% and 43%, vs 79% and 61% in low FAK. FAK in CRC metastases did not correlate with OS (p = 0.945). In contrast, when CRC was compared to breast cancer and melanoma, FAK did not show the same correlations in outcome. Conclusions: For the first time, by standardizing FAK quantification, we have identified that FAK expression in the primary correlates with outcome in CRC. These data may have implications in selection of patients for adjuvant therapy. Normal colon and earlier stage CRC had lower FAK expression compared to more advanced stages, suggesting a therapeutic window for FAK as a target.

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Molecular profiling using the 92-gene assay for tumor classification of brain metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13583 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13583-e13583

Author(s):

Andrew Jacob Brenner ◽

Raul Collazo ◽

Catherine A. Schnabel ◽

F Anthony Greco

Keyword(s):

Brain Metastases ◽

Targeted Therapies ◽

Primary Tumor ◽

Tumor Type ◽

Federal Drug Administration ◽

Gene Assay ◽

Clinical Series ◽

The Us ◽

Tumor Types

e13583 Background: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types/subtypes for patients with uncertain diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. Methods: An IRB-approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. Results: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested ( < 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA) (Table). Conclusions: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival. [Table: see text]

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