Mutational burden of tumors with primary site unknown.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3039-3039 ◽  
Author(s):  
Laurie M. Gay ◽  
David Fabrizio ◽  
Garrett Michael Frampton ◽  
Caitlin F. Connelly ◽  
James Sun ◽  
...  
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Additional Treatment ◽  
Primary Site ◽  
Unknown Primary ◽  
Tumor Type ◽  
Coding Region ◽  
Tissue Samples ◽  
Primary Tumor Site ◽  
Mutational Burden

3039 Background: Higher levels of tumor mutational burden (TMB) can predict sensitivity to immunotherapies (IO), which are FDA approved to treat NSCLC, melanoma, and urothelial carcinoma (Ca). TMB may be a biomarker for sensitivity to IO, irrespective of tumor type. TMB has not been explored widely for tumors of unknown primary site, but may reveal additional treatment options. Methods: Comprehensive genomic profiling of DNA from FFPE tissue samples was performed using hybrid-capture, next-generation sequencing. TMB was calculated by counting all coding short variant alterations (base substitutions and indels), including synonymous alterations, and subtracting from this functionally oncogenic or germline alterations (per ExAC, dbSNPT, or internal algorithmic analysis). To calculate the TMB per Mb, the total number of relevant mutations is divided by the coding region of the bait set (0.8 Mb, 1.1 Mb, or 1.2 Mb). High, intermediate, and low TMB were defined as ≥20 mut/Mb, ≥6 and <20 mut/Mb, or <6 mut/Mb, respectively. Tumor types with >100 samples were analyzed. Results: From a database of 102,878 samples sequenced during routine clinical care, 6116 samples for which the primary tumor site was unclear at sequencing were identified. Table shows TMB metrics (mut/Mb) and median patient age for these cohorts. Conclusions: Significant numbers of patients with each tumor type have high TMB that may indicate benefit from IO, excepting GIST. As expected, urothelial tumors have higher than average TMB and more patients have high TMB. SCC tumors are commonly TMB high (23%), as are tumors difficult to define histologically (15%). For ACUP or CUP, the most common tumors, 8-11% have high TMB. Analysis of responses to treatment with IO are ongoing. [Table: see text]

scholarly journals Multiomics profiling of paired primary and recurrent glioblastoma patient tissues

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Lennard J M Dekker ◽  
Nynke M Kannegieter ◽  
Femke Haerkens ◽  
Emma Toth ◽  
Johan M Kros ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Snare Complex ◽  
Tumor Type ◽  
Tissue Samples ◽  
Individual Patient Level ◽  
Individual Level ◽  
The Individual ◽  
Recurrent Gbm

Abstract Background Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relates to the failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression. Methods Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multiomics approach using transcriptomics, proteomics, and phosphoproteomics. Results In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxinA (synaptogenesis) and afatinib (ERBB4 signaling). Afatinib is currently in clinical trials for GBM. Conclusions A large variation on all omics levels exists between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multiomics approach offers the potential to identify affected pathways on the individual patient level and select treatment options.

Confirmation of non-small cell lung cancer (NSCLC) diagnosis using ALK testing and genetic profiling in patients presenting with carcinoma of unknown primary site (CUP).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
William Charles Penley ◽  
David R. Spigel ◽  
F Anthony Greco ◽  
John D. Hainsworth
Keyword(s):  
Treatment Options ◽  
Specific Treatment ◽  
Primary Site ◽  
Gene Profiling ◽  
Unknown Primary ◽  
Rt Pcr ◽  
Genetic Profiling ◽  
Pathologic Evaluation ◽  
Alk Positive ◽  
Support Methods

e19062 Background: Emerging data suggest real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tumor profiling can predict the primary site in CUP. We report on CUP patients (pts) predicted to have NSCLC by RT-PCR, in whom detection of ALK rearrangements provided further diagnostic support. Methods: 4 pts were diagnosed with CUP based on standard clinical, radiographic, pathologic evaluation with immunohistochemistry (IHC), and bronchoscopy/endoscopy where indicated. All pts had a RT-PCR assay (CancerTYPE ID, bioTheranostics, Inc.) performed on tumor specimens for the purpose of predicting a primary site. Tissue was also tested for ALK by FISH using a break-apart probe. Results: Pt characteristics are shown (Table). RT-PCR results prompted ALK testing in Pts 2 and 3. ALK testing and RT-PCR testing were performed concurrently in Pts 1 and 4. Each specimen was diagnosed as lung adenocarcinoma (AC) by RT-PCR gene profiling, and also tested positive for an EML4-ALKrearrangement. All pts are being followed for clinical outcome. Conclusions: Gene expression profiling in CUP diagnosed lung AC in 4 pts who also had ALK rearrangements supporting the diagnosis. Identifying ALK-positive NSCLC among pts who present with CUP improves the site-specific treatment options. [Table: see text]

scholarly journals Management of cancer of unknown primary

2020 ◽  
Vol 48 (2-3) ◽  
pp. 85-88
Author(s):  
Iva Andrašek ◽  
◽  
Mirna Ravlić ◽  
Martina Mikulandra ◽  
Franjo Cmrečak ◽  
...  
Keyword(s):  
Metastatic Tumor ◽  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Unknown Primary ◽  
Combined Modality Treatment ◽  
Tumor Type ◽  
Patients With Cancer ◽  
Poorly Differentiated ◽  
Primary Origin ◽  
Chemotherapy Agents

Cancer of an unknown primary site is most commonly an aggressive metastatic tumor with a median patient survival of 6 to 9 months. Histologically, it is predominantly adenocarcinoma, and if the primary site is subsequently diagnosed, it is usually the pancreas or lung. Biopsy should be performed whenever possible to classify a tumor of unknown primary origin into one of the following entities: adenocarcinoma, poorly differentiated carcinoma with characteristics similar to adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma, poorly differentiated neoplasm. After determining the primary tumor type, the subtype is determined by immunohistochemical staining. In oligometastatic disease, there is a possibility of surgical treatment. Radiotherapy is used as a part of combined modality treatment. Most patients with cancer of unknown primary have an unfavorable prognosis despite multiple chemotherapy agents, and no protocol can be recommended as standard therapy.

Validation of a clinical score (CS) for patients (pts) with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177 dotatate.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4109-4109
Author(s):  
Satya Das ◽  
Aman Chauhan ◽  
Liping Du ◽  
Katharine Thomas ◽  
Aasems Jacob ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards ◽  
Medical Center ◽  
Cox Proportional Hazards ◽  
Secondary Outcome ◽  
Unknown Primary ◽  
Cancer Center ◽  
Tumor Type ◽  
Primary Tumor Site ◽  
Point Increase

4109 Background: Questions remain regarding when to sequence PRRT and how to categorize pts being considered for the treatment (tx). We previously developed a CS (comprised of 5 categories: available non-PRRT tx for tumor type, prior systemic tx, pt symptoms, tumor burden in critical organs and peritoneal carcinomatosis presence) at Vanderbilt Ingram Cancer Center (VICC) for pts being considered for PRRT to help answer these questions and demonstrated the score to be associated with progression-free survival (PFS) in pts receiving PRRT. Herein, we present the performance of the CS in a validation cohort (VC) and combined cohort (CC). Methods: Our original cohort (OC) included pts with progressive WD NETs (N = 122) under consideration for PRRT between 3/1/2016-3/17/2020 at VICC while our VC included pts under consideration for PRRT (N = 126) between 1/25/2017-11/18/2019 at Ochsner Medical Center (OMC) (N = 51), Markey Cancer Center (MCC) (N = 51) and Rush Medical Center (RMC) (N = 24). All pts in the OC were prospectively scored while pts in the VC were scored retrospectively, with the CS-assigning investigator blinded to patient outcomes. The primary outcome PFS, was estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusting for primary tumor site, tumor grade and number of PRRT doses administered (0, 1-2 or 3-4) was used to analyze effect of CS. Overall survival (OS) was a key secondary outcome. Results: In our VC, on multivariable (MV) analysis, for each 2-point increase in CS, the hazard ratio (HR) for PFS was 2.58 (95% confidence interval (CI) 1.62-4.11). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.89 (95% CI 1.8-4.83). We combined the OC and VC for this analysis in order to increase the predictive power of our originally developed Cox proportional-hazards models. In our CC, of the 248 total pts, median pt age, CS and number of prior tx were 63.3 years, 4 (range 0-8) and 1 (range 0-7), respectively. The most represented primary tumor sites were small intestinal (N = 136), pancreatic (N = 58), unknown primary (N = 26) and lung (N = 14). A total of 140, 82 and 26 pts received 3-4, 0 or 1-2 doses of PRRT, respectively. On MV analysis, for each 2-point increase in CS, the HR for PFS was 2.52 (95% CI 1.90-3.35). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.48 (95% CI 2.33-5.18). No interaction between PRRT doses administered and CS was observed. Conclusions: Increases in CS were strongly associated with worsening PFS and OS in our VC and CC, validating findings from our OC. Although we cannot determine whether the CS specifically predicts PRRT response or is prognostic based upon these data, it is the first presented clinical metric which can categorize pts with WD NETs under consideration for PRRT and estimate anticipated benefit from PRRT for pts.

Differential expression of biomarkers in gastrointestinal versus pulmonary carcinoid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13571-e13571
Author(s):  
Erika Fong ◽  
Gilbert Peterson ◽  
Gargi D. Basu ◽  
Richard Blevins ◽  
Raheela Ashfaq
Keyword(s):  
Differentially Express ◽  
Treatment Options ◽  
Chemotherapeutic Agents ◽  
Primary Site ◽  
Carcinoid Tumors ◽  
Unknown Primary ◽  
Computer Search ◽  
Pulmonary Carcinoid ◽  
Pulmonary System ◽  
Pulmonary Carcinoids

e13571 Background: Carcinoid tumors are endocrine neoplasms that commonly arise in the GI and pulmonary system. About 12,000 cases of carcinoid tumor are diagnosed a year with a 5-year survival rate of 67.2% .The majority of the cases present with advance disease with limited treatment options,therefore evaluation of predictive markers for chemotherapeutic agents is highly desirable. We studied the biomarker expression in carcinoid tumors and evaluated any differences based on site of origin. Methods: By computer search we retrospectively identified all cases submitted to Caris Life Sciences with the diagnosis of “carcinoid”. The cases were classified by primary site into three groups: Pulmonary, GI tract (including esophagus, stomach, small bowel, colon, rectum, appendix and pancreas) and miscellaneous. Biomarker expression performed by IHC and scored semi quantitatively by a pathologist for SPARC mono, SPARC poly, Her2, TOPO2, TOPO1, PGP, MRP1, PTEN, TS, ERCC1, RRM1,MGMT, C-KIT, ER, PR and AR and SSTR2 and SSTR5 analysis by DNA Microarray were compared between the groups. Results: 146 carcinoid tumors were interrogated for biomarkers, 33 pulmonary, 97 GI and 16 miscellaneous (mediastinum, thymus, cervix, breast and unknown primary site). Due to small number of tumors in the miscellaneous category, analysis was restricted to pulmonary and GI carcinoid tumors only. Based on our analysis the pulmonary carcinoids differentially express Topo2, PGP, MGMT, CKIT and PR, while the GI carcinoids differentially express Topo1, RRM1 and ER and SSTR2 and SSTR5. There is equivalent expression of SPARC, MRP1, PTEN, TS, ERCC1 at both sites . All pulmonary and GI carcinoid tumors were negative for Her2. Conclusions: Based on this study it appears that there are differences in biomarker expression in GI and Pulmonary Carcinoid tumors. Treatment with irinotecan, gemcitabine, anti-estrogens and Octreotide may be more relevant in GI carcinoids based on molecular markers present while targets associated with response to anthracyclines, temozolomide, imatinib may be more commonly expressed in pulmonary carcinoid tumors. Further studies are needed to understand the underlying biology and molecular drivers in this group of tumors.

scholarly journals The Diminishing Importance of Primary Site Identification in Cancer of Unknown Primary: A Canadian Single-Center Experience

2021 ◽  
Vol 11 ◽  
Author(s):  
Boaz Wong ◽  
Michael M. Vickers ◽  
Paul Wheatley-Price
Keyword(s):  
Primary Tumor ◽  
Treatment Guidelines ◽  
Descriptive Analysis ◽  
Cancer Of Unknown Primary ◽  
Primary Site ◽  
Unknown Primary ◽  
Primary Tumor Site ◽  
Logistic Regression Models ◽  
Factors Associated ◽  
Site Identification

BackgroundCancer of unknown primary (CUP) describes patients with metastatic disease without an identified primary tumor site. Successful diagnosis and treatment of these patients remains difficult. Published guidelines on CUP have highlighted “favorable” subtype groups. We investigated a series of CUP patients to review adherence to guidelines, and identification of primary cancers or “favorable” subtypes.MethodsPatients with histologically confirmed CUP at an academic institution from 2012 to 2018 were identified. Patient demographics, tumor presentation, diagnostic work-up and treatment information were retrospectively collected from electronic data records for descriptive analysis and compared to published clinical guidelines. The primary endpoint was the proportion of patients where the primary site was identified. Multivariable logistic regression models were used to identify factors associated with primary site identification. Kaplan-Meier survival curves were used to determine factors associated with poorer OS.ResultsThree hundred and five patients were included with a median follow-up time of 4.3 months. Primary tumor sites were identified in 109 patients (37.5%), which was most commonly lung cancer (33%). Statistical analyses did not identify any demographic or initial presentation factors associated with identifying the primary or not. More diagnostic tests did not increase the likelihood of primary site identification (P=0.44). Patients with an identified primary did not have longer OS than other patients (median 5.2 months vs. 4.7 months, P=0.47). 57 patients (18.7%) who had a defined “favorable” subtype experienced superior OS (36.6 months vs. 3.8 months; P&lt;0.0001). Further, patients with good prognostic status who followed published treatment guidelines had longer OS (17.6 months vs. 13.2 months; P=0.04).ConclusionsCUP remains a difficult cancer to diagnose and treat. These results suggest identifying the primary has less impact than anticipated, but particular efforts to identify patients with “favorable” subtypes of CUP is important prognostically.

The role of whole body 18F-FDG PET/CT scan in patients with carcinoma of unknown primary

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22051-e22051
Author(s):  
M. Hu ◽  
J. Yu ◽  
N. Liu ◽  
L. Kong ◽  
P. Zhang
Keyword(s):  
Ct Scan ◽  
Primary Tumor ◽  
Fdg Pet ◽  
Primary Site ◽  
Unknown Primary ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Pet Ct Scan

e22051 Background: Carcinoma of unknown primary (CUP) is a heterogeneous group of tumors and usually follows an aggressive biological and clinical behavior. Difficult challenges in oncology which the identification of the primary tumor and a complete disease staging could offer a more rational and efficient treatment in order to improve the survival time. Our aim was to evaluate the role of 18F-FDG PET/CT scan with two aspects: detection of the primary site, and estimation of tumor biological behavior which essential for the development of new, individual and targeted effective therapies. Methods: One hundred and seventeen patients presenting with histologically confirmed metastatic carcinoma (76 lymph nodes, 41 visceral biopsy proven) of unknown primary site were included in this retrospective study. The evaluations as follows had not revealed a primary site: detailed medical history, full physical and laboratory examinations, and diagnostic imaging methods. All patients underwent PET/CT. Results: In 42 (35.90%) patients, a primary tumor site which was confirmed by follow-up or surgery was showed by PET/CT. In 15 (12.82%) patients, the primary tumor site was suggested by PET/CT but not confirmed. In 60 (51.28%) patients, the primary tumor site was not localized modifying the stage of disease. In the other 17 (14.53%) patients, PET/CT scan identified further unexpected metastases. Overall, the following oncological treatment was influenced by the PET/CT scan, in a total of 38 (32.47%) patients. Between the adenocarcinoma and squamous cell carcinoma groups, no significant difference in SUVmax was found ( t=1.191, p = 0.244). A significantly higher SUVmax was found among patients with poorly or undifferentiated carcinoma compared with patients with well to moderately ( t=4.013, p<0.01) differentiation; In 42 patients with a confirmed primary tumor site, the SUVmax of Metastatic tumours have a closely relationship correlate with those of primary tumours, ( r=0.738, p<0.01). Furthermore, a significantly higher SUVmax was found among metastases compared with primary tumors ( t=3.470, p<0.01). Conclusions: Our data strongly support 18F-FDG PET/ CT imagings not only provide new insights in the diagnosis and staging of patients with CUP, but also evaluate biologic characters of tissue. 1 No significant financial relationships to disclose.

Use of next-generation sequencing (NGS) to identify actionable genomic alterations (GA) in diverse solid tumor types: The Foundation Medicine (FMI) experience with 2,200+ clinical samples.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11020-11020 ◽  
Author(s):  
Vincent A. Miller ◽  
Jeffrey S. Ross ◽  
Kai Wang ◽  
Siraj M. Ali ◽  
Geoff Otto ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Drug Targets ◽  
Treatment Options ◽  
Additional Treatment ◽  
Clinical Samples ◽  
Tumor Type ◽  
Kinase Gene ◽  
Hybridization Capture ◽  
Small Indels ◽  
Tumor Types

11020 Background: ST oncology has been transformed by the linkage of GA with targeted therapeutics. Unfortunately, most STs still have no target detected by clinically available assays. More comprehensive testing platforms are needed to determine GA in ST and thus broaden treatment options. We developed a ST NGS diagnostic assay, optimized for routine clinical FFPE specimens including core and fine needle biopsies and malignant effusions, and analyzed > 2,200 patients’ tumors in a CLIA-certified lab (Foundation Medicine). Methods: Hybridization capture of 3,320 exons from 182 cancer-related genes and 37 introns of 14 genes commonly rearranged in cancer was applied to ≥ 50ng of DNA extracted from 2,200+ consecutive FFPE tumor specimens and sequenced to high unique coverage. GA (base substitutions, small indels, rearrangements, copy number alterations) were categorized as “actionable” if directly linked to a clinically available targeted treatment option or a mechanism-driven clinical trial. Results: 2,112/2,221 (95%) of specimens (most common 1° sites: lung 18%, breast 14%, colon 7%, other 34%) were successfully profiled (mean coverage 1134X). Alterations were reported in 155/182 (85%) of genes. Seventy-six percent of cases harbored ≥1 actionable GA, mean 1.6 (range 0-16); sixty-two percent harbored at least one actionable GA not assayed by available tumor-type specific tests or hotspot panels. This approach has led to novel insights into advanced cancer including: 13 novel, potentially druggable kinase gene fusions; alterations in known drug targets (e.g. ALK, EGFR, ERRB2, KIT, MET, PDGFR α and β, RAF1 and RET) in novel tumor types and new mechanisms of resistance to approved targeted therapies. Several patients demonstrated dramatic responses to treatment with targeted therapies directed against these alterations. Conclusions: Comprehensive NGS genomic profiling was successful in profiling >2,200 unselected clinical cases, identified actionable alterations in 76% of cases and provided additional treatment options for 62% of patients targeting alterations in genes not assayed by available hotspot panels.

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