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  • American Society of Clinical Oncology (ASCO)  (8)
  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 4131-4131
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4131-4131
    Abstract: 4131 Background: CUP management may be viewed as an epitome of personalised medicine as we apply our understanding of biological markers to this heterogeneous disease. There is a significant interest in evaluating actionable mutations in various signaling pathways, receptors and downstream effectors in CUP that may help us understand its biology and serve as the basis for unique targeted therapeutic approaches. Sequenom (SQM) Massarray platform enables rapid mutation profiling in solid tumors which we applied to CUP. Methods: 83 CUP samples were sent for DNA mass array analysis. Sequenom was run on 60 samples; 23 samples lacked sufficient quantity or quality of DNA. Data on clinicopathological features was collected. Results: Of the 60 patient samples run on SQM, 16 patients had changes including 11 mutations and 6 polymorphisms . The 6 polymorphisms were in MET . The mutations reported were :RAS (7; 6 KRAS, 1 NRAS), IDH1 (2), PI3K (1) and MET (1). Atleast 50% of the tumors were poorly differentiated. Interestingly, the 2 patients with IDH1 mutations presented with osseous predominant metastatic disease. Of the 6 patients with KRAS mutations, 4 presented with a gastrointestinal profile ( CDX2+ or CK20+) on IHC; in all 4, the DNA sequencing analysis results matched the sequenom results. Conclusions: The (all-comers) overall mutation rate in a heterogenous CUP population is low (11/60, 18%). No "new" low frequency mutations were found using the current panel (Table). Rare and potentially targetable mutations may be identified with a larger panel. Focusing on CUP subsets using this approach may also provide a higher mutational yield. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4130-4130
    Abstract: 4130 Background: We have previously proposed a “colon cancer profile” (CCP-CUP) favorable subset. CCP-CUP is ~ 8% of all CUP with features resembling lower gastroinestional cancers. Distinguishing this entity from other CUP pts is of significance given the progress in the treatment of metastatic colorectal cancer (CRC). Additionally, emerging data suggests a high level of agreement between histology+IHC and tissue of origin profiling for CCP-CUP. Methods: The retrospective cohort includes 74 pts from MD Anderson (50) and Sarah Cannon (24) Cancer Centers from 2004 -2010. Pts with CDX2+ tumors and pathology suggesting a "GI profile" were chosen. All pts met the definition of CUP and most had a negative colonoscopy. Results: 2 cohorts were created - Cohort 1 (34 pts), labeled “consistent with lower GI profile” [CDX2+, CK20+, CK7-] and Cohort 2 (40 pts), labeled “probable lower GI profile” [CDX2+, irrespective of CK7/CK20 status] . Most pts had a good PS; 58% women, median age 59 yrs; 20 (27%) pts had ascites on presentation and the predominant sites of metastases included liver (30%), carcinomatosis (50%), and nodes (51%). 53 pts received first line CRC regimens (FOLFOX or FOLFIRI based), 15 pts received gemcitabine or taxane based and 3 ‘other’ regimens. OS was 37 mo (C.I 22- 52). 6 of these were "outliers" (Stage 4 NED or indolent pathology). Excluding these, cohorts 1 and 2 had 32 and 36 pts - their OS were 37 and 21 mo respectively. There was no difference in OS of pts with or without ascites on presentation. Kras data was available for 17; 12 were Kras mutant. On multivariate analysis, the factors found to negatively influence survival were age, PS (of 2) and 3 or more sites of disease. Conclusions: Survival of IHC defined CCP-CUP pts (which may include colorectal, appendiceal and small bowel profile) exceeds historical control and illustrates a new "favorable" subset. IHC is not without its limitations – nonetheless, pts with CDX2 + tumors and CUP should undergo evaluation for GI cancers and likely best served with an armamentarium of drugs used for CRC. Since carcinomatosis and liver mets are predominant sites, all patients with abdominal CUP should undergo optimal IHC (CDX-2, CK7, and CK20) testing to rule out a CCP-CUP.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3527-3527
    Abstract: 3527 Background: Liquid biopsy is a promising and minimally invasive genetic test examining plasma circulating tumor DNA. Coupled with the rapidly developing next-generation sequencing (NGS) technologies, it holds the potential for implementation in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid tumors whose tumors were tested with Guardant360 assay, between December 2018 and December 2019. A total of 178 patients were referred for testing by 12 oncologists within a single community cancer center. Results: Referral rates varied widely (2.25% - 22%). The majority of patients (98%) were tested upfront for molecular marker evaluation, in either newly diagnosed advanced cancer patients, or in recurrent patients without enough tissue for testing. Other patients (2%) were evaluated after failure of 1 st line therapy to assess for acquired mutations. A total of 18 histological types were tested, with lung (LCa; n = 90; 50.56%), breast (BCa; n = 31; 17.42%), and colorectal (CRCa; n = 14; 7.87%) cancers being the most common types. In 86.11% of all tests (n = 180), ≥ 1 alteration was detected, while 13.89 % of tests did not reveal any tumor-related mutation, and were considered negative. The average number of alterations per test was 3.1 (±2.14; n = 481), and varied across types: CRCa (4.36), prostate cancer (2.73), BCa (2.97), and LCa (2.59), had the highest average number of alterations per test. Similarly, LCa (48.44%), BCa (19.13%), and CRCa (12.68%), harbored most of the detected somatic alterations (n = 481). Of all the alterations of practical significance (n = 457), TP53 (32.17%), PIK3CA (8.53%), EGFR (7.66%) and KRAS (7.22%), were the most commonly altered genes. Only 1 patient had a positive MSI-H status, amenable to immune-therapy. Of those with positive test results (n = 155), 31 (20%) had ≥ 1 FDA approved, target-matched therapeutic opportunity. Similarly, 71 patients (45.81%) had ≥ 1 target-matched therapeutic opportunity, outside current indications. Lastly, when no FDA-approved target-matched therapy was available (n = 39), results from liquid biopsy testing offered signal-based clinical trial opportunity in 39/39 patients. Conclusions: Implementation of NGS-based liquid biopsy testing is feasible within a community practice. In the era of precision oncology, such assays have the potential to expedite the efforts towards target-matched therapies and signal-based clinical trial opportunities. Further studies are warranted to identify the most-cost effective testing strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 17 ( 2015-06-10), p. 1895-1901
    Abstract: This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. Patients and Methods This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor–negative (≤ 5%), progesterone receptor–negative (≤ 5%), and human epidermal growth factor receptor 2–negative or BRCA1/2 mutation–associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m 2 intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Results Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021). Conclusion Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 5
    In: JCO Clinical Cancer Informatics, American Society of Clinical Oncology (ASCO), , No. 2 ( 2018-12), p. 1-11
    Abstract: The majority of patients with cancer receive treatments that are minimally informed by omics data. We propose a precision medicine computational framework, PANOPLY (Precision Cancer Genomic Report: Single Sample Inventory), to identify and prioritize drug targets and cancer therapy regimens. Materials and Methods The PANOPLY approach integrates clinical data with germline and somatic features obtained from multiomics platforms and applies machine learning and network analysis approaches in the context of the individual patient and matched controls. The PANOPLY workflow uses the following four steps: selection of matched controls to the patient of interest; identification of patient-specific genomic events; identification of suitable drugs using the driver-gene network and random forest analyses; and provision of an integrated multiomics case report of the patient with prioritization of anticancer drugs. Results The PANOPLY workflow can be executed on a stand-alone virtual machine and is also available for download as an R package. We applied the method to an institutional breast cancer neoadjuvant chemotherapy study that collected clinical and genomic data as well as patient-derived xenografts to investigate the prioritization offered by PANOPLY. In a chemotherapy-resistant patient-derived xenograft model, we found that that the prioritized drug, olaparib, was more effective than placebo in treating the tumor ( P 〈 .05). We also applied PANOPLY to in-house and publicly accessible multiomics tumor data sets with therapeutic response or survival data available. Conclusion PANOPLY shows promise as a means to prioritize drugs on the basis of clinical and multiomics data for an individual patient with cancer. Additional studies are needed to confirm this approach.
    Type of Medium: Online Resource
    ISSN: 2473-4276
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3027-3027
    Abstract: 3027 Background: Liquid biopsy is a promising, rapid and minimally invasive genetic test examining circulating tumor DNA. It offers a significant potential in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid cancer whose tumors were tested with the Guardant 360® (Guardant Health) assay between December 2018 and 2019. A follow-up analysis (censor date: 01/06/2021) was carried to assess the actual impact of testing results on treatment assignment and survival. Results: A total of 178 patients underwent testing. Mean age at diagnosis was 65 years. Median (m) Karnofsky Performance Scale was 90% and the majority of patients (89.9%) had ≥ stage III-B disease. Lung (LCa; 50.56%), breast (BCa; 17.42%) and colorectal (CRCa; 7.87%) cancers were the most common cancer types. A positive test was reported in 140/178 patients (78.7%); of those, 105/140 (75%) had an actionable mutation, either with an FDA-approved target-matched therapy (n = 32/105; 30.5%) or with a therapy outside current FDA indication (n = 73/105; 69.5%). In patients with no actionable mutation (n = 35/140; 25%), 85.7% (n = 30/35) had a signal-based clinical trial opportunity. The actual overall signal-based matching rate was 17.8% (24/135; vs. 82.2% no-match rate). Within candidates for FDA-approved treatment, 50% (16/32) received targeted therapy while only 6.9% (5/73) were treated with targeted agents outside current FDA indication: mean matching score (number of matched drugs/number of actionable mutations) was 0.6 (range: 0.33-2) and 0.8 (range: 0.17-2), respectively. Only 10% (3/30) were referred to signal-based clinical trials. Survival analysis of LCa, BCa and CRCa patients with actionable mutations who actually received any therapy (n = 66) revealed post-testing survival advantage for target-matched therapy (n = 22) compared to unmatched therapy (n = 44): overall survival (OS) was longer in the matched cohort (mOS: 13.3 months; 95% CI: 11.8-14.8 vs. 10.7 months; 95% CI: 9-12.4 in unmatched) but did not reach statistical significance ( P = 0.09). Progression free survival (PFS) was significantly longer in patients who received matched therapy (mPFS: 11.3 months; 95% CI: 9.9-12.7 vs. mPFS: 6.8 months; 95% CI: 5.1-8.5 in unmatched; P 〈 0.05). Conclusions: Implementation of liquid biopsy testing is feasible in community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched precision therapies conferred added survival benefit compared to unmatched therapy. Larger sample size studies are needed to validate these findings.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 1003-1003
    Abstract: 1003 Background: TN and BRCA1-deficient breast cancer (BC) cell lines exhibit enhanced sensitivity to DNA damaging agents. This study was designed to assess efficacy, safety and predictors of response to iniparib in combination with GC in early-stage TN and BRCA1/2 mutation-associated BC. Methods: This single-arm, phase II study (NCT00813956) enrolled pts with clinical stage I-IIIA (T ≥ 1cm by MRI) ER-negative (≤ 5%), PR-negative (≤ 5%), and HER2-negative or BRCA1/2 mutation-associated BC. Neoadjuvant G (1000 mg/m 2 ; IV; D1, 8), C (AUC 2; IV; D1, 8), and iniparib (5.6 mg/kg; IV; D1, 4, 8, 11) were given every 21 days for 4 cycles, until the protocol was amended to increase the treatment duration to 6 cycles, with enrollment of 80 pts at multiple PrECOG institutions. The primary endpoint is pathologic complete response (pCR), defined as no invasive carcinoma in the breast and axilla. Pathologic response was centrally assessed by the residual cancer burden (RCB) index. Assuming 76/80 eligible and treated pts, the regimen would be deemed effective if the lower bound of a 90% exact binomial CI on the pCR rate exceeded 25%. Secondary endpoints are safety, MRI response, and breast conservation. Results: Among 80 eligible pts treated with 6 cycles, median age is 48 years, 19 pts have germline BRCA1/2 mutations (90% tested to date) and clinical stage is I (13%), IIA (36%), IIB (36%), IIIA (15%). Pathologic response data (ITT population) are detailed below. 69 pts completed treatment per protocol: 5 progressed, 5 discontinued due to an AE and 1 mutation carrier was lost to follow-up. Most common G3/4 adverse events are neutropenia (49%), elevated ALT/AST (14%), and anemia (10%). Conclusions: Preoperative GC plus iniparib is active in the treatment of early-stage TN and BRCA1/2 mutation-associated BC. Clinical trial information: NCT00813956. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 593-593
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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