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  • American Society of Clinical Oncology (ASCO)  (9)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 29 ( 2011-10-10), p. 3869-3876
    Abstract: Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence. Patients and Methods The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology. Results Among 667 women with a median follow-up of 7.9 years, 220 events occurred—108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P 〈 .001). At 4 months, TAM-OCT had significantly (P 〈 .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P 〈 .001), and higher body mass index (BMI) in models excluding C-peptide (P 〈 .001) were associated with poorer EFS in multivariate analysis. Conclusion Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
    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: 2011
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4154-4154
    Abstract: 4154 Background: ctDNA provides opportunities for identifying targeted therapies, a source to conduct NGS when tissue acquisition is infeasible, detection of minimal residual disease (MRD), and identification of resistance mutations. There are limited large data sets to inform clinical utility and limited correlation of NGS of ctDNA and tumor in PC. Herein, we evaluate the ctDNA detection rate in multiple cohorts of PC and report the ctDNA-tissue genotype concordance in PC at Memorial Sloan Kettering (MSK). Methods: Pts with PC at MSK who had ctDNA prospectively collected using the MSK-ACCESS 129 gene ctDNA NGS assay, were identified. ctDNA detection was defined as the identification of a mutation, copy number (no.) alteration or structural variant. Tissue-based NGS using MSK-IMPACT gene assay was performed for pts with adequate tissue, and matched with ctDNA by date. Clinical, pathologic and outcome data were abstracted. Data are summarized with descriptive statistics. Overall survival (OS) estimated by Kaplan-Meier method from date of ctDNA draw to death/last follow up. Results: From 08/2019 to 07/2022, N= 414 pts with PC and ≥ 1 ctDNA sample included. Median age 69 years (range 29-92), female N=206 (50%). Stage at ctDNA collection: Stage I-III N= 203 (49%); Stage IV N= 211 (51%). ctDNA detection rate by no. of involved organs; 0 organs (MRD), N=7/30 (23%); 1-2 organs, N=158/270 (58.5%); 3-4 organs, N=82/102 (80.4%); 〉 5 organs, 12/12 (100%). CtDNA detection rate by site of metastasis; Liver only, 75/99 (76%); peritoneum only, 15/25 (60%); lung only, 10/22 (45%). In pts with detected ctDNA median CA 19-9 was 494 U/mL (range 0, 247674) vs 100 U/mL (range 1, 22360) in pts with undetected ctDNA. In pts with detected ctDNA median CEA was 7 ng/mL (range 1, 2020) vs 4 ng/mL (range 1, 99) in pts with undetected ctDNA. In stage IV untreated pts, median OS 13 months(m) (95% CI; 7.3, 16) and 10 m (95% CI; 5.6, -) for ctDNA detected vs undetected, respectively. ctDNA detection rates by stage, and concordance between ctDNA and tissue-based NGS for common driver mutations KRAS, TP53, CDKN2A and SMAD4 in N=131 matched pairs are summarized in the table. Conclusions: ctDNA detection rates are high (89%) in pts with untreated stage IV PC, with high concordance between ctDNA and tissue-based NGS (87% - 95%). In untreated stage I-III PC, detection and concordance rates are lower ( 〈 50%). Detection rates are associated with disease burden, site of metastasis, CA 19-9/CEA levels. ctDNA is a promising tool in detection of somatic alterations in PC, particularly in stage IV disease, and is a complementary adjunct to tumor-based NGS. [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: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 294-294
    Abstract: 294 Background: Validated predictive and prognostic biomarkers are needed in PDAC. Such biomarkers could predict response and resistance early in treatment. As 95% of PDAC harbor KRAS mutations (mKRAS), plasma mKRAS has utility as a biomarker. We explored the prognostic value of mKRAS in a PDAC cohort at Memorial Sloan Kettering. Methods: 10 mL of whole blood was collected at diagnosis of localized PDAC and early interval CT scan (approx. 8 weeks). DNA was extracted with QIAamp DNA kits (Qiagen, Valencia, CA). Single locus, if tissue KRAS known, or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with QX200 (BioRad, Hercules, CA) ddPCR system. Disease status was determined by radiographic, CA19-9 and clinical evaluation. Results: N = 18 enrolled (median age: 65 [range 34-85]). Median time between baseline (B) and interval (I) blood was 2.53 months (range 0.9-6). One had locally recurrent disease, 2 AJCC stage IIa, 1 IIb and 14 III. Three had tissue KRAS G12D mutation, 6 G12V and 9 unknown. Eight had gemcitabine-based treatment, 10 5-FU-based and 5 radiation. See table. mKRAS and CA19-9 at B were not associated with progression free survival (PFS) or overall survival (OS). mKRAS detection at I was associated with shorter PFS/OS (P 〈 0.01), but CA19-9 was not. mKRAS change from B to I was also associated with PFS/OS. For every 1 copy/mL increase in the change of mKRAS from B to I, the risk of death or progression/death increased by nearly 2 fold after controlling for baseline value (p = 0.01 for OS, p = 0.03 for PFS). Four patients, all undetectable mKRAS at I, went to surgery; 2/4 resected. Conclusions: In this pilot, 59% of localized PDAC patients had detectable mKRAS at B. mKRAS detection at I and change from B to I were associated with PFS/OS supporting that mKRAS early in treatment may be a useful prognostic and predictive marker in localized PDAC. We have initiated a large prospective trial to evaluate the predictive and prognostic potential of plasma mKRAS in advanced PDAC. [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: 2019
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4132-4132
    Abstract: 4132 Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway. [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: 2019
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 774-774
    Abstract: 774 Background: For individuals ≤ 50 years old, cancer incidence is increasing, particularly gastrointestinal and obesity related cancers (Sung, Lancet Public Health 2019). Limited details are known about young onset PC. Herein, we report the epidemiologic, pathologic, and molecular characteristics of PC in patients (pts) ≤ 50 years. Methods: MSK institutional database was queried for medical and treatment history, genomics, and outcomes in pts ≤ 50 years old diagnosed with PC between January 2008 and July 2018. Neuroendocrine cancers were excluded. Overall survival (OS) from date of PC diagnosis was estimated using Kaplan-Meier methods. Results: N = 450 pts ≤ 50 years old with a diagnosis of PC were identified. Ninety-six percent had adenocarcinoma, and 4% had acinar cell carcinoma/other histologies. Table summarizes demographics. Median OS was 16 months in the entire cohort and 11.3 months in stage IV disease. For N = 236 pts diagnosed after 2014, 119 (50%) underwent successful somatic testing with at least one alteration identified, and 21/119 tumors were RAS wild-type with identification of several actionable alterations (NRG1 fusions (n=2), NTRK fusions (n=2), IDH1 R132C (n=1), and microsatellite unstable tumors (n=1) ). N = 114 pts had germline testing (routine after 2015), and 33/114 (29%) had pathologic germline alterations, including BRCA1/2 (n=18), CHEK2 (n=3), PALB2 (n=3), ATM (n=2), MLH1 (n=1), and MSH3 (n=1). Conclusions: Pathogenic germline alterations are present in a substantial percentage of pts with young onset PC, and actionable somatic alterations were seen frequently in the subgroup of young onset PC RAS-wild type tumors. These observations underpin the need for germline and somatic profiling in PC. [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: 2020
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4140-4140
    Abstract: 4140 Background: Maintenance olaparib improves PFS in g BRCA1/2m (core HRD) in mPDAC (Golan, NEJM 2019). Whether other HRD indicators, such as gene mutations other than g BRCA1/2m (non-Core HRD, Cohort B) and exceptional platinum responders (Cohort C, response 〉 6 months) may benefit from PARPi in mPDAC remains unanswered. We hypothesized that pembrolizumab and olaparib (POLAR) combination may improve outcome by immunogenic cell death. Methods: We conducted an open-label, non-randomized, phase 2 trial of POLAR as maintenance therapy for pts with mPDAC whose disease had not progressed for 4 months (m) in Cohort B or 6 m in C. Herein, we report on Cohorts B & C. Eligibility: ECOG 0-1, mPDAC meeting eligibility of B or C. POLAR (Pembrolizumab 200mg IV Q3W+ OLApaRib 300mg BID) until disease progression or limiting toxicity. Objective response rate (ORR), median PFS (mPFS), median overall survival (mOS), disease control rate (DCR), CA 19-9, cfDNA and baseline HRD mutational signature were analyzed. Results: Cohorts B and C enrolled N=15 each. N=25 pts evaluable by RECIST 1.1. Median follow-up 9.9 (1.3-22.8) and 11.3 (5.8-23) m, respectively. Efficacy details are shown. G3-5 AEs related to treatment: 5/14 (36%): 1 diarrhea (7%), 1 hyperglycemia (7%), 2 anemia (14%), 1 lipase increased (7%). Cohort B: 9/15 (60%) ATM, 3 CHEK2, 2 MUTYH, 1 BLM, 1 FANCC. Canonical gene mutations for mPDAC were less common for pts in Cohort B, especially in ATM PA group (n=9) vs C. Median genomic instability score (GIS) was computed and higher 28 (0-38) vs 9 (0-24) in Cohort B vs C, p=0.052. Median tumor mutation burden (TMB) was not different between B and C (3.3 and 4.1). Conclusions: Clinical activity of POLAR maintenance observed in select pts in B and C. Although PFS was modest (mPFS of 4m [2.1-5.4] in B + C), an intriguing survival signal (mOS at 14m [10-NR] from first POLAR dose) was seen in select patients without chemotherapy. Extensive correlative analyses underway to evaluate response and resistance (SPORE: 1P50CA257881-01A1). Cohort A (core HRD) actively accruing. Clinical trial information: NCT04666740 . [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: 2023
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 639-639
    Abstract: 639 Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay resistance in PDAC (O’Reilly, Cancer, 2018). Herein, we evaluate GC +/- V in a multi-national, randomized phase II trial. Methods: Eligibility: Untreated germline (g)BRCA, PALB2 mut PDAC; measurable stage III/IV; ECOG 0-1. Randomized 1:1 Arm A or B. Treatment: Arm A: G 600 mg/m2 IV, C 25 mg/m2 IV, d3 and 10, V 80 mg PO BID day 1-12, all q 3 weeks or Arm B: GC only. Primary endpoint: RECIST 1.1 response rate (RR). Simon 2-stage per arm: null hypothesis 10% vs promising 28%; type I, II error 10%. Secondary endpoints: progression-free survival (PFS), OS (m), disease control rate (CR+PR+SD), safety and correlative analyses. PFS, OS compared between arms using log-rank test and RR, DCR using Fisher’s exact test between arms. Results: N = 52 enrolled 01/14- 11/18. N = 2 withdrew Arm B. N = 50 for ITT. Male = 22 (44%), Female = 28. Median age = 64 years (range 37-82). BRCA1 N = 12, BRCA2 N = 35, PALB2 N = 3. Stage III N = 8; Stage IV N = 42. Hematologic Toxicity: Arm A vs Arm B: Gd 3-4 neutropenia 13 (48%) vs 7 (30%); Gd 3-4 platelets 15 (55%) vs 2 (9%); Gd 3-4 anemia 14 (52%) vs 8 (35%). Non-hematologic toxicity similar Arm A vs B. Exploratory analyses (combined Arms): Med OS if 〉 4 m platinum → PARPi: 23 m (95%CI 6.5- 53.9). Med OS by BRCA: BRCA1: 14 m (8.1- 18.5); BRCA2: 20.2 m (12.3- 24.4). Med OS by ECOG: ECOG 0: 23 m (13.8- 24.5); ECOG 1: 14.3 (8.1 vs 16.4). Two-year OS rate for entire cohort: 30.6% and 3-year OS: 17.8%. Conclusions: GC +/- V very active in gBRCA/PALB2 mut PDAC with high RR, PFS, OS with both A, B significantly exceeding threshold RR. Improved DCR arm A vs B, but with greater heme toxicity A vs B. Study confirms GC as reference treatment in gBRCA/PALB2 with durable survival in subset. Funding: National Cancer Institute, CTEP, Lustgarten Foundation, AbbVie. Clinical trial information: NCT01585805 . [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: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e13620-e13620
    Abstract: e13620 Background: On the 14th of May 2021 the Irish Health Service Executive (HSE) was the victim of a “Conti” ransomware attack. The HSE is a nationwide organization providing Ireland’s public health service, consisting of approximately 4000 locations and more than 70,000 connected devices. The study aim is to quantify the impact of the cyber attack by examining the effect on the Breast Cancer services at Cork University Hospital 1 of 8 national cancer centres & 1 of 54 HSE acute hospitals. Methods: New patient referrals through the weekly Breast cancer MDT meeting were used as the study nidus. Patient referrals & key performance indexes for a period of 4 weeks prior, during & after the attack were examined. Time was the key metric examined. Results: The attack triggered a Critical Incident Protocol, resulting in the switching off of all HSE IT systems at national level. Disruption to patient care & operations within the HSE was immediate & without warning. Initially encrypted messaging groups were established to facilitate communication & paper based tracking & data management logs were created. Diagnostics, scheduling & radiotherapy services were most severely affected. The attack resulted in the immediate shut down of the hospitals radiotherapy department with all new treatments transferred off site to a private facility, ongoing treatments delayed, replanned or rescheduled. The effect on the radiology department was catastrophic, all outpatient & non-urgent scans were cancelled. Digital report & image stores were unavailable. Historic imaging & ongoing emergency imaging was unavailable. Taking 7 months to restore impacted data storage & to ensure accurate capture of all reports for examinations during the cyber downtime. The average time from surgery to completed pathology went from 7.04 to 15.03 & 11.8 days in the 4 weeks prior, during & after the attack respectively. Services that were least impacted during the IT outage were those that relied on paper records including chemotherapy administration. The average time from biopsy report to up front surgery decreased from 21.75 to 17 & 14 days in the 4 weeks prior, during & after the attack respectively. Likely due to the increased availability of theatre time, as all non cancer related elective procedures were cancelled. There was little effect on the time from MDT discussion to review by medical oncology, taking an average of 6, 5.7 & 5.8 days in the 4 weeks prior, during & after the attack respectively. The majority of new referrals to the service being seen off site in a satellite clinic & infusion unit that relied on a paper based booking system prior to the attack. Conclusions: The cyber attack had significant disruptive effects lasting months. The impact on patient outcome due to delayed or interrupted treatment will take years to clarify. The attack was facilitated by the presence of multiple, fragmented IT platforms & demonstrated a lack of preparedness in the system which needs to be addressed to prevent recurrence.
    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: 2022
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 15, No. 7 ( 1997-07), p. 2762-2762
    Abstract: The institution affiliation section on page 1638 of the April 1997 article entitled, "Treatment of Advanced Hodgkin's Disease With Chemotherapy—Comparison of MOPP/ABV Hybrid Regimen With Alternating Courses of MOPP and ABVD: A Report From the National Cancer Institute of Canada Clinical Trials Group" by Connors, et al (J Clin Oncol 15:1638–1645, 1997) was incomplete. The "London Regional Cancer Centre, London, Ontario, Canada" should have been included in the listing of author-affiliated institutions.
    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: 1997
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