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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. TPS507-TPS507
    Abstract: TPS507 Background: No effective therapy is available for patients (pts) with advanced cholangiocarcinoma (CC) after disease progression on first-line chemotherapy. In Phase I studies, pembrolizumab (pem) showed activity in pts with advanced CC. Interferon alpha-2b was shown to increase tumor immune infiltrates. In order to improve the response rate (RR) of pts with CC to pem, we propose to combine sylatron with pem in an open-label, single-arm, multicenter Phase II study. Methods: To be eligible for study, pts must have CC, manifesting as either intrahepatic, extrahepatic or gallbladder cancer that is unresectable, metastatic, and has either failed to respond to or demonstrated progression on frontline chemotherapy. Forty-four pts will be enrolled on study to receive SC sylatron (200 mg) weekly for 12 weeks, and IV pem (200mg) once every 3 weeks, starting on week 4 (at the same time as the 4th dose of sylatron), until pts experience disease progression or unacceptable toxicity, or withdraw consent. CT scans will be performed every 9 weeks. The primary endpoints are overall RR (ORR) and the safety and tolerability of combined pem and sylatron therapy. Secondary endpoints include OS, PFS, and ORR by irRECIST. An initial 3-week window will exist in which to evaluate the effect of sylatron alone (following prior chemotherapy) on the tumor microenvironment: one biopsy (biopsy 1) will be obtained before the start of sylatron therapy, and another (biopsy 2) after the third but before the fourth injection of sylatron (and the initiation of pem plus sylatron combination therapy). The effect of sylatron on the CC immune microenvironment will be studied by comparing biopsies 1 and 2. Immune microenvironment in pem + sylatron responders will be compared with non-responders. The study will assess whether the addition of sylatron improves the RR of pem from 17% to 35% in pts with advanced CC. Simon’s two-stage optimum design will be used to test the null hypothesis that P ≤ 0.17 vs. the alternative hypothesis that P ≥ 0.350. This study design provides 80% power (one-sided significance level of 0.05). The time-to-event endpoints (PFS, OS) will be estimated using Kaplan-Meier methodology.
    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: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 14, No. 11 ( 2007-10-15), p. 3202-3209
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 2074021-9
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 4_suppl ( 2017-02-01), p. 473-473
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 473-473
    Abstract: 473 Background: Neoadjuvant chemotherapy is increasingly being utilized for locally advanced (LAPC)/borderline resectable pancreatic cancer (BRPC); however, long term follow up data is sparse. At our institution, we use FOLFIRINOX as the regimen of choice. Gemcitabine (Gem) and nab-Paclitaxel (Abraxane) is utilized in patients not suited for FOLFIRINOX or if they have poor radiographic response and/or develop significant toxicities to FOLFIRINOX. The aim of this study was to report our institutional experience with neoadjuvant therapy for patients with advanced pancreatic cancer. Methods: A retrospective review was performed of all patients with BRPC or LAPC who received FOLFIRINOX (or a modified regimen), Gem/nab-Paclitaxel, or both prior to surgical resection. FOLFIRINOX was typically given for 4 – 6 cycles while gem/nab-Paclitaxel was given for 2 cycles. Results: From January 2011 to December 2015, 39 patients were identified who met the study criteria. Eight patients received FOLFIRINOX alone (median age 62), 20 patients received FOLFIRINOX + Gem/nab-Paclitaxel, and 11 received only Gem/nab-Paclitaxel (median age 72). Eighteen patients (46%) completed the intended cycles of chemotherapy. Twenty two patients had a radiologic and/or biomarker response. Exploration was performed in 25 of 39 (64%) patients of whom 20 (51%) underwent curative resection. Of the 20 resected patients, there were no post-operative deaths. The median tumor size, median lymph node ratio, and R0 resection rates were 2.4 cm, 0, and 85% for the entire cohort. Median follow up was 20.7 months. The median overall survival for the resected cohort was not reached vs 13.5 months in the no resection group; two year overall survival for the resection vs. no resection groups was 87% vs 16% (p 〈 .001). Conclusions: FOLFIRINOX and/or Gemcitabine/nab-Paclitaxel as neoadjuvant therapy for LAPC/BRPC is fairly well tolerated, leads to appreciable rates of margin negative surgical resection, and a significant overall survival advantage.
    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: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e18614-e18614
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e18614-e18614
    Abstract: e18614 Background: With longer median survival for NET patients, the impact of symptoms and treatments on QOL and financial well-being throughout the disease course need to be evaluated to understand the true burden of the disease on patients. Current HRQOL data are during active treatments and this prospective biobank was established to capture this information throughout the disease course. Methods: At Roswell Park Comprehensive Cancer Center, with Institutional Review Board (IRB) approval a NET biobank was established in April 2019 for collecting clinical tissue samples, patient demographics, treatment outcomes, access to care and self-reported HRQoL outcomes. Using previously developed HRQoL questionnaires, we examined the impact of the NET on the quality of life of NET patients and data of 144 patients enrolled to date in the biobank is presented here. Linear regression was used to assess the association of baseline characters with QoL variables. The analysis was done with STATA/IC 16.0. Results: A total of 144 patients are enrolled. Males were 27% (n = 39) and females were 73% (n = 105). The mean age of diagnosis was 54 +/- 0.79, with those between 45 to 65 (72%, n = 103). These patients were enrolled through support groups and social media from 30 different states in the US (135) and 9 pts from Canada. After the diagnosis, 27% of patients had to quit their job. Impact on major HRQoL variables are summarized in Table. Only 21% of patients reported that they feel knowledgeable about NET and got the majority of their support from their primary care (60%) and oncologist (57%). When asked about the most pressing need from their care team, 57% of patients requested their care team had more information about available clinical trials. Sex, age groups did not have statistically significant association on the impact of NETs on the HRQoL of patients. Conclusions: NET diagnosis affects the HRQoL of patients including their social, emotional, and financial well-being. A national biobank capturing data on various demographic, risk factors, treatment sequence, symptoms, HRQoL parameters, financial toxicity is a valuable resource to better understand the needs of this patient group.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 3_suppl ( 2015-01-20), p. 370-370
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 370-370
    Abstract: 370 Background: Patients with metastatic neuroendocrine tumors (NETs) benefit from treatment with yttrium-90 radioembolization (Y-90) or transarterial chemoembolization (TACE), however the criteria for patient selection are not well defined. We sought to determine if the proliferative index (Ki67 score) could be utilized to select patients for one therapy over the other. Methods: A single institution analysis of all patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 scoring, and the data was analyzed using multivariate association for survival outcomes. Results: Amongst 72 patients (M: 39, F: 33; median age, 57 years) included in the study, the most common site of tumor origin was small bowel (n=35, 49%), and the most common histology subtype was carcinoid (n=58, 85%). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) in the TACE group. In Y-90 group, there was a higher concomitant use of sandostatin (94% vs 75%, p=0.023), longer time between diagnosis and treatment (median, 32 vs 11 months, p= 〈 0.001), and less number of total treatments completed (89% vs 46%, p 〈 0.001). There was no significant difference in overall survival (OS) between the groups (median, 69 vs 82 months, respectively; p=0.477); however when adjusted for Ki67 score of 3, patients with Ki67 score 〉 3% were found to have better OS when treated with Y-90 as compared to TACE (HR, 0.083; CI, 0.008-0.854). On the other hand, in patients with Ki67 〈 3%, OS was better when treated with TACE (HR, 13.5; CI, 1.2-148.8). Further, patients in Y-90 group had higher incidence of carcinoid syndrome (39% vs 21%, p=0.195) and bilobar liver disease (95% vs 89%, p=0.371), whereas hepatic tumor burden 〉 25% was greater in the TACE group (26% vs 20%, p=0.614), but these differences were not significant. Conclusions: In patients with metastatic NETs, Ki-67 score 〉 3% may be predictive of treatment benefit with Y-90 and 〈 3% with TACE. A longer time from diagnosis and an increased number of prior therapies may indicate a need for aggressive therapy; however a prospective validation is 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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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. TPS275-TPS275
    Abstract: TPS275 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in US. The majority of US patients (pts) receive first-line therapy (Rx) with FOLFOX [Folinic acid (FA), 5-fluorouracil (5-FU) and oxaliplatin (Ox)] + a biologic, making FOLFIRI [FA+ 5-FU+ irinotecan (Iri)] + bevacizumab (Bev) a common second-line Rx. This regimen has a median progression-free survival (PFS) of approximately 6 months (mo) and overall survival (OS) of 12 mo. Further gains are desperately needed. Trifluridine/tipiracil (FTD/TPI) is an oral combination Rx of a thymidine-based nucleoside analogue, FTD, and a phosphorylase inhibitor, TPI. FTD/TPI has a distinct mechanism of action from 5-FU and in preclinical models can overcome 5-FU resistance via DNA incorporation, base excision repair pathway and glycosylation responses to DNA damage. Further, there is an additive effect in combination with Iri. FTD/TPI was FDA approved for use in refractory metastatic CRC (mCRC) based on phase III RECOURSE trial. Phase I data showed combination of FTD/TPI, Iri and Bev to be safe, and an efficacy signal was seen in dose-expansion cohort (NCT01916447). A 12.5% response rate, 83.4 % disease control rate and PFS of 7.9 mo was achieved. As this study largely assessed refractory pts, one might expect a greater efficacy in Iri naïve pts. To test this hypothesis, we are conducting a multi-center phase II study of FTD/TPI, Iri and Bev as second-line Rx in mCRC pts. Methods: Eligible pts have mCRC and received first-line Ox based Rx. Rx to be given in 28-day cycles: Iri (180 mg/m 2 ) and Bev (5 mg/kg) on D1 & 15, and FTD/TPI (25 mg/m 2 ) twice daily on D2-6 & 16-20. Response assessment via CT/MRI to be done q8 wks (RECIST 1.1). Rx to continue until disease progression or unacceptable toxicity. The primary objective is to estimate PFS. Secondary objectives include ORR, OS, and safety. Final analysis to be done either 12 mo after enrollment of the final pt or once all pts have progression, whichever occurs earlier. A total of 40 pts to be accrued, and enrollment to start in January 2020. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14659-e14659
    Abstract: e14659 Background: To retrospectively evaluate the outcome of borderline resectable (BR) and locally advanced unresectable (LA) pancreatic cancer patients treated with concurrent chemoradiotherapy (CRT) with gemcitabine (G) or capecitabine (C). Methods: Retrospective chart review of patients treated between August 2005 and September 2011 generated 30 BR and 40 LA pts. Cases were analyzed for patient and treatment characteristics including age, gender, weight loss, ECOG PS, albumin, stage, grade, location, pathology, laboratory values, chemotherapy (CT) regimens, radiotherapy dose and technique, and toxicity using CTCAE v.4.0. Endpoints evaluated were surgical resection rate, progression free survival (PFS), and median overall survival (mOS). Results: Patient characteristics were comparable between CRT/G and CRT/C in both BR and LA patients. Gemcitabine iv 300mg/m 2 weekly or capecitabine po 825mg/m 2 BID were used during CRT. Among BR patients who received CRT (n=21), 17 (56.6%) received CRT/G, 4 (13.3%) CRT/C, and others received CT alone. For BR, surgical resection was performed in 52.9% of CRT/G patients. The PFS were 17.4 months (m) and 4.8m (p=0.009), and mOS were 21.9m and 5.7m (p=0.004) for CRT/G and CRT/C respectively. For LA patients who received CRT (n=25), 18% of CRT/G underwent surgical resection and none of CRT/C did. The PFS 8.4m and 10.4m (p=0.63) and mOS were 14.9m and 11.5m (p=0.11) for CRT/G and CRT/C respectively. Comparing CRT and CT groups, mOS were not significantly different for LA patients, and longer for BR patients (14.4m vs. 5.5m) although this is likely due to confounding factors such as physician preference and patient selection. No significant differences were noted for grade 3/4 toxicities between both CRT groups. Conclusions: In this series, CRT/G in both BR and LA setting were associated with a high surgical resection rate with acceptable toxicity and potentially improved survival for patients not felt to be surgical candidates at presentation. These data warrant validation in larger prospective randomized studies.
    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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  • 8
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 4_suppl ( 2018-02-01), p. 834-834
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 4_suppl ( 2018-02-01), p. 834-834
    Abstract: 834 Background: Cetuximab is a chimeric IgG1 anti-EGFR monoclonal antibody approved in RAS-wt metastatic colorectal cancer (mCRC). Pre-clinical data have suggested that cetuximab triggers immunogenic cell death and support an immunologic basis of activity. Small clinical data sets demonstrate that EGFR-based therapy preferentially increases TILs in colorectal hepatic metastases. This Phase Ib/II study was designed to assess the safety and clinical activity of cetuximab and pembrolizumab in metastatic colorectal cancer. Methods: Eligible pts were those with RAS-wt mCRC, ECOG performance status (PS) 0-2, with at least 1 prior line of therapy for advanced stage disease, and no prior treatment with an anti-EGFR antibody. The phase Ib study was designed as a safety lead-in with a de-escalation design. Pembrolizumab was administered at a fixed dose of 200 mg q3week with standard cetuximab dosing (400 mg/m2 loading dose, followed by 250 mg/m2 weekly). DLTs were defined as any ≥ grade 3 clinically significant toxicity which is possibly related and occurs within the first 6 weeks of therapy. For rash and hypomagnesemia only ≥ grade 4 toxicities were considered DLTs. Correlative serial biopsies were performed at baseline and at 9 weeks. Results: 9 patients, ages 33-73, were enrolled onto the Phase Ib study between 8/10/16 and 11/2/16. No DLTs were observed. The most common AEs of any cause observed were xerosis, dermatitis acneiform rash, hypomagnesemia, vomiting, and fatigue. ≥ Grade 3 toxicities were uncommon, but included hypomagnesemia (3), rash (1), urticaria (1), hypocalcemia (1), alk phos elevation (1), and ascites (1). 6/9 patients achieved stable disease lasting ≥ 16 weeks. Conclusions: The combination of cetuximab and pembrolizumab is well-tolerated in this study and can be administered at full dosages. Though hypomagnesemia appears prominent, no additional emergent AEs have been observed during or following the DLT period. The associated ongoing phase II study will enroll an additional 33 patients to assess the true efficacy of this regimen with dual primary endpoints of ORR and 6 month PFS. Clinical trial information: NCT02713373.
    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: 2018
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 4_suppl ( 2012-02-01), p. 300-300
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 300-300
    Abstract: 300 Background: There are limited modalities in the treatment of inoperable liver NET metastases. This study compares the efficacy and safety of liver-directed yttrium-90 microspheres, SIR-spheres, to TACE. Methods: Medical records and axial imaging studies were retrospectively reviewed for all patients with NET liver metastases who underwent SIR or doxorubicin based TACE at our institution from Jan 2001 to Dec 2010. The demographics, immediate effects, and time to radiologic progression were assessed and compared between the two treatment modalities. Results: A total of 99 liver directed treatments were performed on 46 pts (n=19 Y-90, n=27 TACE). Median post-treatment follow-up was 20 months (range 4-103). Pt characteristics including age, performance status, type of primary NET, and systemic therapy were similar in both groups. Pts in the SIR group waited longer from the time of metastatic diagnosis to liver-directed therapy (SIR 35 mo vs. TACE 15 mo (p=0.0015)). SIR patients had less liver burden (65% with 〈 25% liver burden) than TACE patients (23% with 〈 25% liver burden). Immediate treatment response (1-3 mo) was measured radiologically using WHO criteria multiplied by EASL criteria. SIR pts achieved 26% complete response (CR), 51% partial response (PR), 15% stable disease (SD), and 8% progressive disease (PR). TACE pts achieved 13% CR, 59% PR, 8% SD, and 21% PD. SIR (44 mo) had a longer radiologic effect than TACE (12 mo) (p=0.015). SIR patients underwent less treatments (95% with 〈 2 treatments) than TACE patients (70% with 〈 2 treatments) (p=0.045). Both treatments were well tolerated with minimal side effects. With only 11/46 (25%) deaths, there was no statistically significant difference in overall survival between the two groups at a median follow up of 104 months (range 12-267). Conclusions: Liver metastasis from NETs can be successfully treated with yttrium-90 radioembolization. Earlier intervention using SIR allows fewer treatments with more durable responses. Prospective studies controlling for rate of disease progression and disease burden 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: 2012
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 4083-4083
    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: 2018
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