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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. 365-365
    Abstract: 365 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stroma and connective tissue growth factor (CTGF) overexpression. Although prolonged overall survival (OS) can be achieved through resection, only approximately 15% to 20% of patients are treated with surgery. Previously, pamrevlumab (P), a fully human monoclonal antibody blocking CTGF, was combined with gemcitabine/erlotinib (G/E) in a study of advanced PDAC. P plasma levels of 〉 150 μg/mL and low baseline CTGF levels resulted in prolonged OS. We hypothesize that neoadjuvant (NA) treatment of LAPC with P + G/nab-paclitaxel (NP) may alter LAPC’s stroma, increase R0 resectability, and improve OS similar to that of patients resectable at presentation. Methods: LAPC subjects, confirmed by NCCN criteria and staging laparoscopy, were randomized 2:1 to G/NP ± P for 6-cycle/24-week treatment. Safety and efficacy (resection rate, OS, progression-free survival, tumor response) were assessed. Resection was performed in subjects who met protocol-defined criteria with no contraindications. Results: As of 26 Sep 2016, 25 subjects were enrolled. Of 14 subjects in Arm A (G/NP + P), 7 completed, 2 discontinued. Of 11 subjects in Arm B (G/NP), 4 completed, 4 discontinued. 6 subjects (43%) in Arm A and 4 (36%) in Arm B experienced SAEs; no P-related SAEs were reported. Out of 7 eligible Arm A subjects, 3 were not resected. Successful resection was achieved in 4 Arm A subjects (3 R0, 1 R1) and 1 Arm B subject (R0) (Table). Conclusions: The combination of G/NP + P is feasible and well-tolerated with no incremental safety signals in this study. The addition of P suggests a trend toward increased resectability among LAPC subjects. Clinical trial information: NCT02210559. [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: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 321-321
    Abstract: 321 Background: As neoadjuvant therapy of locally advanced, borderline resectable pancreatic cancer (BRPC) is becoming more widely utilized; better indicators of progression are needed to help guide therapeutic decisions. The aim of this study is to determine if CA19-9 response during treatment predicts disease progression. Methods: A retrospective review was performed on all patients with BRPC (by AHPBA/SSO consensus criteria) between 2008-2015 who received 24 weeks of neoadjuvant gemcitabine and docetaxel. Patients with medical comorbidities limiting treatment completion were excluded. Serum CA19-9 levels were checked at baseline and every 3 weeks while on therapy. A normal CA19-9 level was defined as 〈 37.5 units/mL and levels with concomitant biliary obstruction were censored. CA19-9 response was analyzed as a predictor of disease progression, recurrence, and survival. Results: Eighty patients were included with a mean of 11 CA19-9 levels checked per patient during treatment. Thirty-two (40%) progressed on treatment (18 local and 14 distant) and 48 (60%) were resected (79% R0). CA19-9 responses were categorized into 5 groups: 1) Always normal [n = 13]; 2) Increasing [n = 3] ; 3) Slow decline [n = 7]; 4) Rapid decline with plateau [n = 41] : and 5)Rapid decline with late rise [n = 16]. Univariate logistic regression analysis found that a final CA19-9 decline 〉 50% of baseline (OR 0.06, p = 〈 .0001), a normal final CA19-9 (OR 0.08, p = 〈 .0001), pattern group 1 (OR 0.16, p =.0001), and group 4 (OR 0.10, p =.0001) were predictive of non-progression. Baseline or maximum CA19-9 levels were not predictive of progression. All patients in group 2 progressed; none were resected. Patients in pattern group 5 that underwent resection had an increased risk of recurrence (HR 12.5, p =.0005). Median overall survival for groups 1-5 were 20.4, 9.3, 20.8, 31.4, and 16.4 months respectively. Conclusions: Patients with measurable CA19-9 levels who do not have rapid decline with sustained low or normal levels should be considered high risk for progression or recurrence and alternative treatment strategies should be entertained prior to curative resection.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 236-236
    Abstract: 236 Background: The optimum approach to maximize R0 resection rate in BRPC is unknown. We evaluated an approach in BRPC using extended duration neoadjuvant CT, typically without neoadjuvant CRT to assess R0 resection rate on an "intent to treat"basis. Methods: Patients (pts) were identified from a prospectively-maintained database from 2008-2012. Pts required (1) BRPC per radiographic staging using NCCN/AHPBA criteria, (2) no prior PC therapy (rx) PC, (3) negative staging laparoscopy prior to rx, and (4) all cancer rx at VMMC prior to decision on "downstaging" surgery (S). Pts were initially treated with gemcitabine/docetaxel CT until (a) disease progression, or (b) 24 weeks (wks), before assessment for local rx. Pts with systemic progression and/or inability to complete 24 wks of CT were excluded from local rx; pts with localized cancer at 24 wks judged unlikely to achieve R0 resection were offered 5FU-based CRT then reassessed; all other pts were offered S. Results: Of 70 identified pts, 12/70 (17%) are on initial CT; 58 are fully evaluable. 51/58 pts (88%) completed 24 wks of CT. Response rates to CT were (a) serologic 42/58 (72%) 〉 50% decline in baseline CA19.9 (median 85%), and (b) radiographic of 47 pts evaluable by RECIST, PR/SD/PD were 60%/32%/8% respectively. 14/58 pts (24%) did not receive local rx (7 intercurrent illness, 7 disease progression). 44/58 pts (76%) were offered local rx- 12/58 (21%) CRT and 32/58 (55%) S. 2 pts receiving CRT later underwent S. CRT. 29 pts (50% total evaluable pts, 85% pts undergoing S) achieved R0 resection;10/29 pts (35%) via en bloc venous resections. 5 pts were inoperable (3 local - subsequently given CRT, 2 systemic). At median f/u of 16 mo, 21/29 (72%) R0 resection pts remain disease free (range 7+-47+mo) along with 4/12 pts (33%) receiving CRT w/o R0 resection (range 12+ -30 mo). 25/58 (43%) fully evaluable pts remain progression free on an "intent to treat" basis. Median OS for all pts is 27 mo (95% CI 15-39 mo); 25/29 R0 resected pts remain alive ( median OS 〉 20 mo). Conclusions: (1) extended neaoadjuvant CT is a feasible approach in BRPC. (2) Gemcitabine/docetaxel has significant activity in localized PC. (3) Neoadjuvant CRT may not be essential to R0 resection in BRPC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 457-457
    Abstract: 457 Background: Curative therapy for PDAC is currently achievable through resection only, but ≤ 15% of patients are candidates for surgery. FG-3019, a recombinant human mAb to connective tissue growth factor (CTGF), plus gemcitabine (G) significantly reduced tumor growth, increased apoptosis and improved survival vs G alone in the KPC mouse model. Higher FG-3019 exposure and lower baseline (BL) CTGF were independently and significantly associated with improved overall median and 1-year survival (OS) in a Ph2a trial with G and erlotinib in stage 3 or 4 PDAC. Neoadjuvant treatment of LAPC with FG-3019 combined with multidrug therapy may change the fibrotic character of LAPC and thus may make it amenable to surgical resection and potentially improve OS. Methods: Patients with unresectable LAPC (confirmed by laparoscopy) are randomized to G/NP ±FG-3019 for 6-cycle/24-week treatment. Safety, efficacy, PK and changes in CT, PET, & CA19.9 from BL through end of treatment (EOT) are assessed. Up to 4 endoscopic ultrasound (EUS) guided core biopsies are collected at BL. Protein microarrays of pre- and post-treatment biopsies are prepared from tumor and stromal cells isolated by laser capture microdissection. Surgical exploration is performed in subjects who achieved the protocol-defined criteria for possible resection. Results: To date, 11 subjects were enrolled with 5 randomized to +FG-3019 arm. There were no complications from laparoscopy or EUS core biopsies that were clinically significant or delayed dosing. Per investigator assessment, no FG-3019-related SAEs were reported, nor any identified toxicity suspected from combination of FG-3019 with chemotherapy. Overall, CA19.9 mean change from BL was −62.7% at Week 8 (n = 8), and target lesions were reduced by 20.6% (n = 6) at Week 16. Three out of 4 subjects had PET SUV max reductions of ≥ 30% at EOT. Additional data from protein microarrays will be presented. Conclusions: Based on the limited data collected so far, this trial design is feasible and the G/NP +FG-3019 combination is well-tolerated and appears to be active. Summary results on surgical exploration of subjects will be provided later. Clinical trial information: NCT02210559.
    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: 2016
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4043-4043
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4043-4043
    Abstract: 4043 Background: The optimal surgical (S) approach to BRPC is unknown. We evaluated an approach to BPRC using extended course chemotherapy (CT) without routine neoadjuvant chemoradiation (CRT). Clinical outcomes were evaluated on an "intent to treat" basis. Methods: Patients (pts) were identified from a prospectively-maintained database started in 2008. Pts required 1) Dx BRPC with non-tail primary per radiographic staging using AHPBA/NCCN guidelines 2) No prior therapy (Rx) 3) Negative staging/exploratory laparoscopy prior to S 4) All cancer Rx at VMMC prior to S. Pts received gemcitabine/docetaxel (G/D) as initial CT. Pts with systemic progression/comorbid complication prior to 24 wks were not offered local Rx; pts with localized cancer at 24 wks judged likely to achieve R0 resection were offered S; all other pts were offered fluoropyrimidine-based CRT. Results: Of 76 identified pts (median age 66), 12 (16%) are on initial CT and not fully evaluable. G/D as sole CT achieved 24 wk disease control in 46/64 (72%) pts and 〉 50% decline in baseline CA 19.9 in 39/55 pts (71%). 53/64 fully evaluable pts (83%) completed 24 wks CT, 11/64 pts (17%) did not (4 systemic progression, 3 Rx- related, 4 intercurrent illness). 50/53 pts attempted local Rx (40 S, 10 CRT, 2 unfit, 1 refused). 30/40 pts (75%) had successful S (all R0), 10/40 pts (25%) had inoperable disease (4 local-subsequently received CRT, 6 systemic). 23/30 pts (77%) have received some form Rx post R0 resection. With median f/o of 20 mo, 23/44 (52%), 17/30 (57%), and 6/14 (43%) receiving any local Rx, S, and CRT-only remain progression free. 13/30 S pts recurred, 3 local (10%) and 10 systemic (33%). 1-yr, 2-yr, 3-yr, and median overall survivals (OS) for fully evaluable pts respectively are 82%, 50%, 36%, and 27 mo. Median OS for pts receiving CT-only (20 pts), CT+CRT (14 pts), and R0 pts are 12 mo, 17 mo, and 〉 20 mo, respectively. 25/30 R0 pts remain alive (range 6-54 mo). Conclusions: 1) Extended neoadjuvant CT without routine neoadjuvant CRT is a feasible approach to BRPC. 2) G/D has significant activity in BRPC. 3) Pretreatment surgical staging combined with the above Rx yields a high probability of R0 resection. 4) OS for both resected and non-resected pt was superior to usual literature comparators.
    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: 2013
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15771-e15771
    Abstract: e15771 Background: Optimum therapy (Rx) for BRPC is unknown. Since 2008, we have used neoadjuvant Rx with extended course chemotherapy (CT) but not routine neoadjuvant chemoradiation (CRT). Initial results were presented in 2013 (Rose et.al. J Clin Oncolabstr 4043). We present updated findings here. Methods: Patients (pts) were prospectively identified in our institutional PC database. Inclusion criteria: 1) bx-proven PC; 2) radiographic staging per AHPBA/NCCN criteria; 3) no prior Rx; 4) negative staging laparoscopy whenever feasible; 5) all neoadjuvant Rx at our institution, 6) followup ≥ 24 weeks (wks) from initial Rx . Unless disease progression or Rx intolerance noted, pts received gemcitabine/docetaxel (G/D) as neoadjuvant CT x 24 weeks . At that time, all pts felt likely to achieve R0 resection offered surgery; other pts offered 5FU –based CRT if medically fit. Results evaluated by "intent to treat". Results: Among 129 pts, characteristics include median age 66 yrs (range 33-88 yrs), ECOG PS 0/1/2+ 86/36/7, 97%/43% venous /arterial involvement. 78% (101/129) pts completed ≥80% intended CT; 38% (6/16) pts age 〉 80 and /or ECOG 2+ (p 〈 0.01) 51% (66/129) pts were resected (44 R0, 22 R1 ≤ 1 mm margin ). 49% (63/129) pts were not (24 disease progression, 17 surgeon decision (anatomy/safety), 11 Rx toxicity/ comorbidity, 6 unresectable at surgery, 5 pt withdrawal). 45% (31/66) and 23% (16/66) resected pts received postop CRT/CT respectively. Median f/u is 47 months (mo). 58% (38/66) resected pts recurred: 18% (12/66) local, 41% (27/66) systemic. For resected pts, median PFS is 25.0 (95% CI: 16.2-32.7) mo, median OS is 37.6 (95% CI: 27.4-58.5) mo. 5-yr OS is 28% ( 95% CI :14-44%). Median OS for non-resected pts is 13.1 (95% CI 10.9-16.9) mo .Median OS for all pts is 22.1 (95% CI: 18.7-28.4) mo. Conclusions: 1.Our series is distinctive with respect to size, use of laparoscopic staging and neoadjuvant G/D CT as standards,and median f/u 2. Pt selection is key; e.g.approach suboptimal for pts 〉 80 yrs/ ECOG PS 2+ 3. Reported OS compares favorably with other BRPC and de novo resectable PC cooperative group results 4. Detailed analysis of our study (e.g. prognostic factors) will aid future clinical research in BRPC.
    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: 2017
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  • 7
    In: Journal of Surgical Oncology, Wiley, Vol. 117, No. 8 ( 2018-06), p. 1655-1663
    Abstract: Although race and socioeconomic status have been shown to affect outcomes in pancreatic ductal adenocarcinoma (PDAC), the impact of rural residence on the delivery of adjuvant therapy (AT) has not been studied. Methods Patients with resected PDAC were identified using the National Cancer Database (NCDB). Individuals were classified as living in a metro area, urban/rural adjacent to a metro area (URA), and urban/rural remote (URR) area. Multivariate logistic regression was used to assess geographic inhabitance as a predictor of receiving AT. Results A total of 32 521 individuals who underwent pancreatectomy for PDAC were identified. Univariate analysis demonstrated individuals in URR areas were less likely to receive adjuvant chemotherapy (ACT) than those living in URA or metro areas (55.3% vs 55.6% vs 58.8%, P  = 0.011). However on multivariate analysis URR inhabitance was no longer a predictor of ACT (OR = 0.911 P  = 0.125) or ART (OR = 0.953 P  = 0.462). Cox proportional hazard modeling demonstrated URR inhabitance remained independently associated with poor OS (HR 1.076; 95% CI [1.008, 1.149], P  〈  0.029). Conclusions URR inhabitance does not impact access to AT, however it is independently associated with a decreased OS. Attention must be focused on optimizing oncologic care to patients with disparate access to healthcare.
    Type of Medium: Online Resource
    ISSN: 0022-4790 , 1096-9098
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1475314-5
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  • 8
    In: Gastrointestinal Endoscopy, Elsevier BV, Vol. 81, No. 5 ( 2015-05), p. AB201-AB202
    Type of Medium: Online Resource
    ISSN: 0016-5107
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2006253-9
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 362-362
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 362-362
    Abstract: 362 Background: Duodenal and ampullary adenocarcinomas are rare gastrointestinal cancers that share similar anatomic location and treatment strategy. We report a single-institution experience regarding the association between clinicopathologic features, treatment, and survival outcomes. Methods: A retrospective review of all patients resected with curative intent for duodenal adenocarcinoma (DUO) between 2005-2015 and ampullary adenocarcinoma (AMP) between 2011-2015 at VMMC was performed. For AMP, histologic subtyping into intestinal (IT) and pancreatobiliary (PB) phenotypes was determined. Demographic and clinicopathologic parameters were compared between DUO and AMP patients using Chi-square test. Overall survival was calculated using Kaplan-Meier analysis and prognostic factors were identified by univariate Cox regression. Results: Patients with DUO (n = 44) presented at higher T-stage (p = 0.002) and with larger tumors (4.35cm vs 2.33cm, p 〈 0.001) than AMP patients (n = 46). DUO patients had a higher rate of surgical complications (68% vs 41%, p = 0.01) with a trend for more pancreatic fistulas (36% vs 20%, p = 0.08). There was no difference in median overall survival between groups. Factors positively influencing survival included Caucasian race (p = 0.02) and normal CA19-9 level at diagnosis (p = 0.01). Tumor factors negatively influencing survival included positive lymph nodes (p = 0.04), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.02). Within AMP, the PB subtype presented at higher T-stage (p = 0.01) and with more positive lymph nodes (p = 0.03) than IT. There was no difference in survival between subtypes. Majority received adjuvant chemotherapy (88.8% in AMP, 76.3% in DUO), fewer received adjuvant radiotherapy (23.3% in AMP, 30% in DUO), but no survival difference was seen. Conclusions: DUO presents with larger tumors and higher T-stage than AMP and is associated with more surgical complications. The PB phenotype has more advanced pathologic features than IT. No survival difference was seen between anatomic locations or subtypes. Better surgical and chemotherapeutic strategies may be needed to overcome high risk features. Longer follow-up with more patients is needed to confirm 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: 2016
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  • 10
    In: The American Journal of Surgery, Elsevier BV, Vol. 213, No. 1 ( 2017-01), p. 94-99
    Type of Medium: Online Resource
    ISSN: 0002-9610
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2003374-6
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