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      Advanced pancreatic adenocarcinoma outcomes with transition from devolved to centralised care in a regional Cancer Centre

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          Abstract

          Background:

          Previous observations suggest suboptimal ‘real world' survival outcomes for advanced pancreatic adenocarcinoma. We hypothesized that centralisation of advanced pancreatic adenocarcinoma management would improve chemotherapy treatment and survival from the disease.

          Methods:

          The data was prospectively collected on all cases of advanced pancreatic adenocarcinoma reviewed through Clatterbridge Cancer Centre according to two groups; 1 October 2009–31st Dec 2010 (devolved care) or 1 January 2013–31 March 2014 (centralised care). Analysis included treatment received, 30-day chemotherapy mortality rate and overall survival (OS).

          Results:

          More patients received chemotherapy with central care (67.0% ( n=115) vs 43.0% ( n=121); P=2.2 × 10 −4) with no difference in 30-day mortality (20.8% vs 25% P=0.573) but reduced time to commencement of chemotherapy (18 vs 28 days, P=1.0 × 10 −3). More patients received second-line chemotherapy with central care (23.4% vs 1.9%, P=1.4 × 10 −4), while OS was significantly increased with central care (median: Five vs three months, HR 0.785, P=0.045). Exploratory analysis suggested that it was those with a poorer performance status, elderly or with metastatic disease who benefited the most from transition to central care.

          Conclusions:

          A centralised clinic model for advanced pancreatic cancer management resulted in prompt, safe and higher use of chemotherapy compared with devolved care. This was associated with a modest survival benefit. Prospective studies are required to validate the findings reported and the basis for improved survival with centralised care.

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          Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.

          William Steward, Srinivasan Madhusudan, Gemma Nanson … (2014)
          We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible patients were treatment naive, aged older than 18 years, with locally advanced or metastatic pancreatic ductal adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned (1:1:1) to receive either chemotherapy alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments were allocated with equal probability by means of computer-generated random permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six cycles of gemcitabine (1000 mg/m(2), 30 min intravenous infusion, at days 1, 8, and 15) and capecitabine (830 mg/m(2) orally twice daily for 21 days, repeated every 28 days). Sequential chemoimmunotherapy included two cycles of combination chemotherapy, then an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 (0·56 mg; days 1, 3, and 5, once on weeks 2-4, and six monthly thereafter). Concurrent chemoimmunotherapy included giving GV1001 from the start of chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall survival; analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN4382138. The first patient was randomly assigned to treatment on March 29, 2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 1062 were randomly assigned to treatment (358 patients were allocated to the chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 patients still alive were followed up for a median of 6·0 months (IQR 2·4-12·2). Median overall survival was not significantly different in the chemotherapy group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 7·1-8·8] vs 6·9 months [6·4-7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97-1·48, p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 7·3-9·7], HR 1·05, 98·25% CI 0·85-1·29, p=0·64; overall log-rank of χ(2)2df=4·3; p=0·11). The commonest grade 3-4 toxic effects were neutropenia (68 [19%] patients in the chemotherapy group, 58 [17%] patients in the sequential chemoimmunotherapy group, and 79 [22%] patients in the concurrent chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the concurrent chemoimmunotherapy group). Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy. Cancer Research UK and KAEL-GemVax. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database.

            David J. Bentrem, Jamie Ritchey, Karl Bilimoria … (2007)
            With the development of stage-specific treatments for pancreatic cancer, controversies exist concerning optimal clinical and pathologic staging. The most recent edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 6(th) Edition included some notable modifications. In anticipation of the 7(th) edition's publication, the authors evaluated the predictive ability of the current pancreatic adenocarcinoma staging system. By using the National Cancer Data Base (1992-1998), 121,713 patients were identified with pancreatic adenocarcinoma. All patients were restaged by AJCC 6(th) edition guidelines. Stage-specific overall survival was estimated by using the Kaplan-Meier method and compared with log-rank tests. Concordance indices were calculated to evaluate the discriminatory power of the staging system. Cox modeling was used to determine the relative impact of T, N, and M classification on survival. For all patients, there was 5-year survival discrimination by stage (P < .0001). For patients who underwent pancreatectomy, stage predicted 5-year survival: stage IA, 31.4%; IB, 27.2%; IIA, 15.7%; IIB, 7.7%; III, 6.8%; IV, 2.8% (P < .0001). The concordance index for the staging system was 0.631 for all patients, 0.613 for those who underwent pancreatectomy, and 0.596 for patients who did not undergo resection. In patients who underwent pancreatectomy, tumor size, nodal status, and distant metastases were independent predictors of survival (P < .0001). This is the first large-scale validation of the pancreatic cancer staging system. AJCC 6(th) edition staging guidelines are accurate with respect to survival. Further investigation is needed to integrate new molecular and biochemical markers into the staging scheme.
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              Impact of centralization of pancreatic cancer surgery on resection rates and survival.

              G A Gooiker, V. Lemmens, M Besselink … (2014)
              Centralization of pancreatic surgery has been shown to reduce postoperative mortality. It is unknown whether resection rates and survival have also improved. The aim of this study was to analyse the impact of nationwide centralization of pancreatic surgery on resection rates and long-term survival.
              Article 0 comments Cited 74 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Journal ID (iso-abbrev): Br. J. Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Print): 14 February 2017
                Publication date (Electronic): 12 January 2017
                Volume: 116
                Issue: 4
                Pages: 424-431
                Affiliations
                [1 ]Department of Medical Oncology, Clatterbridge Cancer Centre , Bebington, Wirral CH63 4JY, UK
                [2 ]Department of Molecular and Clinical Cancer Medicine, University of Liverpool , Liverpool L69 3BX, UK
                [3 ]Clinical Effectiveness Team, Clinical Governance Department, Clatterbridge Cancer Centre , Bebington CH63 4JY, UK
                Author notes
                Article
                Publisher Item ID: bjc2016406
                DOI: 10.1038/bjc.2016.406
                PMC ID: 5318965
                PubMed ID: 28081546
                SO-VID: 0d8f62e1-ce09-4b97-9cf5-832714ae5314
                Copyright © Copyright © 2017 Cancer Research UK
                License:

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                Date received : 04 July 2016
                Date revision received : 21 October 2016
                Date accepted : 14 November 2016
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: adenocarcinoma,advanced,centralised,chemotherapy,pancreatic,survival,supportive care,30-day mortality
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: adenocarcinoma, advanced, centralised, chemotherapy, pancreatic, survival, supportive care, 30-day mortality

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