Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Annals of Surgical Oncology
Erschienen in: Annals of Surgical Oncology 9/2017

12.06.2017 | Pancreatic Tumors

A Prospective Phase II Trial of Neoadjuvant S-1 with Concurrent Hypofractionated Radiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma

verfasst von: Keiichi Okano, MD, PhD, FACS, Hironobu Suto, MD, Minoru Oshima, MD, PhD, Eri Maeda, MD, Naoki Yamamoto, MD, PhD, Keitaro Kakinoki, MD, PhD, Hideki Kamada, MD, PhD, Tsutomu Masaki, MD, PhD, Shigeo Takahashi, MD, Toru Shibata, MD, PhD, Yasuyuki Suzuki, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 9/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

The ideal neoadjuvant treatment protocol for patients with pancreatic cancer (PDAC) remains unclear. We evaluated the efficacy and safety of neoadjuvant hypofractionated chemoradiotherapy with S-1 for patients with resectable (R) and borderline resectable (BR) PDAC.

Methods

Eligibility criteria included patients with R and BR PDAC, performance status 0–1, and age 20–85 years. Hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) was delivered 5 days/week for 2 weeks prior to pancreatectomy.

Results

Fifty-seven patients were enrolled in this study, including 33 R and 24 BR [19 BR tumors with portal vein contact (BR-PV) and 5 BR tumors with arterial contact (BR-A)]. The total rates of protocol treatment completion and resection were 91% (50/57) and 96% (55/57), respectively. Seven patients failed to complete S-1 due to cholangitis (n = 5) or neutropenia (n = 2). The most common grade 3 toxicities [Common Terminology Criteria for Adverse Events (CTCAE) version 4.0] were anorexia (7%), nausea (5%), neutropenia (4%), and leukopenia (4%). No patient experienced grade 4 toxicity. Pathologically negative margins (R0) were achieved in 54 of 55 patients (98%) who underwent pancreatectomy. Pathological response was classified as Evans grade I in 8 patients (15%), IIa in 31 patients (56%), IIb in 14 patients (25%), III in 1 patient (2%), and IV in 1 patient (2%), and operative morbidity (Clavien-Dindo grade IIIb or less) was observed in 4 patients (8%). The 1- and 2-year overall survival (OS) rates were 91 and 83% in R patients, respectively, and 77 and 58% in BR patients, respectively (p = 0.03).

Conclusion

Neoadjuvant S-1 with concurrent hypofractionated radiotherapy is tolerable and appears promising for patients with R and BR PDAC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62(1):10–29.CrossRefPubMed
2.
Wray CJ, Ahmad SA, Matthews JB, et al. Surgery for pancreatic cancer: recent controversies and current practice. Gastroenterology 2005; 128(6):1626–41.CrossRefPubMed
3.
4.
Willett CG, Lewandrowski K, Warshaw AL, et al. Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann Surg 1993; 217(2):144–8.CrossRefPubMedPubMedCentral
5.
Evans DB, Pisters PW, Lee JE, et al. Preoperative chemoradiation strategies for localized adenocarcinoma of the pancreas. J Hepatobiliary Pancreat Surg 1998; 5(3):242–50.CrossRefPubMed
6.
Verma V, Li J, Lin C. Neoadjuvant therapy for pancreatic cancer: systematic review of postoperative morbidity, mortality, and complications. Am J Clin Oncol 2016; 39(3):302–313.CrossRefPubMed
7.
Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010; 7(4):e1000267.CrossRefPubMedPubMedCentral
8.
Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 2016; 388(10041):248–57.CrossRefPubMed
9.
Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013; 310(14):1473–81.CrossRefPubMed
10.
Cloyd JM, Crane CH, Koay EJ, et al. Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Cancer 2016; 122(17):2671–9.CrossRefPubMed
11.
Kim EJ, Ben-Josef E, Herman JM, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer 2013; 119(15):2692–700.CrossRefPubMedPubMedCentral
12.
Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008; 26(21):3487–95.CrossRefPubMed
13.
Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008; 26(21):3496–502.CrossRefPubMed
14.
Cloyd JM, Katz MH, Prakash L, et al. Preoperative therapy and pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a 25-year single-institution experience. J Gastrointest Surg 2017; 21(1):164–74.CrossRefPubMed
15.
16.
Ueno H, Ioka T, Ikeda M, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 2013; 31(13):1640–8.CrossRefPubMed
17.
Ikeda M, Okusaka T, Ito Y, et al. A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer. Br J Cancer 2007; 96(11):1650–5.CrossRefPubMedPubMedCentral
18.
Shinchi H, Maemura K, Noma H, et al. Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer. Br J Cancer 2007; 96(9):1353–7.PubMedPubMedCentral
19.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240(2):205–13.CrossRefPubMedPubMedCentral
20.
Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138(1):8–13.CrossRefPubMed
21.
Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007; 142(5):761–8.CrossRefPubMed
22.
Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 1992; 127(11):1335–9.CrossRefPubMed
23.
Staley CA, Cleary KR, Abbruzzese JL, et al. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas 1996; 12(4):373–80.CrossRefPubMed
24.
O’Reilly EM, Perelshteyn A, Jarnagin WR, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg 2014; 260(1):142–8.CrossRefPubMedPubMedCentral
25.
Takeda Y, Nakamori S, Eguchi H, et al. Neoadjuvant gemcitabine-based accelerated hyperfractionation chemoradiotherapy for patients with borderline resectable pancreatic adenocarcinoma. Jpn J Clin Oncol 2014; 44(12):1172–80.CrossRefPubMed
26.
Ohigashi H, Ishikawa O, Eguchi H, et al. Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg 2009; 250(1):88–95.CrossRefPubMed
27.
Pisters PW, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 1998; 16(12):3843–50.CrossRefPubMed
28.
Pisters PW, Wolff RA, Janjan NA, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol 2002; 20(10):2537–44.CrossRefPubMed
29.
Talamonti MS, Small W, Jr., Mulcahy MF, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol 2006; 13(2):150–8.CrossRefPubMed
30.
Chun YS, Cooper HS, Cohen SJ, et al. Significance of pathologic response to preoperative therapy in pancreatic cancer. Ann Surg Oncol 2011; 18(13):3601–7.CrossRefPubMed
31.
Wang H, Zhao Q. Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with better prognosis. Ann Diagn Pathol 2012; 16(5):427.CrossRefPubMed
32.
Christians KK, Heimler JW, George B, et al. Survival of patients with resectable pancreatic cancer who received neoadjuvant therapy. Surgery 2016; 159(3):893–900.CrossRefPubMed
33.
Lee SM, Katz MH, Liu L, et al. Validation of a proposed tumor regression grading scheme for pancreatic ductal adenocarcinoma after neoadjuvant therapy as a prognostic indicator for survival. Am J Surg Pathol 2016; 40(12):1653–1660.CrossRefPubMed
34.
Mellon EA, Jin WH, Frakes JM, et al. Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy. Acta Oncol 2016;56(3):391–397.CrossRefPubMed
35.
Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012; 118(23):5749–56.CrossRefPubMed
36.
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364(19):1817–25.CrossRefPubMed
37.
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369(18):1691–703.CrossRef
38.
Palmer DH, Stocken DD, Hewitt H, et al. A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol 2007; 14(7):2088–96.CrossRefPubMed
39.
Heinrich S, Pestalozzi BC, Schafer M, et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008; 26(15):2526–31.CrossRefPubMed
40.
Sahora K, Kuehrer I, Eisenhut A, et al. NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery 2011; 149(3):311–20.CrossRefPubMed
41.
Lee JL, Kim SC, Kim JH, et al. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery 2012; 152(5):851–62.CrossRefPubMed
42.
Motoi F, Ishida K, Fujishima F, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg Oncol 2013;20(12):3794–801.CrossRefPubMed
43.
Yeung RS, Weese JL, Hoffman JP, et al. Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A phase II study. Cancer 1993; 72(7):2124–33.PubMed
44.
Hoffman JP, Lipsitz S, Pisansky T, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol 1998; 16(1):317–23.CrossRefPubMed
45.
Moutardier V, Giovannini M, Lelong B, et al. A phase II single institutional experience with preoperative radiochemotherapy in pancreatic adenocarcinoma. Eur J Surg Oncol 2002; 28(5):531–9.CrossRefPubMed
46.
Magnin V, Moutardier V, Giovannini MH, et al. Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer. Int J Radiat Oncol Biol Phys 2003; 55(5):1300–4.CrossRefPubMed
47.
Mornex F, Girard N, Scoazec JY, et al. Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: the French SFRO-FFCD 97-04 phase II trial. Int J Radiat Oncol Biol Phys 2006; 65(5):1471–8.CrossRefPubMed
48.
Turrini O, Viret F, Moureau-Zabotto L, et al. Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in patients with resectable pancreatic head adenocarcinoma: a ten-year single institution experience. Oncology 2009; 76(6):413–9.CrossRefPubMed
49.
Chakraborty S, Morris MM, Bauer TW, et al. Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer. Gastrointest Cancer Res 2014; 7(1):15–22.PubMedPubMedCentral
50.
Casadei R, Di Marco M, Ricci C, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg 2015; 19(10):1802–12.CrossRefPubMed
51.
Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol 2015; 191(1):7–16.CrossRefPubMed
Metadaten
Titel
A Prospective Phase II Trial of Neoadjuvant S-1 with Concurrent Hypofractionated Radiotherapy in Patients with Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma
verfasst von
Keiichi Okano, MD, PhD, FACS
Hironobu Suto, MD
Minoru Oshima, MD, PhD
Eri Maeda, MD
Naoki Yamamoto, MD, PhD
Keitaro Kakinoki, MD, PhD
Hideki Kamada, MD, PhD
Tsutomu Masaki, MD, PhD
Shigeo Takahashi, MD
Toru Shibata, MD, PhD
Yasuyuki Suzuki, MD, PhD
Publikationsdatum
12.06.2017
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 9/2017
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-5921-4

Weitere Artikel der Ausgabe 9/2017

Annals of Surgical Oncology 9/2017 Zur Ausgabe

Hepatobiliary Tumors

LiMAx Test Improves Diagnosis of Chemotherapy-Associated Liver Injury Before Resection of Colorectal Liver Metastases

Endocrine Tumors

Disease Progression in Papillary Thyroid Cancer with Biochemical Incomplete Response to Initial Therapy

Gastrointestinal Oncology

Risk Factors for Poor Compliance with Adjuvant S-1 Chemotherapy for Gastric Cancer: A Multicenter Retrospective Study

Breast Oncology

The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer

Breast Oncology

Impact of Bilateral Prophylactic Mastectomy and Immediate Reconstruction on Health-Related Quality of Life in Women at High Risk for Breast Carcinoma: Results of the Mastectomy Reconstruction Outcomes Consortium Study

Gastrointestinal Oncology

Comparison of Long-Term Outcomes After Non-curative Endoscopic Resection in Older Patients with Early Gastric Cancer

Neu im Fachgebiet Chirurgie

23.04.2024 | Ablationstherapie | Nachrichten

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 | Appendizitis | Nachrichten

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 | Operationsvorbereitung | Nachrichten

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

19.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Ureterstriktur: Innovative OP-Technik bewährt sich
weitere anzeigen

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.