Skip to main content
Erschienen in: Annals of Surgical Oncology 8/2010

01.08.2010 | Pancreatic Tumors

Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration

verfasst von: Francesco Polistina, MD, Giorgio Costantin, MD, Franco Casamassima, MD, PhD, Paolo Francescon, Rosabianca Guglielmi, MD, Gino Panizzoni, MD, Antonio Febbraro, MD, Giovanni Ambrosino, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 8/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

Pancreatic cancer accounts for approximately 3% of cancer deaths in Europe. Locally advanced pancreatic cancer (LAPC) involves vascular structures, and resectability is low, with a median survival time of 6 to 11 months. We conducted a prospective, nonrandomized study of patients with LAPC to assess the effect of stereotactic body radiotherapy (SBRT) on local response, pain control, and quality of life (QOL).

Methods

Twenty-three patients with histologically confirmed LAPC underwent SBRT. Radiotherapy (30 Gy) was delivered in three fractions, and treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE v. 3.0). All patients received also gemcitabine chemotherapy and were followed up until death. Local control was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, pain control was assessed with a visual analog scale, and QOL was assessed with the SF-36 instrument (Italian v. 1.6).

Results

No grade 2 or higher acute or late toxicity was observed. The overall local response ratio was 82.6% (14 partial response, 2 complete response, 3 stable disease). SBRT showed a good short-term efficacy in controlling both pain and QOL. Median survival was 10.6 months, with a median follow-up of 9 months. The LAPC became resectable in 8% of the patients. Median time to progression of disease was 7.3 months. Six patients developed early metastatic disease.

Conclusions

The SBRT method is a promising treatment for LAPC. Local control rates, even compared to historical data from conventional radiotherapy, can be achieved with minimal toxicity. Resectability can also be achieved.
Literatur
1.
Zurück zum Zitat Ferlay J, Bray F, Sankila R, Parkin DM. Cancer incidence, mortality and prevalence in the European Union, 1999. Lyon: IARC Press; 1998. Ferlay J, Bray F, Sankila R, Parkin DM. Cancer incidence, mortality and prevalence in the European Union, 1999. Lyon: IARC Press; 1998.
2.
Zurück zum Zitat Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 1.0. Lyon: IARC Press; 2001. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 1.0. Lyon: IARC Press; 2001.
3.
Zurück zum Zitat Roazzi P, Capocaccia R, Santaquilani M, Carrani E, EUROCARE Working Group. Elecronic availability of EUROCARE-3 data: a tool for further analysis. Ann Oncol. 2003;14:v150–5.CrossRefPubMed Roazzi P, Capocaccia R, Santaquilani M, Carrani E, EUROCARE Working Group. Elecronic availability of EUROCARE-3 data: a tool for further analysis. Ann Oncol. 2003;14:v150–5.CrossRefPubMed
4.
Zurück zum Zitat Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.CrossRefPubMed Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.CrossRefPubMed
5.
Zurück zum Zitat Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91:1410–27.CrossRefPubMed Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91:1410–27.CrossRefPubMed
6.
Zurück zum Zitat Kayahara M, Nagakawa T, Ueno K, et al. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer. 1993;72:2118–23.CrossRefPubMed Kayahara M, Nagakawa T, Ueno K, et al. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer. 1993;72:2118–23.CrossRefPubMed
7.
Zurück zum Zitat Hudson E, Hurt C, Mort D, et al. Induction chemotherapy followed by chemoradiation in locally advanced pancreatic cancer: an effective and well-tolerated treatment. Clin Oncol (R Coll Radiol). 2010;22:27–35. Hudson E, Hurt C, Mort D, et al. Induction chemotherapy followed by chemoradiation in locally advanced pancreatic cancer: an effective and well-tolerated treatment. Clin Oncol (R Coll Radiol). 2010;22:27–35.
8.
Zurück zum Zitat Turrini O, Viret F, Moureau-Zabotto L, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35:1306–11.PubMed Turrini O, Viret F, Moureau-Zabotto L, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35:1306–11.PubMed
9.
Zurück zum Zitat Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.PubMed Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.PubMed
11.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed
12.
Zurück zum Zitat Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil. The Gastrointestinal Tumor Study Group. Cancer. 1981;48:1705–10.CrossRefPubMed Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil. The Gastrointestinal Tumor Study Group. Cancer. 1981;48:1705–10.CrossRefPubMed
14.
Zurück zum Zitat Koong AC, Christofferson E, Le QT, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63:320–3.PubMed Koong AC, Christofferson E, Le QT, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63:320–3.PubMed
15.
Zurück zum Zitat Wilkowski R, Thoma M, Weingandt H, Dühmke E, Heinemann V. Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose. JOP. 2005;6:216–30.PubMed Wilkowski R, Thoma M, Weingandt H, Dühmke E, Heinemann V. Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose. JOP. 2005;6:216–30.PubMed
16.
Zurück zum Zitat Chang DT, Shellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed Chang DT, Shellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.CrossRefPubMed
17.
Zurück zum Zitat Hoyer M, Roed H, Sengelov L, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76:48–53.CrossRefPubMed Hoyer M, Roed H, Sengelov L, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76:48–53.CrossRefPubMed
18.
Zurück zum Zitat Shellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72:678–86. Shellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72:678–86.
19.
Zurück zum Zitat Rezai P, Mulcahy MF, Tochetto SM, Berggruen S, Yaghmai V. Morphological analysis of pancreatic adenocarcinoma on multidetector row computed tomography: implications for treatment response evaluation. Pancreas. 2009;38:799–803.CrossRefPubMed Rezai P, Mulcahy MF, Tochetto SM, Berggruen S, Yaghmai V. Morphological analysis of pancreatic adenocarcinoma on multidetector row computed tomography: implications for treatment response evaluation. Pancreas. 2009;38:799–803.CrossRefPubMed
20.
Zurück zum Zitat White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg. 2001;5:626–33.CrossRefPubMed White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg. 2001;5:626–33.CrossRefPubMed
21.
Zurück zum Zitat Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.PubMed Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.PubMed
22.
Zurück zum Zitat Huang PI, Chao Y, Li CP, et al. Efficacy and factors affecting outcome of gemcitabine concurrent chemoradiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2009;73:159–65.PubMed Huang PI, Chao Y, Li CP, et al. Efficacy and factors affecting outcome of gemcitabine concurrent chemoradiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2009;73:159–65.PubMed
23.
Zurück zum Zitat Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.CrossRefPubMed Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.CrossRefPubMed
24.
Zurück zum Zitat Igarashi H, Ito T, Kawabe K, et al. Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer. World J Gastroenterol. 2008;14:5311–5.CrossRefPubMed Igarashi H, Ito T, Kawabe K, et al. Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer. World J Gastroenterol. 2008;14:5311–5.CrossRefPubMed
25.
Zurück zum Zitat Spry N, Harvey J, Macleod C, et al. 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. Int J Radiat Oncol Biol Phys. 2008;70:1438–46.PubMed Spry N, Harvey J, Macleod C, et al. 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. Int J Radiat Oncol Biol Phys. 2008;70:1438–46.PubMed
26.
Zurück zum Zitat Blackstock AW, Bernard SA, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol. 1999;17:2208–12.PubMed Blackstock AW, Bernard SA, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol. 1999;17:2208–12.PubMed
27.
Zurück zum Zitat Waldmann A, Dreckschmidt J, Pritzkuleit R, Katalinic A. Test-retest reliability of the OVIS questionnaire—an instrument to evaluate oncological care from a patient’s point of view. Gesundheitswesen. 2010;[Epub ahead of print]. Waldmann A, Dreckschmidt J, Pritzkuleit R, Katalinic A. Test-retest reliability of the OVIS questionnaire—an instrument to evaluate oncological care from a patient’s point of view. Gesundheitswesen. 2010;[Epub ahead of print].
28.
Zurück zum Zitat Laenen A, Alonso A. The Functional Living Index—Cancer: estimating its reliability based on clinical trial data. Qual Life Res. 2010;19:103–9.CrossRefPubMed Laenen A, Alonso A. The Functional Living Index—Cancer: estimating its reliability based on clinical trial data. Qual Life Res. 2010;19:103–9.CrossRefPubMed
29.
Zurück zum Zitat McGinn CJ, Zalupski MM, Shureiqi I, et al. Phase I trial of dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001;19:4202–8.PubMed McGinn CJ, Zalupski MM, Shureiqi I, et al. Phase I trial of dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001;19:4202–8.PubMed
30.
Zurück zum Zitat Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP. 2006;7:349–60.PubMed Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP. 2006;7:349–60.PubMed
31.
Zurück zum Zitat Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005;201:359–65.CrossRefPubMed Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005;201:359–65.CrossRefPubMed
32.
Zurück zum Zitat Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg. 2000;135:81–7.CrossRefPubMed Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg. 2000;135:81–7.CrossRefPubMed
33.
Zurück zum Zitat Maximous DW, Abdel-Wanis ME, El-Sayed MI, Abd-Elsayed AA. Preoperative gemcitabine based chemo-radiotherapy in locally advanced non metastatic pancreatic adenocarcinoma. Int Arch Med. 2009;2:7.CrossRefPubMed Maximous DW, Abdel-Wanis ME, El-Sayed MI, Abd-Elsayed AA. Preoperative gemcitabine based chemo-radiotherapy in locally advanced non metastatic pancreatic adenocarcinoma. Int Arch Med. 2009;2:7.CrossRefPubMed
34.
Zurück zum Zitat Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer. 2000;89:314–27.CrossRefPubMed Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer. 2000;89:314–27.CrossRefPubMed
Metadaten
Titel
Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration
verfasst von
Francesco Polistina, MD
Giorgio Costantin, MD
Franco Casamassima, MD, PhD
Paolo Francescon
Rosabianca Guglielmi, MD
Gino Panizzoni, MD
Antonio Febbraro, MD
Giovanni Ambrosino, MD, PhD
Publikationsdatum
01.08.2010
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 8/2010
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1019-y

Weitere Artikel der Ausgabe 8/2010

Annals of Surgical Oncology 8/2010 Zur Ausgabe

Update Chirurgie

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

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.