Intraoperative Irradiation

Second edition

Current Clinical OncologyMaurie Markman, MD, Series Editor

For other titles published in this series, go tohttp://www.springer.com/series/7631

Leonard L. Gunderson • Christopher G. Willett Felipe A. Calvo • Louis B. Harrisoneditors

Intraoperative Irradiation

Techniques and Results

Second edition

EditorsLeonard L. Gunderson, M.D., M.S., FASTRoDepartment of Radiation oncology Mayo Clinic College of Medicine and Mayo Clinic Arizona, Scottsdale, AZ USAllg.scottsdale@cox.net

Christopher G. Willett, M.D. Department of Radiation oncology Duke University Medical Center Durham, NC USAchristopher.willett@duke.edu

Felipe A. Calvo, M.D. Department of oncology Hospital Gregorio Maranón Madrid, Spainfcalvo.hgugm@salud.madrid.org

Louis B. Harrison, M.D., FASTRo Department of Radiation oncologyContinuum Cancer Centers of New York Beth Israel Medical Center, St Luke’s and Roosevelt Hospitals, Albert einstein College of Medicine, New York, NY USAlharriso@chpnet.org

ISBN 978-1-61779-014-0 e-ISBN 978-1-61779-015-7DoI 10.1007/978-1-61779-015-7Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2011924474

© Springer Science+Business Media, LLC 2011All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Humana Press is part of Springer Science+Business Media (www.springer.com)

To Katheryn, my wife and best friend, to our children and their spouses (Chad and Chrissy, Whitney and Jeff, Stacie and Nick, Ryan and Danna, Scott and Cindy) and to our grandchildren (Olivia and Adam; Rebecca, Andrew, Katie and Matthew; Sam, Anna, Michael and Ellie; Grant; Landon and Parker) for their love and support

To colleagues in Surgery, Medical Oncology, and Radiation Oncology for the opportunity to work together as a team in the delivery of multimodality treatment, including IORT, for our patients with cancer

Leonard L. Gunderson

To Mary Sunday for 25 years of love and support

Christopher G. Willett

To my family: wife Marta and children Almudena, Marta, Maria, Covadonga, Felipe-Angel, Sonsoles, Francisco and Paloma; beloved parents Lucia and Felipe, brother Elpidio and sister Tuti; my first love, the school of values in which I learned to understand and serve society

To my teachers, especially Dr Jose Otero and Professor Luther W Brady, with deep gratitude for the privilege of their superb and caring education

To colleagues and institutions involved in IORT procedures during the last three decades for their outstanding and generous commitment to excellence in cancer medicine.

Felipe A. Calvo

To my 6 favorite kids, my 2 daughters, 3 nephews and 1 niece: Barbara Harrison, Michella Harrison, Alan Levy, Ryan Farago, Lance Levy and Sophia Levy. I love all of them and have been lucky to have them in my life.

Louis B. Harrison

vii

Preface

Intraoperative Irradiation: Techniques and Results, Second Edition is a comprehensive textbook on intraoperative irradiation therapy (IoRT) that covers topics of interest to those who have intraopera-tive electron radiation therapy (IoeRT), high-dose-rate brachytherapy (HDR-IoRT) or electronic brachytherapy/low KV IoRT capabilities. Issues of basic science and physics are covered in addi-tion to techniques, indications, and results by disease-site. Most disease-site chapters have multina-tional and multidisciplinary authorship that includes both radiation oncologists and surgeons, which provides a more balanced presentation of techniques and results by disease-site.

The rationale for using IoRT as a component of treatment is based on the realization that tolerable doses of external beam radiation therapy (eBRT) are often insufficient to achieve local control of locally advanced abdominal or pelvic malignancies, even with 3-D conformal or intensity-modulated radiation techniques (3-D CRT; IMRT). A preferred treatment approach is to deliver preoperative eBRT of 45–54 Gy in 1.8–2 Gy fractions, often in conjunction with concurrent chemotherapy, followed by maximal surgical resection and IoRT. The IoRT component of treatment becomes the optimal conformal technique of irradiation, since dose-limiting organs or structures can either be surgically displaced (stomach, small intestine, liver, etc.) or protected by surgical placement of lead shielding or by proper selection of electron energy.

The textbook is again divided into five major sections. The book begins with chapters on the general rationale for and historical perspectives of IoRT and the radiobiology of IoRT. It then pro-ceeds to a discussion of methods and techniques of treatment and a presentation of normal tissue and organ tolerance to IoRT. In the methods and techniques section, a new chapter is included on “electronic Brachytherapy/Low KV IoRT: Physics and Techniques” which is a possible alternative IoRT treatment approach. The tolerance chapter is essential reading for any individual or institution contemplating a program in IoRT; the implications of tolerance are far-reaching both for the patients who receive IoRT as a component of treatment and the physicians who deliver the IoRT. The largest section of the text is the presentation of techniques and results by disease-site which includes outcomes data on disease control, survival, and treatment tolerance. outcomes with non-IoRT treatment approaches are compared with those using IoRT-containing regimens in many of the chapters. The closing section is a chapter on conclusions and future possibilities that was written by the four coeditors of the textbook.

one of the conclusions of the closing chapter is that long-term experience has shown that the use of IoRT as a component of treatment in conjunction with other modalities (eBRT, concurrent and maintenance chemotherapy, maximal surgical resection) is feasible and practical if close multidis-ciplinary cooperation exists. In addition, the IoRT-containing, multimodality regimens appear to improve local disease control, if not survival, in many disease-sites when compared with non-IoRT treatment approaches. For patients in whom gross total resection of their cancer is not safely fea-sible, the ability to achieve central or local control is lessened, thus creating the need for prospective clinical trials that address the addition of radiation dose modifiers during both eBRT and IoRT.

viii Preface

Patients with locally advanced or locally recurrent cancers who are candidates for IoRT containing regimens often have high systemic risks as well. Prospective trials that address the addition of aggressive systemic therapy to the locally aggressive combined treatment are also necessary. The closing chapter also addresses improvements in technology that make IoRT more feasible in a larger number of institutions and thus facilitate the conduct of prospective trials in a multi-institu-tion national or international setting. This technology includes mobile IoeRT equipment (Mobetron, Novac-7, LIAC), HDR brachytherapy, and electronic brachytherapy/low-KV equipment that can be used in either an outpatient or operating room setting.

The four coeditors have personally been involved in utilizing IoRT as a component of treatment in the care of thousands of patients in a multispecialty, multimodality setting. We are therefore delighted that IoRT is becoming available to more physicians and patients worldwide as a result of the changes in technology that are discussed in Intraoperative Irradiation: Techniques and Results, Second Edition.

Scottsdale, AZ, USA Leonard L. Gunderson, M.D., M.S., FASTRoDurham, NC, USA Christopher G. Willett, M.D.Madrid, Spain Felipe A. Calvo, M.D.New York, NY, USA Louis B. Harrison, M.D., FASTRo

ix

Contents

Part I General Rationale and Historical Perspective

1 Rationale and Historical Perspective of Intraoperative Irradiation ............................. 3Leonard L. Gunderson, Felipe A. Calvo, Christopher G. Willett, and Louis B. Harrison

2 Biology of Large Dose per Fraction Irradiation ............................................................. 27Paul okunieff, Srinath Sundararaman, Su Metcalfe, and Yuhchyau Chen

Part II Methods and Techniques of Treatment

3 Intraoperative Electron Beam Irradiation: Physics and Techniques ............................ 51Peter Biggs, Christopher G. Willett, Harm Rutten, Mario Ciocca, Leonard L. Gunderson, and Felipe A. Calvo

4 HDR-IORT: Physics and Techniques ............................................................................... 73eli e. Furhang, Jussi K. Sillanpaa, Kenneth S. Hu, and Louis B. Harrison

5 Electronic Brachytherapy/Low KV-IORT: Physics and Techniques ............................ 85Uta Kraus-Tiefenbacher, Peter Biggs, Jayant Vaidya, and Dario Francescatti

6 IORT with Electron-Beam, High-Dose-Rate Brachytherapy or Low-KV/Electronic Brachytherapy: Methodological Comparisons ........................ 99Subir Nag, Christopher G. Willett, Leonard L. Gunderson, Louis B. Harrison, Felipe A. Calvo, and Peter Biggs

Part III Normal Tissue Tolerance – IORT

7 Normal-Tissue Tolerance to IOERT, EBRT, or Both: Animal and Clinical Studies ........................................................................................................... 119Zeljko Vujaskovic, Christopher G. Willett, Joel e. Tepper, Timothy J. Kinsella, and Leonard L. Gunderson

x Contents

Part IV Results of IORT Alone or Plus EBRT by Disease Site

8 Central Nervous System Tumors .................................................................................... 141David ortiz de Urbina, Patrick Schueller, Normann Willich, Kintomo Takakura, osami Kubo, and Felipe A. Calvo

9 Head and Neck Cancer .................................................................................................... 163Kenneth S. Hu, Sue Yom, Michael J. Kaplan, Rafael Martinez-Monge, and Louis B. Harrison

10 Breast Cancer ................................................................................................................... 189Felix Sedlmayer, Jean-Bernard DuBois, Roland Reitsamer, Gerd Fastner, David olilla, and Roberto orecchia

11 Lung Cancer ..................................................................................................................... 201Javier Aristu, Felipe A. Calvo, Marta Moreno, Rafael Martínez, Jesús Herreros, Maria esperanze Rodriguez, Jean-Bernard DuBois, and Scott Fisher

12 Gastric Cancer ................................................................................................................. 223Rafael Martinez-Monge, Miren Gaztañaga, Javier Álvarez-Cienfuegos, Robert C. Miller, and Felipe A. Calvo

13 Pancreas Cancer .............................................................................................................. 249Robert C. Miller, Vincenzo Valentini, Adyr Moss, Giuseppe R. D’Agostino, Matthew D. Callister, Theodore S. Hong, Christopher G. Willett, and Leonard L. Gunderson

14 Bile Duct and Gallbladder Cancer ................................................................................. 273Takeshi Todoroki, Gernot M. Kaiser, Wolfgang Sauerwein, and Leonard L. Gunderson

15 Primary Colorectal Cancer ............................................................................................. 297Nils D. Arvold, Theodore S. Hong, Christopher G. Willett, Paul C. Shellito, Michael G. Haddock, Harm Rutten, Vincenzo Valentini, Felipe A. Calvo, Brian Czito, and Leonard L. Gunderson

16 Recurrent Colorectal Cancer .......................................................................................... 323Michael G. Haddock, Heidi Nelson, Vincenzo Valentini, Leonard L. Gunderson, Christopher G. Willett, Harm Rutten, Felipe A. Calvo, Louis B. Harrison, Warren enker, and J.L. Garcia-Sabrido

17 Retroperitoneal Sarcomas ............................................................................................... 353Brian Czito, John Donohue, Christopher G. Willett, Doug Tyler, Ivy A. Petersen, Robert Krempien, Kenneth S. Hu, Felipe A. Calvo, Matthew D. Callister, Kaled M. Alektiar, Michael eble, and Ana Alvarez

18 Extremity and Trunk Soft-Tissue Sarcomas ................................................................. 387Ivy A. Petersen, Robert Krempien, Christopher Beauchamp, Michael eble, Felipe A. Calvo, Ignacio Azinovic, Matthew D. Callister, and Ana Alvarez

xiContents

19 Bone Sarcomas ................................................................................................................. 407Felipe A. Calvo, Luis Sierrasesumaga, Ana Patiño, Carmen González, Manuel González, Carlos Ferrer, Normann Willich, and José Cañadell

20 Gynecologic Malignancies ............................................................................................... 431Kaled M. Alektiar, Michael G. Haddock, Dennis Chi, Felipe A. Calvo, and Ivy A. Petersen

21 Genitourinary Cancer ..................................................................................................... 459Marco Krengli, Felipe A. Calvo, Carlo Terrone, Michael G. Haddock, Jean-Michel Hannoun-Levi, Juliette Thariat, Jean-Pierre Gerard, and Roberto orecchia

22 Pediatric Malignancies .................................................................................................... 481Nadia N. Issa Laack, Paula J. Schomberg, Suzanne Wolden, and Jesus Vazquez

Part V Conclusions and Future Possibilities

23 Conclusions and Future Possibilities: IORT ................................................................. 503Leonard L. Gunderson, Christopher G. Willett, Felipe A. Calvo, and Louis B. Harrison

Index .......................................................................................................................................... 519

xiii

Contributors

Kaled M. Alektiar, M.D. Department of Radiation oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ana Alvarez, M.D. Department of oncology, University Hospital Gregorio Maranón, Madrid, Spain

Javier Álvarez-Cienfuegos, M.D. Department of Surgery, Navarra University Clinic, Pamplona, Spain

Javier Aristu, M.D. Department of Radiation oncology, Navarra University Clinic, Pamplona, Spain

Nils D. Arvold, M.D. Department of Radiation oncology, Massachusetts General Hospital, Boston, MA, USA

Ignacio Azinovic, M.D. Department of Radiation oncology, Navarra University Clinic, Pamplona, Spain

Christopher Beauchamp, M.D. Department of orthopedic oncology, Mayo Clinic, Scottsdale, AZ, USA

Peter Biggs, Ph.D. Department of Physics, Massachusetts General Hospital, Boston, MA, USA

Matthew D. Callister, M.D. Department of Radiation oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA

Felipe A. Calvo, M.D. Department of oncology, Hospital Gregorio Maranón, Madrid, Spain

José Cañadell, M.D, Ph.D. emaritus Professor, Department of orthopedic Surgery, Clinica Universitaria de Navarra, Pamplona, Spain

Yuhchyau Chen, M.D., Ph.D. Department of Radiation oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

Dennis Chi, M.D. Department of Gynecologic oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

xiv Contributors

David Ortiz de Urbina, M.D. Department of Radiation oncology, Institutu onkologikoa of Guipuzcoa, San Sebastian, Spain

Mario Ciocca, Ph.D. Division of Medical Physics, european Institute of oncology, Milan, Italy

Brian Czito, M.D. Department of Radiation oncology, Duke University Medical Center, Durham, NC, USA

Giuseppe R. D’Agostino, M.D. Department of Radiotherapy, Universita Cattolica del Sacro Cuore, Rome, Italy

John Donohue, M.D. Department of General Surgery, Mayo Clinic, Rochester, MN, USA

Jean-Bernard DuBois, M.D. Department of Radiotherapy, Centre Regional de Lutte Contre Le Cancer (CRLC), Montpellier, France

Michael Eble, M.D. Department of Radiation oncology, Aachen University, Aachen, Germany

Warren Enker, M.D. Surgical oncology, Beth Israel, New York, NY, USA

Gerd Fastner, M.D. Department of Radiotherapy and Radio-oncology, Paracelsus Medical University Clinics, Salzburg, Austria

Carlos Ferrer, M.D. Institute of oncology, Hospital Provincial de Castellón, Castellón, Spain

Scott Fisher, M.D. Department of Radiation oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA

Dario Francescatti, M.D., J.D. Department of Surgery, Rush Medical Center, Chicago, IL, USA

Eli E. Furhang, Ph.D. Department of Radiation oncology, Continuum Cancer Centers of New York, Beth Israel Medical Center, St Luke’s and Roosevelt Hospitals, Albert einstein College of Medicine, New York, NY, USA

J.L. Garcia-Sabrido, M.D. Surgical oncology, Hospital Gregorio Maranón, Madrid, Spain

Miren Gaztañaga, M.D. Department of Radiation oncology, University of Navarra, Avda Pío XII, Pamplona, Spain

Jean-Pierre Gerard, M.D. Department of Radiation oncology, Centre Antoine Lacassagne, Nice, France

Carmen González, M.D. Department of Radiation oncology, Hospital Gregorio Maranón, Madrid, Spain

Manuel González, M.D. Department of Radiation oncology, Hospital Gregorio Maranón, Madrid, Spain

xvContributors

Leonard L. Gunderson, M.D., M.S. Department of Radiation oncology, Mayo Clinic College of Medicine and Mayo Clinic Arizona, Scottsdale, AZ, USA

Michael G. Haddock, M.D. Department of Radiation oncology, Mayo Clinic, Rochester, MN, USA

Jean-Michel Hannoun-Levi, M.D. Department of Radiation oncology, Centre Antoine Lacassagne, Nice, France

Louis B. Harrison, M.D. Department of Radiation oncology, Continuum Cancer Centers of New York, Beth Israel Medical Center, St Luke’s and Roosevelt Hospitals, Albert einstein College of Medicine, New York, NY, USA

Jesús Herreros, M.D. Department of Cardiovascular Surgery, Clínica Universitaria de Navarra, Pamplona, Spain

Theodore S. Hong, M.D. Department of Radiation oncology, Massachusetts General Hospital, Boston, MA, USA

Kenneth S. Hu, Ph.D. Department of Radiation oncology, Continuum Cancer Centers of New York, Beth Israel Medical Center, St Luke’s and Roosevelt Hospitals, Albert einstein College of Medicine, New York, NY, USA

Gernot M. Kaiser, M.D. Department of General, Visceral and Transplantation Surgery, University Hospital essen, essen, Germany

Michael J. Kaplan, M.D. Department of otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA

Timothy J. Kinsella, M.D., M.S. Department of Radiation oncology, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA

Uta Kraus-Tiefenbacher, M.D. Department of Radiation oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

Robert Krempien, M.D. Department of Radiation oncology, University of Heidelberg, Heidelberg, Germany

Marco Krengli, M.D. Department of Radiotherapy, University of Piemonte orientale, Novara, Italy

Osami Kubo, M.D. Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

Nadia N. Issa Laack, M.D., M.S. Department of Radiation oncology, Mayo Clinic, Rochester, MN, USA

Rafael Martinez-Monge, M.D. Department of Radiation oncology, Navarra University Clinic, Pamplona, Spain

xvi Contributors

Su Metcalfe, M.D, M.P.H Department of Radiation oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

Robert C. Miller, M.D. Department of Radiation oncology, Mayo Clinic, Rochester, MN, USA

Marta Moreno, M.D. Department of Radiation oncology, Navarra University Clinic, Pamplona, Spain

Adyr Moss, M.D. Division of General Surgery Mayo Clinic in Arizona, Scottsdale, AZ, USA

Subir Nag, M.D. Department of Radiation oncology, Northern California Kaiser Permanente, Santa Clara, CA, USA

Heidi Nelson, M.D. Department of Colorectal Surgery, Mayo Clinic, Rochester, MN, USA

Paul Okunieff, M.D. Department of Radiation oncology, University of Florida, Gainesville, FL, USA

David Olilla, M.D. Department of Surgery, Division of Surgical oncology and endocrine Surgery, University of North Carolina, USA

Roberto Orecchia, M.D. Department of Radiotherapy, european Institute of oncology, Milan, Italy

Ana Patiño, M.D. Department of Pediatrics, Clínica Universitaria de Navarra, Pamplona, Spain

Ivy A. Petersen, M.D. Department of Radiation oncology, Mayo Clinic, Rochester, MN, USA

Roland Reitsamer, M.D. Department of Special Gynecology/Breast Unit, General Hospital, Paracelsus Medical University Clinics, Salzburg, Austria

Maria Esperanza Rodriguez, M.D. Department of Radiation oncology, Navarra University Clinic, Pamplona, Spain

Harm Rutten, M.D. Department of Surgery, Catharina Hospital, eindhoven, The Netherlands

Wolfgang Sauerwein, M.D. Department of Radiation oncology, University Hospital essen, essen, Germany

Paula J. Schomberg, M.D. Department of Radiation oncology, Mayo Clinic, Rochester, MN, USA

Patrick Schueller, M.D. Competence Center for oncology of the Medical Service of the German Health Insurances, Duesseldorf, Germany

Felix Sedlmayer, M.D. Department of Radiotherapy and Radio-oncology, Paracelsus Medical University Clinics, Salzburg, Austria

xviiContributors

Paul C. Shellito, M.D. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Luis Sierrasesumaga, M.D. Department of Pediatrics, Clínica Universitaria de Navarra, Pamplona, Spain

Jussi K. Sillanpaa, Ph.D. Department of Radiation oncology, Continuum Cancer Centers of New York, Beth Israel Medical Center, St Luke’s and Rooseuelt Hospital, Albert einstein College of Medicine, New York, NY, USA

Srinath Sundararaman, M.D. Radiation oncology Branch, National Cancer Institute, Hollywood, FL, USA

Kintomo Takakura, M.D. Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan

Joel E. Tepper, M.D. Department of Radiation oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Carlo Terrone, M.D. Department of Urology, University of Piemonte orientale, Novara, Italy

Juliette Thariat, M.D. Department of Radiation oncology, Centre Antoine Lacassagne, Nice, France

Takeshi Todoroki, M.D. Department of Surgery, Kita-ibaraki Municipal General Hospital, Kita-Ibaraki, Japan

Doug Tyler, M.D. Division of General Surgery, Duke University Medical Center, Durham, NC, USA

Jayant Vaidya, M.D. Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London, UK

Vincenzo Valentini, M.D. Radiation oncology, Polyclinico Universitario A. Gemelli, Rome, Italy

Jesus Vazquez, M.D. Department of Pediatric Surgery, Hospital General Universitario Gregorio Marañon, Madrid, Spain

Zeljko Vujaskovic, M.D., Ph.D. Department of Radiation oncology, Duke University Medical Center, Durham, NC, USA

Christopher G. Willett, M.D. Radiation oncology, Duke University, Durham, NC, USA

Normann Willich, M.D. Department of Radiation oncology, University Hospital Muenster, Muenster, Germany

Suzanne Wolden, M.D. Department of Radiation oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Sue Yom, M.D. Department of Radiation oncology, University of California, San Francisco, CA, USA