Intraoperative Irradiation. Second edition

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2 Intraoperative Irradiation Second edition

3 Current Clinical Oncology Maurie Markman, MD, Series Editor For other titles published in this series, go to

4 Leonard L. Gunderson Christopher G. Willett Felipe A. Calvo Louis B. Harrison Editors Intraoperative Irradiation Techniques and Results Second edition

5 Editors Leonard L. Gunderson, M.D., M.S., Fastro Department of Radiation Oncology Mayo Clinic College of Medicine and Mayo Clinic Arizona, Scottsdale, AZ USA Christopher G. Willett, M.D. Department of Radiation Oncology Duke University Medical Center Durham, NC USA Felipe A. Calvo, M.D. Department of Oncology Hospital Gregorio Maranón Madrid, Spain Louis B. Harrison, M.D., FASTRO 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 lharriso@chpnet.org ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2011 All 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 (

6 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

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8 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 intraoperative 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 addition to techniques, indications, and results by disease-site. Most disease-site chapters have multinational 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 Gy in 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 proceeds 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 noniort 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 multidisciplinary 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 feasible, 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. vii

9 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-institution 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 Durham, NC, USA Madrid, Spain New York, NY, USA Leonard L. Gunderson, M.D., M.S., FASTRO Christopher G. Willett, M.D. Felipe A. Calvo, M.D. Louis B. Harrison, M.D., FASTRO

10 Contents Part I General Rationale and Historical Perspective 1 Rationale and Historical Perspective of Intraoperative Irradiation... Leonard L. Gunderson, Felipe A. Calvo, Christopher G. Willett, and Louis B. Harrison 3 2 Biology of Large Dose per Fraction Irradiation... Paul Okunieff, Srinath Sundararaman, Su Metcalfe, and Yuhchyau Chen 27 Part II Methods and Techniques of Treatment 3 Intraoperative Electron Beam Irradiation: Physics and Techniques... Peter Biggs, Christopher G. Willett, Harm Rutten, Mario Ciocca, Leonard L. Gunderson, and Felipe A. Calvo 51 4 HDR-IORT: Physics and Techniques... Eli E. Furhang, Jussi K. Sillanpaa, Kenneth S. Hu, and Louis B. Harrison 73 5 Electronic Brachytherapy/Low KV-IORT: Physics and Techniques... Uta Kraus-Tiefenbacher, Peter Biggs, Jayant Vaidya, and Dario Francescatti 85 6 IORT with Electron-Beam, High-Dose-Rate Brachytherapy or Low-KV/Electronic Brachytherapy: Methodological Comparisons... Subir Nag, Christopher G. Willett, Leonard L. Gunderson, Louis B. Harrison, Felipe A. Calvo, and Peter Biggs Part III 7 99 Normal Tissue Tolerance IORT Normal-Tissue Tolerance to IOERT, EBRT, or Both: Animal and Clinical Studies... Zeljko Vujaskovic, Christopher G. Willett, Joel E. Tepper, Timothy J. Kinsella, and Leonard L. Gunderson 119 ix

11 x Contents Part IV Results of IORT Alone or Plus EBRT by Disease Site 8 Central Nervous System Tumors... David Ortiz de Urbina, Patrick Schueller, Normann Willich, Kintomo Takakura, Osami Kubo, and Felipe A. Calvo Head and Neck Cancer... Kenneth S. Hu, Sue Yom, Michael J. Kaplan, Rafael Martinez-Monge, and Louis B. Harrison Breast Cancer... Felix Sedlmayer, Jean-Bernard DuBois, Roland Reitsamer, Gerd Fastner, David Olilla, and Roberto Orecchia Lung Cancer... Javier Aristu, Felipe A. Calvo, Marta Moreno, Rafael Martínez, Jesús Herreros, Maria Esperanze Rodriguez, Jean-Bernard DuBois, and Scott Fisher Gastric Cancer... Rafael Martinez-Monge, Miren Gaztañaga, Javier Álvarez-Cienfuegos, Robert C. Miller, and Felipe A. Calvo Pancreas Cancer... Robert C. Miller, Vincenzo Valentini, Adyr Moss, Giuseppe R. D Agostino, Matthew D. Callister, Theodore S. Hong, Christopher G. Willett, and Leonard L. Gunderson Bile Duct and Gallbladder Cancer... Takeshi Todoroki, Gernot M. Kaiser, Wolfgang Sauerwein, and Leonard L. Gunderson Primary Colorectal Cancer... Nils 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 Recurrent Colorectal Cancer... Michael 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 Retroperitoneal Sarcomas Brian 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... Ivy A. Petersen, Robert Krempien, Christopher Beauchamp, Michael Eble, Felipe A. Calvo, Ignacio Azinovic, Matthew D. Callister, and Ana Alvarez 387

12 Contents xi 19 Bone Sarcomas... Felipe A. Calvo, Luis Sierrasesumaga, Ana Patiño, Carmen González, Manuel González, Carlos Ferrer, Normann Willich, and José Cañadell Gynecologic Malignancies... Kaled M. Alektiar, Michael G. Haddock, Dennis Chi, Felipe A. Calvo, and Ivy A. Petersen Genitourinary Cancer... Marco Krengli, Felipe A. Calvo, Carlo Terrone, Michael G. Haddock, Jean-Michel Hannoun-Levi, Juliette Thariat, Jean-Pierre Gerard, and Roberto Orecchia Pediatric Malignancies... Nadia N. Issa Laack, Paula J. Schomberg, Suzanne Wolden, and Jesus Vazquez 481 Part V 23 Conclusions and Future Possibilities Conclusions and Future Possibilities: IORT... Leonard L. Gunderson, Christopher G. Willett, Felipe A. Calvo, and Louis B. Harrison 503 Index

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14 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 xiii

15 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

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