Strahlenther Onkol DOI 10.1007/s00066-015-0832-4

O r i g i n a l A rt i c l e

The use of IMRT in Germany Thorsten Frenzel · Andreas Krüll

Received: 12 November 2014 / Accepted: 3 March 2015 © Springer-Verlag Berlin Heidelberg 2015

Abstract Background  Intensity modulated radiotherapy (IMRT) is frequently used, but there are no data about current frequency regarding specific tumor sites and equipment used for quality assurance (QA). Materials and methods  An online survey about IMRT was executed from April to October 2014 by the collaborative IMRT working group (AK IMRT) of the German Association of Medical Physicists (DGMP). Results  A total of 23 German institutions took part in the survey. Most reports came from users working with Elekta, Varian, and Siemens treatment machines, but also from TomoTherapy and BrainLab. Most frequent IMRT technology was volumetric modulated arc therapy (58.37 %: VMAT/“rapid arc”), followed by step-and-shoot IMRT (14.66 %), dynamic MLC (dMLC: 14.53 %), TomoTherapy (9.25 %), and 3.2 % other techniques. Different commercial hard- and software solutions are available for QA, whereas many institutes still develop their own phantoms. Data of 26,779 patients were included in the survey; 44 % were treated using IMRT techniques. IMRT was most frequently used for anal cancer, (whole) craniospinal irradiation, head and neck cancer, prostate cancer, other tumors in the pelvic region, gynecological tumors (except for breast cancer), and brain tumors.

Dr. rer. nat. Dr. med. T. Frenzel () · PD Dr. med. A. Krüll Universitätsklinikum Hamburg-Eppendorf, Bereich Strahlentherapie, Ambulanzzentrum des UKE GmbH, Martinistraße 52, 20246 Hamburg, Deutschland e-mail: [email protected] PD Dr. med. A. Krüll e-mail: [email protected]

Discussion  An estimated 10 % of all patients treated in 2014 with radiation in Germany were included in the survey. It is representative for the members of the AK IMRT. Conclusion  IMRT may be on the way to replace other treatment techniques. However, many scientific questions are still open. In particular, it is unclear when the IMRT technique should not be used. Keywords  Radiotherapy, intensity-modulated · Guideline · German Society for Radiation Oncology (DEGRO) · German Society of Medical Physicists (DGMP) · Survey Einsatz der IMRT in Deutschland Zusammenfassung Hintergrund  Intensitätsmodulierte Bestrahlungstechniken (IMRT) werden oft eingesetzt. Es gibt jedoch keine Daten über deren Häufigkeit in Abhängigkeit von den Tumorentitäten und welche Geräte für die Qualitätssicherung (QA) zum Einsatz kommen. Materialien und Methoden  Der Arbeitskreis IMRT (AK IMRT) der Deutschen Gesellschaft für Medizinische Physik (DGMP) hat von April bis Oktober 2014 eine Online-Umfrage zu diesem Themenbereich durchgeführt. Ergebnisse  An der Umfrage haben 23 deutsche strahlentherapeutische Einrichtungen teilgenommen. Am häufigsten wurden Therapiegeräte von Elekta, Varian und Siemens angegeben. Ebenso auch Geräte von TomoTherapy, BrainLab und anderen Firmen. Mit 58,37 % waren die volumenmodulierten Rotationstechniken (VMAT/“rapid arc”) am häufigsten, gefolgt von “step-and-shoot”-IMRT (14,66 %), dynamischem MLC (dMLC: 14,53%), TomoTherapy (9,25 %) und 3,2 % anderen Techniken. Meist werden kommerzielle Produkte

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für die QA eingesetzt, viele Einrichtungen bauen jedoch noch eigene Prüfkörper. Es wurden die Daten von 26.779 Patienten in die Umfrage eingebracht. Eine IMRT bekamen 44 % aller Patienten. Mehrheitlich wurde IMRT bei folgenden Tumorentitäten eingesetzt: Analkarzinomen, kraniospinalen Bestrahlungen, Kopf-Hals-Tumoren, Prostatakarzinomen, anderen Tumoren im Beckenbereich, gynäkologischen Tumoren (ohne Mammakarzinome) und Hirntumoren. Diskussion  Geschätzte 10 % aller Patienten, die pro Jahr in Deutschland bestrahlt werden, sind in diese Umfrage eingegangen. Sie ist repräsentativ für die Mitglieder des AK IMRT. Schlussfolgerung  Die IMRT verdrängt andere Bestrahlungstechniken. Wissenschaftliche Fragestellungen hierzu sind jedoch noch offen. Insbesondere ist unklar, wann keine IMRT-Techniken eingesetzt werden sollten. Schüsselwörter  Intensitätsmodulierte Strahlentherapie · Leitlinie · Deutsche Gesellschaft für Radioonkologie (DEGRO) · Deutsche Gesellschaft für Medizinische Physik (DGMP) · Umfrage Introduction Intensity modulated radiotherapy (IMRT) has become part of clinical routine in the last few decades. However, no data about the frequency of IMRT applications in Germany were previously available. For this reason, the collaborative IMRT working group (AK IMRT) of the German Association of Medical Physicists (DGMP) performed an online survey on this topic in 2014 (April through October). The survey included technical aspects like treatment machines, treatment planning systems, etc., as well as medical concerns like indications for the use of IMRT techniques. This information will help determine in which areas IMRT has already become a standard technique. Methods Historical background The Germany Society for Radiation Oncology (DEGRO) started to support the implementation of IMRT in clinical routine by founding a collaborative working group on this topic on 09 September 2001 in the city of Hamburg (heads: Prof. Dr. Dr. J. Debus, PD Dr. A. Krüll). Shortly thereafter, the official AK IMRT of the DGMP was founded on 26 November 2001, also in Hamburg (head: Dr. Dr. Th. Frenzel) which cooperated with the previously existing AK Strahlenschutz (former head: Prof. Dr. L. Bogner). Since then there is at least one scientific meeting of the AK IMRT

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per year. More information can be found on the homepage of the AK IMRT [1]. Previous questionnaires The first survey was done in 2002 by Prof. Dr. B. Poppe, which is available online [1]. At that time, 24 clinics in Germany took part (13 of them university hospitals). These clinics had treated a total of 98 patients, most of them were prostate cancer cases or tumors in the pelvic region. Back then compensators, dynamic multileaf collimators (dMLC) or step-and-shoot MLC were used. Films, ionization chambers, thermoluminescent dosimeters (TLD), BANG® Gel, digital radiographs, and megavoltage imaging systems were used for quality assurance. The next survey followed in 2010 by one of the authors and focused on IMRT quality assurance (QA). At that time 20 clinics took part in the survey [1]. All users of Varian treatment machines (Varian Medical Systems, Inc., Palo Alto, CA, USA) were using dMLC or volumetric modulated arc therapy (VMAT/“rapid arc”), whereas users of Siemens (Siemens Medical Systems, Erlangen, Germany) treatment machines continued with step-and-shoot MLC. The users of Elekta (Elekta AB, Stockholm, Sweden) treatment machines reported about VMAT and step-and-shoot IMRT. Many physicists still reported about custom-made IMRT phantoms. QA was done with ionization chamber arrays, radiochromic films, standard ionization chambers, area detectors, portal imaging systems, TLD, and volumetric detectors. Commercial software products were mainly used. Topics of the questionnaire in 2014 The questionnaire in 2014 was done using web-based formulas created with Google forms (Google, Mountain View, CA, USA). The questions were about the types of treatment machines, IMRT techniques, numbers of patients treated in specific anatomical regions with IMRT, treatment planning systems, dosimeters for QA, dosimetric phantoms, and software used for QA. The survey was confidential so that no published data can be backtracked to a specific clinic. Information about the survey was distributed via a mailing list of the AK IMRT. Every institute was invited to take part in the survey from April to October 2014. Results Institutions that participated in the survey A total of 23 German institutions took part in the questionnaire, 23 of them delivered data about technical aspects of IMRT delivery, 21 also added information about patient-spe-

The use of IMRT in Germany

Fig. 1  Distribution of the treatment machines

cific IMRT applications. The institutes comprised 11 medical practices (“Medizinisches Versorgungszentrum”), 7 private practices, 6 university hospitals, and 6 nonuniversity hospitals. Duplicate responses were possible. Treatment machines The number of treatment machines were nearly equally distributed between Elekta (22 machines), Varian (20 machines), Siemens (19 machines), TomoTherapy (5 machines), BrainLab (2 machines), and 3 machines of other brands (not specified). Details are given in Fig. 1. Manufacturers of the treatment systems were ●● ●● ●● ●● ●●

Elekta AB, Stockholm, Sweden, Varian Medical Systems, Inc., Palo Alto, CA, USA, Siemens Medical Systems, Erlangen, Germany, TomoTherapy, Madison, WI, USA, and BrainLab AG, Feldkirchen, Germany.

Treatment planning systems One institute reported having five different treatment planning systems for IMRT, 1 institute had four, 3 had three, 2 had two, and 16 institutes had only one treatment planning system. The distribution of treatment planning systems for IMRT reported is given in Fig. 2: The manufacturers of the treatment planning systems were ●● Eclipse: Varian Medical Systems, Inc., Palo Alto, CA, USA, ●● Pinnacle, CMS Focus: Philips GmbH, Hamburg, Germany, ●● Masterplan: Nucletron, ●● TomoTherapy: TomoTherapy, Madison, WI, USA, ●● BrainLab: BrainLab AG, Feldkirchen, Germany,

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Fig. 2  Distribution of the treatment planning systems

●● Hyperion: Eberhard Karls University of Tuebingen (UKT), Germany, ●● Monaco: Elekta AB, Stockholm, Sweden, ●● Ray Search: RaySearch Laboratories AB, Stockholm, Sweden, ●● Prowess Panther: Prowess Inc., Concord, CA, USA, and ●● KonRad: Siemens Medical Systems, Erlangen, Germany. IMRT techniques The most frequent IMRT technology mentioned, covering 58.37 % of all cases, was volumetric modulated arc therapy (VMAT), followed by step-and-shoot IMRT (14.66 %), dynamic MLC (dMLC, 14.53 %), TomoTherapy (9.25 %), and 3.2 % of other techniques (not specified). Hard- and software for IMRT quality assurance Different devices are used for IMRT quality assurance (QA). The survey distinguished between different methods for machine QA, patient-specific QA for most of the patients, and such methods that are only used for a limited number of patient-specific cases. The results are given in Fig. 3. Machine QA (according to DIN standards and in-house QA programs) is dominated by the use of ionization chambers, matrix detectors (e.g., ionization chambers, diodes, 2D arrays), built-in megavoltage imaging systems, film dosimetry, and specific detectors like the ArcCheck (Sun Nuclear Corporation, Melbourne, FL, USA), Delta 4 (ScandiDos, Uppsala, Sweden), Octavius (PTW-Freiburg, Freiburg, Germany), or other specific devices. These systems were also used for patient-related QA (Patient QA: executed explicitly for all patients), but less frequently. It is also possible to only use them when needed if there are specific patient-related problems (Specific QA). Only a few institutes explicitly mentioned systems like Compass (IBA Dosimetry GmbH, Schwarzen-

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Fig. 3  Devices for IMRT quality assurance

bruck, Germany), memory film, thermoluminescent dosimeters (TLD), Argus ionization chamber, and the OSL Landauer (Landauer Corporate Office, Glenwood, IL, USA). Also different phantoms were used for QA purposes. Most frequently used are slab phantoms made of RW3 (14 institutes), followed by the commercial Octavius phantom (PTW-Freiburg, Freiburg, Germany) used by 13 institutes, custom-made phantoms (11 institutes), and phantoms made of Perspex (9 institutes). Other phantoms like the Alderson–Rando phantom (The Phantom Laboratory, Salem, NY, USA / 2 institutes), Multicube or Compass (both IBA Dosimetry GmbH, Schwarzenbruck, Germany / 2 and 1 institute) were mentioned less frequently. Most institutes (21) reported using commercial software for dosimetric purposes. There were 12 institutes that used integrated software of the linear accelerator companies, 5 institutes had software for independent monitor unit (MU) calculation, 4 institutes software for film dosimetry, and 2 institutes used their own custom-made software. The following products were mentioned by single institutes only but may also be subsumed under the heading commercial software: Artiscan Aquilab (Aquilab, Loos les Lille, France), Compass (IBA Dosimetry GmbH, Schwarzenbruck, Germany), Delta 4 (ScandiDos, Uppsala, Sweden), ImageJ (National Institutes of Health, USA), OmniPro IMRT (IBA Dosimetry GmbH, Schwarzenbruck, Germany), and Verisoft (PTW-Freiburg, Freiburg, Germany).

treated per year at each institute. A total of 26,779 patients were reported in this survey: 44 % (11,779 patients) received IMRT techniques, 3.4 % proton IMRT (400 patients), and 3.4 % heavy ion IMRT (400 patients). The frequencies of site-specific IMRT applications are shown in Fig. 4: Most patients with anal cancer, craniospinal treatment (Spine), head and neck cancer, prostate cancer, other tumors in the pelvic region (Pelvis), gynecological tumors except of breast cancer (Gyn), and brain tumors (Brain) received IMRT treatment. Also greater than average number of IMRT treatments (All sites) were reported for rectal cancer (Rectum), extracranial stereotactical treatments (Ext. stereo), and other cancer in the thoracic region (Thoracic). Less than the average number of IMRT treatments were reported for lung tumors (Lung), tumors of the extremities, bone metastases (Ossa), breast tumors (Breast), brain metastases (Brain met), and other tumor sites not specified (Other). We wanted to investigate the site-specific frequency of IMRT applications in different institutes. Each institute stated having a specific percentage of IMRT cases for each tumor site. A boxplot of this data is given in Fig. 5. Most institutes treat head and neck, anal, and prostate cancer with IMRT. The variation between IMRT and no IMRT is much larger for other tumor sites.

Frequency of IMRT applications

The 2014 survey included approximately 10 % of all patients treated annually with radiation in Germany. To our knowledge, a more comprehensive study that describes the frequency of IMRT techniques is not available. From this point of view, the answers may be representative for IMRT appli-

Specific numbers of patients receiving and not receiving IMRT applications at specific tumor sites were reported by 21 institutes. The data correspond to the number of patients

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Discussion

The use of IMRT in Germany

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Fig. 4  Site-specific frequencies of IMRT applications. Spine craniospinal tumors, Pelvis other tumors in the pelvic region, Gyn gynecological tumors except of breast cancer, Rectum rectal cancer, Ext. Stereo extracranial stereotactical treatments, Thoracic other cancer in the thoracic region, Other tumor sites not otherwise specified, Ossa bone metastases, Brain met brain metastases

Fig. 5  Boxplot of the site-specific frequency of IMRT in different institutes. Abbreviations as listed in Fig. 4

cations in Germany. But on the other hand, participation in the study was voluntary so that more institutes promoting IMRT techniques may have participated. It is representative for the members of the AK IMRT. Nevertheless, the number of patients receiving IMRT is impressive: from less than 100 patients in 2002, more than 11,000 patients in 2014 received IMRT. From this point of view, IMRT might become the most frequent way to treat patients with radiation in the near future. The IMRT guideline published by DGMP and DEGRO in 2005 [2] could not account for this rapid development and should be adapted. In addition, the use of modifiers / compensators did not play a role in our survey, whereas rotational IMRT / VMAT is currently the most frequent technology [3]. In this context, IMRT has become faster and easier to apply. Several commercial hard- and software products that make IMRT QA safe are now available. From this perspective, one has to think about IMRT applications in general: As they became in many cases as fast and easy as other 3D conformal treatment technologies they can be

applied for many more cases than in the past. The time consumption for IMRT in comparison with conventional 3D conformal therapy was also part of the QUIRO study [4]. Not only curative cases but also palliative cases may benefit from lower doses to organs at risk. This raises the question of the higher costs of IMRT techniques. Health insurance companies may argue that the usage of IMRT to such an extent is not necessary and from a certain point of view one could agree with them: IMRT may not improve survival [5] or only in specific cases [6] and there are no blind studies for all IMRT applications proving that IMRT is distinctly better than other techniques. However, in some cases like head and neck tumors, it was shown that IMRT reduces side effects [7–9] and, thus, allows for better quality of life. In addition, our daily experience shows IMRT achieves dose distributions conforming precisely to the planning target volume and so sparing organs at risk. We consider this as a worthwhile benefit to such an extent that in the future any such blind studies might not be considered ethical. But discussions are still open: What are the longterm effects of low doses given to larger amounts of tissue and more scatter dose to the body? Conclusion IMRT may be on the way to replace other types of therapy. The application of IMRT is widely spread and is already standard treatment for many tumor sites. However, it is still not clear in which indications IMRT should not be used. Acknowledgments  We would like to thank following colleagues participating the online IMRT survey: Dr. rer. nat. Wolfgang Baus (Köln) Dipl.-Ing. Ute Birkenhagen (Pinneberg)

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T. Frenzel, A. Krüll Dr. Eyck Blank (Neuruppin) Dipl.-Phys. Mathias Dierl (Bayreuth) Dr. Jörg Eckardt (Bochum) Dr. Niels Götting (Berlin) Dr.-Ing. Daniel Hummel (Stuttgart) Dr. rer. nat. Thomas Koch (Bamberg) Dr. rer. nat. Ulrike Lambrecht (Erlangen) Prof. Dr. Frank Lohr (Mannheim) Dipl.-Phys. Torsten Peil (Halle/Saale) Dipl.-Ing. (FH) Mathias Pfaender (Berlin) Dipl.-Phys. Marcel Renz (Braunschweig) Dipl.-Ing. Bjørne Riis (Lübeck) Dipl.-Phys. Steffen Rocjor (Cottbus) Dr. Nada Schmidt-Petersen (Stade) PD Dr. Florian Sterzing (Heidelberg) Dipl.-Ing. Sophie Taubner (Nürnberg) M. Sc.. Stefan Waurig (Fürth) Prof. Dr. Ulrich Wolf (Leipzig) We also thank two colleagues who participated anonymously.

Ethical standards statement Conflict of interest T. Frenzel and A. Krüll state that there are no conflicts of interest. The accompanying manuscript does not include studies on humans or animals.

References 1. AK IMRT der DGMP and der DEGRO. www.uke.de/extern/ akimrt/IMRT_Startseite.htm. Accessed 12 March 2015

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2. Leitlinie zur Strahlentherapie mit fluenzmodulierten Feldern (IMRT) (2005) www.degro.org. Accessed 12 March 2015 3. Popple RA, Balter PA (2014) Because of the advantages of rotational techniques, conventional IMRT will soon become obsolete. Med Phys 41:100601 4. Dunst J, Willich N, Sack H, Engenhart-Cabillic R, Budach V, Popp W (2014) The QUIRO Study (assurance of quality and innovation in radiooncology): methodology, instruments and practices. Strahlenther Onkol 190:138–148 5. Gao K, Ding L, Li L (2014) Analysis of clinical efficacy of intensity-modulated radiation therapy and the prognosis factors in advanced cervical cancer. Zhonghua Fu Chan Ke Za Zhi 49:30–35 6. Gandaglia G, Karakiewicz PI, Briganti A, Trinh QD, Schiffmann J, Tian Z et al (2014) Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study. Ann Oncol 25:979–986 7. Jang-Chun L, Jing-Min H, Yee-Min J, Dai-Wei L, Chang-Ming C, Chun-Shu L et al (2014) Comparisons of quality of life for patients with nasopharyngeal carcinoma after treatment with different RT technologies. Acta Otorhinolaryngol Ital 34:241–246 8. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C et al (2011) Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 12:127–136 9. Tribius S, Bergelt C (2011) Intensity-modulated radiotherapy versus conventional and 3D conformal radiotherapy in patients with head and neck cancer: is there a worthwhile quality of life gain? Cancer Treat Rev 37:511–519