ESTRO 35 Abstract Book

ESTRO 35

29 April - 3 May 2016 Turin, Italy

Radiotherapy &Oncology Journal of the European SocieTy for Radiotherapy and Oncology

INFORMATION FOR AUTHORS

ARTICLES should deal with original research or reviews of topics defined in the aims of the journal. Radiotherapy and Oncology publishes original material only. It is therefore understood that the content of the paper has not previously been published in the same or a similar form and that it is not under consideration for publication elsewhere. The act of submitting a manuscript to the journal carries with it the right to publish that paper. Radiotherapy and Oncology uses an online manuscript submission and peer review process. Papers and correspondence should be submitted online at http://www.ees.elsevier.com/ro and the instructions on the site should be closely followed. Authors may submit manuscripts and track their progress to final decision. Reviewers can download manuscripts and submit their reports to the Editors electronically.

The full contact details for the Editorial Office are shown below:

Professor Jens Overgaard, M.D., Radiotherapy and Oncology Secretariat, Department of Experimental Clinical Oncology, Aarhus University Hospital, No¨rrebrogade 44, Building 5, DK-8000 Aarhus C, Denmark (Tel.: +45 78 46 26 29; Fax: +45 86 19 71 09; E-mail: ro@oncology.dk)

TYPES OF PAPERS

1. Full length original papers (max. 3000 words) Describe original scientific work in the field of radiation oncology or related areas. The content of the paper should be sufficient to reach valid conclusions. Full papers should include a structured abstract and be divided into sections (Introduction; Materials and Methods; Results; Discussion; References; Tables; Figures) and should not normally exceed 6 printed pages, including references and a maximum of 6 tables/figures. Additional material can be submitted as supplementary files. 2. Short communications and Technical notes (max. 2000 words) Provide a brief but complete account of a particular piece of work, e.g. Phase I or II study, and should in total be no longer than 4 printed pages, normally including a maximum of 2 figures or tables. A summary of not more than 50 words should be included (not a structured abstract), but the manuscript can have fewer subheadings (e.g. short introduction; materials and methods; results and discussion). Authors are advised to see a recent issue of the journal for size and lay-out. 3. Review articles Rigorous critical assessment of clinical and/or laboratory research in a field of interest to the journal and its subscribers. Reviews are normally solicited by the editors, and it is suggested that authors wishing to contribute a review article contact the editor-in-chief. 4. Editorials and commentaries Editorials and commentaries relate to articles in the journal or to issues of relevance for the readership. This type of communication is normally solicited by the editors. 5. Letters to the Editor On topics of current interest or comment upon material previously or simultaneously published in the journal. They should be limited to 500 words and may include 1 table or figure. 6. Announcements The inclusion of announcements, etc. is at the discretion of the Editors and the Publisher and subject to space availability. Request for inclusion of meeting announcement should be send to the ESTRO secretariat (see address in journal). Author inquiries For inquiries relating to the submission of articles (including electronic submission where available) please visit this journal’s homepage at http:// www.elsevier.com/locate/radonc. For detailed instructions on the preparation of electronic artwork, please visit http://www.elsevier.com/ artworkinstructions. Contact details for questions arising after acceptance of an article, especially those relating to proofs, will be provided by the publisher. You can track accepted articles at http://www.elsevier.com/trackarticle. You can also check our Author FAQs at http://www.elsevier. com/authorFAQ and/or contact Customer Support via http://support.elsevier.com Language services. Authors who require information about language editing and copyediting services pre- and post-submission please visit http:// webshop.elsevier.com/languageediting or our customer support site at http://support.elsevier.com.

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ESTRO 35 content

Saturday 30 April 2016

Teaching Lecture

Technology assessment (Abs. 1)

CRISPR/CAS technology: from cells to mice to stem cell therapy (Abs. 2)

Partial Breast Irradiation: who, when and how? (Abs. 3)

New tools to reduce toxicity in pelvic radiation (Abs. 4)

Role of brachytherapy in the management of paediatric tumors (Abs. 5)

Challenges in MR guided radiotherapy (Abs. 6)

Patient specific quality assurance in proton therapy (Abs. 7)

Balancing toxicity and disease control in the evolution of radiotherapy technology (Abs. 8)

Symposium

Selection of patients for proton therapy (Abs. 9-11)

Mitigating normal tissue toxicity (Abs. 12-14)

Regional nodal irradiation for breast cancer (Abs. 15-17)

Assessment and management of rectal morbidity (Abs. 18-20)

Towards user oriented QA procedures for treatment verification (Abs. 21-23)

Robust and accurate functional MRI for radiotherapy (Abs. 24-26)

Joint Symposium

ESTRO-IAEA: Joint ESTRO-IAEA efforts on dosimetry, QA and audit for advanced treatment techniques (Abs. 27-29)

Symposium

Strategies for treatment planning (Abs. 30-32)

Poster Viewing

1: Brachytherapy (Abs. 33-40)

Symposium

Protons or heavy ions? (Abs. 41-43)

Proffered Papers

Radiobiology 1: Radiation effects on normal tisssues and the microenviroment (Abs. 44-48)

Clinical 1: Breast (Abs. 49-54)

Clinical 2: Adverse effects in radiotherapy (Abs. 55-60)

Brachytherapy 1: Prostate (Abs. 61-66)

Physics 1: Images and analyses (Abs. 67-72)

Physics 2: Basic dosimetry (Abs. 73-78)

RTT 1: Novelties in treatment planning (Abs. 79-84)

Poster Viewing

2: Clinical: Health economics, urology and brain (Abs. 85-91)

Presidential Symposium

Presidential (Abs. 92)

Award Lecture

E. Van der Schueren Award (Abs. 93)

Symposium with Proffered Papers

Hot topics in SABR: time for randomised clinical trials? (Abs. 94-97)

Symposium

Tumour targeting - considering normal tissue biology (Abs. 98-101)

Debate

This house believes that progress in the treatment of locally advanced NSCLC will come from: (Abs. 102-103)

Symposium

Active surveillance for low risk prostate cancer: to treat or not to treat? (Abs. 104-106)

Achieving excellence in image guided brachytherapy (Abs. 107-109)

Imaging markers for response prediction and assessment (Abs. 110-112)

Debate

There are many existing IGRT options for highly accurate dose delivery. Is there a need for large-scale in-room MR-guidance? (Abs. 113-114)

Symposium

Additional tools for contouring (Abs. 115-117)

Poster Viewing

3: Clinical: Gastrointenstinal and gynaecology (Abs. 118-125)

Joint Symposium

ESTRO-ESR: MR-PET (Abs. 126-128)

Proffered Papers

Radiobiology 2: Interplay between cancer stem cells ,hypoxia and the radiation response (Abs. 129-134)

Clinical 3: Lung (Abs. 135-140)

Clinical 4: Late breaking abstracts (Abs. 141-146)

Brachytherapy 2: EYE GI (Abs. 147-152)

Physics 3: Anatomical CT and MR imaging for treatment preparation (Abs. 153-158)

Physics 4: Inter-fraction motion management I (Abs. 159-164)

RTT 2: Improving quality for breast cancer treatments (Abs. 165-170)

Poster Viewing

4: Physics: Treatment planning: applications III (Abs. 171-176)

Honorary Members Lecture

Honorary Members (Abs. 177-179)

Sunday 1 May 2016

Teaching Lecture

Trade off between standardisation and individualisation (Abs. 180)

DNA repair and response for beginners (Abs. 181)

Anal cancer: current guidelines and remaining questions (Abs. 182)

Radiotherapy and immune-therapy, biological basis and potential for future clinical trials (Abs. 183)

Underestimated importance of Intraluminal brachytherapy: bronchus, oesophageal, anorectal and hepatobiliary duct cancer (Abs. 184)

Big data in radiotherapy: technology, challenges and opportunities (Abs. 185)

The role of dosimetry audit in safety, quality and best practice for external beam and brachytherapy (Abs. 186-187)

General introduction to head and neck radiotherapy (Abs. 188)

e-Learning for Professionals in Radiation Oncology: What, Why and How? (Abs. 189)

Symposium with Proffered Papers

Quality beyond accuracy: are we failing to see the forest for the trees? (Abs. 190-193)

Symposium

Targeting DNA repair / DDR pre-clinical evidence (Abs. 194-196)

New approaches in rectal cancer (Abs. 197-199)

Changing paradigm in the management of kidney cancer (Abs. 200-202)

Modern techniques for old indications (Abs. 203-205)

Quantitative imaging to individualise radiotherapy (Abs. 206-208)

Proffered Papers

Physics 5: Intra-fraction motion management I (Abs. 209-215)

Symposium

Head and neck: reduction of margins and side effects (Abs. 216-218)

The future of Radiation Oncology publishing: views through the Red and Green telescopes (Abs. 219-221)

Poster Viewing

5: RTT (Abs. 222-230)

Symposium

QA in clinical trials: processes, impact and future perspectives (Abs. 231-233)

Proffered Papers

Radiobiology 3: Novel targeting approaches in combination with radiation (Abs. 234-238)

Clinical 5: Upper and lower GI (Abs. 239-244)

Clinical 6: Hadron therapy (Abs. 245-250)

Brachytherapy 3: Detectors and dose verification (Abs. 251-256)

Physics 6: Radiobiological modelling (Abs. 257-262)

Physics 7: Treatment planning: optimization algorithms (Abs. 263-268)

RTT 3: Ensuring quality in head and neck treatment (Abs. 269-274)

Poster Viewing

6: Clinical: Lung, palliation, sarcoma, haematology (Abs. 275-281)

Proffered Papers

Donal Hollywood Award (Abs. 282)

Highlights of Proffered Papers (Abs. 283-286)

Symposium

Planning ahead: how to finish your residency / PhD project with a job

offer (Abs. 287-290)

Symposium with Proffered Papers

Standardisation in clinical practice (Abs. 291-295)

Symposium

DNA repair inhibition and radiotherapy: moving towards clinic (Abs.

296-298)

Radiotherapy of prostate cancer: technical challenges (Abs. 299-301)

Debate

This house believes that SBRT should become the standard of care for

T1 and small T2 NSCLC tumours (Abs. 302-303)

Is brachytherapy the best for partial breast irradiation? (Abs. 304-307)

Symposium

New challenges in modelling dose-volume effects (Abs. 308-310)

Automated treatment plan generation in the clinical routine (Abs. 311-313)

Elderly and radiation therapy (Abs. 314-316)

A Joint session of Young Radiation Oncologists National Societies & YROG (Abs. 317-321)

Poster Viewing

7: Physics: Intra-fraction motion management II (Abs. 322-329)

Symposium with Proffered Papers

Uncovering the gap between optimal and actual utilisation of radiotherapy in Europe (Abs. 330-334)

Debate

Maximising tumour control: crank up the volume or turn off the switches? (Abs. 335-338)

Proffered Papers

Clinical 7: Urology (Abs. 339-344)

Clinical 8: Adult and paediatric CNS malignancies (Abs. 345-350)

Brachytherapy 4: Gynae-Breast (Abs. 351-356)

Physics 8: Dose measurement and dose calculation I (Abs. 357-362)

Physics 9: Adaptive RT for inter-fraction motion management (Abs. 363-368)

RTT 4: How to increase the knowledge for patients and staff (Abs. 369-374)

Poster Viewing

8: Physics: Inter-fraction motion management II (Abs. 375-379)

Award Lecture

Academic award: Jack Fowler University of Wisconsin Award (Abs. 380)

Company Award Lectures (Abs. 381-382)

Monday 2 May 2016

Teaching Lecture

How to bring QUANTEC into the 21st century? (Abs. 383)

Shared decision making (Abs. 384)

The study of therapy resistance in genetically engineered mouse models for BRCA1-mutated breast cancer (Abs. 385)

SBRT/SABR for oligometastatic disease (Abs. 386)

Advanced treatment strategies for head and neck cancer (Abs. 387)

Dose to water vs. dose to tissue in advanced treatment planning: myths, realities and concerns (Abs. 388)

Nanodosimetry: from radiation physics to radiation biology (Abs. 389)

Brachytherapy for the pelvic region: status and perspective for the future (Abs. 390-391)

Symposium with Proffered Papers

Adaptive radiotherapy for coping with anatomical variations: hope or hype? (Abs. 392-395)

Time is not on our side: cardiovascular toxicity after radiotherapy (Abs. 396-400)

Symposium

Emerging biomarkers (Abs. 401-404)

SBRT for oligometastatic disease (Abs. 405-407)

Head and neck: state-of-the-art and directions for future research (Abs. 408-410)

SBRT in lung - choices and their impact on related uncertainties (Abs. 411-413)

Proffered Papers

Physics 10: Functional Imaging I (Abs. 414-420)

Symposium

Adaptive treatments in the pelvic region (Abs. 421-423)

Poster Viewing

9: Radiobiology (Abs. 424-432)

Symposium

Modern ART based on functional / biological imaging (Abs. 433-435)

Secondary cancer after radiotherapy: from cancer registries to clinical implications (Abs. 436-438)

Proffered Papers

Radiobiology 4: Molecular biomarkers for patient selection (Abs. 439-443)

Clinical 9: SBRT and oligometastatic disease (Abs. 444-448)

Clinical 10: Head and neck (Abs. 449-454)

Physics 11: Dose measurement and dose calculation II (Abs. 455-460)

Physics 12: Treatment planning: applications I (Abs. 461-466)

RTT 5: Optimizing treatment planning and delivery in the pelvic region (Abs. 467-472)

Poster Viewing

10: Physics: Functional Imaging II (Abs. 473-478)

Proffered Papers

Selected randomised trials (Abs. 479-481)

Award Lecture

Breur Award Lecture (Abs. 482)

Joint Symposium

ESTRO-ASTRO: In room adaptive imaging with a focus on MRI (Abs. 483-486)

Symposium

Communication with patients (Abs. 487-490)

Imaging biology (Abs. 491-493)

Debate

This house believes that centralised large radiotherapy units will provide the best academia and the best treatment quality (Abs. 494-495)

Joint Symposium

ESTRO-ILROG: Modern radiotherapy in lymphoma (Abs. 496-498)

ESTRO-PTCOG: ART in particle therapy (Abs. 499-503)

Symposium

Small animal irradiation (Abs. 504-506)

Focus on the pelvic region (Abs. 507-509)

Poster Viewing

11: Clinical: Breast, head and neck (Abs. 510-519)

Symposium

Dose painting: those pending issues (Abs. 520-522)

ACROP (Abs. 523-525)

Proffered Papers

Radiobiology 5: Imaging and molecular biomarkers in radiation

oncology (Abs. 526-530)

Clinical 11: Health Economics and patient reported outcomes (Abs. 531-536)

Clinical 12: Rare tumours (Abs. 537-542)

Physics 13: New Technology and QA (Abs. 543-548)

Physics 14: Treatment planning: applications II (Abs. 549-554)

RTT 6: Advanced radiation techniques in prostate cancer (Abs. 555-560)

Poster Viewing

12: Physics: Dose measurement and dose calculation III (Abs. 561-566)

General Assembly

General Assembly

Tuesday 3 May 2016

Teaching Lecture

The new ‘Rs’ in radiation biology (Abs. 567)

Texture analysis of medical images in radiotherapy (Abs. 568)

Biology of high-energy proton and heavy ion particle therapy versus photon therapy: recent developments (Abs. 569)

Neuroendocrine tumours – personalised diagnosis and treatment using radiolabelled peptides (Abs. 570)

Radiotherapy for paediatric brain tumours (Abs. 571)

Role and validation of deformable image registration in clinical practice (Abs. 572)

VMAT QA: To do and not to do, those are the questions (Abs. 573)

Optimising workflow in a radiotherapy department - an introduction to lean thinking (Abs. 574)

Symposium

New concepts of tumour radioresistance (Abs. 575-577)

Symposium with Proffered Papers

Towards Personalised Radiation Oncology (PRO) (Abs. 578-582)

Symposium

The tumour in 3D: the role of tumour microenvironment (Abs. 583-586)

WBRT for brain metastases- the end of an era? (Abs. 587-589)

Radiotherapy "autovaccination" with systemic immune modulators for modern immunotherapy (Abs. 590-592)

Joint Symposium

ESTRO-AAPM-EFOMP: Functional / biological imaging and radiotherapy physicists: new requests/challenges and the need for better and more specific training (Abs. 593-595)

Symposium

The future of QA lies in automation (Abs. 596-599)

Management and optimisation of the daily workflow (Abs. 600-602)

Combining radiotherapy with molecular targeted agents: learning from successes and failures (Abs. 603-605)

Symposium with Proffered Papers

Radiomics - the future of radiotherapy? (Abs. 606-609)

Symposium

Radiobiology of proton / carbon / heavy ions (Abs. 610-612)

New insights in treating vertebral metastases (Abs. 613-615)

IMRT, the new standard in treatment of gynaecological, lung and breast cancers? (Abs. 616-618)

Symposium with Proffered Papers

Plan of the day (PotD): current status (Abs. 619-621)

Debate

We don’t need better dose calculation, it’s doing more bad than good (Abs. 622-623)

Are we precisely inaccurate in our adaption? (Abs. 624-625)

Moving away from 2 Gray: are we ready for a paradigm shift? (Abs. 626-629)

Posters

Clinical track: Head and neck (Abs. 630-640)

Clinical track: CNS (Abs. 641-661)

Clinical track: Haematology (Abs. 662-671)

Clinical track: Breast (Abs. 672-677)

Clinical track: Lung (Abs. 678-695)

Clinical track: Upper GI (oesophagus, stomach, pancreas, liver) (Abs. 696-714)

Clinical track: Lower GI (colon, rectum, anus) (Abs. 715-722)

Clinical track: Gynaecological (endometrium, cervix, vagina, vulva) (Abs. 723-735)

Clinical track: Prostate (Abs. 736-758)

Clinical track: Urology-non-prostate (Abs. 759-760)

Clinical track: Skin cancer / malignant melanoma (Abs. 761-763)

Clinical track: Sarcoma (Abs. 764-768)

Clinical track: Paediatric tumours (Abs. 769-771)

Clinical track: Palliation (Abs. 772-779)

Clinical track: Elderly (Abs. 780-782)

Clinical track: Health services research / health economics (Abs. 783-789)

Clinical track: Other (Abs. 790-791)

Physics track: Basic dosimetry and phantom and detector development (Abs. 792-801)

Physics track: Dose measurement and dose calculation (Abs. 802-832)

Physics track: Radiation protection, secondary tumour induction and low dose (incl. imaging) (Abs. 833-836)

Physics track: Treatment plan optimisation: algorithms (Abs. 837-841)

Physics track: Treatment planning: applications (Abs. 842-869)

Physics track: (Radio)biological modelling (Abs. 870-877)

Physics track: Intra-fraction motion management (Abs. 878-893)

Physics track: Inter-fraction motion management (excl. adaptive radiotherapy) (Abs. 894-904)

Physics track: Adaptive radiotherapy for inter-fraction motion management (Abs. 905-911)

Physics track: CT Imaging for treatment preparation (Abs. 912-918)

Physics track: (Quantitative) functional and biological imaging (Abs. 919-931)

Physics track: Images and analyses (Abs. 932-938)

Physics track: Implementation of new technology, techniques, clinical protocols or trials (including QA & audit) (Abs. 939-951)

Physics track: Professional and educational issues (Abs. 952)

Brachytherapy track: Breast (Abs. 953-955)

Brachytherapy track: Gynaecology (Abs. 956-963)

Brachytherapy track: Head and neck (Abs. 964-965)

Brachytherapy track: Physics (Abs. 966-973)

Brachytherapy track: Prostate (Abs. 974-979)

Radiobiology track: Molecular targeted agents and radiotherapy (Abs. 980-985)

Radiobiology track: Tumour biology and microenvironment (Abs. 986-989)

Radiobiology track: Normal tissue effects: pathogenesis and treatment (Abs. 990-992)

Radiobiology track: Biomarkers and biological imaging (Abs. 993-994)

Radiobiology track: Cellular radiation response (Abs. 995-998)

Radiobiology track: Radiobiology of protons and heavy ions (Abs. 999-1000)

RTT track: Strategies for treatment planning (Abs. 1001-1009)

RTT track: Head and neck reduction of margins and side effect (Abs. 1010)

RTT track: Elderly and radiation therapy (Abs. 1011)

RTT track: Adaptive treatments in the pelvic region (Abs. 1012-1014)

RTT track: Other topics for RTTs (Abs. 1015-1022)

RTT track: Position verification (Abs. 1023-1026)

Electronic Posters

Clinical track: Head and neck (Abs. 1027-1110)

Clinical track: CNS (Abs. 1111-1137)

Clinical track: Haematology (Abs. 1138-1143)

Clinical track: Breast (Abs. 1144-1199)

Clinical track: Lung (Abs. 1200-1255)

Clinical track: Upper GI (oesophagus, stomach, pancreas, liver) (Abs. 1256-1279)

Clinical track: Lower GI (colon, rectum, anus) (Abs. 1280-1310)

Clinical track: Gynaecological (endometrium, cervix, vagina, vulva) (Abs. 1311-1332)

Clinical track: Prostate (Abs. 1333-1385)

Clinical track: Urology-non-prostate (Abs. 1386-1390)

Clinical track: Skin cancer / malignant melanoma (Abs. 1391-1397)

Clinical track: Sarcoma (Abs. 1398-1410)

Clinical track: Paediatric tumours (Abs. 1411-1421)

Clinical track: Palliation (Abs. 1422-1440)

Clinical track: Elderly (Abs. 1441-1449)

Clinical track: Health services research / health economics (Abs. 1450-1459)

Clinical track: Communication (Abs. 1460-1462)

Clinical track: Other (Abs. 1463-1481)

Physics track: Basic dosimetry and phantom and detector development (Abs. 1482-1517)

Physics track: Dose measurement and dose calculation (Abs. 1518-1604)

Physics track: Radiation protection, secondary tumour induction and low dose (incl. imaging) (Abs. 1605-1624)

Physics track: Treatment plan optimisation: algorithms (Abs. 1625-1644)

Physics track: Treatment planning: applications (Abs. 1645-1711)

Physics track: (Radio)biological modelling (Abs. 1712-1728)

Physics track: Intra-fraction motion management (Abs. 1729-1774)

Physics track: Inter-fraction motion management (excl. adaptive radiotherapy) (Abs. 1775-1804)

Physics track: Adaptive radiotherapy for inter-fraction motion management (Abs. 1805-1825)

Physics track: CT Imaging for treatment preparation (Abs. 1826-1849)

Physics track: (Quantitative) functional and biological imaging (Abs. 1850-1885)

Physics track: Images and analyses (Abs. 1886-1910)

Physics track: Implementation of new technology, techniques, clinical protocols or trials (including QA & audit) (Abs. 1911-1952)

Physics track: Professional and educational issues (Abs. 1953-1956)

Brachytherapy track: Breast (Abs. 1957-1959)

Brachytherapy track: Gynaecology (Abs. 1960-1981)

Brachytherapy track: Head and neck (Abs. 1982-1984)

Brachytherapy track: Physics (Abs. 1985-1998)

Brachytherapy track: Prostate (Abs. 1999-2013)

Brachytherapy track: Anorectal (Abs. 2014)

Brachytherapy track: Miscellaneous (Abs. 2015-2022)

Radiobiology track: Molecular targeted agents and radiotherapy (Abs. 2023-2036)

Radiobiology track: Tumour biology and microenvironment (Abs. 2037-2040)

Radiobiology track: Normal tissue effects: pathogenesis and treatment (Abs. 2041-2046)

Radiobiology track: Biomarkers and biological imaging (Abs. 2047-2061)

Radiobiology track: Cellular radiation response (Abs. 2062-2070)

Radiobiology track: Radiobiology of protons and heavy ions (Abs. 2071-2073)

RTT track: Strategies for treatment planning (Abs. 2074-2087)

RTT track: Additional tools for contouring (Abs. 2088-2089)

RTT track: Head and neck reduction of margins and side effect (Abs. 2090-2092)

RTT track: Adaptive treatments in the pelvic region (Abs. 2093-2100)

RTT track: Other topics for RTTs (Abs. 2101-2108)

RTT track: Position verification (Abs. 2109-2119)

ABSTRACTS

ESTRO 35 29 April – 3 May 2016

S1

Turin, Italy ______________________________________________________________________________________________________

chemically synthesized single-stranded DNA oligonucleotides comprising 80-120 nucleotides are highly effective. We have optimized the protocol for single base-pair substitution in the genome of mouse embryonic stem (ES) cells by oligonucleotide-templated HDR of a CRISPR/Cas9-generated break, achieving precise introduction of a planned modification in 50% of the recovered cells. Furthermore, we studied the influence of the cell’s DNA mismatch repair system on the efficiency of gene modification. Fanconi anemia (FA) is a recessive heritable disorder characterized by skeletal abnormalities, progressive anemia and cancer predisposition. The disease is caused by bi-allelic defects in any of 17 genes, designated FANCA , B , C , etc. When a matching donor is available, bone marrow failure can often be treated by hematopoietic stem cell transplantation. Also, bone marrow transplantation from a non-matching donor can be offered, however, this is often associated with severe complications. An alternative strategy to re-establish a functional hematopoietic system may be the functional correction of the FA defect in the patient’s own cells. Ideally, the defect is restored in the patient’s own hematopoietic stem cells (HSC), which can subsequently be used to reconstitute the entire hematopoietic system. For FA patients with insufficient bone marrow cellularity, the FA defect may first be corrected in patient-derived primary fibroblasts. The corrected fibroblasts subsequently need to be reprogrammed into HSCs, most likely requiring the generation of induced pluripotent stem cells (iPSCs). As a first step towards this approach, we demonstrated that CRISPR/Cas9 genome editing can effectively be exploited to repair a deleterious mutation in Fancf and restore the FA pathway in cultured mouse ES cells and fibroblasts. The next step is to use this protocol to correct the Fancf mutation in mouse-derived hematopoietic stem cells (HSC) and iPSCs. Gene-edited HSCs will subsequently be transplanted into lethally-irradiated recipient mice to determine their potential to drive long-term hematopoiesis. These preclinical studies are aimed to pave the way for the clinical development of CRISPR/Cas9-mediated gene correction protocols to restore FA gene defects and relieve bone marrow failure in Fanconi anemia patients. Teaching Lecture: Partial Breast Irradiation: who, when and how? SP-0003 Partial Breast Irradiation: who, when and how? C. Coles 1 Addenbrooke's Hospital, Oncology Centre University of Cambridge, Cambridge, United Kingdom 1 This lecture will explore the rationale for partial breast irradiation and then discuss the results from randomised trials to date. These will include intra-operative radiotherapy, brachytherapy and external beam radiotherapy. There is considerable heterogeneity between these techniques in terms of target volume, dose and fractionation and possible consequences from these differences will be considered. Appropriate patient selection for partial breast irradiation and treatment outside clinical trials will also be discussed. Teaching Lecture: New tools to reduce toxicity in pelvic radiation SP-0004 New tools to reduce toxicity in pelvic radiation I. Joye 1,2 , K. Haustermans 1 KU Leuven - University of Leuven, Department of Oncology, Leuven, Belgium 1,2 2 University Hospitals Leuven, Department of Radiation Oncology, Leuven, Belgium

Teaching Lecture: Technology assessment

SP-0001 Technology assessment D. Verellen 1 Universitair Ziekenhuis Brussel, Radiotherapy, Brussels, Belgium 1 Radiation therapy is a highly technology driven discipline, and as treatments become more complex and automated, safe implementation and quality assurance become less intuitive. Moreover, the discipline seems to face a dichotomous situation in that on one hand there is a tendency towards truly individualized treatments adapted to patient specific characteristics, short or long term variations in anatomy and delivered dose, that require flexible interventions and optimizations. These individualized treatments call for dedicated QA/QC programs. On the other hand the automatization in delineation and treatment planning in combination with the need to optimize workflows, drive development towards template driven, almost “app-like” solutions. The latter, seems to facilitate workflows and QA/QC procedures in that a strong standardization reduces the need for detailed verification. In fact, commercial solutions are being offered as “plug-and- play” with limited user interaction and QA/QC, almost ignoring the department’s responsibilities towards patient safety and quality. Mix the previous with rapid succession of upgrades and updates, and it becomes clear that the assessment and QA of technology (still) requires constant attention and vigilance. Special care should be given to the workflow and how the individual components are integrated and mutually influence each other in this constantly evolving and increasingly complex situation. The presentation will also focus on the discussion between “one shoe fits all” solutions versus the need for dedicated technology. Are these decisions driven by clinical relevance or a “me-too” argumentation? Finally, some comments will be given comparing mono-vendor and multi-vendor situations. Teaching Lecture: CRISPR/CAS technology: from cells to mice to stem cell therapy SP-0002 CRISPR/Cas9 technology: from cells to mice to stem cell therapy H. Te Riele 1 Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Division of Biological Stress Response, Amsterdam, The Netherlands 1 , T. Harmsen 1 , H. Van de Vrugt 1 , J. Riepsaame 1 Protocols to efficiently generate small genomic sequence alterations in a targeted fashion are of great value to fundamental and clinical applications. We are particularly interested in developing protocols to correct the genetic defects underlying bone marrow failure in Fanconi anemia patients. The most promising protocols for targeted correction or deletion of small mutations in terms of efficiency and facility make use of site-specific nucleases designed to generate a DNA double-strand break (DSB) in the genomic DNA closely located to the site to be modified. The Streptococcus pyogenes derived RNA-guided nuclease Cas9 combines strong and site-specific endonuclease activity with unprecedented design simplicity. By exploiting the endogenous error-free homology-directed repair (HDR) pathway that makes use of sequence homology, repair of the DSB can be accompanied by the introduction of specific base-pair alterations. When a double- or single-stranded DNA template is offered, the HDR reaction copies subtle sequence alterations present in the template sequence effectuating their introduction into the genomic DNA. For introduction of small alterations, short

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cure-rate. At Gustave Roussy Hospital, since decades, brachytherapy –when possible– has been proposed as an alternative to external irradiation or radical surgery. So far, more than 150 children have been treated with brachytherapy, in the context of multidisciplinary approach, including chemotherapy +/- conservative surgery. The most frequent tumour sites were vagina/uterine cervix, bladder/prostate and nasolabial fold, the most common histopathological type being RMS. In a series of 39 girls treated between 1971 and 2005, interstitial brachytherapy was used for vulval tumors, and endocavitary brachytherapy was used in vaginal tumours with individually tailored moulded vaginal applicators. Among them, 20 patients were treated before 1990, where the initial tumoral extension was included in the brachytherapy volume, while after 1990, only residual disease after initial chemotherapy was treated. The usual prescribed dose was 60-65 Gy delivered in one to three brachytherapy applications, taking into account the doses to organs at risk. With a median follow of 8.4 years, local recurrence was reported in 2 patients (5.1%) in the first year following the treatment, regional relapse in 1 patient (2.6%) and distant recurrences in 7 patients (17.9%). Among the 20 patients treated before 1990, 15 presented long-term sequelae, (vaginal or urethral sclerosis or stenosis) with three requiring surgical treatment. By contrast, among the 19 patients treated after 1990, four patients had vaginal or urethral stenosis, none of them requiring surgery. A recent long-term toxicity analysis confirmed the increase of the total number of G3-4 late effects in patients treated before 1990. From 1991 to 2007, 26 boys with bladder/prostate RMS were treated with brachytherapy as a perioperative procedure. All of them underwent a conservative surgical procedure, with bladder-neck and urethra preservation. Brachytherapy was systematically performed after tumor resection, consisting of two loops encompassing the prostate and the bladder-neck area. A total dose of 60 Gy was delivered with low dose rate. With a median follow-up of 4 years (10 months-14.5 years), only one patient locally relapsed out of the brachytherapy treated area. Among 11 boys older than 6 years, 9 (82%) were normally continent, two had diurnal dribbling treated by bladder education. Recently, sexual and urinary functions, assessed with a quality of life (QoL) questionnaire, were studied in a cohort of 22 long-term survivors. The results showed that the great majority of long terms surviving males (76%) considered themselves as having normal QoL. Between 1971 and 2005, 16 children with RMS of the nasolabial fold were treated with brachytherapy. Ten presented embryonal RMS and six alveolar RMS. In 12 cases, brachytherapy was combined with local excision. The doses ranged from 50 to 70 Gy, depending on chemotherapy response, and surgical margins. With a median follow-up of 4.4 years (1.7–33), 10 patients relapsed: 4 local, 6 regional, and 2 metastatic failures were reported. In this particular context, brachytherapy provided an acceptable local control rate, but with a poor regional control. The ballistic interest of BT has been clearly demonstrated in paediatric RMS, with a very high dose gradient, sparing normal tissue and very high tumor dose. In our experience low dose-rate brachytherapy was used and recently had to move to pulsed dose-rate brachytherapy. Such conservative approach, minimizing late sequelae without detrimental effect on local control, should be offered whenever possible. This treatment is a clear demonstration of the multidisciplinary team approach, including surgeons, pediatricians and radiation oncologists. SP-0006 Challenges in MR guided radiotherapy J. Jonsson 1 Umeå University - Norrlands Universitetssjukhus, Department of Radiation Sciences, Umeå, Sweden 1 Radiotherapy has relied on computed tomography (CT) for both target definition and treatment planning during the last decades. However, the increasing accuracy in radiation Teaching Lecture: Challenges in MR guided radiotherapy

Radiotherapy plays an important role in the treatment of pelvic tumors. The advances in patients’ prognosis come at the expense of radiation-induced late toxicity. Progressive cell depletion and inflammation are the leading mechanisms of acute toxicity which is observed during or shortly after treatment. The pathogenetic pathways of late toxicity, developing 90 days or later after the onset of radiotherapy, are more complex and involve processes such as vascular sclerosis and fibrosis. Since many patients have become long- term survivors, awareness and recognition of radiation- related toxicity has gained in importance and increased efforts are made for its prevention and management. Technical innovations contribute to a reduction in radiotherapy-associated toxicity. The steep dose gradients of highly-conformal radiotherapy techniques allow for an accurate dose delivery with optimal sparing of the normal tissues. Several studies have demonstrated the dosimetrical benefit of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) compared to conventional radiotherapy techniques. It has been shown that the dosimetrical benefit of IMRT translated into a clinically significant reduction in lower gastrointestinal toxicity compared with three-field conventional radiotherapy. In the near future MRI-linacs and proton therapy are likely to broaden the therapeutic window further. Prone positioning on a bellyboard reduces small bowel toxicity by pushing away the small bowel loops from the high dose region. Image- guided radiotherapy allows for an accurate definition, localization and monitoring of tumor position, size and shape before and during treatment and may help to reduce set-up margins. Small randomized controlled trials have shown that the administration of several agents might have a beneficial effect for the prevention of acute (e.g. intrarectal amifostine, oral sulfasalazine and balsalazide) and/or late- onset radiation-induced toxicity (intrarectal beclomethasone and oral probiotics). Once severe toxicity develops, total replacement of the diet with elemental formula may be appropriate. Probiotics influence the bacterial microflora and seem promising in reducing the incidence and severity of radiation-induced diarrhea. Currently there is insufficient evidence for cytoprotective and anti-inflammatory drugs in the management of radiation-induced toxicity. Future challenges lie in the prediction of treatment-related toxicity, which might be a promising step towards an individualized risk-adapted treatment. Teaching Lecture: Role of brachytherapy in the management of paediatric tumors SP-0005 Role of brachytherapy in the management of paediatric tumours C. Haie-Meder 1 Institut Gustave Roussy, Brachytherapy Service- Radiation Onocolgy Department, Villejuif, France 1 , H. Martelli 2 , C. Chargari 3 , I. Dumas 4 , V. Minard-Colin 5 2 CHU Bicêtre-Paris XI, Department of Pediatric Surgery, Le Kremlin-Bicêtre, France 3 Gustave Roussy, Brachytherapy Service-Radiation Oncology Department, Villejuif, France 4 Gustave Roussy, Physics Department, Villejuif, France 5 Gustave Roussy, Pediatric Department, Villejuif, France As the cure rates for childhood cancers continue to improve with better local control and outcome, the incidence and management of long-term consequences are a constant challenge. Conservative treatments include a combination of chemotherapy, radiotherapy and surgery that may lead to 5 year-survival rates > 90%. The use of brachytherapy, whenever feasible, is an attractive alternative when ionizing radiation is needed for the treatment of paediatric cancers, especially rhabdomyosarcomas (RMS). In genital RMS, brachytherapy represents an alternative to radical surgery: hysterectomy or colpectomy in girls and cysto-prostatectomy in boys. When brachytherapy is properly applied, the probability of late complications remains low with a high

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to complete machine maintenance, routine quality assurance, and patient specific quality assurance. With the advent of advanced delivery techniques such as pencil beam scanning, the complexity of patient specific quality assurance is increasing. However, there is a need to improve efficiency of these tests whilst maintaining accuracy. This presentation will summarize contemporary patient specific quality assurance practice for both passive scattering and pencil beam scanning proton therapy, and describe off- line tests that potentially enable improved efficiency. Teaching Lecture: Balancing toxicity and disease control in the evolution of radiotherapy technology SP-0008 Balancing toxicity and disease control in the evolution of radiotherapy technology B. O'Sullivan 1 Princess Margaret Cancer Centre, Toronto, Canada 1 , S. Huang 2 2 Princess Margaret Cancer Centre/University of Toronto, Radiation Oncology, Toronto, Canada Radiotherapy (RT) is an effective option for treatment of many cancers. It offers organ and functional preservation and enhances surgical outcomes when administered pre- operatively or post-operatively, and for some diseases, such as nasopharyngeal cancer, it is often the only curative option. Disease control is generally of paramount importance to most patients during the urgent point of decision-making following diagnosis. However toxicity will almost certainly emerge as being just as relevant in the aftermath of treatment and in the subsequent follow-up period. In essence, when a patient dies of toxicity or treatment-related complications, it is just as tragic as dying of disease. The long-term result of RTOG 9111 and 9501 suggest that treatment -related deaths are blunting originally observed difference in cancer-related outcome. The recent RTOG 0617 trial was designed to test whether a higher RT dose (74 Gy vs 60 Gy) +/- cetuximab could confer a survival benefit but showed an unexpected therapeutic “disadvantage” with higher RT dose attributable to significant acute and late toxicities. These findings highlight the importance of balancing toxicity and disease control to optimize therapeutic gain. Several strategies have been employed to mitigate toxicities, such as respecting the biology of radiation injury by altered dose fractionation (typically using smaller than conventional fractions), or optimising radiotherapy technical delivery to reduce dose to vulnerable anatomy. Implementing novel RT technologies need to be closely monitored to prove clinical benefit. Historical lessons have shown that putative benefits may not always transfer to real clinical advantages since many unforeseen factors may modify potential anticipated gains. While modern RT technologies, such as IMRT-IGRT, adaptive, and IMPT provide opportunities to reduce RT late toxicity by providing more conformal dose distribution to spatially avoid normal tissue, the steps to achieve this are complex. One needs to appreciate many diverse factors. These include radiobiology of normal tissue (dose/constraints), optimal imaging quality and registration, systematic quality control involving “target” delineation to delivery, and knowledge of a variety of inherent pitfalls in the process(e.g. poor delineation, dose dumping, erratic planning, tumor or normal tissue deformation, and set up uncertainties that may emerge throughout the treatment course). For example, beam path toxicities have been reported due to “dose dumping” from parotid-sparing IMRT in head and neck cancer. Increased local failure has been observed when delivering tight margin carotid-sparing partial organ irradiation for T2 glottic cancer using vertebrae rather than laryngeal soft tissue as the image guidance surrogate. Adaptive radiotherapy appears to be feasible in some situations but the therapeutic advantages are yet to be proven and may be tedious and inefficient under the current technical configurations of many departments. Also, while intensity-modulated proton therapy (IMPT) is an attractive emerging approach that is probably able to spare normal tissue, indications and clinical benefit

delivery, through highly conformal techniques such as intensity modulated radiotherapy (IMRT) and image guided radiotherapy (IGRT), has highlighted deficiencies in target delineations based on CT. Several studies have shown large variability in target definitions based on CT, for multiple treatment sites. To address this issue, magnetic resonance imaging (MRI) has made its way into the clinical routine at modern radiotherapy departments over the last years. This, however, has presented several new problems that need to be solved. The traditional method of including MR information in the radiotherapy process is as a complement to the CT. To accomplish this in an integrated and accurate fashion, the images must be placed in a common coordinate system through image registration. This process in itself introduces new uncertainties into the treatment chain, which must be quantified and minimized. Another method of using MR information is to base the entire treatment on MR and exclude the CT altogether. This alleviates uncertainties that stem from the image registration process, but introduces another set of problems. To perform accurate dose calculations, heterogeneity corrections based on CT data have been the clinical standard for many years. MR data does not provide information that can be used for such corrections; however, much research effort has been invested in creating valid photon attenuation maps from MR data over the last years. Whatever method employed, MR for radiotherapy purposes also imposes practical issues that need to be addressed. The patient needs to be positioned in the same way that will be employed during the radiotherapy itself. This includes a flat table top and immobilization devices such as cast masks and tilted boards, which may not be MR compatible. For example, many radiotherapy fixation devices can contain metal parts such as nuts and bolts, which cannot be used in the MR. Plastic replacements must be used instead. Also, the standard MR coils will often not accommodate the immobilized patient, which forces MR adopters to acquire special coils or coil holders for flexible coils to be able to scan the patient in the radiotherapy treatment position. MR images do not have the same geometric integrity as CT, which is an issue in the radiotherapy setting. The image distortions can come from the machine itself or from the patient that is in the machine. Machine specific distortions are caused by inhomogeneity in the main magnetic field or gradient non-linearity. Patient specific distortions are mostly caused by susceptibility effects. The machine specific distortions can be measured, modelled and corrected for to a certain extent, while patient specific distortions often needs to be handled by choosing imaging parameters wisely. In the end, the images acquired from the MR scanner must be of sufficient quality to allow physicians to base the radiotherapy treatment on them. MR for radiotherapy has a different set of demands on the images than their diagnostic counterparts, for example slice thickness and gap, as well as other parameters. Also, the vast variety of MR contrasts may be an initial obstacle for radiotherapy oncologists. Many studies have shown differences in target definitions based on CT and MR images, and the effects of these changes in target volumes have not yet been studied in clinical trials. Teaching Lecture: Patient specific quality assurance in proton therapy SP-0007 Patient specific quality assurance in proton therapy R. Amos 1 University College London Hospitals NHS Foundation Trust, Department of Radiotherapy Physics, London, United Kingdom 1 Interest in proton therapy continues to grow worldwide, yet access to proton therapy facilities remains relatively low compared to those offering conventional radiotherapy. As a consequence, pressure exists to maximize patient throughput in each facility. Most facilities operate 24 hours per day, 7 days per week to meet the demands of the clinical load and