RISK OF NEW PRIMARY NON-BREAST CANCERS AFTER BREAST CANCER TREATMENT

RISK OF NEW PRIMARY NON-BREAST CANCERS AFTER BREAST CANCER TREATMENT

S 60 S YMPOSIUM Small-animal dosimetry is an example of small-scale dosimetry that has seen recent developments. Rodents (mice or rats) have been st...

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S 60

S YMPOSIUM

Small-animal dosimetry is an example of small-scale dosimetry that has seen recent developments. Rodents (mice or rats) have been studied to model the propagation media by segmenting images obtained from living or dead animals, in order to derive a "reference" dosimetric model. Monte-Carlo codes have then been used to compute S values (i.e. absorbed doses per unit cumulated activity in Gy.Bq-1 .s-1 ) for various source/target combinations.The study of cellular dosimetry has also been considered important in the quest to correlate radiobiologic findings with delivered absorbed doses. Analytical approaches based on spherical cells with a spherical concentric nucleus have been published by the MIRD committee providing S values for several source/target configurations (activity in the whole cell, in the cytoplasm, on the cell surface, etc.).Most dosimetric approaches are macrodosimetric approaches, albeit at the microscopic scale. True microdosimetric approaches, i.e. considering the stochastic nature of energy deposition, have also been proposed, mostly for cellular or infra-cellular studies and alpha or Auger dosimetry. That kind of modelling provides for a complete description of the pattern of energy delivery. However, from a practical point of view, the amount of data generated by such approaches may be hard to analyse and difficult to relate to radiobiological observations.

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vated risks of solid cancers following HL have generally been attributed to radiotherapy. The relative risk of solid tumors increases steadily with increasing follow-up time from 5 till at least 25 years since first treatment. The absolute excess risks of solid malignancies increase at a much steeper rate than the relative risks, due to the fact that, with longer follow-up, patients grow older and their background rate of cancer rises strongly. Thus, the absolute excess risk amounts to about 100 excess cancer cases per 10,000 20-year survivors/yr. Breast cancer in females and lung cancer account for most of the absolute excess risk of solid tumors in 20 year survivors (42/10,000/yr and 17/10,000/yr). The risks of lung and breast cancer after HL increase with higher radiation dose. Chemotherapy can also increase the risk of solid malignancy, in particular lung cancer risk. By contrast, chemotherapy may decrease the risk of radiation-associated breast cancer, through its effect on premature menopause. The relative risk of solid tumors increases strongly with younger age at first treatment; this effect is most notable for breast cancer. Smoking appears to multiply the radiation- and chemotherapy-associated risks of lung cancer. Therefore, all cancer patients should be strongly advised to stop smoking. 166 speaker

164 speaker ADVANTAGE OF DOSIMETRY IN RADIONUCLIDE THERAPY L. Bodei1 , F. Botta2 , M. Cremonesi2 , G. Paganelli1 1 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Nuclear Medicine, Milan, Italy 2 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Health Physics, Milan, Italy

Radionuclide therapy is a unique form of internal radiotherapy, which uses a suitably radiolabelled molecule (radiopharmaceutical) to deliver a therapeutic dose to a pathological target tissue and induce a response. The first experiences of radionuclide therapies belongs to the 1940’, with the use of radioiodine in thyroid cancer patients and strontium-89 in bone metastases from prostate cancer. This field expanded enormously over the last decades, both in clinical practice and research, covering different types of therapies and diseases. Dosimetric modelling in radionuclide therapy has traditionally been considered as a complex process, and often been discarded towards a cautious, although rough estimate of the planned activity, by administering fixed activities or activities adjusted on patient’s parameters. Nevertheless, the risk of under-treatment, on one side, or of giving unnecessary toxicity, on the other side, prompted, in the last years, a more intense integration between nuclear medicine physicians and physicists, in order to tailor the treatment to each patient, by giving the highest possible absorbed dose to the tumour while sparing as much as possible the normal organs involved. Dosimetry, in fact, provides information useful for appropriate therapy indication, protocol rationales, treatment planning, toxicity prevention, and efficacy. The lecture will examine the main traditional and innovative radionuclide therapy techniques, such as radioiodine therapy, radioimmunotherapy, peptide receptor radionuclide therapy, radioembolization, or IART, and will illustrate the radiopharmaceutical characteristics and the principal clinical consequences and advantages of dosimetric studies and radiobiological models, such as the evaluation and preservation of critical organs and the maximization of target tissue irradiation.

Radiation induced secondary cancer reviewed 165 speaker RADIATION INDUCED SECONDARY CANCERS: THE EPIDEMIOLOGISTS’ VIEW F. van Leeuwen1 1 N ETHERLANDS C ANCER I NSTITUTE, Department of Epidemiology, Amsterdam, Netherlands

OUT OF FIELD DOSE FROM ADVANCED TREATMENT TECHNIQUES S. Kry1 1 U.T. M.D. A NDERSON C ANCER C ENTER, Radiation Physics, Houston, TX, USA

Dose outside of the treatment volume is an unavoidable consequence of radiation therapy. This undesirable radiation is a concern because of the potential for even low doses of radiation to cause such late effects as cancer induction, heart disease, or stroke. These low doses are present outside of the treatment volume in patients receiving radiation therapy, necessitating the understanding and limitation of their impact. In recent years, the risk of such late effects for radiotherapy patients has increased due to a combination of factors. First, increased patient survival from more efficacious treatments has resulted in more long-term survivors who are subsequently at risk of developing a late effect. Compounding this, modern radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT) may increase the out-of-field dose, increasing the risk per person of developing a late effect. As this potential risk receives increased attention, it is important to be aware of the sources of out-of-field doses associated with different treatment options, and the parameters that influence these doses. This presentation will examine the out-of-field dose associated with a variety of different treatment modalities that are currently available. The out-of-field dose from conventional photon treatments will be discussed as a baseline, and the relative importance of head leakage, collimator scatter, and patient scatter will be compared. Parameters that impact the out-of-field dose will also be examined. Additionally, more advanced photon techniques such as IMRT, Tomotherapy, Cyberknife, and Gamma Knife treatments will be discussed and compared. The impact of treatment energy will be discussed, particularly in the context of neutron production and the biological potency of neutrons. Finally, dose outside the treatment volume from proton and other particle beams will be examined. The contributions to the out-of-field dose from internally and externally produced neutrons and photons will be compared. The treatment parameters for proton therapy that impact the out-of-field dose/dose equivalent will also be discussed. After seeing this lecture, the attendee will have acquired knowledge about the sources of out-of-field dose from different treatment techniques and also be aware of treatment parameters that most impact the out-of-field dose. The attendee will also have gained a sense for what treatments produce relatively higher doses outside the target volume. 167 speaker RISK OF NEW PRIMARY NON-BREAST CANCERS AFTER BREAST CANCER TREATMENT M. Schaapveld1 , F. van Leeuwen1 1

Now that modern chemotherapy and radiotherapy have substantially increased the survival of patients with cancer, it becomes increasingly important to evaluate the long-term complications of treatment. Second cancers are among the most serious sequelae of cancer treatment because they do not only cause substantial morbidity, but also considerable mortality. Second malignancy studies in survivors of Hodgkin Lymphoma (HL) stood model for such research in other cancer survivors. Among long-term survivors of HL, second cancer deaths are the largest contributor to the substantial excess mortality that these patients experience.Survivors of HL experience strongly increased relative risks of leukemia, non-Hodgkin’s lymphoma (NHL), sarcoma and thyroid cancer, and moderately increased risks (2- to 4 fold) for a variation of other (solid) tumors, such as cancers of the lung, breast, stomach, esophagus, cervix, and melanoma. Because leukemia and NHL have a low incidence in the population, even a high relative risk translates into a low absolute excess risk. Compared with the general population, HL patients experience an excess of about 45 malignancies per 10,000 person-years of observation. Solid tumors account for the majority of excess cancers. Ele-

N ETHERLANDS C ANCER I NSTITUTE - A NTONI VAN L EEUWENHOEK H OSPITAL, Epidemiology, Amsterdam, Netherlands

Breast cancer survival has increased considerably during the last decades, largely as a result of earlier diagnosis due to breast screening and increasing use of adjuvant therapies, and breast cancer is currently the most frequent and most prevalent cancer in the Western World.Although breast cancer patients are at risk of developing another cancer just by surviving their breast cancer, several studies have shown that the cancer risk among breast cancer survivors does not follow the same pattern as cancer risk among women in general. Several cancers occur more frequently among breast cancer patients than would be expected. Common hereditary predisposition and other shared etiologic factors explain an important part of this increased risk of developing new cancers among breast cancer survivors, such as the increased risk of cancers of the ovaries and uterus and melanoma skin cancer. However several reports have shown that breast cancer treatment may also be associated with an increased risk of developing second cancers, some of

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which may only become manifest decades after treatment.Postmastectomy radiotherapy has been associated with a 2-3 fold increase in ipsilateral lung cancer risk in long-term survivors. In contrast postlumpectomy radiotherapy has thus far not been found to increase lung cancer risk. The risk of squamous cell esophageal cancer has also been reported to be 2-5 fold increased in patients who underwent postmastectomy radiotherapy and were followed for at least 10 years. Most patients in these studies were treated with now outmoded radiation techniques. Modern treatment approaches, which use lower fraction size (or dose) and limit the exposure of surrounding normal tissue to radiation, are less likely to cause radiation-associated cancers. Risk of developing soft tissue sarcomas was also 2-3 fold increased for patients treated with radiotherapy. It remains unclear to what extent the strongly increased risk of angiosarcomas is due to radiation or chronic lymphedema. Radiotherapy has also been associated with increased risk of leukemia especially among patients who also received alkylating chemotherapy (including cyclophosphamide, doxorubicin and epirubicin). Leukaemia risk increased with increasing cumulative dose of alkylating agents and with higher radiation dose to active bone marrow. Leukaemia risk was more strongly increased following combined treatment with, either post-mastectomy or post-lumpectomy, radiotherapy and chemotherapy compared to chemotherapy alone. Adjuvant chemotherapy has not been associated with increased risk of any solid (epithelial) cancers. Tamoxifen treatment has consistently been associated with an increased risk of cancer of the uterus, with higher risks with increasing duration of use.Breast cancer patients diagnosed during the 1980s and 1990s experienced a small but significant excess risk of developing a secondary non-breast cancer. Although only a very small proportion of these second non-breast cancers are attributable to the breast cancer treatment in absolute terms, clinicians should be aware of these risks when trying to distinguish breast cancer recurrences from new primary malignancies. The benefits of adjuvant therapy far outweigh the risks of developing second non-breast cancers. Nonetheless, the effects of new treatment regimens including taxanes, monoclonal antibodies and aromatase inhibitors need to be monitored in the future.

Immobilisation techniques 168 speaker THE INFLUENCE OF IMMOBILISATION AND HOW TO MEASURE IT G. Vandevelde1 U NIVERSITY H OSPITAL G ASTHUISBERG, Department of Radiotherapy, Leuven, Belgium

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Accurate and reproducible positioning throughout a treatment course is critical in patients with head-and-neck (H&N) tumors treated with 3DCRT (3D conformal radiotherapy) or IMRT (Intensity Modulated Radiotherapy). Treatment setup inaccuracies can lead to underdosage of the target volume, increasing the risk of treatment failure while setup errors can lead to overdosing of adjacent normal tissues and organs at risk which could result in increased treatment morbidity.Several factors can effect the precise fitting of a mask and the rigidity of an immobilization device.A whole range of immobilization systems (vacuum-formed shells, different thermoplastic systems) have been introduced and evaluated throughout the last decades.Small improvements in accuracy and immobilization were found with the introduction of more concaved and individualized neck supports (W. Grush). More rigid thermoplastics with strenghtening bars are promising and may reduce the left-right and cranio-caudal movement (I. Cowlew et al). Since almost all thermoplastic masks have shown a large flexibility in the left-right direction with and without the patient, additional improvement in this direction might be obtained by using an external fixation such as a nose bridge or an individual mouth piece.Finally, high precision with reduced margins of 2-3 mm (D. Georg et al.) could be obtained by a thermoplastic mask-based stereotactic head and neck fixation and even less than 1 mm (A. Kassaee et al.) by a modified non-invasive stereotactic frame. Problems in reproducibility might arise from setup factors, patient factors and "methods-and-material" factors.Regular portal imaging and on-line correction protocols are most often used to evaluate inter-fractional variability (set-up errors) and accuracy during treatment. Changes in patient anatomy (eg weight loss, shrinkage of nodes), introducing intrafractional variability might have a substantial impact on how accurate a mask will fit and are not always detected in an early stage since no effective control tools exist. On board-imaging facilities like ConeBeam CT offer new ways to detect these intrafractional variations. Finally regular quality control of the procedures (mask construction, storage of masks) and materials (checking head and neck rests, base plates), might detect small problems in an early stage.

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169 speaker RADIOTHERAPY FOR CNS AND H&N CANCER: THE INFLUENCE OF THE HEAD SUPPORT N. Raaijmakers1 , S. van der Meer1 , A. Houweling1 , C. Terhaard1 , E. van der Wal1 U.M.C. U TRECHT, Radiotherapy, Utrecht, Netherlands

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Purpose/Objective: The purpose of this work was to compare the standard head-rest with an individualised thermoplastic head support for head-andneck radiotherapy. Materials/Methods: For 22 patients, cone-beam CT scans were made before and after the treatment fractions for a minimum of 8 fractions. All patients were immobilized using a five-point thermoplastic mask; 10 patients were positioned on a standard head rest; 12 on an individually-moulded thermoplastic support. The accuracy of matching the cone-beam CT data to the reference helical CT data made for treatment planning was determined by comparing the results for two matching algorithms and two different but anatomically fixed regions. Intra- and interfraction movements for both head supports were determined for five regions of interest: the complete head-and-neck region, the skull, the mandible, vertebrae C1-C3 and vertebrae C4-C6. All movements were expressed as table movements without applying rotations. The correction reference point was located in the centre of the region of interest. The movements were averaged over the three directions and were expressed as 1 standard deviation. Results: The match accuracy amounted to approximately 0.5 mm. For the standard head rest, the intrafraction movement averaged over all directions ranged from 0.5 mm for the skull to approximately 1.0 mm for the mandible. For the individual head support, these values were approximately 0.3 mm smaller. The random interfraction movement (σ ) amounted to 1.2 mm for all regions for the standard head support. For the individual support, a σ -value of 0.9 mm was observed. The systematic movement (Σ) without applying a correction protocol varied from 1 mm for the skull to 2-3 mm for region C4C6, for the standard support. For the individual support comparable Σ-values were obtained indicating that this uncertainty was not related to the fixation of the patient. However, with the individualised head support less deformation was observed than with the standard head support. With a no-action level off-line correction protocol, Σ-values of 0.6 mm could be obtained for all regions of interest separately but, due to deformations, not for all regions simultaneously. The estimated CTV-PTV margin amounted to 2-3 mm in the region where the correction was optimised. Outside this region, a CTV-PTV margin of 4-6 mm was estimated. Conclusions: Applying an individualised head support reduces the patients movements during the irradiation and reduces the random interfraction movements compared with the use of a standard head rest. Furthermore, less deformations were observed in the individualised head support. Consequently, smaller CTV-PTV margins might be applied when applying an individualised head support. 170 speaker IMPLEMENTATION OF A BITE-BLOCK IMMOBILISATION SYSTEM FOR CRANIAL STEREOTACTIC RADIOSURGERY M. Leech1 , M. Broderick1 1 T RINITY C OLLEGE, Division of Radiation Therapy

Many systems are available for accurate positioning and immobilisation in cranial stereotactic radiosurgery. Previously, only invasive frames were used due to the high precision involved in the procedure and the perceived rigidity offered by such frames. The development of non-invasive, relocatable immobilisation devices for intracranial stereotactic targets was based on a move towards fractionated treatments. The implementation of a bite-block immobilisation system in a radiotherapy department can allow Radiation Therapists to expand their role. The responsibility of accurate immobilisation of the patient using rigid frames previously lay with the Radiation Oncologist/Neurosurgeon who attached the frame. Implementing a bite-block immobilisation system gives Radiation Therapists the responsibility of ensuring accurate immobilisation, as with other sites. Careful implementation of a bite-block system by Radiation Therapists into a department is necessary for its subsequent successful use. Issues such as training on the system, change in work practices, workload and time constraints must be addressed. Identification of suitable patients for the bite-block system must be made by the Radiation Therapist as patient compliance is paramount to the success of the system. The advantages and disadvantages of a bite block immobilisation system for cranial stereotactic radiosurgery should be identified prior to its implementation.