30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

Ocular proton therapy, pencil beam scanning high energy proton therapy or stereotactic radiotherapy for uveal melanoma; an in silico study.

PURPOSE: In radiotherapy, the dose and volumes of the irradiated normal tissues is correlated to the complication rate. We assessed the performances of low-energy proton therapy (ocular PT) with eye-dedicated equipment, high energy PT with pencil-beam scanning (PBS) or CyberKnifeR  -based stereotactic irradiation (SBRT). MATERIAL AND METHODS: CT-based comparative dose distribution between external beam radiotherapy techniques was assessed using an anthropomorphic head phantom. The prescribed dose was 60Gy_RBE in 4 fractions to a typical posterior pole uveal melanoma. Clinically relevant structures were delineated, and doses were calculated using radiotherapy treatment planning softwares and measured using Gafchromic dosimetry films inserted at the ocular level. RESULTS: Precision was significantly better with ocular PT than both PBS or SBRT in terms of beam penumbra (80%-20%: laterally 1.4 vs. ≥10mm, distally 0.8 vs. ≥2.5mm). Ocular PT duration was shorter, allowing eye gating and lid sparing more easily. Tumor was excellent with all modalities, but ocular PT resulted in more homogenous and conformal dose compared to PBS or SBRT. The maximal dose to ocular/orbital structures at risk was smaller and often null with ocular PT compared to other modalities. Mean dose to ocular/orbital structures was also lower with ocular PT. Structures like the lids and lacrimal punctum could be preserved with ocular PT using gaze orientation and lid retractors, which is easier to implement clinically than with the other modalities. The dose to distant organs was null with ocular PT and PBS, in contrast to SBRT. CONCLUSIONS: ocular PT showed significantly improved beam penumbra, shorter treatment delivery time, better dose homogeneity, and reduced maximal/mean doses to critical ocular structures compared with other current external beam radiation modalities. Similar comparisons may be warranted for other tumor presentations.

[Results of surgical and radiotherapeutic treatment of adenoid cystic carcinoma of the salivary glands]. / Resultate der operativen und strahlentherapeutischen Behandlung von adenoidzystischen Karzinomen der Speicheldrüsen.

Surgical treatment in patients with rare adenoid cystic carcinoma (ACC) of the salivary glands is considered to be the state of the art. With respect to an additional radiotherapy there are different approaches regarding the type of radiotherapy and timing. In this study the overall survival and recurrence-free survival in 52 individuals with salivary gland ACC who were treated at the University Hospital in Essen and received irradiation with fast neutrons and photons (mixed beam technique) either A) immediately following surgical treatment or B) only after the appearance of local recurrence were compared. Group A (n = 28, first diagnosis, FD September 1991-September 2009) received adjuvant radiotherapy immediately postoperative, group B (n = 24, FD June 1979-November 2001) underwent primarily surgical tumor resection according to the treatment regimen at that time and were irradiated only on the appearance of a local recurrence. In comparison to group B, patients in group A showed a lower recurrence rate and a significantly longer local relapse-free survival. Group B, however, showed a significantly higher overall survival. The frequency of distant metastasis occurred equally in both groups but the onset of distant metastasis was significantly earlier in group A. In general, overall survival was negatively influenced by distant metastasis. The local recurrence rate was very high after primary surgical treatment only. The immediate adjuvant high-linear energy transfer (LET) radiotherapy reduced the local recurrence rates. Irradiation after the appearance of a recurrence had a positive influence on overall survival. Overall, definitive high-LET radiotherapy in the mixed beam technique enabled high local control rates both primarily postoperative and also locoregional recurrences.

[Malignant tumours of the eye: Epidemiology, diagnostic methods and radiotherapy]. / Tumeurs malignes ophtalmologiques : indications de la radiothérapie et techniques.

Malignant tumours of the eye are not common, barely representing 1 % of all cancers. This article aims to summarise, for each of the main eye malignant diseases, aspects of epidemiology, diagnostic methods and treatments, with a focus on radiation therapy techniques. The studied tumours are: eye metastasis, intraocular and ocular adnexal lymphomas, uveal melanomas, malignant tumours of the conjunctive, of the lids, and retinoblastomas. The last chapter outlines ocular complications of radiation therapy and their management.

[Operative therapy and irradiation of conjunctival melanoma]. / Operative Therapie und Bestrahlung konjunktivaler Melanome.

BACKGROUND: Radiotherapy of conjunctival melanoma has gained in importance in recent years compared to less invasive therapeutic approaches. This is due to the high recurrence rates achieved by omitting adjuvant therapy and to the increasing availability of suitable radiotherapeutic methods, so that tumors formerly not amenable to organ-preserving therapy can now be treated. OBJECTIVE: This article presents the current radiotherapeutic options for conjunctival melanoma. The aim is to describe the diagnostic and therapeutic strategies and the course of therapy of malignant conjunctival melanoma. It is the authors' intention to justify the necessity of the adjuvant therapy of conjunctival melanoma and to emphasize the need for interdisciplinary cooperation during the course of tumor therapy. METHODS: The article is based on results published in the literature as well as on data collected and experience gained in our centre.

A geometrical model for the Monte Carlo simulation of the TrueBeam linac.

Monte Carlo simulation of linear accelerators (linacs) depends on the accurate geometrical description of the linac head. The geometry of the Varian TrueBeam linac is not available to researchers. Instead, the company distributes phase-space files of the flattening-filter-free (FFF) beams tallied at a plane located just upstream of the jaws. Yet, Monte Carlo simulations based on third-party tallied phase spaces are subject to limitations. In this work, an experimentally based geometry developed for the simulation of the FFF beams of the Varian TrueBeam linac is presented. The Monte Carlo geometrical model of the TrueBeam linac uses information provided by Varian that reveals large similarities between the TrueBeam machine and the Clinac 2100 downstream of the jaws. Thus, the upper part of the TrueBeam linac was modeled by introducing modifications to the Varian Clinac 2100 linac geometry. The most important of these modifications is the replacement of the standard flattening filters by ad hoc thin filters. These filters were modeled by comparing dose measurements and simulations. The experimental dose profiles for the 6 MV and 10 MV FFF beams were obtained from the Varian Golden Data Set and from in-house measurements performed with a diode detector for radiation fields ranging from 3 × 3 to 40 × 40 cm(2) at depths of maximum dose of 5 and 10 cm. Indicators of agreement between the experimental data and the simulation results obtained with the proposed geometrical model were the dose differences, the root-mean-square error and the gamma index. The same comparisons were performed for dose profiles obtained from Monte Carlo simulations using the phase-space files distributed by Varian for the TrueBeam linac as the sources of particles. Results of comparisons show a good agreement of the dose for the ansatz geometry similar to that obtained for the simulations with the TrueBeam phase-space files for all fields and depths considered, except for the 40 × 40 cm(2) field where the ansatz geometry was able to reproduce the measured dose more accurately. Our approach overcomes some of the limitations of using the Varian phase-space files. It makes it possible to: (i) adapt the initial beam parameters to match measured dose profiles; (ii) reduce the statistical uncertainty to arbitrarily low values; and (iii) assess systematic uncertainties (type B) by using different Monte Carlo codes. One limitation of using phase-space files that is retained in our model is the impossibility of performing accurate absolute dosimetry simulations because the geometrical description of the TrueBeam ionization chamber remains unknown.

Management of choroidal metastases.

BACKGROUND: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS: A systematic review of literature was performed from 1974 to 2014. RESULTS: Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION: Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

[Molecular approaches to systemic therapy of adenoid cystic carcinoma of the head and neck area]. / Molekulare Ansatzpunkte für systemische Therapien adenoidzystischer Karzinome im Kopf-Hals-Bereich.

The adenoid cystic carcinoma (ACC) is a neurotropic salivary gland tumor with a high blood-borne metastasis tendency. The treatment of choice for localized disease consists of radical surgical resection and, depending on resection status, adjuvant radiotherapy. Due to the high recurrence rate with limited local therapeutic options and frequent occurrence of distant metastases, one is confronted inevitably with the search for an adequate systemic therapy. ACC shows little response to a variety of chemotherapeutic agents, partial or complete remissions are extremely rare. Beside classical chemotherapies, immunotherapeutics and targeted therapies with more favorable side effect profiles were tested in trials, but due to the small number of patients, a definitive statement on the effectiveness can be hardly made. This results in the need for prospective multicenter studies that allow clear recommendations for systemic therapy of the tumor. The present paper gives an overview of the sub-cellular and genetic characteristics of ACC, which represent possible targets for systemic therapies and have partly already been included in running clinical trials.

The influence of the local effect model parameters on the prediction of the tumor control probability for prostate cancer.

In carbon ion beams, biological effects vary along the ion track; hence, to quantify them, specific radiobiological models are needed. One of them, the local effect model (LEM), in particular version I (LEM I), is implemented in treatment planning systems (TPS) clinically used in European particle therapy centers. From the physical properties of the specific ion radiation, the LEM calculates the survival probabilities of the cell or tissue type under study, provided that some determinant input parameters are initially defined. Mathematical models can be used to predict, for instance, the tumor control probability (TCP), and then evaluate treatment outcomes. This work studies the influence of the LEM I input parameters on the TCP predictions in the specific case of prostate cancer. Several published input parameters and their combinations were tested. Their influence on the dose distributions calculated for a water phantom and for a patient geometry was evaluated using the TPS TRiP98. Changing input parameters induced clinically significant modifications of the mean dose (up to a factor of 3.5), spatial dose distribution, and TCP predictions (up to factor of 2.6 for D50). TCP predictions were found to be more sensitive to the parameter threshold dose (Dt) than to the biological parameters α and ß. Additionally, an analytical expression was derived for correlating α, ß and Dt, and this has emphasized the importance of [Formula: see text]. The improvement of radiobiological models for particle TPS will only be achieved when more patient outcome data with well-defined patient groups, fractionation schemes and well-defined end-points are available.

Monte Carlo study for designing a dedicated "D"-shaped collimator used in the external beam radiotherapy of retinoblastoma patients.

PURPOSE: Retinoblastoma is the most common intraocular malignancy in the early childhood. Patients treated with external beam radiotherapy respond very well to the treatment. However, owing to the genotype of children suffering hereditary retinoblastoma, the risk of secondary radio-induced malignancies is high. The University Hospital of Essen has successfully treated these patients on a daily basis during nearly 30 years using a dedicated "D"-shaped collimator. The use of this collimator that delivers a highly conformed small radiation field, gives very good results in the control of the primary tumor as well as in preserving visual function, while it avoids the devastating side effects of deformation of midface bones. The purpose of the present paper is to propose a modified version of the "D"-shaped collimator that reduces even further the irradiation field with the scope to reduce as well the risk of radio-induced secondary malignancies. Concurrently, the new dedicated "D"-shaped collimator must be easier to build and at the same time produces dose distributions that only differ on the field size with respect to the dose distributions obtained by the current collimator in use. The scope of the former requirement is to facilitate the employment of the authors' irradiation technique both at the authors' and at other hospitals. The fulfillment of the latter allows the authors to continue using the clinical experience gained in more than 30 years. METHODS: The Monte Carlo code PENELOPE was used to study the effect that the different structural elements of the dedicated "D"-shaped collimator have on the absorbed dose distribution. To perform this study, the radiation transport through a Varian Clinac 2100 C/D operating at 6 MV was simulated in order to tally phase-space files which were then used as radiation sources to simulate the considered collimators and the subsequent dose distributions. With the knowledge gained in that study, a new, simpler, "D"-shaped collimator is proposed. RESULTS: The proposed collimator delivers a dose distribution which is 2.4 cm wide along the inferior-superior direction of the eyeball. This width is 0.3 cm narrower than that of the dose distribution obtained with the collimator currently in clinical use. The other relevant characteristics of the dose distribution obtained with the new collimator, namely, depth doses at clinically relevant positions, penumbrae width, and shape of the lateral profiles, are statistically compatible with the results obtained for the collimator currently in use. CONCLUSIONS: The smaller field size delivered by the proposed collimator still fully covers the planning target volume with at least 95% of the maximum dose at a depth of 2 cm and provides a safety margin of 0.2 cm, so ensuring an adequate treatment while reducing the irradiated volume.

An indirect in vivo dosimetry system for ocular proton therapy.

Secondary radiation, particularly neutron radiation, is a cause of concern in proton therapy. However, one can take advantage of its presence by using it to retrieve useful information on the primary proton beam. At the Centre Antoine Lacassagne the secondary radiation in the treatment room has been studied in function of the beam modulation. A strong correlation was found between the secondary ambient dose equivalent per proton dose H*(10)/D and proton dose rate D/MU. A large volume ionisation chamber fixed on the wall at 2.5 m from the nozzle was used with an in-house computer interface to retrieve the value of D/MU derived from the measurement of photon H*(10) integrated over treatment time, using the correlation curve. This system enables the verification of D and D/MU to be made independently of the monitoring of the primary beam and represents a first step towards an alternative in vivo dosimetry in proton therapy.

Quantification of dose perturbations induced by external and internal accessories in ocular proton therapy and evaluation of their dosimetric impact.

PURPOSE: Proton scattering on beam shaping devices and protons slowing down on media with different densities within the treatment volume may produce dose perturbations and range variations that are not predicted by treatment planning systems. The aim of this work was to assess the dosimetric impact of elements present in ocular proton therapy treatments that may disturb the prescribed treatment plan. Both distal beam shaping devices and intraocular elements were considered. METHODS: A wedge filter, tantalum fiducial marker, hemispherical compensator, two intraocular endotamponades (densities 0.97 and 1.92 g cm(-3)) and an intraocular eye lens (IOL) were considered in the study. For these elements, longitudinal dose distributions were measured and∕or calculated in water in beam alignment for a clinical spread-out Bragg peak. Under the same conditions, the unperturbed dose distributions were similarly measured and∕or calculated in the absence of the element. The dosimetric impact was assessed by comparison of unperturbed and perturbed dose distributions. Measurements and calculations were carried out with two methods. Measurements are based on EBT3 films with dedicated software, which makes use of a calibration curve and correction for the quenching effect. Calculations are based on the Monte Carlo (MC) code MCNPX and reproduce the experimental conditions. Both dose maps are obtained with a resolution of 300 dpi. RESULTS: The degree of disturbance of distal beam shaping devices is low for the wedge filter (2% overdose ripple all along the central axis) and moderate for the hemispherical compensator (two bands of variable overdose of up to 10% downstream the compensator lateral edges and -5% underdose on the plateau at off-axis distance of 5 cm). Tantalum clips produce important dose shadows (-20% behind the clip parallel to the beam and range reduction of 1.1 mm) and bands of overdose (15%). The presence of endotamponades modifies the dose distribution very significantly (-5% underdose on the plateau and 3 mm range prolongation for the tamponade with density 0.97 g cm(-3) and -15% underdose on plateau and 8 mm range reduction for that with density 1.92 g cm(-3)). No dose perturbations were found for the IOL. The high performance of EBT3 film and MC tools used was confirmed and good agreement was found between them (percentage of pixels passing the gamma test >87%). CONCLUSIONS: The degree of disturbance by external beam shaping devices remains low in ocular proton therapy and can be reduced by bringing accessories closer to the eye. Tantalum fiducial markers must be located in such a way that dose perturbation is not projected on the tumor. The treatment of patients with intraocular endotamponades must be carefully managed. It is fundamental that radiation oncologists and medical physicists are informed about the presence of such substances prior to the treatment.

[Diagnosis and treatment of retinoblastoma: current strategies for effective tumour control and preservation of vision]. / Diagnose und behandlung des retinoblastoms: aktuelle konzepte zur sicheren tumorkontrolle bei erhalt des sehvermögens.

There are approximately 40 new cases of retinoblastoma in Germany per year. Children in whom the tumour is detected when still intraocular have an excellent overall survival rate (> 95%). However, the prognosis of metastasised retinoblastoma remains poor. About 40% of retinoblastoma patients have tumours in both eyes. For these children in particular it is important to save the eye and visual function as much as possible. There are several options for conservative treatment of localised retinoblastoma including laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. In recent years, systemic chemotherapy has become the established standard for primary treatment of intraocular retinoblastoma. In case series, intra-arterial, intravitreal and periocular applications of chemotherapy were also shown to be effective in treating intraocular retinoblastoma. Genetic testing is an integral part of the routine diagnostics of all patients. Mutation analysis of tumour material is invaluable for identification of somatic mutations including mutational mosaicism. Genetic testing also identifies children with heritable retinoblastoma, which represent 50% of cases. These children also have a predisposition for the development of tumours outside of the eye (second primary neoplasm). To adequately address these and other late effects in survivors of retinoblastoma, a multidisciplinary approach is needed that optimises therapy and long-term follow-up. Upcoming multicentre clinical trials will evaluate treatment concepts for localised and metastasised retinoblastoma to improve survival rates and quality of life of children with retinoblastoma. This article was translated and modified and was primarily published in Klin Padiatr 2012; 224: 339-347.

Accurate estimation of dose distributions inside an eye irradiated with 106Ru plaques.

BACKGROUND: Irradiation of intraocular tumors requires dedicated techniques, such as brachytherapy with (106)Ru plaques. The currently available treatment planning system relies on the assumption that the eye is a homogeneous water sphere and on simplified radiation transport physics. However, accurate dose distributions and their assessment demand better models for both the eye and the physics. METHODS: The Monte Carlo code PENELOPE, conveniently adapted to simulate the beta decay of (106)Ru over (106)Rh into (106)Pd, was used to simulate radiation transport based on a computerized tomography scan of a patient's eye. A detailed geometrical description of two plaques (models CCA and CCB) from the manufacturer BEBIG was embedded in the computerized tomography scan. RESULTS: The simulations were firstly validated by comparison with experimental results in a water phantom. Dose maps were computed for three plaque locations on the eyeball. From these maps, isodose curves and cumulative dose-volume histograms in the eye and for the structures at risk were assessed. For example, it was observed that a 4-mm anterior displacement with respect to a posterior placement of a CCA plaque for treating a posterior tumor would reduce from 40 to 0% the volume of the optic disc receiving more than 80 Gy. Such a small difference in anatomical position leads to a change in the dose that is crucial for side effects, especially with respect to visual acuity. The radiation oncologist has to bring these large changes in absorbed dose in the structures at risk to the attention of the surgeon, especially when the plaque has to be positioned close to relevant tissues. CONCLUSION: The detailed geometry of an eye plaque in computerized and segmented tomography of a realistic patient phantom was simulated accurately. Dose-volume histograms for relevant anatomical structures of the eye and the orbit were obtained with unprecedented accuracy. This represents an important step toward an optimized brachytherapy treatment of ocular tumors.

Radiotherapy for ocular tumours.

Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour.

Study of the secondary neutral radiation in proton therapy: toward an indirect in vivo dosimetry.

PURPOSE: Secondary particles produced in the collision of protons with beam modifiers are of concern in proton therapy. Nevertheless, secondary radiation can provide information on the dosimetric parameters through its dependency on the modulating accessories (range shifter and range modulating wheel). Relatively little data have been reported in the literature for low-energy proton beams. The present study aims at characterizing the neutron and photon secondary radiation at the low-energy proton therapy facility of the Centre Antoine Lacassagne (CAL), and studying their correlation to the dosimetric parameters to explore possible practical uses of secondary radiation in the treatment quality for proton therapy. METHODS: The Monte Carlo code MCNPX was used to simulate the proton therapy facility at CAL. Neutron and photon fluence, Φ, and ambient dose equivalent per proton dose, H∗(10)∕D, were determined across the horizontal main plane spanning the whole treatment room. H∗(10)∕D was also calculated at two positions of the treatment room where dosimetric measurements were performed for validation of the Monte Carlo calculations. Calculations and measurements were extended to 100 clinical spread-out Bragg Peaks (SOBPs) covering the whole range of therapeutic dose rates (D∕MU) employed at CAL. In addition, the values of D and MU were also calculated for each SOBP and the results analyzed to study the relationship between secondary radiation and dosimetric parameters. RESULTS: The largest production of the secondary particles takes place at the modulating devices and the brass collimators located along the optical bench. Along the beam line and off the beam axis to 2.5 m away, H∗(10)∕D values ranged from 5.4 µSv∕Gy to 5.3 mSv∕Gy for neutrons, and were 1 order of magnitude lower for photons. H∗(10)∕D varied greatly with the distance and angle to the beam axis. A variation of a factor of 5 was found for the different range of modulations (SOBPs). The ratios between calculations and measurements were 2.3 and 0.5 for neutrons and photons, respectively, and remained constant for all the range of SOBPs studied, which provided validation for the Monte Carlo calculations. H∗(10)∕D values were found to correlate to the proton dose rate D∕MU with a power fit, both for neutrons and photons. This result was exploited to implement a system to obtain D∕MU values from the measurement of the integrated photon ambient dose equivalent H∗(10) during treatment, which provides a method to control the dosimetric parameters D∕MU and D. CONCLUSIONS: The treatment room at CAL is moderately polluted by secondary particles. The constant ratio between measurements and calculations for all SOBPs showed that simulations correctly predict the dosimetric parameters and the dependence of the production of secondary particles on the modulation. The correlation between H∗(10)∕D and D∕MU is a useful tool for quality control and is currently used at CAL. This system works as an indirect in vivo dosimetry method, which is so far not feasible in proton therapy. This tool requires very simple instrumentation and can be implemented from the measurement of either photons or neutrons.

Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming for safe tumor control and vision preservation.

Retinoblastoma affects approximately 40 children in Germany per year. Most children are diagnosed early with localized intraocular disease, and the overall survival rate exceeds 95%. However, the prognosis of metastasized retinoblastoma remains poor. In 40% of the patients, retinoblastoma occurs bilaterally and, especially for these children, the salvage of the eye and visual function is of major importance. The variety of conservative treatment options for localized retinoblastoma includes laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. While systemic chemotherapy has nearly completely replaced external beam radiotherapy in the primary treatment of intraocular retinoblastoma, intra-arterial, intravitreal and periocular application of chemotherapy was also shown to be effective in treating intraocular retinoblastoma in case series. Genetic testing is an integral part of the routine diagnostics of all patients. Available tumor material should be analyzed to detect mutational mosaicism, that affects >10% of children with unilateral retinoblastoma. Genetic testing also identifies children with heritable (50% of patients) retinoblastoma. These children have a genetic predisposition for second malignancies. For this reason, late effects are an increasing concern and the care of patients with retinoblastoma requires a multidisciplinary approach to tailor therapy and long-term follow-up. Multicenter clinical trials are being developed to evaluate evidence-based treatment concepts for localized and metastasized retinoblastoma to improve survival rates and quality of life of children with retinoblastoma.

Retinoblastoma external beam photon irradiation with a special 'D'-shaped collimator: a comparison between measurements, Monte Carlo simulation and a treatment planning system calculation.

Retinoblastoma is the most common eye tumour in childhood. According to the available long-term data, the best outcome regarding tumour control and visual function has been reached by external beam radiotherapy. The benefits of the treatment are, however, jeopardized by a high incidence of radiation-induced secondary malignancies and the fact that irradiated bones grow asymmetrically. In order to better exploit the advantages of external beam radiotherapy, it is necessary to improve current techniques by reducing the irradiated volume and minimizing the dose to the facial bones. To this end, dose measurements and simulated data in a water phantom are essential. A Varian Clinac 2100 C/D operating at 6 MV is used in conjunction with a dedicated collimator for the retinoblastoma treatment. This collimator conforms a 'D'-shaped off-axis field whose irradiated area can be either 5.2 or 3.1 cm(2). Depth dose distributions and lateral profiles were experimentally measured. Experimental results were compared with Monte Carlo simulations' run with the penelope code and with calculations performed with the analytical anisotropic algorithm implemented in the Eclipse treatment planning system using the gamma test. penelope simulations agree reasonably well with the experimental data with discrepancies in the dose profiles less than 3 mm of distance to agreement and 3% of dose. Discrepancies between the results found with the analytical anisotropic algorithm and the experimental data reach 3 mm and 6%. Although the discrepancies between the results obtained with the analytical anisotropic algorithm and the experimental data are notable, it is possible to consider this algorithm for routine treatment planning of retinoblastoma patients, provided the limitations of the algorithm are known and taken into account by the medical physicist and the clinician. Monte Carlo simulation is essential for knowing these limitations. Monte Carlo simulation is required for optimizing the treatment technique and the dedicated collimator.

Chromosomal aberrations in peripheral blood lymphocytes exposed to a mixed beam of low energy neutrons and gamma radiation.

Cells exposed to thermal neutrons are simultaneously damaged by radiations with high and low linear energy transfer (LET). A question relevant for the assessment of risk of exposure to a mixed beam is whether the biological effect of both radiation types is additive or synergistic. The aim of the present investigation was to calculate whether the high and low LET components of a thermal neutron field interact when damaging cells. Human peripheral blood lymphocytes were exposed to neutrons from the HB11 beam at the Institute for Energy and Transport, Petten, Netherlands, in a 37 °C water phantom at varying depths, where the mix of high and low LET beam components differs. Chromosomal aberrations were analysed and the relative biological effectiveness (RBE) values as well as the expected contributions of protons and photons to the aberration yield were calculated based on a dose response of aberrations in lymphocytes exposed to (60)Co gamma radiation. The RBE for 10 dicentrics per 100 cells was 3 for mixed beam and 7.2 for protons. For 20 dicentrics per 100 cells the respective values were 2.4 and 5.8. Within the limitations of the experimental setup the results indicate that for this endpoint there is no synergism between the high and low LET radiations.

[Malignant epibulbar tumours: new strategies in diagnostics and therapy]. / Maligne epibulbäre Tumoren: Neue Strategien in Diagnostik und Therapie.

In this article we discuss the complex diagnostic approaches and therapeutic options for the most important conjunctival malignancies. Conjunctival melanoma can be a diagnostic challenge as it can be difficult to distinguish from benign melanocytic conjunctival tumours. Complete surgical excision accompanied by a coherent adjuvant concept is the key for a curative therapy. Moderate and severe conjunctival intraepithelial neoplasias (CIN) are precancerous lesions and can progress to invasive squamous cell carcinoma. The involvement of large parts of the ocular surface can prevent an R 0-resection. Adjuvant therapeutic concepts are therefore especially important to gain tumour control and preserve the function of the affected eye. Lymphomas are the most common malignant primary tumours of the orbit and ocular adnexa. They can present as primary or secondary tumours of the conjunctiva, the lacrimal gland, the orbital fat, the eye lid or the lacrimal sac. The most common manifestation site of ocular MALT lymphoma is the conjunctiva with 20 - 33 % of all epibulbar lymphomas. More than 75 % of ocular lymphoma patients develop only one lymphomatous lesion. Immunophenotyping allows the exact differentiation between the lymphoma entities. Infectious agents (e.g., Chlamydia psittaci) seem to play a role in the pathogenesis. An overview over radiotherapeutic approaches that are conclusively applicable at the conjunctiva completes the article.