Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience.

PURPOSE: The purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique. PATIENTS AND METHODS: In a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined. RESULTS: The median age of this series of 832 women was 61.5 years (range: 29-90 years). Various types of fractionation were used: 50Gy in 25 fractions (17.9%), 66Gy in 33 fractions (50Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66Gy in 33 fractions.) (46.5%), 40Gy in 15 fractions or 41.6Gy in 13 fractions (26.1%) and 30Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P=0.2). In this population of 36 patients, 28 (3.3%) had "in-breast" local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P<0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P<0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P=0.14). CONCLUSION: The results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.

[Locoregional control and patterns of locoregional failure in women with breast cancer treated by highly conformal electron beam irradiation]. / Caractérisation des rechutes locorégionales chez des patientes atteintes d'un cancer du sein traité par irradiation pariétale par électrons : expérience monocentrique de l'institut Curie.

PURPOSE: The purpose of this study was to evaluate locoregional control and describe the patterns of locoregional failure in women with breast cancer irradiated by a previously described post-mastectomy highly conformal electron beam radiotherapy technique. MATERIAL AND METHODS: We included all women irradiated by post-mastectomy highly conformal electron beam radiotherapy technique for non-metastatic breast cancer between 2007 and 2011 in our department. All cases of bilateral breast cancer were excluded. All patients who experienced locoregional recurrence have been studied. Mapping patterns of regional recurrences was also performed and compared with the European Society for Radiotherapy and Oncology (ESTRO) and Radiotherapy Oncology Group (RTOG) guidelines of volume definition and delineation guidelines. RESULTS: With a median follow-up of 64 months (range: 6-102 months), 5-year locoregional recurrence-free and overall survival probabilities were 90 % (95 % confidence interval [95 %CI]: 88.1-92.4) and 90.9 % (95 %CI: 88.9-93), respectively. Among the 796 patients included in the study, 23 patients (2.9 %) presented locoregional recurrences of them only 13 (1.6%) were presented with local recurrence. The majority of them presented aggressive biological features with grade III tumours in 17 patients (74 %) with high mitotic index in 16 cases (70 %) and triple negative tumours in 12 (52 %). Lymphovascular invasion was observed in 11 cases (48 %). In 14 cases the locoregional recurrences were diagnosed at the same time as the metastatic disease whereas 4 patients presented distant metastases secondarily. Locoregional recurrences occurred in 11 cases "in field" although adequate doses and volumes were used and in 12 cases "outfield", out of irradiated volume. Local recurrences occurred in 13 patients with 12 recurrences within the irradiated volumes. Regional recurrences occurred in 13 patients with 15 lymph nodes metastases identified. Four nodal recurrences occurred outside the ESTRO clinical target volume and within the RTOG clinical target volume and two occurred outside both RTOG and ESTRO clinical target volumes. CONCLUSION: In presented series, the local recurrence resulted mostly from of biologic radio resistance whereas regional recurrences were caused by geographical miss. A number of nodal recurrences could occur outside the target volumes defined by ESTRO and RTOG.

Comparison of passive-beam proton therapy, helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy.

PURPOSE: Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy. PATIENTS AND METHODS: Fourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy. RESULTS: Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P<0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy. CONCLUSIONS: Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.

Proton minibeam radiation therapy: Experimental dosimetry evaluation.

PURPOSE: Proton minibeam radiation therapy (pMBRT) is a new radiotherapy (RT) approach that allies the inherent physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. This dosimetry work aims at demonstrating the feasibility of the technical implementation of pMBRT. This has been performed at the Institut Curie - Proton Therapy Center in Orsay. METHODS: Proton minibeams (400 and 700 µm-width) were generated by means of a brass multislit collimator. Center-to-center distances between consecutive beams of 3200 and 3500 µm, respectively, were employed. The (passive scattered) beam energy was 100 MeV corresponding to a range of 7.7 cm water equivalent. Absolute dosimetry was performed with a thimble ionization chamber (IBA CC13) in a water tank. Relative dosimetry was carried out irradiating radiochromic films interspersed in a IBA RW3 slab phantom. Depth dose curves and lateral profiles at different depths were evaluated. Peak-to-valley dose ratios (PVDR), beam widths, and output factors were also assessed as a function of depth. RESULTS: A pattern of peaks and valleys was maintained in the transverse direction with PVDR values decreasing as a function of depth until 6.7 cm. From that depth, the transverse dose profiles became homogeneous due to multiple Coulomb scattering. Peak-to-valley dose ratio values extended from 8.2 ± 0.5 at the phantom surface to 1.08 ± 0.06 at the Bragg peak. This was the first time that dosimetry in such small proton field sizes was performed. Despite the challenge, a complete set of dosimetric data needed to guide the first biological experiments was achieved. CONCLUSIONS: pMBRT is a novel strategy in order to reduce the side effects of RT. This works provides the experimental proof of concept of this new RT method: clinical proton beams might allow depositing a (high) uniform dose in a brain tumor located in the center of the brain (7.5 cm depth, the worst scenario), while a spatial fractionation of the dose is retained in the normal tissues in the beam path, potentially leading to a gain in tissue sparing. This is the first complete experimental implementation of this promising technique. Biological experiments are needed in order to confirm the clinical potential of pMBRT.

[Irradiation of internal mammary nodes: State of the art]. / État de l'art de l'irradiation des ganglions de la chaîne mammaire interne.

In the adjuvant breast cancer treatment, postoperative radiotherapy plays a principal part with an action against the microscopic residual disease in the lymph nodes after mastectomy as well as after breast conserving surgery. This positive effect is observed also in the case of small inner lesions in patients without lymph node involvement. At the same time, there is a recognized risk of cardiac toxicity directly related to the irradiation of internal mammary nodes. This paper is a report on the current available techniques to irradiate the internal mammary nodes, including promising new technology that may help limiting the risk of cardiac toxicity.

Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy.

OBJECTIVE: To determine the relationship between the dose to the inner ear or pituitary gland and radiation-induced late effects of skull base radiation therapy. METHODS: 140 patients treated between 2000 and 2008 were considered for this study. Hearing loss and endocrine dysfunction were retrospectively reviewed on pre- and post-radiation therapy audiometry or endocrine assessments. Two normal tissue complication probability (NTCP) models were considered (Lyman-Kutcher-Burman and log-logistic) whose parameters were fitted to patient data using receiver operating characteristics and maximum likelihood analysis. The method provided an estimation of the parameters of a generalized equivalent uniform dose (gEUD)-based NTCP after conversion of dose-volume histograms to equivalent doses. RESULTS: All 140 patients had a minimum follow up of 26 months. 26% and 44% of patients experienced mild hearing loss and endocrine dysfunction, respectively. The fitted values for TD50 and γ50 ranged from 53.6 to 60.7 Gy and from 1.9 to 2.9 for the inner ear and were equal to 60.6 Gy and 4.9 for the pituitary gland, respectively. All models were ranked equal according to Akaike's information criterion. CONCLUSION: Mean dose and gEUD may be used as predictive factors for late ear and pituitary gland late complications after skull base proton and photon radiation therapy. ADVANCES IN KNOWLEDGE: In this study, we have reported mean dose effects and dose-response relationship of small organs at risk (partial volumes of the inner ear and pituitary gland), which could be useful to define optimal dose constraints resulting in an improved therapeutic ratio.

Plastic surgery for breast conservation therapy: how to define the volume of the tumor bed for the boost?

PURPOSE: To describe the procedure of definition of the boost volume using pre- and post-operative computed tomography (CT) and surgical clips in the tumor bed after oncoplastic surgical procedure. PATIENTS AND METHODS: Thirty-one consecutive breast cancer patients who underwent simple lumpectomy or oncoplastic surgery were studied. All of them underwent pre- and post-operative CT scan in treatment position to evaluate the planning target volume (PTV) boost volume and define the primary tumor (gross tumor volume (GTV)) and tumor bed zones (CTV), with an overall margin of 5 mm in lateral and 10 mm in craniocaudal directions, corresponding to localization and setup uncertainties. RESULTS: Thirteem patients underwent simple lumpectomy and 18 oncoplastic surgery. The volumetric analysis showed that the intersection between GTV and CTV clips was significantly higher in patients with three and more clips (28.4% vs 3.14%; p < 0.001). In the case of patients with oncoplastic surgery, more than three clips were needed to define the tumor bed volume with accuracy. The number of clips was directly related to the exact definition of the boost volume. CONCLUSIONS: The use of more than three clips allows better definition of the PTV boost volume after oncoplastic surgical procedure.

[Preliminary results of whole breast helical tomotherapy with simultaneous integrated boost in the adjuvant treatment of breast cancer]. / Résultats préliminaires d'une tomothérapie hélicoïdale adjuvante avec boost intégré dans le cadre d'un traitement conservateur d'un cancer du sein.

PURPOSE: To evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery. PATIENTS AND METHODS: Twenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8 Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. RESULTS: Twenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % ± 0.5 SD, V95 = 98.4 % ± 1.9 SD; PTV breast: -V107 = 7.8 % ± 17.3 SD, V95 = 96.8 % ± 2.2 SD; PTV LN: V107 = 2.5 % ± 4.2 SD, V95 = 92.7 % ± 13.2 SD. The mean V20 of the homolateral lung was 18.9 % ± 3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 % ± 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 % ± 11.8 ET, controlateral lung: 38.9 % ± 21, heart (left side breast): 57.3 % ± 21, controlateral breast: 15.5 % ± 9.6. Median shifts were as follow: x-axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm ± 5.51 (IC 95: -0.88 +0.14), z-axis 2.90 mm ± 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 ± 1.10 (IC 95: -0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity. CONCLUSIONS: Helical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies.

Visualisation of the left anterior descending coronary artery on CT images used for breast radiotherapy planning.

OBJECTIVE: To assess the visualisation of the left anterior descending (LAD) coronary artery on CT images used for breast radiation treatment planning. METHODS: Delineation of the LAD artery was achieved for 25 breast patients by 1 radiologist and 1 radiation oncologist independently on two sets of images for each patient: one pre-operative CT scan using intravenous (IV) contrast media to determine the primary gross tumour volume (GTV) and one post-operative CT scan used for treatment planning. A Student's paired t-test was used to compare the number of CT slices in which the LAD was visible for each patient in the two series. Interpolations and extrapolations of the LAD volume were performed for the left-sided cases using a published heart atlas in order to report doses to the LAD structure. RESULTS: There was a non-significant difference between the results with and without IV contrast media (p=0.34 for the radiologist; p=0.90 for the radiation oncologist). The visible LAD artery corresponded to a 30% portion (range 12-47%) of the interpolated structure. The maximum dose to the left artery varied widely, from 2.7 to 41.7 Gy, in the group of patients with left breast tumours. The largest values (>25 Gy) corresponded to those patients in whom the LAD artery distal extremity lay inside the breast fields. CONCLUSIONS: With the current planning CT protocol, only one-third of the LAD artery could be objectively visualised. Contrast-enhanced imaging used for GTV delineation before the breast surgery did not improve the visualisation of the artery. ADVANCES IN KNOWLEDGE: This study has revealed the lack of consistency that may be encountered when contouring heart vessels, thereby questioning the reliability of dose reporting.

Potential benefits of using cardiac gated images to reduce the dose to the left anterior descending coronary during radiotherapy of left breast and internal mammary nodes.

PURPOSE: To assess the benefits of using cardiac gated images for treatment planning of breast and internal mammary nodes. PATIENTS AND METHODS: Inspiration breath hold computed tomography (CT) series acquired at prospectively gated diastolic phase were used for planning. Three different techniques were compared. Technique A used tangents and an internal mammary nodes field covering the three first inter-rib spaces; technique B used an extended internal mammary nodes including part of the medial breast in junction with tangential fields; the 3(rd) technique used helical tomotherapy. For each technique, two treatment plans were performed: one plan (plan-01) where mean dose and V(25) to the heart were considered for plan evaluation and a second plan (plan-02) where the irradiation of the left anterior descending artery was minimized. RESULTS: V(25) to the heart was found to be less than 5% for all six plans. Mean doses to the heart were within 4.8 to 7.2 Gy. By attempting to lower the dose to the left anterior descending artery, heart D(mean) was decreased by 20-30% for the two techniques A and B while being unchanged for tomotherapy. Regarding target coverage, there was no marked difference between plans where only heart dose was considered (plans-01) and plans where the left anterior descending artery dose was minimized (plans-02). When the left anterior descending artery dose was part of plan evaluation, D(mean) to the left anterior descending artery could be decreased by 24, 19 and 9% for techniques A, B and tomotherapy respectively. The three techniques exposed segments of the left coronary to different levels of dose. CONCLUSION: This study showed that evaluation of the dose to the left anterior descending artery coronary may change the treatment strategy. Cardiac gated images without IV contrast permitted a good visualization of the coronaries in order to optimize the dose on these structures. In addition to heart V(25,) the dose to the coronaries should be included in prospective studies on radiotherapy related heart toxicity in association with all additional risk factors.

[Radiotherapy for breast cancer and pacemaker]. / Radiothérapie pour un cancer du sein et stimulateur cardiaque.

PURPOSE: Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients. PATIENTS AND METHODS: From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist. RESULTS: Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy. CONCLUSION: The multidisciplinary work with position change of the pacemaker before radiotherapy and everyday monitoring permitted the safe treatment of our patients. Updated guidelines are definitely needed with more details about acceptable doses at the different parts of the pacemaker.

Simplified rules for everyday delineation of lymph node areas for breast cancer radiotherapy.

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas "Help of delineation for breast cancer treatment". In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.

[Definition of nodal volumes in breast cancer treatment and segmentation guidelines]. / Définition des volumes ganglionnaires dans le cadre du traitement d'un cancer du sein et règles de contourage.

PURPOSE: To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented: heart, lungs, contralateral breast, thyroid, esophagus and humeral head. RESULTS: A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas. CONCLUSION: A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.

Anatomical, clinical and radiological delineation of target volumes in breast cancer radiotherapy planning: individual variability, questions and answers.

The purpose of the study was to evaluate the individual variability of anatomical and radiological delineation for breast cancer radiotherapy (RT) in preparation for new techniques and to propose practical solutions to improve delineation in everyday practice. In the first phase, a patient with stage T3N3M0 breast cancer and complete response after neoadjuvant chemotherapy was assessed by CT scan in the treatment position before RT. 11 radiation oncologists (5 breast cancer specialists and 6 residents) independently delineated the breast and lymph node (LN) regions before definition of target volumes. Organs at risk (heart, lung, thyroid and brachial plexus) were also delineated. All regions (breast, axilla, supraclavicular LN, infraclavicular LN and internal mammary chain) were delineated and compared in terms of volume. Comparative analysis was performed with Aquilab software. Differences in the clinical and radiological assessment were observed between the various radiation oncologists. Simplified rules of delineation were developed in the department. Using these rules, the second patient's CT was delineated by the same physicians and better results were observed. Simplified rules of delineation were developed. In conclusion, major differences in anatomical and radiological delineation for breast cancer RT were observed among the physicians. This study led to the development of written delineation protocols. The study is ongoing with evaluation of the dosimetric impact and definition of different target volumes.

Technique alternatives for breast radiation oncology: Conventional radiation therapy to tomotherapy.

Breast conserving radiotherapy uses tangential fields and compensating wedges. This conventional approach can be improved by a field-in-field technique using the linac multi-leaf collimator (MLC). A simplified field-in-field technique that planners can easily achieve and which improves dose uniformity in the breast volume is presented here. Field junction problems are more easily solved by the use of a virtual simulation. A unique isocenter can be set at the junction between the supra-clavicular field and the breast tangential fields. However, careful quality assurance of the treatment planning system must be performed. Tomotherapy has promising clinical advantages: the ability of a tomographic image to correct for random set-up errors, a continuous cranio-caudal delivery which suppresses junction problems, the conformality of the dose distribution throughout the complex volumes formed by the lymph nodes and the breasts. Tomotherapy is a valuable recourse for complex irradiations like bilateral breast or mammary plus axillary irradiation while a field-in-field associated with a unique isocenter technique can be used for majority of the patients.

[Radiotherapy for breast cancer: respiratory and set-up uncertainties]. / Irradiation du cancer du sein: incertitudes liées aux mouvements respiratoires et au repositionnement.

Adjuvant Radiotherapy has been shown to significantly reduce locoregional recurrence but this advantage is associated with increased cardiovascular and pulmonary morbidities. All uncertainties inherent to conformal radiation therapy must be identified in order to increase the precision of treatment; misestimation of these uncertainties increases the potential risk of geometrical misses with, as a consequence, underdosage of the tumor and/or overdosage of healthy tissues. Geometric uncertainties due to respiratory movements or set-up errors are well known. Two strategies have been proposed to limit their effect: quantification of these uncertainties, which are then taken into account in the final calculation of safety margins and/or reduction of respiratory and set-up uncertainties by an efficient immobilization or gating systems. Measured on portal films with two tangential fields, CLD (central lung distance), defined as the distance between the deep field edge and the interior chest wall at the central axis, seems to be the best predictor of set-up uncertainties. Using CLD, estimated mean set-up errors from the literature are 3.8 and 3.2 mm for the systematic and random errors respectively. These depend partly on the type of immobilization device and could be reduced by the use of portal imaging systems. Furthermore, breast is mobile during respiration with motion amplitude as high as 0.8 to 10 mm in the anteroposterior direction. Respiratory gating techniques, currently on evaluation, have the potential to reduce effect of these movements. Each radiotherapy department should perform its own assessments and determine the geometric uncertainties with respect of the equipment used and its particular treatment practices. This paper is a review of the main geometric uncertainties in breast treatment, due to respiration and set-up, and solutions proposed to limit their impact.

Smoothing intensity-modulated beam profiles to improve the efficiency of delivery.

Intensity-modulated beam profiles are generated by an inverse planning or optimization algorithm, a process that, being computationally complex and intensive, is inherently susceptible to noise and numerical artifacts. These artifacts make delivery of the beams more difficult, oftentimes for little, if any, observable improvement in the dose distributions. In this work we examine two approaches for smoothing the beam profiles. The first approach is to smooth the beam profiles subsequent to each iteration in the optimization process (method A). The second approach is to include a term within the objective function that specifies the smoothness of the profiles as an optimization criterion (method B). The two methods were applied to a phantom study as well as three clinical sites: paraspinal, nasopharynx, and prostate. For the paraspinal and nasopharynx cases, which have critical organs with low tolerance doses in close proximity, method B produced sharper dose gradients, better target dose homogeneity, and more critical organ sparing. In the less demanding prostate case, the two methods give similar results. In addition, method B is more efficient during optimization, requiring fewer iterations, but less efficient during DMLC delivery, requiring a longer beam-on time.

Dose rate definition with microSelectron-HDR and Selectron-MDR in brachytherapy for carcinoma of the cervix.

BACKGROUND: Reproducibility of dose rate at point A is the main characteristic of Manchester system for dose prescription for cancer cervix brachytherapy. Here, we investigated dose rate variations at point A in the application of Selectron-MDR and microSelectron-HDR. MATERIALS AND METHODS: All applications were compared for their physical aspects (loading and geometry). Two points A(rev) and A(or) (revised and original definitions) were checked for dose rate variations. Here we proposed a tool "dose rate radium equivalent" (Ra-eq.DR) to cancel the effect of source decay on the variation of dose rate values. RESULTS: Both techniques showed very similar geometry, tandem-ovoid loading ratio, and Ra-eq.DR at A(rev) and A(or). However, the best reproducibility of dose rate was achieved with A(or). Also, time variable-dose rate definition affected the difference between the 2 treatments modalities. CONCLUSIONS: Clear definition of both the point of dose prescription and the time variable used for dose rate calculation are important for brachytherapy for cancer of the cervix.

HDR and MDR intracavitary treatment for carcinoma of the uterine cervix. A prospective randomized study.

AIM: Treatment of carcinoma of the uterine cervix by remote afterloading brachytherapy has been accompanied with new isotopes having dose rates different from the classical low-dose rate (LDR) radium source. The dose rate conversion factor from LDR to high-dose rate (HDR) found to be around 0.54 in most studies. As regards medium-dose rate (MDR) brachytherapy, the published data are very few and the experience is still short. In this study the experience of Osaka University Hospital with micro-HDR-Selectron and Selectron-MDR, as a preliminary report of the clinical trial, is presented. PATIENTS AND METHOD: From August 1991 through April 1993, a total of 45 patients with carcinoma of the uterine cervix were randomly allocated to either microSelectron-HDR or Selectron-MDR at the Osaka University Hospital. As regards HDR, dose to point A was adjusted to 32 Gy (for stages I and II). 30 Gy/4 fractions, and 22.5 Gy/3 fractions, for stages III, and IV, respectively. The corresponding values in case of MDR were 35.6, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. External irradiation, according to the stage, was the same in the 2 groups. Nucletron Planning System (NPS) was used for pre-treatment dose calculation at point A, rectal and bladder wall. The dose rate at point A ranged from 24 to 75.6 cGy/min for the HDR group, while for the MDR group ranged among 174.8 to 229.6 cGy/h. RESULTS: The 3-year survival and loco-regional control rates for both modalities were nearly equivalent (62% and 67% for HDR and 68% and 74% for MDR). The cumulative rectal and bladder complication rates were the same in both groups (29% at 3 years), with only 1 patient (MDR-group) developed grade 3 rectal and bladder complication. In this study, point A dose rate correction factor from LDR to HDR was 0.53 and 0.6 from LDR to MDR. CONCLUSIONS: From the previous reports from Osaka University Medical School, as well as others, HDR was proposed as an alternative to LDR brachytherapy for treatment of carcinoma of the uterine cervix. In this report, Selectron-MDR was nearly equivalent to the microSelectron-HDR as regards survival and loco-regional control rates as well as radiation-induced complication. This is a preliminary report, and the study still needs larger number of patients, and longer follow-up period.

Comparison of radiobiological effective depths in 65-MeV modulated proton beams.

To assess the achievement of uniformity of radiobiological effectiveness at different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research Center for Nuclear Physics (RCNP) of Osaka University. We selected four different irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and 23 mm depths, corresponding to different positions in the SOBP. Cell survival curves were generated with the in vitro colony formation method and fitted to the linear-quadratic model. With 137Cs gamma-rays as the reference irradiation, the relative biological effectiveness (RBE) values for a surviving fraction (SF) level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm respectively. A significant difference was found between the survival curves at 10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm. There was a significant dependence of RBE on depths in modulated proton beams at the 0.1 surviving fraction level (P < 0.05). Moreover, the rise of RBEs significantly depended on increasing SF level or decreased approximately in correspondence with irradiation dose (P = 0.0001). To maintain uniformity of radiobiological effectiveness for the target volume, careful attention should be paid to the influence of depth of beam and irradiation dose.