Probability Of Local Control Research Articles

Carcinoma of the nasal cavity and paranasal sinuses

To determine the outcomes after radiotherapy (RT) alone or combined with surgery at the University of Florida for patients with carcinomas of the nasal cavity and paranasal sinuses. Between November 1964 and June 2005, 109 patients were treated with curative intent. Patients with maxillary sinus carcinomas were excluded. Fifty-six patients were treated with definitive RT, and 53 patients received surgery and preoperative (eight patients) or postoperative (45 patients) RT. Median follow-up was 4.3 years (range, 0.2-35.9 years). Median follow-up on living patients was 9.4 years (range, 2.0-35.9 years). The 5-year local control rates were: T1-T3, 82%; T4, 50%; and overall, 63%. Local control at 5 years was 43% after definitive RT versus 84% after surgery and adjuvant RT (P < .0001). Multivariate analysis of local control revealed that both overall stage and treatment group (definitive RT versus surgery and adjuvant RT) significantly impacted this endpoint. Cause-specific survival rates were: stages I to III, 81%; stage IV, 54%; and overall, 62%. Multivariate analysis revealed that T-stage, N-stage, and treatment group significantly influenced this endpoint. Thirty-one (20%) of 109 patients sustained severe complications; 17 of 56 patients (16%) after definitive RT and 14 of 53 patients (25%) after surgery and adjuvant RT. The probability of local control and cause-specific survival is better after surgery and RT compared with definitive RT. There is a modest increase in the risk of complications after surgery and RT. Thus, the preferred treatment is surgery combined with preoperative or postoperative RT.

Comparison of predicted and clinical response to radiotherapy: A radiobiology modelling study

Introduction. A model to predict clinical outcome after radiation therapy would be a valuable aid in the effort of developing more tailored treatment regimes for different patients. In this work we evaluate the clinical utility of a model that incorporates the following individually measured radiobiology parameters: intrinsic radiosensitivity, proliferation and number of clonogenic cells. The hypothesis underlying the study was that the incorporation of individually measured tumour parameters in a model would increase its reliability in predicting treatment outcome compared with the use of average population derived data. Material and methods. Forty-six patients with head and neck tumours were analyzed, the majority of whom received both external beam radiotherapy and brachytherapy. Eighteen patients received external beam treatment alone and statistical analyses were carried out on this subgroup. Results. Four of the 18 patients had a >95% calculated probability of cure and none developed a local recurrence resulting in a negative predictive value of 100% (compared with 67% for population-derived data). The sensitivity of the model in predicting local recurrence was 75% (compared with 38% for population-derived data). Using a model that incorporated individually measured radiobiology data, there was a statistically significant difference in local control levels for patients with >95% and <5% predicted probability of local control (χ2, p = 0.04). Discussion. This study suggests, therefore, that incorporation of measured biological data within a radiobiological model improves its ability to predict radiation therapy outcome compared with the use of population-derived data.

Sphere of Equivalence—A Novel Target Volume Concept for Intraoperative Radiotherapy Using Low-Energy X Rays

Accelerated partial breast radiotherapy with low-energy photons from a miniature X-ray machine is undergoing a randomized clinical trial (Targeted Intra-operative Radiation Therapy [TARGIT]) in a selected subgroup of patients treated with breast-conserving surgery. The steep radial dose gradient implies reduced tumor cell control with increasing depth in the tumor bed. The purpose was to compare the expected risk of local recurrence in this nonuniform radiation field with that after conventional external beam radiotherapy. The relative biologic effectiveness of low-energy photons was modeled using the linear-quadratic formalism including repair of sublethal lesions during protracted irradiation. Doses of 50-kV X-rays (Intrabeam) were converted to equivalent fractionated doses, EQD2, as function of depth in the tumor bed. The probability of local control was estimated using a logistic dose-response relationship fitted to clinical data from fractionated radiotherapy. The model calculations show that, for a cohort of patients, the increase in local control in the high-dose region near the applicator partly compensates the reduction of local control at greater distances. Thus a "sphere of equivalence" exists within which the risk of recurrence is equal to that after external fractionated radiotherapy. The spatial distribution of recurrences inside this sphere will be different from that after conventional radiotherapy. A novel target volume concept is presented here. The incidence of recurrences arising in the tumor bed around the excised tumor will test the validity of this concept and the efficacy of the treatment. Recurrences elsewhere will have implications for the rationale of TARGIT.

Cutaneous Squamous Cell Carcinoma Metastatic to Parotid‐Area Lymph Nodes

Metastatic spread to parotid-area lymph nodes (PALN) occurs in 1% to 3% of patients with cutaneous squamous cell carcinoma of the head and neck. Presented herein is the University of Florida experience using radiation therapy (RT) to treat patients with PALN metastases from a skin primary. From November 1969 to February 2005, 121 parotids in 117 patients received irradiation for nonmelanotic skin carcinoma metastatic to PALN. Patients were staged by the O'Brien staging system. Of the 121 parotids receiving RT, 17 (14%) were treated preoperatively, 87 (72%) postoperatively, and 17 with RT alone. Five-year actuarial probabilities of local (parotid) control, local-regional control, disease-free survival and overall survival were 78%, 74%, 70%, and 54%, respectively. When patients were separated by O'Brien P-stage, statistically significant differences were seen among the groups for local (parotid) control, local-regional control, and disease-free survival. A statistically significant decrease in local control was seen in patients treated with positive surgical margins (92% vs. 76%) and in local-regional control for patients treated with preoperative RT or RT alone when compared with postoperative RT (59% and 47% vs. 83%, respectively). The 5-year actuarial probability of freedom from distant metastases was 92%. Three (2.6%) patients suffered severe complications. PALN metastases from a cutaneous head and neck primary site are best treated with surgery and postoperative RT. Our data support the hypothesis that the O'Brien staging system is superior to the American Joint Committee on Cancer system for the staging of cutaneous metastases to PALN. Positive surgical margins confer a worse prognosis in terms of local-regional control and disease-free survival. Patients treated with preoperative RT seem to have a worse prognosis than those treated postoperatively, likely a result of patient selection and the surgeon's inability to accurately assess viable tumor extent after preoperative RT. Severe complications are uncommon after surgery and RT for PALN metastases.

Postoperative Radiotherapy for Patients with Intracranial Ependymoma: Patterns of Failure and Role of Craniospinal Radiotherapy

To analyze the outcome of intracranial ependymoma patients treated with surgery and postoperative radiotherapy and to evaluate the role of craniospinal radiotherapy (CSRT). From January 1979 through June 2006, 70 patients with intracranial ependymoma received radiotherapy with curative intent at our institution. World Health Organization (WHO) Grade I, II, and III ependymoma were found in 1, 56, and 13, respectively. The median patient age was 9.7 years (range, 1.3-62.7 years). The majority of patients were male (59%), and had infratentorial tumor (83%). Seven patients (10%) had M+ disease at initial diagnosis. Gross total resection was achieved in 21 patients (30%), near total resection in 14 (20%), subtotal resection in 29 (41%), partial resection in 4 (6%), and biopsy only in 2 (3%). All patients received postoperative radiotherapy to a median total dose of 54 Gy (range, 44.7-61.2 Gy). A CSRT was used in 40 patients (57%). Median radiotherapy treatment duration was 48 days (range, 37-104 days). Twelve patients (17%) received chemotherapy. The median follow-up duration was 52 months (range, 3 ∼228). The 5-year and 10-year overall survival (OS) rates for all patients were 86.2% and 62.9%, respectively. The 5-year and 10-year progression free survival (PFS) rates for all patients were 46.3% and 34.9%, respectively. The 5-year and 10-year OS rates for patients aged ≤4 years were 70.6% and 34.9%, compared with 91.8% and 75.8% for patients aged >4 years (p = 0.041). For 63 patients with M0 disease, there were no significant differences in OS, PFS, and leptomeningeal failure rates between the patients with CSRT and those without CSRT. Thirty-two (51%) patients with M0 disease had progressed disease as follows: local in 25 patients, leptomeninges in 2, and local plus leptomeninges in 5. In patients with M+ disease, 2 had progressed disease (leptomeninges). In patients with WHO Grade III ependymoma, there was no leptomeningeal failure. Twenty-eight patients with progressed disease had salvage treatment and 20 patients were successfully salvaged. Our data suggested that CSRT has no role in M0 ependymoma because the major pattern of failure of ependymoma is local failure. The new treatment strategies are required to improve the probability of local control.

Long-Term Results and Prognostic Factors of Fractionated Strontium-90 Eye Applicator for Pterygium

To evaluate the long-term safety, effectiveness, and prognostic factors of fractionated postoperative beta-irradiation. Between 1993 and 2005, 623 patients with 737 pterygium lesions were treated with a strontium-90 eye applicator after surgical excision. The median follow-up period was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93 were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to a total dose of 35 Gy in five to seven fractions was used. A total of 73 local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were noted within 3 years after treatment. The 5- and 10-year probability of local control was 90% and 88%, respectively. The multivariate analysis for all cases demonstrated that gender, age, total radiation dose, recurrent pterygia, and interval between surgery and RT affected the overall local control rate. Late toxicities that might have been associated with strontium-90 RT included scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight, cataracts in six, and scleral ulcer in five eyes. Fractionated strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions results in a similar local control rate as higher doses in other series, with an acceptable complication rate.

Hyperfractionated Accelerated Radiotherapy for T1,2 Glottic Carcinoma

Hyperfractionated accelerated radiotherapy without a split (AF) has been performed to improve the local control probability of early glottic carcinomas since 1990 in the authors’ institution. Here, they report their experience treating early glottic cancer patients with AF in a single institution who have a long follow-up period. 131 T1 N0 M0 glottic cancers and 65 T2 N0 M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with AF since 1990. CF consisted of five daily fractions of 2 Gy per week, to a total dose of 64 Gy. AF consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, to a total dose of 55 or 58.5 Gy. The 5-year local control probability for T1 tumors was 94% with 58.5 Gy and 87% with 55 Gy of AF, whereas it amounted to 80% with CF. For T2 tumors, it was 56% with 58.5 Gy and 68% with 55 Gy of AF, whereas it amounted to 64% with CF. The data of T2 should be evaluated with caution due to the small number of patients. Patients with AF had more severe mucosal reactions but no severe late reactions. AF significantly improved the local control rates for T1 glottic cancer.

TU‐D‐352‐04: Novel Decision Aid for IMRT Treatment Plans Generated Using Multiobjective Optimization

Purpose: To develop the decision making component of a multiobjective IMRT optimization procedure for prostate cancer that incorporates disparate sources of information used in clinical decision making, the uncertain outcomes inherent in radiation therapy and the preferences of the patient. Method and Materials: Currently, many IMRT plans are developed for each patient without indication of which plan provides the optimal balance between tumor control and complication probability. Coupled with the typical number of objectives, plan selection is difficult. We chose a Bayesian Network (BN) coupled with a Markov Model (MM) and utility theory to calculate Quality Adjusted Life Expectancy (QALE) for IMRT treatment of prostate cancer. The BN was constructed with the advice of experts; conditional probabilities were obtained from research and clinical trial publications and expert opinion. Local, regional, and distant control were included as were complications to bladder and rectum. The MM relied on transition probabilities derived from the BN, published clinical trials and life expectancy tables. Utilities were obtained from the literature. Plan ranking was based on QALE or any of the components, e.g. local control or complications. Results: Probabilities of local and distant control as a function of disease state matched published values well, as did life expectancies. Sensitivity analyses highlighted the critical nodes in the network. Analysis of outcomes versus probability of lymph node involvement provided a basis for decisions regarding pelvic irradiation. A BN is well‐suited to handle rigorously conditional probabilities and the disparate nature of clinical variables. QALE provides a method for ranking plans based on clinically relevant criteria that incorporates the probabilistic nature of the outcome. Conclusion: A decision aid was constructed using a Bayesian Network coupled to a Markov Model. This resulted in the ability to rank competing plans based either on QALE or specific outcomes.

MO‐B‐AUD C‐01: Proton Therapy

The clinical advantages of proton beams have become widely recognized and there has recently been a significant increase in interest for building additional proton therapy facilities. There are currently over 25 institutions worldwide treating patients with proton beams and over 55,000 patients have been treated. There are at least 25 new facilities in various stages of planning and building. However, the fraction of patients treated with protons each year remains extremely small compared to the total number of cancer patients treated with external beam photons and electrons. The advantage of proton beams lies primarily in their excellent dose localization as compared to that which can be achieved using photon beams. Due to the Bragg peak characteristic in the depth dose of proton beams, the integral dose from proton therapy is, in general, about two times less that that for photon treatments. This allows higher doses to be delivered to target volumes, resulting in increased probabilities of local control, and lower doses delivered to critical normal tissues, resulting in decreased probabilities of treatment‐related morbidity. There are many challenges associated with increasing the accessibility of proton therapy not the least of which is the very limited number of clinical staff with knowledge of and training in proton therapy. The aim of the present Continuing Education Course is to provide a basic understanding of the rationale for proton therapy, physics of proton beams, technology of proton beam acceleration and transport, delivery of proton treatments, proton treatment planning and clinical results of proton therapy.Educational Objectives:1. Understanding of the physical characteristics of proton beams and interactions in tissues.2. Understanding of the beam production and treatment delivery technology for proton beams.3. Understanding of the clinical commissioning of proton therapy beams.4. Understanding of the basic principles of proton treatment planning.5. Understanding of the clinical results for proton therapy.

LINEAR ACCELERATOR STEREOTACTIC RADIOSURGERY FOR METASTATIC BRAIN TUMORS

To review one of the largest single-institution experiences treating metastatic brain disease with stereotactic radiosurgery. We performed a retrospective analysis of 619 patients who underwent linear accelerator-based stereotactic radiosurgery for 1569 brain metastases between May 1989 and February 2006. Patient characteristics and treatment parameters were obtained prospectively. Patients were followed up at regular intervals clinically and with imaging studies to document local control, regional control, and survival. Cox proportional hazards analysis was performed using SAS version 9.1 software (SAS Institute, Cary, NC). Median actuarial survival was 7.9 months. 1- and 2-year actuarial survival probabilities were 0.36 and 0.14, respectively. Radiation Therapy Oncology Group Recursive Partitioning Analysis Class I or II was associated with improved survival, but the difference between the two was insignificant. Female sex, younger age, higher Karnofsky performance status, controlled primary tumor, absence of systemic metastases, asynchronous presentation of brain metastasis, fewer brain metastases, smaller total volume of brain metastases, surgery prior to radiosurgery, and multiple radiosurgical treatments were also associated with improved survival. Melanoma metastasis was associated with impaired survival. Local control was achieved in 84.3% of all lesions treated. 1- and 2-year actuarial local control probabilities were 0.82 and 0.72, respectively. Whole brain radiation therapy prior to radiosurgery was associated with improved regional control. Linear accelerator-based stereotactic radiosurgery is a safe and effective treatment for patients with metastatic brain tumors. Selection of patients who are likely to benefit most from radiosurgery is complex and treatment decisions should be based on the entire clinical picture.

FDG-PET in der Bestrahlungsplanung von nichtkleinzelligen Bronchialkarzinomen

Besides the use of FDG-PET in staging and restaging of patients with non-small cell lung cancer (NSCLC), the integration of PET-data into the radiotherapy planning process is a promising field for PET in radiooncology. The possible benefit of the patients lies in the more exact definition of malignant structures for target volume definition. Especially in cases with post-obstructive atelectasis the use of FDG-PET significantly improves the inter-observer-variability of target volumes. Moreover, the higher diagnostic accuracy in lymph node staging compared to CT could lead to a restriction of irradiation fields to FDG positive areas, if clinical target volume concepts were adapted to the new technologies available. Still unsolved is the problem of which is the best method for technical delineation of PET-based target volumes, as due to resolution and movement effects, the FDG-accumulations appear blurred. Here, possibly contrast-oriented methods are of use. Clinical studies will show the benefit of FDG-PET based target volume definition for patients with NSCLC concerning local control and normal tissue complication probability. The aim is to apply higher radiation doses in more exactly defined volumes, while simultaneously sparing normal tissues.

Quantification of Dosimetric Impact of Implementation of On-Board Imaging (OBI) for IMRT Treatment of Head-And-Neck Malignancies

Implementation of daily kilovoltage imaging for setup verification improves the reproducibility of treatment by eliminating small random setup errors. We evaluate the dosimetric consequences of such shifts, not yet evaluated, in a group of head-and-neck cancer patients (ENT) treated with intensity modulated radiation therapy (IMRT) at Emory University. Twelve patients with ENT malignancies were analyzed. On-Board Imaging (OBI) was used in at least 70% of each patient’s treatment sessions. An isodose distribution was generated for each fraction, with the isocenter shifted to its calculated location prior to OBI repositioning. These plans were summed and then compared to the simulation plan for coverage of target structures. For these 12 patients, there were a total of 18 planning target volumes (PTV). The mean (range) percent reduction in minimum dose was 12.1% (−1.0 to 43.3). For 10 right necks and 9 left necks treated, the mean percent reduction in minimum dose was 11.8% (−0.6 to 39.7) and 13.3% (−3.6 to 31.2), respectively. The mean reduction in mean dose to the PTV was 1.3% (0 to 5.1). The mean reduction in mean dose to the right and left necks was 1.0% (0.2 to 3.9) and 1.13% (0.4 to 3.4), respectively. From this analysis, we conclude that the shifts made were small and random, with essentially no change in mean dose delivered to target structures. There is, however, significant improvement in the minimum dose delivered. Underdosing even a small portion of the tumor potentially sacrifices the probability of local control; correcting these setup errors seems desirable.

Paragangliomas of the Head and Neck Treated With External-Beam Radiotherapy

To evaluate the results of treatment for 104 patients with 121 paragangliomas of the temporal bone, carotid body, or glomus vagale who were treated with radiation therapy (RT) alone or after subtotal resection at the University of Florida between 1968 and 2004. Eighty-nine (86%) patients were treated with conventional megavoltage techniques, 15 (14%) patients with stereotactic fractionated radiotherapy (SRT), 6 (6%) patients with stereotactic radiosurgery (SRS), and 11 (11%) patients with IMRT. One hundred four lesions were previously untreated, whereas 17 had undergone prior treatment (surgery, 14 lesions; RT, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All 3 patients who received prior RT had been treated at other institutions. Four (4%) patients had metastatic neck disease at presentation. Patients had minimum follow-up times as follows: 2 years, 104 patients (100%); 5 years, 78 patients (75%); 10 years, 42 patients (40%); 15 years, 21 patients (20%); 20 years, 12 patients (11%); 25 years, 5 patients (5%); and 30 years, 4 patients (4%). There were 6 local recurrences at 0.7 years, 1.4 years, 2.6 years, 4.5 years, 5.2 years, and 8.2 years. Five were in glomus jugulare tumors and one was in a carotid body tumor. Two of the six recurrences had been treated previously at other institutions with RT and/or surgery. A third recurrence occurred after a geographic miss with stereotactic radiosurgery (SRS). Treatment for a fourth recurrence was discontinued against medical advice before receiving the prescribed dose. There were, therefore, only 2 failures in 104 previously untreated lesions receiving the prescribed course of RT. One recurrence was successfully salvaged with additional RT. Salvage attempts in 2 other patients were unsuccessful. The actuarial local-control probability and cause-specific survival at 10 years were 94% and 95%, respectively. The overall crude local-control rate for all 121 lesions was 95%, with an ultimate local-control rate of 96%. The incidence of grade 1 and 2 treatment-related complications was low. There were no severe treatment complications. Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone and neck.

70 INVITED Recent childhood cancer survival in Europe

Dermatofibrosarcoma protuberans (DFSP), a fibrohistiocytic tumour of intermediate malignancy, has a strong tendency to recur locally. Wide local excision is the recommended treatment modality. A retrospective analysis was performed on 38 consecutive DFSP patients presenting to The Netherlands Cancer Institute, to define the role of radiotherapy. Of the 21 patients treated surgically (all with negative resection margins) seven recurred, a local control probability of 67%. Combined modality treatment was given to 17 patients. Prior to radiotherapy, these patients experienced 33 occurrences of DFSP, but after irradiation only three recurrences were seen, a local control probability of 82%. These results are in keeping with the recent literature where increasing value is being given to both adjuvant and curative radiotherapy in the local management of DFSP. We recommend radiotherapy in DFSP patients where repeated surgery may cause mutilation or functional impairment.

IMRT optimization including random and systematic geometric errors based on the expectation of TCP and NTCP

The purpose of this work was the development of a probabilistic planning method with biological cost functions that does not require the definition of margins. Geometrical uncertainties were integrated in tumor control probability (TCP) and normal tissue complication probability (NTCP) objective functions for inverse planning. For efficiency reasons random errors were included by blurring the dose distribution and systematic errors by shifting structures with respect to the dose. Treatment plans were made for 19 prostate patients following four inverse strategies: Conformal with homogeneous dose to the planning target volume (PTV), a simultaneous integrated boost using a second PTV, optimization using TCP and NTCP functions together with a PTV, and probabilistic TCP and NTCP optimization for the clinical target volume without PTV. The resulting plans were evaluated by independent Monte Carlo simulation of many possible treatment histories including geometrical uncertainties. The results showed that the probabilistic optimization technique reduced the rectal wall volume receiving high dose, while at the same time increasing the dose to the clinical target volume. Without sacrificing the expected local control rate, the expected rectum toxicity could be reduced by 50% relative to the boost technique. The improvement over the conformal technique was larger yet. The margin based biological technique led to toxicity in between the boost and probabilistic techniques, but its control rates were very variable and relatively low. During evaluations, the sensitivity of the local control probability to variations in biological parameters appeared similar for all four strategies. The sensitivity to variations of the geometrical error distributions was strongest for the probabilistic technique. It is concluded that probabilistic optimization based on tumor control probability and normal tissue complication probability is feasible. It results in robust prostate treatment plans with an improved balance between local control and rectum toxicity, compared to conventional techniques.

A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

WE‐C‐BRA‐03: TCP Model Parameters — Extracting These From Clinical Data on ‘Movable’ Patients

The Tumor Control Probability function (TCP, Webb &amp; Nahum) models radiation induced cell kill and uses Poisson statistics to estimate the probability of local control. Its parameters may be derived by correlating archived plan data and treatment outcome results of clinical trials. We will exploit the data of a large randomized prostate trial (68Gy against 78Gy, 600+ patients) of patients treated between the years 1999 and 2003. For these patients the planning CT scan and organ delineations, and the 3D dose distribution as generated by the treatment planning system are electronically available.However, we have no patient specific information on the location of tumor tissue inside the prostate (as could nowadays be imaged using MRI). Furthermore, the dose absorbed by the clonogen cells will have been influenced by errors in daily set‐up and by organ motion. Although portal images were acquired for an off‐line bony set‐up protocol, no in‐room soft tissue imaging was available to monitor organ motion. An additional uncertainty is introduced by the fact that the primary method of clinical follow‐up is based on blood PSA levels, which means a detected failure may not be local.To describe the interplay between the location of clonogen cells and the varying day‐to‐day position of the prostate, we use Monte Carlo treatment plan evaluation software that was developed in‐house. This software samples population distributions of random and systematic errors to simulate many possible treatment histories. Maximum likelihood methods are then applied to determine the most probable TCP model parameters α and σα. Inspired by surveys of pathological specimens, the assumed density distribution of clonogen cells inside the prostate is modulated, and a body of clonogens located posteriorly outside the CTV is introduced to model extra capsular extension. The effects of such modulations on the TCP parameters and on the likelihood of the fit is studied.In future trials, additional imaging will increase the amount of patient specific data on geometric variations and cell distributions, leading to a more accurate TCP model.The TCP parameters thus acquired may be used for treatment planning purposes. If MRI imaging is available to gain knowledge about the location of tumor tissue inside the gland, treatment planning may be performed by optimizing the TCP function using a heterogeneous clonogen cell distribution. By using probability based optimization techniques (in which the effect of geometric errors on the tumor cell kill is modeled in the same way as in the TCP fitting procedure above), no PTVs need to be defined, and the optimization procedure can directly aim for the largest expected TCP (for a given expected rectum NTCP).Educational Objectives:1. Identify sources of uncertainty when basing a TCP model on clinical data.2. Understand a method to determine TCP parameters in the face of such uncertainties.3. Understand how these parameters may be used for treatment planning.

SU-FF-T-263: Influence of Implanted Gold Markers On the Dose Distributions for Therapeutic Proton Beam

Purpose: The aim of this work is to examine the influence of implanted gold markers on the dose distributions in proton therapy and to investigate the dependency on the marker position in Spread Out Bragg Peak (SOBP) proton beam. Methods and Materials: The implanted gold marker has a cylindrical shape of 3mm length and 1.2mm diameter. The dose influence of the gold marker was verified in the condition of various locations of the proton beam field, which has 20 cm range in patient and 5cm of SOBP. Spatial dose distributions were measured using 3‐Dimensional moving water phantom and a stereotactic diode detector with 0.5 mm of effective diameter. Also, a film dosimetry using EBT film was performed. For Monte Calro simulation, GEANT4 simulation tool kit was used to confirm the measurement and to simulate the dose influence of multi‐implanted condition. Results:Gold is high‐Z material, which is good for CT marker but give more proton beam divergency and more under‐dosed volume. The under‐dosed volume of cold spots due to the single gold marker is measured to be 0.035 cc which has less than 80% of a prescription dose. The effect on the volume‐dose relation has been studied. Monte Calro simulation made us enable to study the various conditions of marker position. Conclusion: Cold spots inside the target volume affect the probability of the local tumor control. Cold volume due to the gold marker is very small but is not trivial in the view of the local control probability in proton therapy. The position of gold markers and the conditions of the proton beam field give the effect on the dose distribution at the target region implanted gold markers.

The safety of breast‐conserving therapy in patients with breast cancer aged ≤40 years

The objectives of this study were to study the probability of local control after breast-conserving therapy (BCT) in a large population of patients with early-stage breast cancer aged < or = 40 years and to determine which factors had prognostic value. All patients (n = 758) aged < or = 40 years with clinical stage I or II breast cancer who underwent BCT in general hospitals in the southern part of the Netherlands between 1988 and 2002 were selected for the current analysis. BCT included local excision of the tumor followed by irradiation of the breast. Of 758 patients, 329 patients (43%) received adjuvant systemic treatment, and 36 patients (5%) underwent a microscopically incomplete excision. The median follow-up was 8.5 years. During follow-up, 95 patients developed a local recurrence without evidence of distant disease at the time the recurrence was diagnosed. Contralateral breast cancer was diagnosed in 59 patients. The 5- and 10-year actuarial local recurrence rates were 9.0% (95% confidence interval [95% CI], 6.6-11.4%) and 17.9% (95% CI, 14.1-21.7%), respectively. In a multivariate analysis, adjuvant systemic treatment reduced the risk of local recurrence (hazards ratio [HR], 0.47; 95% CI, 0.28-0.78) and contralateral breast cancer (HR, 0.46; 95% CI, 0.24-0.87) by >50%. The risk of local recurrence in young patients who underwent BCT was reduced strongly by using adjuvant systemic treatment. This finding may provide an argument if favor of advising the use of systemic treatment for all patients aged < or = 40 years who undergo BCT.

Effectiveness of Carbon Ion Radiotherapy in the Treatment of Skull-Base Chordomas

The aim of this study was to evaluate the effectiveness and toxicity of carbon ion radiotherapy in chordomas of the skull base. Between November 1998 and July 2005, a total of 96 patients with chordomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft für Schwerionenforschung (GSI) in Darmstadt, Germany. All patients had gross residual tumors. Median total dose was 60 CGE (range, 60-70 CGE) delivered in 20 fractions within 3 weeks. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG) / European Organization for Research and Treatment of Cancer (EORTC) score. Mean follow-up was 31 months (range, 3-91 months). Fifteen patients developed local recurrences after carbon ion RT. The actuarial local control rates were 80.6% and 70.0% at 3 and 5 years, respectively. Target doses in excess of 60 CGE and primary tumor status were associated with higher local control rates. Overall survival was 91.8% and 88.5% at 3 and 5 years, respectively. Late toxicity consisted of optic nerve neuropathy RTOG/EORTC Grade 3 in 4.1% of the patients and necrosis of a fat plomb in 1 patient. Minor temporal lobe injury (RTOG/EORTC Grade 1-2) occurred in 7 patients (7.2%). Carbon ion RT offers an effective treatment option for skull-base chordomas with acceptable toxicity. Doses in excess of 75 CGE with 2 CGE per fraction are likely to increase local control probability.