C. Lambert

Assessment in the Context of Uncertainty Using the Script Concordance Test: More Meaning for Scores

Background: The Script Concordance Test (SCT) uses authentic, ill-defined clinical cases to compare medical learners’ judgment skills with those of experienced physicians. SCT scores are meant to measure the degree of concordance between the performance of examinees and that of the reference panel. Raw test scores have meaning only if statistics (mean and standard deviation) describing the panel’s performance are concurrently provided. Purpose: The purpose of this study is to suggest a method for reporting scores that standardizes panel mean and standard deviation, allowing examinees to immediately gauge their performance relative to panel members. Methods: Based on a statistical method of standardization, a new method for computing SCT scores is described. According to this method, test raw scores are converted into a scale in which the panel mean is set as the value of reference, and the standard deviation of the panel serves as a yardstick by which examinee performance is measured. Results: The effect of this transformation on four data sets obtained from SCTs in radio-oncology, surgery, neurology, and nursing is discussed. Conclusion: This transformation method proposes a common metric basis for reporting SCT scores and provides examinees with clear, interpretable insights into their performance relative to that of physicians of the field. We recommend reporting SCT scores with the mean and standard deviation of panel scores set at standard scores of 80 and 5, respectively. Beyond SCT, our transformation method may be generalizable to the scoring of other test formats in which the performance of examinees and those of a panel of reference undertaking the same cognitive tasks are compared.

Script concordance testing: more cases or more questions?

Script concordance test (SCT) is a case based assessment format of clinical reasoning in which questions are nested into several cases. Recent results using Q4 format suggest that nested questions contribute more to reliability of measure than cases. The present study aims at documenting variance components associated with SCT cases and nested questions and to determine what are the optimal number and combinations of cases and nested questions. Data from SCT in three different fields are presented. G study and D study methodology are used to estimate variance component and to determine optimal number and combinations of cases and questions. Questions nested into cases contributed a large amount of score variance (more than 70%). D studies with varying samples show that, depending on the reliability of the test, an optimal number of 2–4 questions nested into 15–25 cases represents the best combination. Nested questions contribute to a significant portion of score variance, with the implication that formulation of up to 5 questions per case is an efficient way to optimize the reliability of SCT scores.

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial.

BackgroundIncreasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.Materials and MethodsWe conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.ResultsBetween 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.ConclusionsWeekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

Combined Hypofractionated Radiation and Hormone Therapy for the Treatment of Intermediate-Risk Prostate Cancer

PURPOSE Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. METHODS AND MATERIALS Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. RESULTS Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. CONCLUSIONS Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

A Monte Carlo based formalism to identify potential locations at high risk of tumor recurrence with a numerical model for glioblastoma multiforme

PURPOSE The strategy currently used to treat glioblastoma multiforme (GBM) patients, which mostly relies on population-based failure patterns, does not consider the important variability in such patterns reported in the literature. As part of the multidisciplinary efforts being made to develop personalized therapeutic approaches, numerical models of tumor growth and treatment are increasingly being used by different groups around the world. In this study, a new formalism relying on the proliferation-invasion model is developed to identify potential locations of GBM recurrences. The authors assess the sensitivity of the location of potential tumor recurrences to the input parameter values predicted for a given patient by varying those values using a Monte-Carlo based approach. Our approach is designed to be prospective in the sense that it relies on patient-specific imaging data that can be gathered in one single preradiotherapy imaging session. METHODS The authors modeled the infiltration paths of glial cells using patient-specific diffusion tensor imaging (DTI) data. Nine GBM patients with preradiotherapy DTI data are considered in this study. The possible locations of tumor recurrences are determined by randomly selecting many ensembles of values for each of the growth and radiobiological parameters in the GBM growth model. A novel concept, the occurrence probability (OP), is introduced to assess the sensitivity of potential tumor recurrence locations to the input parameter values. For a given patient, the OP map is derived from a superposition of all potential tumor recurrence locations obtained with all sets of parameter values. RESULTS For eight out of nine of patients, the authors have identified a statistically significant region where the OP is above 50%. For two patients, these high risk regions are found to be located at a distance greater than 3.9 cm from the border of the gross tumor volume highlighting the inaccuracy of current margins for some patients. The exact location and size of these volumes with OP > 50 % are, however, sensitive to the number N of ensembles of parameter values for N ≲ 400. On the other hand, the authors have identified for each patient a threshold OP, the OP(T), which defines a volume that converges more rapidly with increasing N. The OP(T) for each patient varies between 20% and 40%. The volume defined by OP > OP(T) may be an adequate candidate to define a personalized margin for radiotherapy treatment planning of GBM patients. CONCLUSIONS A new Monte-Carlo based formalism was described and used to assess the variability of sites of potential recurrence predicted by the proliferation-invasion model to input parameter values. The authors have shown that high risk areas could be consistently identified with a limited number of sets (N ≲ 400) of randomly chosen parameter values. A major strength of this formalism is its potential prospective nature. Although a validation of the accuracy of the model-predicted tumor recurrence location still remains to be done, our method is potentially applicable to orient patient-specific definition of margins.

Successful treatment of anaplastic meningioma metastatic to cervical lymph nodes.

Cervical lymph node metastases of meningioma represent an important diagnostic and treatment challenge. Not only has this entity been rarely described, but successful treatment has never been reported in the literature.

Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma

Abstract Background. A direct association between radiotherapy dose, side-effects and secondary cancers has been described in patients with seminoma. A treatment planning study was performed in order to compare computed tomography-based traditional radiotherapy (CT-tRT) versus bone marrow-sparing intensity-modulated radiation therapy (BMS-IMRT) in patients with Stage I seminoma. Material and methods. We optimized in 10 patients a CT-tRT and a BMS-IMRT treatment plan to deliver 20 Gy to the para-aortic nodes. CT-tRT and IMRT consisted of anteroposterior-posterioranterior parallel-opposed and seven non-opposed coplanar fields using 16 and 6-MV photon energies, respectively. Dose-Volume Histograms for clinical target volume (CTV), planning target volume (PTV) and organs at risk (OARs) were compared for both techniques using Wilcoxon matched-pair signed rank-test. Results. Dmean to CTV and PTV were similar for both techniques, even if CT-tRT showed a slightly improved target coverage in terms of PTV-D95% (19.7 vs. 19.5 Gy, p = 0.005) and PTV-V95% (100 vs. 99.7%, p = 0.011) compared to BMS-IMRT. BMS-IMRT resulted in a significant reduction (5.2 Gy, p = 0.005) in the Dmean to the active bone marrow (ABM). The V100% and V75% of the OARs were reduced with BMS-IMRT by: ABM-V100% = 51.7% and ABM-V75% = 42.3%; bowel-V100% = 15.7% and bowel-V75% = 16.8%; stomach-V100% = 22% and stomach-V75% = 27.7%; pancreas-V100% = 37.1% and pancreas-V75% = 35.9% (p = 0.005 for all variables). Conclusions. BMS-IMRT reduces markedly the dose to the OARs compared to CT-tRT. This should translate into a reduction in acute and long-term toxicity, as well as into the risk of secondary solid and hematological cancers.

Long-term results of radiosurgery for cerebral arteriovenous malformations.

BACKGROUND Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM). OBJECTIVE To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates. METHODS We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician. RESULTS AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%. CONCLUSION Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.

TU-A-BRC-07: Toward Predicting the Location of GBM Recurrence after Radiotherapy Using Patient-Specic DTI and Numerical Modelling

Purpose: Patients diagnosed with glioblastoma multiforme (GBM), the most aggressive form of braintumour, have a median survival of 15 months when receiving standard treatment. We have developed a three‐dimensional reaction‐diffusion model which uses patient‐specific diffusiontensorimaging (DTI) and real dose distributions to simulate the growth and radiotherapy treatment of a GBM. We highlight paths for tumour recurrence and predict a gain in survival when treatment margins are adjusted according to model inputs. Methods: A DTI sequence is added to pre‐ and post‐treatment MRI for ten GBM patients receiving standard treatment in our department. Our numerical model uses clinically available images to initialize the tumour cell density and to measure invasion velocity. Patient‐ specific DTI is used to modeltumour cell motility and to prioritize migration along white matter fibres. The treatment dose distribution is used to simulate the radiotherapy treatment actually received by the patient. Finally, we simulate an alternative treatment plan that increases the dose in the region where the model predicts the formation of a recurrent tumour. Results: The general behaviour of the model was evaluated and found to be adequate for a patient with no DTI but whose post‐treatment images were available. For another patient, model initialization with pre‐ treatment DTI shows that a second tumour focus forms outside the original radiation field in a region where the tumour migration is high due to white matter fibres. The application of an alternative virtual plan integrating the location of the recurrence suggests a 2‐month gain of survival time, based on tumour cell density. Conclusions: Our results indicate that a reaction‐ diffusionmodel using patient‐specific DTI information could potentially be used to modify GBM treatment margins, leading to an increased survival time. Integrating a long‐term outcome study will allow us to verify the predictive efficiency of the model. This work is funded by the Fonds quebecois de la recherche sur la nature et les technologies (FQRNT) and by the Natural Sciences and Engineering Research Council of Canada (NSERC).

Modeling of early PSA kinetics in intermediate risk prostate cancer

16080 Background: Absolute changes in prostate specific antigen (PSA) values within the first year after radiotherapy can predict biochemical outcome on later follow up years. Other robust indicato...