Learning from Acceleration Data to Differentiate the Posture, Dynamic and Static Work of the Back: An Experimental Setup.

Information on body posture, postural change, and dynamic and static work is essential in understanding biomechanical exposure and has many applications in ergonomics and healthcare. This study aimed at evaluating the possibility of using triaxial acceleration data to classify postures and to differentiate between dynamic and static work of the back in an experimental setup, based on a machine learning (ML) approach. A movement protocol was designed to cover the essential degrees of freedom of the back, and a subject wearing a triaxial accelerometer implemented this protocol. Impulses and oscillations from the signals were removed by median filtering, then the filtered dataset was fed into two ML algorithms, namely a multilayer perceptron with back propagation (MLPBNN) and a random forest (RF), with the aim of inferring the most suitable algorithm and architecture for detecting dynamic and static work, as well as for correctly classifying the postures of the back. Then, training and testing subsets were delimitated and used to evaluate the learning and generalization ability of the ML algorithms for the same classification problems. The results indicate that ML has a lot of potential in differentiating between dynamic and static work, depending on the type of algorithm and its architecture, and the data quantity and quality. In particular, MLPBNN can be used to better differentiate between dynamic and static work when tuned properly. In addition, static work and the associated postures were better learned and generalized by the MLPBNN, a fact that could provide the basis for cheap real-world offline applications with the aim of getting time-scaled postural profiling data by accounting for the static postures. Although it wasn't the case in this study, on bigger datasets, the use of MLPBPNN may come at the expense of high computational costs in the training phase. The study also discusses the factors that may improve the classification performance in the testing phase and sets new directions of research.

Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

PURPOSE: Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. MATERIALS AND METHODS: RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). RESULTS: Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). CONCLUSION: Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue.

Duration of androgen suppression in the treatment of prostate cancer.

BACKGROUND: The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS: We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS: A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS: The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: dummy run and individual case review.

INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.

BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. METHODS: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. FINDINGS: All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8-33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. INTERPRETATION: Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival.

Profile of European radiotherapy departments contributing to the EORTC Radiation Oncology Group (ROG) in the 21st century.

PURPOSE: Since 1982, the Radiation Oncology Group of the EORTC (EORTC ROG) has pursued an extensive Quality Assurance (QA) program involving all centres actively participating in its clinical research. The first step is the evaluation of the structure and of the human, technical and organisational resources of the centres, to assess their ability to comply with the current requirements for high-tech radiotherapy (RT). MATERIALS AND METHODS: A facility questionnaire (FQ) was developed in 1989 and adapted over the years to match the evolution of RT techniques. We report on the contents of the current FQ that was completed online by 98 active EORTC ROG member institutions from 19 countries, between December 2005 and October 2007. RESULTS: Similar to the data collected previously, large variations in equipment, staffing and workload between centres remain. Currently only 15 centres still use a Cobalt unit. All centres perform 3D Conformal RT, 79% of them can perform IMRT and 54% are able to deliver stereotactic RT. An external reference dosimetry audit (ERDA) was performed in 88% of the centres for photons and in 73% for electrons, but it was recent (<2 years) in only 74% and 60%, respectively. CONCLUSION: The use of the FQ helps maintain the minimum quality requirements within the EORTC ROG network: recommendations are made on the basis of the analysis of its results. The present analysis shows that modern RT techniques are widely implemented in the clinic but also that ERDA should be performed more frequently. Repeated assessment using the FQ is warranted to document the future evolution of the EORTC ROG institutions.

Prophylactic cranial irradiation in extensive small-cell lung cancer.

BACKGROUND: We conducted a randomized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy. METHODS: Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were randomly assigned to undergo prophylactic cranial irradiation (irradiation group) or receive no further therapy (control group). The primary end point was the time to symptomatic brain metastases. Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present. RESULTS: The two groups (each with 143 patients) were well balanced regarding baseline characteristics. Patients in the irradiation group had a lower risk of symptomatic brain metastases (hazard ratio, 0.27; 95% confidence interval [CI], 0.16 to 0.44; P<0.001). The cumulative risk of brain metastases within 1 year was 14.6% in the irradiation group (95% CI, 8.3 to 20.9) and 40.4% in the control group (95% CI, 32.1 to 48.6). Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after randomization. The 1-year survival rate was 27.1% (95% CI, 19.4 to 35.5) in the irradiation group and 13.3% (95% CI, 8.1 to 19.9) in the control group. Irradiation had side effects but did not have a clinically significant effect on global health status. CONCLUSIONS: Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival. (ClinicalTrials.gov number, NCT00016211 [ClinicalTrials.gov].).

Long-term protective effect of mature DC-LAMP+ dendritic cell accumulation in sentinel lymph nodes containing micrometastatic melanoma.

PURPOSE: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP(+) DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs. EXPERIMENTAL DESIGN: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP(+) DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and >or=200/mm(2)). RESULTS: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP(+) DC scores (kappa score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36). CONCLUSION: This study is the first to report the prognostic value of DC-LAMP(+) DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (>or=200/mm(2)) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.

[Case solution and plan evaluation in intensity modulation radiotherapy for simple and complex volumes]. / Planificarea si evaluarea planurilor de tratament in radioterapia conformationala prin modularea intensi- tatii in fascicol pentru volume simple sau complexe.

UNLABELLED: The objective of the study was to evaluate the feasibility of the high dose IMRT pacification in small and medium volumes, simple and complexes. MATERIAL AND METHOD: The European Society of Therapeutic Radiation Oncology yearly organizes the course of IMRT. We detail the clinical case solution plans realised for two cases proposed in 2003: locally relapsed lung cancer (first case) and ethmoidal cancer (second case). The prescribed doses were 80 Gy in the lung cancer and 70 Gy in the ethmoid cancer. To the choice of the number and beam direction is added the low tolerance of surrounding normal tissue, the respiratory movement in the lung case and the high tissue heterogeneity, which modify the dose distribution in these regions. For the plans evaluation we used the dose homogeneity (U) in treated volume (PTV), the cover factor (FC), the normal tissue spare factor (FP) and the conformity index (CI). 1 is considered optimal value for FC, FP and CI. RESULTS: In the first case, the plan with five beams symmetric displayed improved the homogeneity in the PTV (of 0.3%) and the FP (of 24%) and thus, slightly improved CI (0.7 vs. 0.6) when compared with the "beam eye view technique". The last plan decreased the dose at the oesophagus, lung and cardiac volume but the general tissue spare (FP) significantly decreased. In the second case we used five symmetric displayed beams as standard plan. Adding a no-coplanar field oblique anterior and using a smaller PTV contribute to slightly improve the conformity index with the same factor (0.70, 0.71 vs. 0,67 respectively). CONCLUSION: Reduced PTV, symmetric displayed coplanar beams and a limited number of non-coplanar beams can contribute to improve the IMRT plan quality in small to medium PTV's simple or complex.

Quality assurance in breast cancer: EORTC experiences in the phase III trial on irradiation of the internal mammary nodes.

The EORTC 22922/10925 trial randomly compares irradiation or no irradiation of the internal mammary and medio supraclavicular (IM-MS) nodes for stage I-III breast cancer. We report on the characteristics of 4004 participating patients, aspects of quality assurance and compliance to protocol treatment. The actual population has intermediate-risk disease: 51.8% stage II, 56% positive axillary nodes. The allocated treatment was not followed in 3.2% in the IM-MS irradiation arm versus 2% in the no IM-MS irradiation arm. In the IM-MS arm, there were major deviations for dose in 0.8%, surgery-to-radiotherapy time interval in 3.9% and in overall treatment time in 0.9% cases. Major deviations were found in 7.9% patients in the IM-MS group and in 2% patients in the no IM-MS group. In the final trial analysis, a sensitivity analysis should evaluate the subgroup of patients receiving an optimal treatment to verify the robustness of the results and the true impact of IM-MS irradiation.

Cancer evolution assessment using artificial neural networks.

Artificial Neural Networks have demonstrated good utility to establish disease prognostic, if there are correctly trained. Our aim was to realize Artificial Neural Networks in different cancer types, to evaluate time survival. For the beginning this was applied for breast cancer. The conclusion is that the homogeneity of data entrance sets, the number, and their coding in relation with their importance for cancer prognostic are decisive for the results of the trained ANN. These results can be useful in the physician clinical decision.