Survival discrepancy between patients treated in a clinical trial and routine practice is well recognized. No study has assessed the health-related quality of life (HRQL) of long-term Hodgkin’s ...lymphoma survivors (HLS) according to trial participation. We applied a population-based approach to examine the differences in HRQL, healthcare utilization, and satisfaction with healthcare among long-term HLS who had participated in a trial (tHLS) and those treated in routine care (rHLS). All HLS diagnosed during the period 1989–1998 and living in southern Netherlands were selected from the Netherlands Cancer Registry in 2004 to participate in the Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry study. Data linkage with the European Organisation for Research and Treatment of Cancer was performed in 2015 to identify trial participation. The 65 tHLS and 67 rHLS had comparable demographic and clinical characteristics. Unadjusted and adjusted models indicated no association between trial participation and HRQL. There was no evidence of differences in healthcare satisfaction. Trial participation was associated with 48% more visits to specialists in the past year (adjusted 95% confidence interval: 10–99). No association of trial participation with cancer-related contacts was observed. tHLS and rHLS had comparable long-term HRQL. Although trial participation was associated with more specialist visits, there was no evidence of an association with healthcare satisfaction and the number of cancer-related visits. Identification of trial participation in population-based cancer registry through data linkage with clinical trials enables a population-based approach to examine patient-reported outcomes differences between tHLS and rHLS.
Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, ...PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (
n
= 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (
n
= 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.
A 512/spl times/512 CMOS active pixel sensor (APS) was designed and fabricated in a standard 0.5-/spl mu/m technology. The radiation tolerance of the sensor has been evaluated with Co-60 and proton ...irradiation with proton energies ranging from 11.7 to 59 MeV. The most pronounced radiation effect is the increase of the dark current. However, the total ionizing dose-induced dark current increase is orders of magnitude smaller than in standard devices. It behaves logarithmically with dose and anneals at room temperature. The dark current increase due to proton displacement damage is explained in terms of the nonionizing energy loss of the protons. The fixed pattern noise does not increase with total ionizing dose. Responsivity changes are observed after Co-60 and proton irradiation, but a definitive cause has not yet been established.
Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, ...PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.
CMOS image sensors with logarithmic response are attractive devices for applications where a high dynamic range is required. Their strong point is the high dynamic range. Their weak point is the ...sensitivity to pixel parameter variations introduced during fabrication. This gives rise to a considerable fixed pattern noise (FPN) that deteriorates the image quality unless pixel calibration is used. In the present work a technique to remove the FPN by employing on-chip calibration is introduced, where the effect of threshold voltage variations in pixels is cancelled. An image sensor based on an active pixel structure with five transistors has been designed, fabricated, and tested. The sensor consists of 525/spl times/525 pixels measuring 7.5 /spl mu/m/spl times/10 /spl mu/m, and is fabricated in a 0.5-/spl mu/m CMOS process. The measured dynamic range is 120 dB while the FPN is 2.5% of the output signal range.
Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid ...Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.
Abstract Background: In this phase I/II study, the addition of lapatinib (LAP) was investigated in combination with the sequential use of both approaches TPF induction chemotherapy (ICT) followed by ...chemoradiation (CRT) in locally advanced larynx or hypopharynx squamous cell carcinoma. Patients and methods: Objectives were to assess maximum tolerated dose, dose-limiting toxicity (DLT) and to recommend a safe dose of LAP when administered with 4 cycles of TPF followed by CRT. Results: Seven male patients were included. Three patients were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF). Renal toxicity was observed among these three patients (grade 3 n = 1, grade 2 n = 1 and grade 1 n = 1), with 1 DLT, leading to treatment interruption in this group. Nephrotoxicity was reversible after stopping LAP and hydration of the patients. In a second cohort of four patients administering docetaxel from the second cycle, 3 more DLTs were observed (grade 2 renal toxicity and grade 3 diarrhea, grade 3 anorexia and grade 3 stomatitis, and grade 4 neutropenia). Based on the occurrence of 4 DLTs at the first dose level of LAP, patient recruitment was closed. Conclusion: These data indicate that LAP cannot be combined safely with full dose TPF.
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