Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.     

Search for large genomic alterations of the BRCA1 gene in a Finnish population

Mutations in the BRCA1 and BRCA2 genes are known to predispose to breast cancer. In Finland, however, only 21% of all breast cancer families have mutations in these genes. Recent studies have shown that large genomic alterations of BRCA1 are common in many countries. Because such alterations will be missed in conventional mutation screening strategies, we decided to screen Finnish breast and ovarian cancer families for genomic alterations by using a multiplex polymerase chain reaction method. The most characteristic features of BRCA1-related breast cancer were used to select patients, namely (1) both breast and ovarian cancer in the family (48 patients), (2) four or more breast cancers in family (22 patients), or (3) young age (< or =40 years) of onset (58 patients). A total of 128 patients were included in the study. All exons of BRCA1 were analyzed but no alterations were found. This study excludes the frequent occurrence of large genomic alterations in the BRCA1 gene in Finland. Here, again, Finland differs from other countries with a mixed population structure. Our results are in agreement with the common hypothesis that there are still unknown breast cancer susceptibility gene(s) that are responsible for breast cancer predisposition.     

Associations between Self-Reported Daily Affect Ratings and Sleep Duration during the First Two Weeks of Antidepressant Therapy

ABSTRACT

Background: In the context of a randomized controlled trial evaluating the efficacy of augmenting fluoxetine treatment in young adults with major depressive disorder (MDD) using a modified repeated partial sleep deprivation protocol contrasting 2 weeks of restricted time in bed (i.e., 6 h TIB) to no time in bed restriction (i.e., 8 h TIB) the study examines whether sleep duration and the timing of repeated partial sleep deprivation predicts patient-reported affect ratings.

Participants: Participants included 58 young adults with DSM-IV-diagnosed MDD.

Methods: Daily ratings of affect and sleep were collected during the first 2 weeks of initiating fluoxetine treatment, yielding 630 person-days. Actigraphy monitoring was employed to assess compliance with time in bed condition.

Results: Negative affect ratings and positivity ratios in the morning were more improved among participants assigned to the 6 h TIB condition compared to the 8 h TIB group. Participants whose bedtime was delayed by 2-h nightly demonstrated the most significant improvement in negative affect and positivity ratio during the first 2 weeks of fluoxetine therapy. Moreover, the trajectory of morning negative affect ratings in the first 2 weeks was predictive of remission after 4 weeks of fluoxetine therapy.

Conclusions: These findings suggest that monitoring changes in daily affect may be a valuable marker of early treatment response in young adults with MDD.     

Consistency of patient- and doctor-assessed cosmetic outcome after conservative treatment of breast cancer

The cosmetic results of the breast (144 patients)were analysed after segmental resection and axillary dissectionwith or without postoperative radiotherapy for early low-riskbreast cancers. Cosmetic results were assessed over time(3, 9, 18, 36, 48 months respectively) bythe patient and by the physician. Patients ratedthe overall cosmetic result good or excellent in92% of cases after 3 months. The proportionof good or excellent cosmetic results decreased overtime and after four years 89% of patientsclassified themselves in this category, whereas the physicianassessed the outcome as good or excellent in91% of cases after 3 months and 75%after 4 years. The inter-observer consistency between physicianand patient in assessing the cosmetic outcome was=0.42 at the beginning and decreasedover time (=0.07 after 4 years).The intra-observer variation over time was =0.53 for the patient and =0.32for the physician.Inter-observer consistency between patient and physician was moderateimmediately following treatment but decreased over time. Thefeeling of satisfaction of the patient was relativelystable whereas the opinion of the physician becamesomewhat more critical over time. Therefore the intra-observerconsistency over time was somewhat better for thepatient than for the physician.     

Diabetic neuropathies

Diabetic neuropathies are the most common type of neuropathies seen in clinical practice. These neuropathies can range clinically from asymptomatic to manifesting symptoms caused by motor, sensory, and autonomic nerve dysfunction. These neuropathies can affect the peripheral nervous system, pain receptors, cardiovascular, urogenital, and gastrointestinal systems. This monograph presents an overview of the different types of diabetic neuropathies, their presentations, diagnostic tools, and strategies for management.     

The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients

The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan–Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant.Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004).In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up.     

Classifying subgroups of patients with symptoms of acute coronary syndromes: A cluster analysis

The purpose of the study was to identify subgroups of patients presenting with acute coronary syndromes based on symptom clusters. Two hundred fifty‐six patients completed a symptom assessment in their hospital rooms. Latent class cluster analysis and analysis of variance were used to classify subgroups of patients according to selected clinical characteristics. Four subgroups were identified and labeled as Heavy Symptom Burden, Chest Pain Only, Sweating and Weak, and Short of Breath and Weak (model fit χ² [130,891, n = 256] = 867.5, p = 1.00). The largest group of patients experienced classic symptoms of chest pain and shortness of breath but not sweating. Younger patients were more likely to cluster in the Heavy Symptom Burden group (F = 5.08, p = .002). Interpretation of the clinical significance of these groupings requires further study. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:386–397, 2010     

Symptoms of unstable angina in patients with and without diabetes

Patients with diabetes experience cardiac autonomic neuropathy that may affect the way they perceive the symptoms of unstable angina (UA). The purpose of this study was to examine symptom differences in patients with and without diabetes during an episode of UA. A convenience sample of 50 women and 50 men were recruited. Patients with diabetes were more likely to have a history of hypercholesterolemia (83% vs. 60%), prior history of heart disease (85% vs. 65%), and prior angiogram (85% vs. 67%). Patients with diabetes reported having less nausea (20% vs. 40%), less squeezing (25% vs. 48%) and less aching (25% vs. 45%) type pain, and more hyperventilation (27.5% vs. 11.7%). Other cardiac symptoms were similar between the groups. Further study of symptom presentation in patients with diabetes is warranted given their high levels of morbidity and mortality from cardiac disease.