Population-based patient care study for breast cancer

Background: Different approaches for an effective quality management are funded by the Ministry of Health to verify, to assess and, if necessary to optimize the quality of health care using the tracer diagnoses of breast, rectal, and lung cancer in eight regions in Germany. The conception of these observational studies and initial findings are shown here, using breast cancer in the region of Munich (population 2.4 million) as an example. Patients and Methods: The study started on April 1, 1996. The recruitment phase for all primary boast cancer patients in this region is planned for 2 years with a 3-5-year follow-up. Established documentation sheets are used to document basic medical information of each patient, along with the original reports (pathology: radiotherapy, doctors' reports, etc.), follow-up reports and quality of life questionnaires (QLQ, including the EORTC QLQ C30). Results: In 1996, the Munich region has a crude incidence of 125/100,000 women (world standard 71.5). After almost complete documentation the incidence is 10-15% higher. In the period from April 1 1996 to June 30, 1997 1,360 patients have been recruited into the study. 79% of the patients were 50 years of age or older. pT stages are distributed as follows: pTIS 5%, pT1 54%, pT2 32%, pT3 4%, pT4 6%. 4.5% had primary metastases. Breast-conserving therapy (BCT) was performed in 57% of patients. Five of the 46 departments involved recruited more than 50 patients each within these 14 months. These larger departments treat 59% of all patients. The proportion of older patients and pT4 stages is significantly higher in the smaller departments. BCT is performed significantly more often in the larger departments. First results of quality of life show dependencies on age, but no differences between mastectomy and BCT 3 months after operation. Not only the addressed patients (response rate to QLQ over 80%) but also almost all hospitals and many physicians are milling to support and to partake in quality assurance. 35 hospitals, 46 surgical departments. 80 heads of department and surgically: active general practioners, 330 general practioners. 7 radiotherapy departments, and 13 pathology departments have so far documented for this study. Conclusions: An effective quality management in oncology needs a modern cancer registry which uses documentation sheets as well as original reports and organizes the complicated infrastructure for an interdisciplinary cooperation. To be able to evaluate the health care reality it is necessary to carry out a data analysis and assess each individual case. A feedback of the results have to be available for each physician and each department. The cost of this information management is approximately 0.3% of the health care cost for this group of patients

Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations

Abstract Background Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany. Methods A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually. Results All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY. Conclusion Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs

Breast cancer: are long-term and intermittent endocrine therapies equally effective?

PURPOSE In breast cancer (BC), the duration of endocrine adjuvant therapies (AT) has been extended continuously up to 10~years. We present an alternative explanation for the effect, which could enable shorter treatments. METHOD The relevant literature on chemoprevention and (neo-)adjuvant therapy was reviewed. Data for initiation and growth of primary and contralateral BCs and their metastases (MET) were considered. Also, population-based data from the Munich Cancer Registry for MET-free survival, time trends of MET patterns, and survival achieved by improved ATs are used to estimate all events in the long-term follow-up. RESULTS Extended ATs (EAT) that continue after 1, 2, or 5~years reduce mortality only slightly. The effect is delayed, occurring more than 5~years after extension. EATs does not affect the prognosis of 1stBCs, they preventively eradicate contralateral 2ndBCs and thus their future life-threatening METs. Because chemoprevention can eradicate BCs from the smallest clusters to almost detectable BCs, ATs can be temporarily suspended without imposing harm. Results equal to EATs can be achieved by short-term ATs of the 1stBC and by repeated neo-ATs targeted at the indefinitely developing 2ndBCs. Considering this potential in de-escalation, a 70-80% reduction of overtreatment seems possible. CONCLUSION Knowledge of initiation and growth of tumors with known effects of neo-ATs suggest that intermittent endocrine ATs may achieve the same results as EATs but with improved quality of life and survival because of fewer side effects and better compliance. The challenge for developments of repeated ATs becomes: how short is short enough

Matching Study to Registry data: Maintaining Data Privacy in a Study on Family based Colorectal Cancer

Confidentiality of patient data in the field of medical informatics is an important task. Leaked sensitive information within this data can be adverse to and being abused against a patient. Therefore, when working with medical data, appropriate and secure models which serve as guidelines for different applications are needed. Consequently, this work presents a model for performing a privacy preserving record linkage between study and registry data. The model takes into account seven requirements related to data privacy. Furthermore, this model is exemplified with a study on family based colorectal cancer in Germany. The model is very strict and excludes possible violations towards data privacy protection to a reasonable degree. It should be applicable to similar use cases which are in need of a mapping between medical data of a study and a registry database

Analysis of FoxP3+T-Regulatory Cells and CD8+T-Cells in Ovarian Carcinoma: Location and Tumor Infiltration Patterns Are Key Prognostic Markers

Purpose: Tumor infiltrating CD4+CD25+FoxP3+ regulatory immune cells (Treg) have been associated with impaired antitumor immune response and unfavorable prognosis for patients affected by ovarian carcinoma, whereas CD8+T-cells have been found to positively influence survival rates in a large panel of solid tumors. Recently, density, location and tumor infiltration patterns of the respective immune cell subtypes have been identified as key prognostic factors for different types of tumors. Patients and Methods: We stained 210 human ovarian carcinoma samples immunhistochemically for FoxP3 and CD8 to identify the impact different immune cell patterns have on generally accepted prognostic variables as well as on overall survival. Results: We found that FoxP3+ cells located within lymphoid aggregates surrounding the tumor were strongly associated with reduced survival time (P = 0.007). Central accumulation of CD8+ effector cells within the tumor bed shows a positive effect on survival (P = 0, 001). Conclusion: The distribution pattern of immune cells within the tumor environment strongly influences prognosis and overall survival time of patients with ovarian carcinoma

Deletion of the Ca2+ Channel Subunit α2δ3 Differentially Affects Cav2.1 and Cav2.2 Currents in Cultured Spiral Ganglion Neurons Before and After the Onset of Hearing

Voltage-gated Ca2+ channels are composed of a pore-forming α1 subunit and auxiliary β and α2δ subunits, which modulate Ca2+ current properties and channel trafficking. So far, the partial redundancy and specificity of α1 for α2δ subunits in the CNS have remained largely elusive. Mature spiral ganglion (SG) neurons express α2δ subunit isoforms 1, 2, and 3 and multiple Ca2+ channel subtypes. Differentiation and in vivo functions of their endbulb of Held synapses, which rely on presynaptic P/Q channels (Lin et al., 2011), require the α2δ3 subunit (Pirone et al., 2014). This led us to hypothesize that P/Q channels may preferentially co-assemble with α2δ3. Using a dissociated primary culture, we analyzed the effects of α2δ3 deletion on somatic Ca2+ currents (ICa) of SG neurons isolated at postnatal day 20 (P20), when the cochlea is regarded to be mature. P/Q currents were the dominating steady-state Ca2+ currents (54% of total) followed by T-type, L-type, N-type, and R-type currents. Deletion of α2δ3 reduced P/Qand R-type currents by 60 and 38%, respectively, whereas L-type, N-type, and T-type currents were not altered. A subset of ICa types was also analyzed in SG neurons isolated at P5, i.e., before the onset of hearing (P12). Both L-type and N-type current amplitudes of wildtype SG neurons were larger at P5 compared with P20. Deletion of α2δ3 reduced L-type and N-type currents by 23 and 44%, respectively. In contrast, small P/Q currents, which were just being up-regulated at P5, were unaffected by the lack of α2δ3. In summary, α2δ3 regulates amplitudes of L- and N-type currents of immature cultured SG neurons, whereas it regulates P/Q- and R-type currents at P20. Our data indicate a developmental switch from dominating somatic N- to P/Q-type currents in cultured SG neurons. A switch from N- to P/Q-type channels, which has been observed at several central synapses, may also occur at developing endbulbs of Held. In this case, reduction of both neonatal N- (P5) and more mature P/Q-type currents (around/after hearing onset) may contribute to the impaired morphology and function of endbulb synapses in α2δ3-deficient mice

Matching Study to Registry data: Maintaining Data Privacy in a Study on Family based Colorectal Cancer

Confidentiality of patient data in the field of medical informatics is an important task. Leaked sensitive information within this data can be adverse to and being abused against a patient. Therefore, when working with medical data, appropriate and secure models which serve as guidelines for different applications are needed. Consequently, this work presents a model for performing a privacy preserving record linkage between study and registry data. The model takes into account seven requirements related to data privacy. Furthermore, this model is exemplified with a study on family based colorectal cancer in Germany. The model is very strict and excludes possible violations towards data privacy protection to a reasonable degree. It should be applicable to similar use cases which are in need of a mapping between medical data of a study and a registry database