Excellent long-term pain response and local control following postoperative radiotherapy in patients with multiple myeloma.

PURPOSE: Multiple myeloma is associated with osteolytic bone lesions, often requiring surgery of the spine and postoperative radiotherapy (RT). Although common, data for clinical and informed decision-making are sparse. In this monocentric retrospective study, we aim to report the outcome of patients who underwent spinal surgery and postoperative RT due to multiple myeloma. METHODS: A total of 54 patients with multiple myeloma who underwent prior spinal surgery and postoperative RT at our institution between 2009 and 2020 were analyzed. Spinal instability neoplastic score (SINS) and Bilsky score, posttherapeutic adverse events, clinical data, and outcomes were collected and analyzed. The primary endpoint of this study was overall survival (OS), secondary endpoints were progression-free survival (PFS), pain response, local control, and skeletal-related events (SRE). RESULTS: The 3­ and 5­year overall survival (OS) was 74.9% (95% confidence interval [CI]: 63.5-88.4%) and 58% (95% CI: 44.5-75.6%), respectively. Median survival was not reached and 75% survival was 34.3 months (95% CI: 28.7-95.4 months). Median follow-up was 63 months (95% CI: 49-94 months). The number of patients with good to adequate performance status (Karnofsky performance score [KPS] ≥ 70) significantly increased after surgery (p < 0.01). We observed no grade 3/4 toxicity and only 13 (24%) grade 1/2 adverse events. Two patients (4%) experienced SRE. Overall, 92% of patients reported reduced pain after radiotherapy, with 66% reporting complete pain response. There was no difference in pain response between patients with different Bilsky scores. Bisphosphonate therapy and lower Bilsky score at the start of RT were associated with improved OS in univariate analysis (all p < 0.05). Multivariate Cox regression confirmed a Bilsky score of 2 or 3 as an independent negative prognostic factor (HR 3.89; 95 CI 1.4-10.7; p < 0.01). We observed no in-field recurrences. CONCLUSION: In this study, we were able to show that the current standard of RT after spinal surgery of osteolytic lesions is safe. In addition, we observed a very low rate of SRE (4%) and no in-field recurrences, demonstrating the local efficacy of RT in multiple myeloma patients. Higher Bilsky scores were associated with worse OS in multivariate analysis, but had no effect on pain response.

Temporal patterns of childhood cancer survival 1991 to 2016: A nationwide register-study based on data from the German Childhood Cancer Registry.

Childhood cancer is the leading disease-related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long-term well-being remain primary goals. With this report, we provide the first long-term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years. Using data from the German Childhood Cancer Registry, we assessed temporal patterns of cancer survival among children (0-14 years) diagnosed in Germany from 1991 to 2016, by cancer type, age at diagnosis and sex. We calculated overall survival (OS) and average annual percentage changes of the respective 5-year OS estimates. OS improved across all cancer types, age groups as well as for boys and girls over time. Five-year OS for all childhood cancers combined increased from 77.8% in 1991-1995 to 86.5% in 2011-2016, with stronger improvements during the early 1990s. The most pronounced survival improvement was seen for acute myeloid leukaemia, at 2% annually and 5-year OS recently reaching 81.5%. Survival improvements for some diagnoses such as neuroblastoma, renal tumours and bone tumours have flattened out. Tremendous enhancements in diagnostics, treatment and supportive care have affected average survival improvements for most cancer types. Recently, survival improvements have decelerated overall and for some cancer types, it plateaued at an unsatisfactory level. As not all children benefited equally from the survival improvements, personal factors (eg, socioeconomic circumstances, health literacy, access to care) likely affect individual prognosis and warrant further investigation.

Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa).

PURPOSE: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. METHODS: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. RESULTS: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25). CONCLUSIONS: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Adjuvant chemoradiotherapy in elderly patients with head and neck cancer: a monoinstitutional, two-to-one pair-matching analysis.

PURPOSE: About one fifth of patients with head and neck cancer are aged 70 years and older at the time of diagnosis. In these patients, risk factors (R1 status or extracapsular extension of lymph node metastases, ECE) often lead to a need for combined chemoradiotherapy (CRT) in the postoperative setting. However, there is considerable concern about the toxicity of such therapy in this age group. METHODS: Retrospective evaluation of the data of 53 patients ≥ 70 years of age who underwent surgery in our hospital between 1999 and 2015 for tumors of the oral cavity, the oropharynx, the hypopharynx, or the larynx, who subsequently received adjuvant radiation therapy. Two younger patients (< 70 years) were assigned to each of the elderly patients in a matching procedure based on anatomic sublocalization and tumor stage. The total cohort was comprised of 154 patients. RESULTS: Univariate analyses revealed a statistically significant influence of many factors on overall survival (OS) and progression-free survival (PFS), including Karnofsky performance score (KPS), alcohol consumption, smoking, R status, ECE, chemotherapy, and discontinuation of RT. Younger patients had better OS and PFS compared to the elderly (p = 0.013 and 0.012, respectively). In a multivariate Cox regression, no independent influence of age on OS and PFS was found. Survival was primarily dependent on the addition of chemotherapy to radiotherapy (RT), application of the full course of RT, continued alcohol abuse, KPS, and the presence of ECE. Toxicity analysis showed a higher incidence of chronic renal failure but, generally, side effects for elderly patients were not substantially greater. CONCLUSION: Performance status and behavioral risk factors but not chronological age are crucial for the prognosis of patients who require adjuvant chemoradiation.

[Explaining the age-adjusted excess mortality with COVID-19-attributed deaths from January 2020 to July 2021]. / Erklärbarkeit der altersadjustierten Übersterblichkeit mit den COVID-19-attribuierten Sterbefällen von Januar 2020 bis Juli 2021.

BACKGROUND: Estimating COVID-19 mortality is impeded by uncertainties in cause of death coding. In contrast, age-adjusted excess all-cause mortality is a robust indicator of how the COVID-19 pandemic impacts public health. However, in addition to COVID-19 deaths, excess mortality potentially also reflects indirect negative effects of public health measures aiming to contain the pandemic. OBJECTIVES: The study examines whether excess mortality in Germany between January 2020 and July 2021 is consistent with fatalities attributed to COVID-19 or may be partially due to indirect effects of public health measures. METHODS: Excess mortality trends for the period from January 2020 to July 2021 were checked for consistency with deaths attributed to COVID-19 in both the German federal states and districts of Rhineland-Palatinate. The expected monthly mortality rates were predicted based on data from 2015-2019, taking into account the population demographics, air temperature, seasonal influenza activity, and cyclic and long-term time trends RESULTS: COVID-19-attributed mortality was included in the 95% prediction uncertainty intervals for excess mortality in 232 of 304 (76.3%) month-state combinations and in 607 of 684 (88.7%) month-district combinations. The Spearman rank correlation between excess mortality and COVID-19-attributed mortality across federal states was 0.42 (95% confidence interval [0.31; 0.53]) and 0.21 (95% confidence interval [0.13; 0.29]) across districts. CONCLUSIONS: The good agreement of spatiotemporal excess mortality patterns with COVID-19 attributed mortality is consistent with the assumption that indirect adverse effects from public health interventions to contain the COVID-19 pandemic did not substantially contribute to excess mortality in Germany between January 2020 and July 2021.

Association of COVID-19 mortality with COVID-19 vaccination rates in Rhineland-Palatinate (Germany) from calendar week 1 to 20 in the year 2021: a registry-based analysis.

Vaccination is among the measures implemented by authorities to control the spread of the COVID-19 pandemic. However, real-world evidence of population-level effects of vaccination campaigns against COVID-19 are required to confirm that positive results from clinical trials translate into positive public health outcomes. Since the age group 80 + years is most at risk for severe COVID-19 disease progression, this group was prioritized during vaccine rollout in Germany. Based on comprehensive vaccination data from the German federal state of Rhineland-Palatinate for calendar week 1-20 in the year 2021, we calculated sex- and age-specific vaccination coverage. Furthermore, we calculated the proportion of weekly COVID-19 fatalities and reported SARS-CoV-2 infections formed by each age group. Vaccination coverage in the age group 80 + years increased to a level of 80% (men) and 75% (women). Increasing vaccination coverage coincided with a reduction in the age group's proportion of COVID-19 fatalities. In multivariable logistic regression, vaccination coverage was associated both with a reduction in an age-group's proportion of COVID-19 fatalities [odds ratio (OR) per 5 percentage points = 0.89, 95% confidence interval (CI) = 0.82-0.96, p = 0.0013] and of reported SARS-CoV-2 infections (OR per 5 percentage points = 0.82, 95% CI 0.76-0.88, p < 0.0001). The results are consistent with a protective effect afforded by the vaccination campaign against severe COVID-19 disease in the oldest age group.

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses.

In breast cancer radiotherapy, substantial radiation exposure of organs other than the treated breast cannot be avoided, potentially inducing second primary cancer or heart disease. While distant organs and large parts of nearby ones receive doses in the mGy-Gy range, small parts of the heart, lung and bone marrow often receive doses as high as 50 Gy. Contemporary treatment planning allows for considerable flexibility in the distribution of this exposure. To optimise treatment with regards to long-term health risks, evidence-based risk estimates are required for the entire broad range of exposures. Here, we thus propose an approach that combines data from medical and epidemiological studies with different exposure conditions. Approximating cancer induction as a local process, we estimate organ cancer risks by integrating organ-specific dose-response relationships over the organ dose distributions. For highly exposed organ parts, specific high-dose risk models based on studies with medical exposure are applied. For organs or their parts receiving relatively low doses, established dose-response models based on radiation-epidemiological data are used. Joining the models in the intermediate dose range leads to a combined, in general non-linear, dose response supported by data over the whole relevant dose range. For heart diseases, a linear model consistent with high- and low-dose studies is presented. The resulting estimates of long-term health risks are largely compatible with rate ratios observed in randomised breast cancer radiotherapy trials. The risk models have been implemented in a software tool PASSOS that estimates long-term risks for individual breast cancer patients.

Methodological considerations for interrupted time series analysis in radiation epidemiology: an overview.

Interrupted time series analysis (ITSA) is a method that can be applied to evaluate health outcomes in populations exposed to ionizing radiation following major radiological events. Using aggregated time series data, ITSA evaluates whether the time trend of a health indicator shows a change associated with the radiological event. That is, ITSA checks whether there is a statistically significant discrepancy between the projection of a pre-event trend and the data empirically observed after the event. Conducting ITSA requires one to consider specific methodological issues due to unique threats to internal validity that make ITSA prone to bias. We here discuss the strengths and limitations of ITSA with respect to bias and confounding, data quality, and statistical aspects. We provide recommendations to strengthen the robustness of ITSA studies and reduce their susceptibility to producing spurious results as a consequence of arbitrary modelling decisions.

[Mental burden, resilience and tendency towards absenteeism among healthcare personnel in Germany during the first wave of the COVID-19 pandemic in spring 2020 : An ad hoc survey]. / Psychische Belastung, Resilienz und Absentismusneigung bei Gesundheitspersonal in Deutschland während der ersten COVID-19-Pandemiewelle im Frühjahr 2020 : Eine Ad-hoc-Befragung.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is associated with extensive changes in the public and private life in Germany. Healthcare personnel are particularly exposed to additional stressors. OBJECTIVE: To identify the mental burden, resilience, tendency towards absenteeism and associated factors during the COVID-19 pandemic in an anonymous cross-sectional survey. METHODS: Data on sociodemographics, occupational situation, contact to COVID-19 patients, mental burden, stressors, resilience, risk and protective factors were assessed among a convenience sample of healthcare personnel in spring 2020 (5 April 2020-7 May 2020). A comparison with the general population in Germany before and during the COVID-19 pandemic was conducted. RESULTS: After the evaluation of 650 completed questionnaires, an increased mental burden was found compared to the German general population before the pandemic, while the mental burden was reduced compared to the general population during the pandemic. The self-reported resilience was slightly higher compared to the general population before and during the pandemic. The COVID-19-related stressors and worries were the most important risk factors, self-efficacy and optimism the most important protective factors. The mental burden was moderately correlated with the intention to change the profession and the tendency towards absenteeism. CONCLUSION: Mental burden in healthcare personnel during the COVID-19 pandemic is associated with a higher tendency towards taking sick leave. In order to support healthcare personnel interventions that foster resources, such as self-efficacy and optimism should be offered to particularly vulnerable groups .

Impact of physicians' participation in non-interventional post-marketing studies on their prescription habits: A retrospective 2-armed cohort study in Germany.

BACKGROUND: Non-interventional post-marketing studies (NIPMSs) sponsored by pharmaceutical companies are controversial because, while they are theoretically useful instruments for pharmacovigilance, some authors have hypothesized that they are merely marketing instruments used to influence physicians' prescription behavior. So far, it has not been shown, to our knowledge, whether NIPMSs actually do have an influence on prescription behavior. The objective of this study was therefore to investigate whether physicians' participation in NIPMSs initiated by pharmaceutical companies has an impact on their prescription behavior. In addition, we wanted to analyze whether specific characteristics of NIPMSs have a differing impact on prescription behavior. METHODS AND FINDINGS: In a retrospective 2-armed cohort study, the prescription behavior of 6,996 German physicians, of which 2,354 had participated in at least 1 of 24 NIPMSs and 4,642 were controls, was analyzed. Data were acquired between 6 October 2016 and 8 June 2018. Controls were matched by overall prescription volume and number of prescriptions of the drug studied in the NIPMS in the year prior to the NIPMS. Primary outcome was the relative rate of prescriptions of the drug studied in the NIPMS by participating physicians compared to controls during the NIPMS and the following year. Secondary outcomes were the proportion of prescriptions of the studied drug compared to alternative drugs used for the same indication, the revenue generated by these prescriptions, and the association between the marketing characteristics of the NIPMS and prescription habits. Of the 24 NIPMSs, the 2 largest drug groups studied were antineoplastic and immunomodulatory agents (7/24, 29.2%) and agents for the nervous system (4/24, 16.7%). Physicians participating in an NIPMS prescribed more of the studied drug during and in the year after the NIPMS, at a relative rate of 1.08 (95% CI 1.07-1.10; p < 0.001) and 1.07 (95% CI 1.05-1.09); p < 0.001), respectively. Participating physicians were more likely than controls to prescribe one of the studied drugs rather than alternative drugs used for the same indication (odds ratio 1.04; 95% CI 1.03-1.05). None of the marketing characteristics studied were significantly associated with prescription practices. The main limitation was the difficulty in controlling for confounders due to privacy laws, with a resulting lack of information regarding the included physicians, which was mainly addressed by the matching process. CONCLUSIONS: Physicians participating in NIPMSs prescribe more of the investigated drug than matching controls. This result calls the alleged non-interventional character of NIPMSs into question and should lead to stricter regulation of NIPMSs.

Cohort study of occupational cosmic radiation dose and cancer mortality in German aircrew, 1960-2014.

OBJECTIVES: To determine cancer mortality compared with the general population and to examine dose-response relationships between cumulative occupational radiation dose and specific cancer outcomes in the German aircrew cohort. METHODS: For a cohort of 26 846 aircrew personnel, standardised mortality ratios (SMR) were calculated. Dose-response analyses were carried out using Poisson regression to assess dose-related cancer risks for the period 1960-2014. Exposure assessment comprises recently available dose register data for all cohort members and newly estimated retrospective cabin crew doses for 1960-2003. RESULTS: SMR for all-cause, specific cancer groups and most individual cancers were reduced in all aircrew groups. The only increases were seen for brain cancer in pilots (n=23, SMR 2.01, 95% CI 1.15 to 3.28) and for malignant melanoma (n=10, SMR 1.88, 95% CI 0.78 to 3.85). Breast cancer mortality among female cabin crew was similar to the general population (n=71, SMR 1.06, 95% CI 0.77 to 1.44). Overall median cumulative effective dose was 34.2 mSv (max: 116 mSv) for 1960-2014. No dose-response associations were seen in any of the models. For brain cancer, relative risks were elevated across dose categories. An indicative negative trend with increasing dose category was seen for large intestine cancer in female cabin crew (n=23). CONCLUSIONS: There was no evidence for significant dose-response patterns for the considered cancer types. Interpretation of results remains difficult as cumulative dose is closely related to age. Future work should focus on investigating radiation jointly with other risk factors that may contribute to risks for specific cancers among aircrew.

Higher BDNF plasma levels are associated with a normalization of memory dysfunctions during an antidepressant treatment.

One important symptom of patients with major depressive disorder (MDD) is memory dysfunction. However, little is known about the relationship between memory performance and depression severity, about the course of memory performance during antidepressant treatment as well as about the relationship between memory performance and brain-derived neurotrophic factor (BDNF). Memory function [learning and delayed recall) was assessed in 173 MDD patients (mean age 39.7 ± 11.3 years] treated by a pre-defined treatment algorithm within the early medication change (EMC) study at baseline, days 28 and 56. Depression severity was assessed in weekly intervals, BDNF plasma levels were measured at baseline, days 14 and 56, BDNF exon IV and p11 methylation status at baseline. Linear mixed regression models revealed that the course of depression severity was not associated with the course of learning or delayed recall in the total group. 63 (36%) of the investigated patients showed memory deficits (percent range ≤ 16) at baseline. Of those, 26(41%) patients experienced a normalization of their memory deficits during treatment. Patients with a normalization of their delayed recall performance had significantly higher plasma BDNF levels (p = 0.040) from baseline to day 56 than patients with persistent deficits. Baseline BDNF exon IV promoter and p11 gene methylation status were not associated with memory performance. Our results corroborate a concomitant amelioration of learning and delayed recall dysfunctions with successful antidepressant therapy in a subgroup of patients and support a role of BDNF in the neural mechanisms underlying the normalization of memory dysfunctions in MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.

Effects of age on depressive symptomatology and response to antidepressant treatment in patients with major depressive disorder aged 18 to 65 years.

BACKGROUND: There is evidence that symptomatology in patients with major depressive disorder (MDD) changes with age. However, studies comparing depressive symptomatology between different age groups during antidepressant therapy are rare. We compared demographic and clinical characteristics in depressed patients of different age groups at baseline and during treatment. METHODS: 889 MDD inpatients were divided into four age groups (18-29, 30-39, 40-49, 50-65 yrs.). Demographic and clinical characteristics including depressive symptomatology (assessed by the Inventory of Depressive Symptoms) were assessed at baseline and weekly during treatment. RESULTS: At baseline, young patients (18-29 years) significantly more often reported cognitive symptoms like irritability, suicidality, negative self-concept and interpersonal sensitivity and more often suffered from drug abuse and comorbid personality disorders. Late middle aged patients (50-65 years) significantly more often suffered from neuro-vegetative symptoms such as reduced general interest, sexual interest and sleep disturbances and more often showed a recurrent MDD and comorbid physical disorders. During therapy, symptoms such as interpersonal sensitivity in young patients and low interest in sex in late middle aged patients persisted until the end of treatment while all other symptoms declined until day 56. LIMITATIONS: The herein presented age differences in depressive symptomatology only hold true for the study medication and are not generalizable to other antidepressants agents. CONCLUSION: There are substantial differences in the clinical presentation of depression between age groups. Whereas many of these differences disappear during treatment, some differences persisted until the end of treatment. These findings my help to more specifically tailor the treatment of depressed patients.

Stability and survival analysis of elderly patients with osteolytic spinal bone metastases after palliative radiotherapy : Results from a large multicenter cohort.

PURPOSE: This retrospective study aimed to evaluate the stability and fracture rates of osteolytic spinal bone metastases (SBM) in elderly patients following palliative radiotherapy (RT) and to derive prognostic factors for stability and survival. METHODS: A total of 322 patients aged at least 70 years received palliative RT at two major German academic medical centers or at the German Cancer Research Center. Stability assessment was based on the validated Taneichi score prior to RT and at 3 and 6 months after RT. The survival time following RT was assessed, and prognostic factors for stability and survival were analyzed. RESULTS: Prior to RT, 183 patients (57%) exhibited unstable SBM and 68 patients (21%) pathological fractures. At 3 and 6 months after RT, significant recalcification and stabilization were evident in 19% (23/118) and 40% (31/78) of surviving patients, respectively. Only 17 patients (5%) experienced new pathological fractures following RT. Tumor histology was found to significantly influence stabilization rates with only breast cancer patients exhibiting increased stabilization compared to patients with other histologies. The median survival time and 6­month survival rates following RT were 5.4 months (95% confidence interval 4.4-7.2 months) and 48%, respectively. The patients' performance status was found to be the strongest predictor for survival after RT in this patient cohort; further factors demonstrating a significant association with survival were the application of systemic treatment, the number of SBM and the primary tumor histology. To analyze the influence of age on survival after RT, study patients were stratified into 3 age groups (i.e., 70-74 years, 75-79 years, and ≥80 years). The subgroup of patients aged at least 80 years showed a strong trend towards a worse survival time following RT compared to younger patients (i.e., 6­month survival rate 39% vs. 51%; p = 0.06, log-rank test). CONCLUSIONS: Prognostic factors influencing overall survival such as performance status and histology should guide the choice for palliative RT for SBM. Strongly hypofractionated RT regimes may be advisable for most elderly patients considering the overall poor prognosis in order to reduce hospitalization times.

Evaluation of the psychological burden during the early disease trajectory in patients with intracranial tumors by the ultra-brief Patient Health Questionnaire for Depression and Anxiety (PHQ-4).

PURPOSE: Depressive symptoms of patients with intracranial tumors need to be assessed adequately. The Patient Health Questionnaire for Depression and Anxiety (PHQ-4) is an ultra-short screening tool consisting of four items, a cutoff of six indicates depressive symptoms. The aim was to assess patients' psychological burden by the PHQ-4 compared with the results of well-established screening instruments. METHODS: Patients were screened three times after primary diagnosis postoperatively (t1), after 3 (t2) and 6 (t3) months using the PHQ-4, the Hornheide Screening Instrument (HSI), the NCCN Distress Thermometer (DT), and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire with its brain module (EORTC QLQ-C30 + BN20). Demographic, tumor-related data, and Karnofsky Performance Scale (KPS) were analyzed. A cutoff value for PHQ-4 indicating a need for support or increased distress was determined by applying receiver operating characteristic (ROC). RESULTS: The proportion of patients reaching a total score ≥ 6 was n = 32 out of 139 (23%) at t1; at t2, n = 12 out of 117 (10%) scored ≥ 6. At t3, n = 8 out of 96 (8%) scored ≥ 6. At t1, PHQ-4 scores did not differ significantly between gender, age groups, and tumor laterality. A cutoff value of 2.5 was identified to moderately discriminate between patients in or not in distress (sensitivity 76.8%) and between patients wishing further, specific support or not (sensitivity 82.5%). CONCLUSION: The PHQ4 can be applied in this patient cohort to detect those with relevant psychological comorbidities. The cutoff value should be re-evaluated in a larger cohort as we observed that a cutoff of 6, as recommended previously, may be too high in order to detect affected patients adequately.

Local excision followed by early radical surgery in rectal cancer: long-term outcome.

BACKGROUND: In rectal cancers, radical surgery should follow local excisions, in cases of unexpected, unfavorable tumor characteristics. The oncological results of this completion surgery are inconsistent. This retrospective cohort study assessed the clinical and long-term oncological outcomes of patients that underwent completion surgery to clarify whether a local excision compromised the results of radical surgery. METHODS: Forty-six patients were included, and the reasons for completion surgery, intraoperative complications, residual tumors, local recurrences (LRs), distant metastases, and cancer-specific survival (CSS) were assessed. The results were compared to 583 patients that underwent primary surgery without adjuvant therapy, treated with a curative intention during the same time period. RESULTS: The median follow-up was 14.6 years. The reasons for undergoing completion surgery were positive resection margins (24%), high-risk cancer (30%), or both (46%). Intraoperative perforations occurred in 10/46 (22%) cases. Residual tumor in the rectal wall or lymph node involvement occurred in 12/46 (26%) cases. The risk of intraoperative perforation and residual tumor increased with the pT category. Intraoperative perforations did not increase postoperative complications, but they increased the risk of LRs in cases of intramural residual tumors (p = 0.003). LRs occurred in 2.6% of pT1/2 and 29% of pT3 tumors. Both the 5- and 10-year CSS rates were 88.8% (95% CI 80.0-98.6). Moreover, the LRs of patients with pT1/2 cancers were lower in patients with completion surgery than in patients with primary surgery. CONCLUSIONS: Rectal wall perforations at the local excision site and residual cancer were the main risks for poor oncological outcomes associated with completion surgery. Local excisions followed by early radical surgery did not appear to compromise outcomes compared to patients with primary surgery for pT1/2 rectal cancer. Improvements in clinical staging should allow more appropriate selection of patients that are eligible for a local excision of rectal cancer.

Ionising radiation and lens opacities in interventional physicians: results of a German pilot study.

We assessed the feasibility of an epidemiological study on the risk of radiation-related lens opacities among interventional physicians in Germany. In a regional multi-centre pilot study associated with a European project, we tested the recruitment strategy, a European questionnaire on work history for the latter dosimetry calculation and the endpoint assessment. 263 interventional physicians and 129 non-exposed colleagues were invited. Questionnaires assessed eligibility criteria, risk factors for cataract, and work history relating to occupational exposure to ionising radiation, including details on type and amount of procedures performed, radiation sources, and use of protective equipment. Eye examinations included regular inspection by an ophthalmologist, digital slit lamp images graded according to the lens opacities classification system, and Scheimpflug camera measurements. 46 interventional (17.5%) and 30 non-exposed physicians (23.3%) agreed to participate, of which 42 and 19, respectively, met the inclusion criteria. Table shields and ceiling suspended shields were used as protective equipment by 85% and 78% of the interventional cardiologists, respectively. However, 68% of them never used lead glasses. More, although minor, opacifications were diagnosed among the 17 interventional cardiologists participating in the eye examinations than among the 18 non-exposed (59% versus 28%), mainly nuclear cataracts in interventional cardiologists and cortical cataracts in the non-exposed. Opacification scores calculated from Scheimpflug measurements were higher among the interventional cardiologists, especially in the left eye (56% versus 28%). Challenges of the approach studied include the dissuading time investment related to pupil dilatation for the eye examinations, the reliance on a retrospective work history questionnaire to gather exposure-relevant information for dose reconstructions and its length, resulting in a low participation rate. Dosimetry data are bound to get better when the prospective lens dose monitoring as foreseen by 2013 European Directives is implemented and doses are recorded.

Cardiac late events in German breast cancer patients: a validation study on the agreement between patient self-reports and information from physicians.

BACKGROUND: Self-administered health-status questionnaires are important tools in epidemiology. The objective of the presented validation study is to measure the agreement between breast cancer patients' self-reports and their physicians' information on late cardiac events, and to investigate determinants of agreement. To estimate possible misclassification is an important requirement for observational studies on cardiovascular endpoints. METHODS: A retrospective, multi-center cohort study included 11,982 women diagnosed with breast cancer in Germany in 1998-2008. In 2014, a questionnaire survey assessed cardiovascular risk factors and incident cardiac events after therapy. A validation study was conducted, based on a sample of 3091 breast cancer patients from two university hospitals. Among them, 2261 women (73%) sent back the questionnaire on cardiovascular events, and 1316 women gave consent to request medical records from their general practitioners. A total of 1212/1316 (92.1%) medical records could be obtained for validation. Cohen's kappa coefficient was calculated, and multivariate regression was applied to study the influence of patient characteristics on agreement between both data sources. RESULTS: Overall agreement for the composite endpoint of any cardiac event was 84.5% (kappa 0.35). Of 1055 breast cancer patients reporting no cardiac event, 950 (90%) had no such diagnosis in physicians' medical records. A total of 157 breast cancer survivors indicated a cardiac event, and the same diagnosis was confirmed by GPs for 74 (47%) women. For specific diagnoses, moderate to substantial agreement of self-reports was found for myocardial infarction (kappa 0.54) and stroke (kappa 0.61). Poor to fair agreement was present for angina pectoris, valvular heart disease, arrhythmia, and congestive heart failure. Younger age, higher education and a more recent cancer diagnosis were found to be associated with greater total agreement. CONCLUSIONS: For the composite endpoint, survivors of breast cancer report the absence of cardiac disease accurately. However, for specific diagnoses, self-reported morbidity data from breast cancer patients may not fully agree with information from physicians. The agreement is moderate for acute events like myocardial infarction and stroke, but poor to fair for chronic diseases.

Comorbidity-dependent adherence to guidelines and survival in breast cancer-Is there a role for guideline adherence in comorbid breast cancer patients? A retrospective cohort study with 2137 patients.

In the treatment of breast cancer, decisions on adjuvant treatment reflect individual patient characteristics like age and comorbidity. This study assessed the association between adherence to guidelines for adjuvant treatment and survival while taking into account age at diagnosis and comorbidities. We collected the Charlson comorbidity index at baseline for 2179 women treated for primary breast cancer from 1992 to 2008 who participated in a German retrospective multicenter cohort study. We assessed subsequent adjuvant therapy guideline adherence and survival in relation to baseline comorbidities. Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in patients with higher Charlson score. Patients with higher Charlson scores received chemotherapy and radiotherapy less often and had higher rates of mastectomy. Irrespective of comorbidity (Charlson score 0, 1-2, ≥3), patients with 100% guideline-adherent adjuvant treatment showed better overall and disease-free survival (DFS) compared to patients with guideline violations (GVs). Controlling for age, comorbidity and tumor characteristics, the hazard ratio for at least one GV was 1.65 (95% confidence interval [CI]: 1.33-2.07) for overall survival and 1.84 (95% CI: 1.53-2.22) for DFS. Guideline-adherent treatment was significantly less frequent in comorbid patients, although guideline adherence was strongly associated with improved survival, irrespective of severity, and number of comorbid diseases.