Long-Term Outcome of Chest Wall and Diaphragm Repair with Biological Materials.

INTRODUCTION: Chest wall and/or diaphragm reconstruction aims to preserve, restore, or improve respiratory function; conserve anatomical cavities; and upkeep postural and upper extremity support. This can be achieved by utilizing a wide range of different grafts made of synthetic, biological, autologous, or bioartificial materials. We aim to review our experience with decellularized bovine pericardium as graft in the past decade. PATIENTS AND METHODS: We conducted a retrospective analysis of patients who underwent surgical chest wall and/or diaphragm repair with decellularized bovine pericardium between January 1, 2012 and January 13, 2022 at our institution. All records were screened for patient characteristics, intra-/postoperative complications, chest tube and analgesic therapy duration, length of hospital stay, presence or absence of redo procedures, as well as morbidity and 30-day mortality. We then looked for correlations between implanted graft size and postoperative complications and gathered further follow-up information at least 2 months after surgery. RESULTS: A total of 71 patients either underwent isolated chest wall (n = 51), diaphragm (n = 12), or pericardial (n = 4) resection and reconstruction or a combination thereof. No mortality was recorded within the first 30 days. Major morbidity occurred in 12 patients, comprising secondary respiratory failure requiring bronchoscopy and invasive ventilation in 8 patients and secondary infections and delayed wound healing requiring patch removal in 4 patients. There was no correlation between the extensiveness of the procedure and extubation timing (chi-squared test, p = 0.44) or onset of respiratory failure (p = 0.27). CONCLUSION: A previously demonstrated general viability of biological materials for various reconstructive procedures appears to be supported by our long-term results.

Calcineurin-inhibitor free immunosuppression after lung transplantation - a single center case-control study in 51 patients converted to Mechanistic Target of Rapamycin (mTOR) inhibitors.

BACKGROUND: Data on calcineurin-inhibitor (CNI) free immunosuppression after lung transplantation (LTx) are limited. Aim of this study was to investigate CNI-free immunosuppression using mechanistic target of rapamycin (mTOR) inhibitors. METHODS: This retrospective analysis was performed at a single center. Adult patients after LTx without CNI during the follow-up period were included. Outcome was compared to those LTx patients with malignancy who continued CNI. RESULTS: Among 2,099 patients in follow-up, fifty-one (2.4%) were converted median 6.2 years after LTx to a CNI-free regimen combining mTOR inhibitors with prednisolone and an antimetabolite, two patients were switched to mTOR inhibitors with prednisolone only. In 25 patients, malignancies without curative treatment options were the reason of the conversion, with a 1-year survival of 36%. The remaining patients had a 1-year survival of 100%. Most common non-malignant indication was neurological complications (n = 9). Fifteen patients were re-converted to a CNI-based regimen. The median duration of CNI-free immunosuppression was 338 days. No acute rejections were detected in 7 patients with follow-up biopsies. In multivariate analysis, CNI-free immunosuppression were not associated with improved survival after malignancy. The majority of patients with neurological diseases improved 12 months after conversion. Glomerular filtration rate increased by median 5 (25 and 75% percentiles -6; +18) ml/min/1.73 m2. CONCLUSIONS: mTOR inhibitor based CNI-free immunosuppression may be safely performed in selected patients after LTx. This approach was not associated with improved survival in patients with malignancy. Significant functional improvements were observed in patients with neurological diseases.

Dynamic contrast enhanced MRI of pulmonary adenocarcinomas for early risk stratification: higher contrast uptake associated with response and better prognosis.

BACKGROUND: To explore the prognostic value of serial dynamic contrast-enhanced (DCE) MRI in patients with advanced pulmonary adenocarcinoma undergoing first-line therapy with either tyrosine-kinase inhibitors (TKI) or platinum-based chemotherapy (PBC). METHODS: Patients underwent baseline (day 0, n = 98), and post-therapeutic DCE MRI (PBC: day + 1, n = 52); TKI: day + 7, n = 46) at 1.5T. Perfusion curves were acquired at 10, 40, and 70 s after contrast application and analysed semiquantitatively. Treatment response was evaluated at 6 weeks by CT (RECIST 1.1); progression-free survival (PFS) and overall survival  were analysed with respect to clinical and perfusion parameters. Relative uptake was defined as signal difference between contrast and non-contrast images, divided by the non-contrast signal. Predictors of survival were selected using Cox regression analysis. Median follow-up was 825 days. RESULTS: In pre-therapeutic and early post-therapeutic MRI, treatment responders (n = 27) showed significantly higher relative contrast uptake within the tumor at 70 s after application as compared to non-responders (n = 71, p ≤ 0.02), response defined as PR by RECIST 1.1 at 6 weeks. There was no significant change of perfusion at early MRI after treatment. In multivariate regression analysis of selected parameters, the strongest association with PFS were relative uptake at 40 s in the early post-treatment MRI and pre-treatment clinical data (presence of liver metastases, ECOG performance status). CONCLUSION: Higher contrast uptake within the tumor at pre-treatment and early post-treatment MRI was associated with treatment response and better prognosis. DCE MRI of pulmonary adenocarcinoma may provide important prognostic information.

NSCLC with uncommon EGFR mutations treated with atezolizumab plus bevacizumab and chemotherapy.

OBJECTIVES: For refractory NSCLC patients with EGFR mutations, recent studies have demonstrated a favorable response to the combination of anti-angiogenic therapy and checkpoint inhibition but included only very few patients with uncommon EGFR mutations for which treatment options are still limited despite new targeted treatments. MATERIALS AND METHODS: Sixteen stage IV NSCLC patients with uncommon EGFR mutations from 9 different German centers were treated in first or further line with Atezolizumab, Bevacizumab, Carboplatin and (nab-)Paclitaxel (ABCP). PFS was evaluated from start of ABCP and OS from time of initial diagnosis of stage IV. RESULTS: Patients with either an Exon 20 insertion (n = 9) or other uncommon EGFR mutations (n = 7) received ABCP in first, second or further line. Nine patients had received a TKI therapy in first line with an ORR of 66.7 % and a median time-to-next-treatment of 6.7 months. After a median number of 4 ABCP cycles, 4 patients (25.0 %) required a dose reduction of chemotherapy and 5 patients (31.3 %) suffered from grade 3 or 4 toxicity. Overall response rate was 81.3 % and disease control rate 87.5 %. 14 patients (87.5 %) received a maintenance with AB and the median follow-up after initial diagnosis was 24.3 months. Median PFS was 13.6 months for both the entire cohort and for Exon 20 insertions. Corresponding median OS was either not reached or 30.7 months. Landmark analysis at 12 months gave a PFS of 42.8 % and an OS of 93.3 %. Four patients were rechallenged with ABCP while progressing under maintenance and responded again. In further line therapy, clinical benefit was achieved in all of 3 patients receiving Amivantamab, but in only one of four patients receiving mobocertinib. CONCLUSION: In this retrospective analysis, ABCP achieves an encouraging outcome for patients with uncommon EGFR mutations and is a valuable option in the early treatment course.

[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

Time Trends and Income Inequalities in Cancer Incidence and Cancer-Free Life Expectancy - a Cancer Site-Specific Analysis of German Health Insurance Data.

Cancer represents a major burden of morbidity and mortality globally. So far, however, little is known on time trends and inequalities in the lengths of life spent free of any cancer. This study steps into this gap by analyzing time trends and income inequalities in cancer-free life expectancy (CFLE). For this retrospective cohort study, data of a large German health insurer were used (N = 3,405,673individuals, 2006-2018). Income inequalities were assessed using individual income (<60% of German average income (GAI) and ≥60% of GAI). Trends in incidence risks were analysed employing proportional-hazard regression models by splitting the observation time into three periods of 52 months. Trends in CFLE in total and for the most common site-specific cancers were calculated based on multiple decrement life tables. Incidence rates declined in almost all cancers and CFLE increased substantially over time (49.1 (95% CI 48.8-49.4) to 51.9 (95% CI 51.6-52.2) years for men, 53.1 (95% CI 52.7-53.5) to 55.4 (95% CI 55.1-55.8) years for women at age 20 for total cancer) and income groups. Considerable income inequalities in cancer risks were evident in both sexes, but were more pronounced in men (total cancer HR 0.86 (95% CI 0.85-0.87)), with higher-income individuals having lower risks. The highest income inequalities were found in colon (HR 0.90 (95% CI 0.87-0.93)), stomach (HR 0.78 (95% CI 0.73-0.84)), and lung cancer (HR 0.58 (95% CI 0.56-0.60)) in men. A reverse gradient was found for skin (HR 1.39 (95% CI 1.30-1.47) men; HR 1.27 (95% CI 1.20-1.35) women) and prostate cancer (HR 1.13 (95% CI 1.11-1.15)). The proportion of CFLE in total life expectancy declined for lung, skin and cervical cancer in women, indicating a relative shortening of lifetime spent cancer-free. In contrast, increasing proportions were found in breast and prostate cancer. To our knowledge, this is the first study analysing trends and income inequalities in CFLE. The life span free of cancer increased clearly over time. However, not all cancer types contributed equally to this positive development. Income inequalities persisted or tended to widen, which underlines the need for increased public health efforts in socioeconomically vulnerable groups.

Potential Roles of Acute Phase Proteins in Cancer: Why Do Cancer Cells Produce or Take Up Exogenous Acute Phase Protein Alpha1-Antitrypsin?

An association between acute-phase proteins (APPs) and cancer has long been established and there are numerous reports correlating altered levels and/or molecular forms of APPs with different types of cancers. Many authors have shown a positive correlation between high levels of APPs, like alpha1-antitrypsin (AAT), and unfavorable clinical outcome in cancers. Conversely, others proposed that high levels of APPs are probably just a part of nonspecific inflammatory response to cancer development. However, this might not be always true, because many cancerous cells produce or take up exogenous APPs. What is the biological significance of this and what benefit do cancer cells have from these proteins remains largely unknown. Recent data revealed that some APPs, including AAT, are able to enhance cancer cell resistance against anticancer drug-induced apoptosis and autophagy. In this review, we specifically discuss our own findings and controversies in the literature regarding the role of AAT in cancer.

Socioeconomic inequalities in lung cancer - a time trend analysis with German health insurance data.

BACKGROUND: Lung Cancer (LC) is one of the most prevalent cancer diseases. Due to the lack of databases which allow the combination of information on individual socioeconomic status (SES) and cancer incidence, research on social inequalities in LC among the German population is rare. The aim of the study is to analyse time trends in social inequalities in LC in Germany. METHODS: The analyses are based on data of a large statutory health insurance provider. The data contain information on diagnoses, occupation and education (working age), and income (full age range) of the insurance population. Trends were analysed for two subpopulations (retirement age and working age) and stratified by sex. The analyses are based on incidence rates and proportional hazard models spanning the periods 2006-2009, 2010-2013 and 2014-2017. RESULTS: Incidence rates declined in men but increased in women. For men, inequalities were strongest in terms of income and the decline in incidence was most pronounced in middle- and higher-income men. Among women at retirement age, a reversed income gradient was found which disappeared in the second period. The educational gradient among the working-age population decreased over time due to the trend towards increasing incidence among individuals with higher education. Declining gradients were also found for occupational position. CONCLUSION: The findings reveal considerable inequalities in LC and that trends vary with respect to SES, sex and age. Widening income inequalities were found in the retired population, while educational and occupational inequalities tend to narrow among the working-age population.

miRNAs in lung cancer. A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer.

Lung cancer (LC) is the leading cause of cancer-related death worldwide and miRNAs play a key role in LC development. To better diagnose LC and to predict drug treatment responses we evaluated 228 articles encompassing 16,697 patients and 12,582 healthy controls. Based on the criteria of ≥3 independent studies and a sensitivity and specificity of >0.8 we found blood-borne miR-20a, miR-10b, miR-150, and miR-223 to be excellent diagnostic biomarkers for non-small cell LC whereas miR-205 is specific for squamous cell carcinoma. The systematic review also revealed 38 commonly regulated miRNAs in tumor tissue and the circulation, thus enabling the prediction of histological subtypes of LC. Moreover, theranostic biomarker candidates with proven responsiveness to checkpoint inhibitor treatments were identified, notably miR-34a, miR-93, miR-106b, miR-181a, miR-193a-3p, and miR-375. Conversely, miR-103a-3p, miR-152, miR-152-3p, miR-15b, miR-16, miR-194, miR-34b, and miR-506 influence programmed cell death-ligand 1 and programmed cell death-1 receptor expression, therefore providing a rationale for the development of molecularly targeted therapies. Furthermore, miR-21, miR-25, miR-27b, miR-19b, miR-125b, miR-146a, and miR-210 predicted response to platinum-based treatments. We also highlight controversial reports on specific miRNAs. In conclusion, we report diagnostic miRNA biomarkers for in-depth clinical evaluation. Furthermore, in an effort to avoid unnecessary toxicity we propose predictive biomarkers. The biomarker candidates support personalized treatment decisions of LC patients and await their confirmation in randomized clinical trials.

Diagnosis and Differential Diagnosis of Neurological Adverse Events during Immune Checkpoint Inhibitor Therapy.

Therapy with immune checkpoint inhibitors (ICIs) has improved overall survival and cancer-related morbidity of cancer treatment even in cancer entities with poor prognosis. Since the approval of the first ICI, ipilimumab, for treatment of advanced melanoma by the Food and Drug Administration (FDA) in 2011, the spectrum of indications and approved ICIs has grown, rapidly. Up to now, seven different ICIs for more than 20 indications are available. However, their mechanisms of action can lead to immune-related adverse events (irAEs). In particular, neurological irAEs are clinically relevant. Although they are rare, an early and accurate diagnosis is challenging and neurological disease course and sequelae are potentially fatal. Between 08/2017 and 03/2020, 31 patients received ICI treatment at Hannover Medical School and presented with neurological adverse events (N-irAEs). Treated malignancies were metastatic melanoma, bronchial carcinoma, and urothelial cell carcinoma. All patients received comprehensive neurological diagnostics including clinical examination and magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) analysis was obtained in 21 patients and electroneurography was performed in 22 patients. Although N-irAEs were suspected in all 31 patients, 11 patients had other conditions leading to neurological symptoms including tumor metastases in seven patients and hemorrhagic or ischemic stroke in four patients. In the following, these patients are referred to as the differential diagnosis (DD) group. Patients with N-irAEs suffered from immune mediated neuropathy (9/20), myositis and/or myasthenic syndrome (6/20), or encephalitis/cerebellitis (5/20). Except for cell count, CSF results did not differ between the N-irAEs and the DD group. Symptoms related to N-irAEs are rather unspecific potentially mimicking other tumor-related symptoms such as metastases. Patients with malignancy are predominantly not treated by neurologists. Because of the complexity of neurological symptoms, detailed neurological investigations in specialized institutions are necessary in patients with new neurological symptoms and need to be critically discussed with treating oncologists.

Compression, expansion, or maybe both? Growing inequalities in lung cancer in Germany.

BACKGROUND: Lung Cancer (LC) is one of the most common malign diseases worldwide. So far, it is unclear if the development of LC incidence and mortality leads to morbidity compression or expansion and whether these developments differ by socioeconomic characteristics. This study analyses time trends in social and gender inequalities in life years with and without LC in Germany. METHODS: The study is based on data of a large German statutory health insurance provider (N = 2,511,790). Incidence and mortality risks were estimated from multistate survival models. Trends in life years with and without LC were analysed using multistate life table analyses. All analyses were performed separately for gender, time period (2006-2009 and 2014-2017), and income group (<60% and ≥60% of the German average income). RESULTS: Among men, declining LC incidence rates resulted in gains of life years free of LC and declining LC- affected life years and led to a relative compression, which was strongest in men with higher incomes. Among women, a clear increase in life years with LC led to an expansion of the lifespan affected by LC. This expansion was mainly driven by increasing incidence rates in women with low incomes. Overall, income inequalities in LC increased in both genders. CONCLUSIONS: Our analyses reveal that developments in the length of life affected by LC differed substantially by gender and income and led to widening health inequalities over time. Public health efforts should mainly focus on vulnerable groups to reduce the persisting social inequalities in LC.

Are there social gradients in the occurrence of lung cancer and in the survival of lung cancer patients? Findings from an observational study using German claims data of Lower Saxony.

OBJECTIVES: Only a few studies on health inequalities in terms of lung cancer are available. We examined whether social inequalities are present for the occurrence of lung cancer. Confining the analyses to patients, it was also examined whether survival over the observation period and over a standardised period of 18 months differed by occupational position and income. METHODS: Our findings are based on claims data from a German statutory health insurance covering 2005-2016. The database comprised N=3 163 211 women (50.7%) and men (49.3%) aged 18 years and older. Diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision: C34.0 to C34.9) were hospital-based, and income and occupational position were used as indicators of socioeconomic position. Analyses on social gradients were performed for employed and retired insured, but only for employed insured information on occupation and on income were available, for retired women and men only income was available. Analyses were performed by means of proportional hazard regression. RESULTS: In employed women, social gradients for the occurrence emerged for occupational position, but not for income. In men, social differences were found for both indicators. For retired insured, income gradients were found in men. Looking at overall survival, neither in women nor in men social gradients emerged. CONCLUSIONS: The reported social inequalities in the occurrence of lung cancer are pointing towards social differences in smoking behaviour, exposition to hazardous occupation-related substances and differences in preventive strategies. The absence of social inequalities in survival after lung cancer suggests equality in medical treatment of the disease.

CXCR4/MIF axis amplifies tumor growth and epithelial-mesenchymal interaction in non-small cell lung cancer.

Overexpression of C-X-C chemokine receptor type 4 (CXCR4) has been shown in several cancers, including non-small cell lung cancer (NSCLC) and is linked to early metastasis and worse prognosis. The crosstalk between cancer cells and tumor stroma promotes the growth and metastasis and CXCR4 signaling is a key element of this crosstalk. To test the effects of CXCR4 overexpression (CXCR4-OE), we transduced the human NSCLC cell line A549 by using a lentiviral vector. A 3D cell culture model showed generations of tumorspheres and the effects derived by the co-culturing of lung fibroblasts. Using a xenograft mouse model, we also studied the effects of CXCR4-OE in pulmonary cell engraftment and tumor burden in vivo. Our data indicate that CXCR4-OE leads to increased tumorsphere formation and epithelial-mesenchymal transition (EMT). CXCR4-OE by A549 cells resulted in a significant increase in the production of the CXCR4-ligand macrophage migration inhibitory factor (MIF) compared to those transduced with an empty vector (EV) or in which the CXCR4 expression was deleted (KO). In our in vitro system, we did not detect any production of the canonical CXCR4 ligand CXCL12. Autocrine MIF production and CXCR4 signaling are part of a self-perpetuating loop that amplifies tumor growth and EMT. Co-culture with lung fibroblasts further increased tumorsphere formation, partially driven by an increase in IL-6 production. When A549 cells were injected into murine lungs, we observed more abundant and significantly larger tumor lesions in recipients of CXCR4-OE A549 cells compared to those receiving EV or KO cells, consistent with our in vitro findings. Treatment of mice with the MIF antagonist ISO-1 resulted in significantly less tumor burden. In conclusion, our data highlight the role of the CXCR4-OE/MIF/IL-6 axis in epithelial mesenchymal crosstalk and NSCLC progression.

Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages.

Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R2 = 0.78, R2 = 0.71, and R2 = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients' outcome.

Response to Checkpoint Inhibition in Non-Small Cell Lung Cancer with Molecular Driver Alterations.

AIMS: Non-small cell lung cancer (NSCLC) patients with EGFR mutations do not respond well to checkpoint inhibitors. However, little is known about the activity of immunotherapy in NSCLC with other driver mutations. The increasing use of next-generation sequencing (NGS) leads to molecular findings that face the clinician with problems while choosing the best treatment. This study aims at analyzing response of NSCLC with driver mutations to immunotherapy. PATIENTS AND METHODS: We retrospectively included 84 NSCLC patients diagnosed and treated at 2 German tertiary-care lung cancer centers using NGS and treatment with immunotherapy. Response to immunotherapy was analyzed in correlation to molecular findings. RESULTS: 51 patients harbored at least 1 driver mutation. PIK3CA, EGFR, and STK11 mutations did not respond to immunotherapy. KRAS, TP53, and MET exon 14 skipping mutations responded well. One patient with NF-1 mutation showed durable response. CONCLUSIONS: Molecular testing may be of use in guiding treatment decision making in NSCLC.

Temporal and spatial dose distribution of radiation pneumonitis after concurrent radiochemotherapy in stage III non-small cell cancer patients.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is the most common subacute side effect after concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer. Several clinical and dose-volume (DV) parameters are associated with a distinct risk of symptomatic RP. The aim of this study was to assess the spatial dose distribution of the RP volume from first occurence to maximum volume expansion of RP. MATERIAL AND METHODS: Between 2007 and 2015, 732 patients with lung cancer were treated in an institution. Thirty-three patients met the following inclusion criteria: an RP grade II after CRT and a radiation dose ≥60 Gy and no prior medical history of cardiopulmonary comorbidities. The images of the first chest computed tomography (CT) confirming the diagnosis of RP and the CT images showing the maximum expansion of RP were merged with the treatment plan. The RP volume was delineated within the treatment plan, and a DV analysis was performed to evaluate the lung dose volume areas in which the RP manifested over time and whether dose volume changes within the RP volume occurred. RESULTS: A change from clinical diagnosis to maximum expansion of RP was observed as the RP at clinical appearance mainly manifested in the lower dose areas of the lung, whereas the RP volume at maximum expansion manifested in the higher dose areas, resulting in a significant shift of the assessed relative mean dose volume proportions within the RP volume. The mean relative dose volume proportion 0- ≤ 20 Gy decreased from 30.2% (range, 0-100) to 21.9% (range, 0-100; p = 0.04) at the expense of the dose volume > 40 Gy which increased from 39.2% (range, 0-100) to 49.8% (range, 0-100; p = 0.02), whereas the dose relative volume proportion > 20- ≤ 40 Gy showed no relevant change and slightly decreased from 30.6% (range, 0-85.7) to 28.3%, (range, 0-85.7; p = 0.34). CONCLUSION: We observed a considerable increase in the relative dose proportions within the RP volume from diagnosis to maximum volume extent from low dose zones below 20 Gy to zones above 40 Gy. Although the clinical impact on RP remains unknown, a reduction of healthy healthy lung tissue receiving >40 Gy (V40) might be an additional parameter for irradiation planning in lung cancer patients.

Therapy preferences of patients with lung and colon cancer: a discrete choice experiment.

OBJECTIVES: There is increasing interest in studies that examine patient preferences to measure health-related outcomes. Understanding patients' preferences can improve the treatment process and is particularly relevant for oncology. In this study, we aimed to identify the subgroup-specific treatment preferences of German patients with lung cancer (LC) or colorectal cancer (CRC). METHODS: Six discrete choice experiment (DCE) attributes were established on the basis of a systematic literature review and qualitative interviews. The DCE analyses comprised generalized linear mixed-effects model and latent class mixed logit model. RESULTS: The study cohort comprised 310 patients (194 with LC, 108 with CRC, 8 with both types of cancer) with a median age of 63 (SD =10.66) years. The generalized linear mixed-effects model showed a significant (P<0.05) degree of association for all of the tested attributes. "Strongly increased life expectancy" was the attribute given the greatest weight by all patient groups. Using latent class mixed logit model analysis, we identified three classes of patients. Patients who were better informed tended to prefer a more balanced relationship between length and health-related quality of life (HRQoL) than those who were less informed. Class 2 (LC patients with low HRQoL who had undergone surgery) gave a very strong weighting to increased length of life. We deduced from Class 3 patients that those with a relatively good life expectancy (CRC compared with LC) gave a greater weight to moderate effects on HRQoL than to a longer life. CONCLUSION: Overall survival was the most important attribute of therapy for patients with LC or CRC. Differences in treatment preferences between subgroups should be considered in regard to treatment and development of guidelines. Patients' preferences were not affected by sex or age, but were affected by the cancer type, HRQoL, surgery status, and the main source of information on the disease.