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Background: Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments., Materials and Methods: A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy., Results: Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis., Conclusion: VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC., Competing Interests: Disclosure Thomas Decker Christensen has been on the speaker bureaus for AstraZeneca, Boehringer–Ingelheim, Pfizer, Roche Diagnostics, Takeda, Merck Sharp & Dohme (MSD) and Bristol–Myers Squibb (BMS) and on Advisory Board for Bayer, Merck MSD, AstraZeneca, and Sanofi. René Horsleben Petersen has received a speaker's fee from Medtronic, AMBU, Medela, and AstraZeneca and on the advisory board for AstraZeneca, Roche, MSD, and BMS. Torben Bjerregaard Larsen reports a relationship with Bayer, Pfizer, Janssen Pharmaceuticals, Roche Diagnostics, and Bristol Meyers Squibb that includes: consulting or advisory. Peter Meldgaard has received research support from Astra Zeneca, MSD, Novartis, Roche, and Takeda; and on advisory board for MSD, Roche, Astra Zeneca, BMS, Takeda, Novartis, and Amgen. Flemming Skjøth has received consultancy fees from Bayer. Simon Noble had received research support and been on speakers bureau from Leo Pharma. Anette Arbjerg Højen has received research grants from the Danish Heart Foundation and The Novo Nordisk Foundation, been on the speaker bureaus for Bayer, Pfizer, MSD, Leo Pharma, and BMS; and on Advisory Board for Bayer and BMS. Other authors: None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Venous thromboembolism (VTE) is a potentially preventable serious complication in patients with lung cancer undergoing thoracic operation. We examined the risk and timing of VTE after surgery for primary non-small cell lung cancer (NSCLC)., Methods: All patients undergoing operation for NSCLC in Denmark between 2003 and 2021 were identified in the Danish Lung Cancer Registry. VTE events in the year after operation were assessed by stage, patient characteristics, and surgical procedure., Results: We identified 13,197 patients who underwent operation for NSCLC in 2003 to 2021 (mean age, 67.6 years; 50% female); 10,524 (79.7%) had stage I-II NSCLC, and 2673 (20.3%) had stage III-IV. During 1-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI, 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I vs 3.9% for stage IV) but varied little by pathologic type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%; 95% CI, 3.2-6.9), followed by pneumonectomy (3.5%; 95% CI, 2.3-5.0). The hazard of VTE was highest during the first 3 months after operation, after which it declined. For stage IV cancer, hazards increased again after 6 months. At 1 year, all-cause death was 12.6% (95% CI, 12.0%-13.1%)., Conclusions: VTE developed in 3.3% of patients undergoing operation for NSCLC, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We examined the number of lung cancers diagnosed, the quality of care and the socio-economic and clinical characteristics among patients with lung cancer during the COVID-19 pandemic compared to previous years., Methods: We included all patients ≥ 18 years old diagnosed with lung cancer from 01 January 2018 to 31 August 2021 as registered in the Danish Lung Cancer Registry. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of the associations between the pandemic and socioeconomic and clinical factors, and indicators of quality., Results: We included 18,113 patients with lung cancer (82.0% non-small cell lung cancer (NSCLC)), which was similar to the preceding years, although a decline in NSCLC cases occurred during the first lockdown period in 2020. No difference in distribution of income or educational level was observed. No difference was observed in the quality of treatment - as measured by curative intent, proportion of patients resected or who died within 90 days of diagnosis., Conclusion: Using nationwide population-based data, our study reassuringly shows no adverse effects of the COVID-19 pandemic on the diagnosis, socio-economic characteristics nor quality of treatment of lung cancer, as compared to the preceding years., Competing Interests: Declaration of Competing Interest The authors report that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Concerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA)., Methods: This prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made., Results: The study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment., Conclusion: Shared decision making did not take significantly longer time and led to slightly more conservative decisions., Practice Implications: SDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer., Patients and Methods: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR)., Results: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP., Conclusion: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population., Clinical Trial Information: NCT01506609., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Mediastinal staging is of paramount importance for planning of treatment in non-small cell lung cancer (NSCLC). Single institution reports recently claimed that subcarinal lymph node dissection during resection of upper lobe NSCLC could be spared. We used a complete national lung cancer registry to investigate patterns of unsuspected mediastinal lymph node involvement after lobectomy., Methods: During an 11-year period (2004 to 2014) 5,577 consecutive patients who underwent operations for NSCLC were investigated for unsuspected mediastinal lymph node involvement (N2 disease) discovered at final histopathology. The analysis excluded patients with clinical N2 disease. We used a national registry to extract information for each patient about tumor location, histopathology, clinical and pathologic TNM stage, preoperative imaging modalities, and type of invasive mediastinal staging., Results: Mediastinal lymph node dissection was performed in 5,577 patients during the operation, and unsuspected N2 disease was discovered in 612 (11.0%), and 193 (3.5%) had subcarinal metastasis. Subcarinal N2 disease was significantly more common in patients with lower-lobe or middle-lobe cancers compared with upper-lobe cancers (5.8% vs 1.6%, p < 0.01). Preoperative invasive mediastinal staging was performed in 73.4% (4,097 of 5,577) of all patients and significantly more frequently in patients who eventually had N2 disease (87.3% [534 of 612], p < 0.01) as well subcarinal N2 disease (89.6% [173 of 193], p < 0.01)., Conclusions: Subcarinal lymph node metastases were common despite frequent use of preoperative invasive mediastinal staging in lower-lobe, middle-lobe, and upper-lobe NSCLC. Subcarinal lymph nodes should be dissected or sampled routinely during operations for NSCLC to avoid understaging-regardless of preoperative invasive mediastinal staging and tumor location., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Comorbidity, such as diseases of the cardiovascular, pulmonary, and other systems, may influence prognosis in lung cancer and complicate its treatment. The performance status of patients, which is a known prognostic marker, may also be influenced by comorbidity. Due to the close link between tobacco smoking and lung cancer, and because lung cancer is often diagnosed in advanced ages (median age at diagnosis in Denmark is 70 years), comorbidity is present in a large proportion of lung cancer patients., Methods: Patients with any stage lung cancer who did not have surgical treatment were identified in the Danish Lung Cancer Registry. Danish Lung Cancer Registry collects data from clinical departments, the Danish Cancer Registry, Danish National Patient Registry, and the Central Population Register. A total of 20,552 patients diagnosed with lung cancer in 2005 to 2011 were identified. Comorbidity data were extracted from the Danish National Patient Registry, which is a register of all in- and outpatient visits to hospitals in Denmark. By record linkage, lung cancer patients who had previously been diagnosed with comorbid conditions were assigned a Charlson comorbidity index. Initial cancer treatment was categorized as chemotherapy, chemoradiation, radiotherapy, or no therapy. Data on Charlson comorbidity index, performance status, age, sex, stage, pulmonary function (forced expiratory volume in 1 second), histology, and type of initial treatment (if any) were included in univariable and multivariable Cox proportional hazard analyses., Results: Treatment rates for chemotherapy and chemoradiation declined with increasing comorbidity and in particular increasing age. Women received treatment more often than men. In a univariable analysis of all patients combined, stage, performance status, age, sex, lung function, and comorbidity were all associated with survival. Apart from excess mortality among patients with unspecified histological subtypes (hazard ratio), there was no clear difference between the specified subtypes. When adjusting for the other factors, particularly age, sex, performance status, and stage proved to be robust while risk estimates for comorbidity were attenuated somewhat. When grouped by the three types of cancer treatment or no treatment, there was no influence of comorbidity on radiation therapy and modest influence on survival after chemotherapy and chemoradiation. In contrast, age remained a strong negative prognosticator after multivariate adjustment as did stage and performance status., Conclusion: Comorbidity has a limited effect on survival and only for patients treated with chemotherapy. It is rather the performance of the patient at diagnosis than the medical history that prognosticates survival in this patient group.

Background: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, case-control studies. We used a complete national lung cancer registry., Methods: For better comparison and reduction of selection bias, we analyzed only patients who underwent standard lobectomy for clinical stage 1 NSCLC and subsequently had unsuspected lymph node metastases discovered at final histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy., Results: During a 6-year period (2007 to 2012), 1,968 patients underwent standard lobectomy for clinical stage 1 NSCLC by video-assisted thoracoscopic surgery (n=990; 50.3%) or thoracotomy (n=978; 49.7%). Unsuspected nodal upstaging was later found in 341 patients (17.3%), and 313 were analyzed: 189 patients (60.4%) received adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p<0.001) and comorbidity index (p=0.003) but increased with N2 status (p=0.02). No significant difference between video-assisted thoracoscopic surgery and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41)., Conclusions: Complete national data do not support the widespread assumption that adjuvant chemotherapy compliance is superior after thoracoscopic lobectomy for NSCLC. Instead, significant predictors of chemotherapy compliance are patient's age, comorbidity, and pathologic N status., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: To improve prognosis and quality of lung cancer care the Danish Lung Cancer Group has developed a strategy consisting of national clinical guidelines and a clinical quality and research database. The first edition of our guidelines was published in 1998 and our national lung cancer registry was opened for registrations in 2000. This article describes methods and results obtained by multidisciplinary collaboration and illustrates how quality of lung cancer care can be improved by establishing and monitoring result and process indicators., Methods: A wide range of indicators was established, validated, and monitored. By registration of all lung cancer patients since the year 2000, data on more than 40,000 patients have been included in the database. Results are reported periodically/quarterly and submitted to formal auditing on an annual basis., Results: Improvements in all outcome indicators are documented and statistically significant. Thus the 1-year overall survival rate has increased between 2003 and 2011 from 36.6% to 42.7%, the 2-year survival rate from 19.8% to 24.3%, and the 5-year survival rate from 9.8% to 12.1%. Five-year survival after surgical resection has increased from 39.5% to 48.1%. Improvements of waiting times, accordance between cTNM and pTNM, and resection rates are documented., Conclusion: The Danish experience shows that a national quality management system including national guidelines, a database with high data quality, frequent reports, audit and commitment from all stakeholders can contribute to improve clinical practice, improve core results, and reduce regional differences.

Background: Nodal upstaging after surgical intervention for non-small cell lung cancer (NSCLC) occurs when unsuspected lymph node metastases are found during the final evaluation of surgical specimens. Recent data from The Society of Thoracic Surgery (STS) database demonstrated significantly lower nodal upstaging after thoracoscopic (VATS) lobectomy than after thoracotomy. STS data, however, may be biased from voluntary reporting, and survival was not investigated. We used a complete national registry to compare nodal upstaging and survival after lobectomy by VATS or thoracotomy., Methods: The Danish Lung Cancer Registry was used to identify patients who underwent lobectomy for clinical stage I NSCLC from 2007 to 2011. Patient demographics, comorbidity, preoperative staging, surgical approach, number of lymph nodes harvested, final pathology, and survival were evaluated. Nodal upstaging was identified by comparing cT N M with pT N M., Results: Lobectomy for clinical stage I NSCLC was performed in 1,513 patients: 717 (47%) by VATS and 796 (53%) by thoracotomy. Nodal upstaging occurred in 281 patients (18.6%) and was significantly higher after thoracotomy for N1 upstaging (13.1% vs 8.1%; p<0.001) and N2 upstaging (11.5% vs 3.8%; p<0.001). Overall unadjusted survival was significantly higher after VATS, but after adjusting for differences in sex, age, comorbidity, and pT N M by Cox regression analysis, we found no difference between VATS and thoracotomy (hazard ratio, 0.98; 95% confidence interval, 0.80 to 1.22, p=0.88)., Conclusions: National data confirm that nodal upstaging was lower after VATS than after open lobectomy for clinical stage I NSCLC. Multivariate survival analysis, however, showed no difference in survival, indicating that differences in nodal upstaging result from patient selection for reasons not captured in our registry., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

An immunocytochemical method, involving four monoclonal antibodies (MAbs) previously selected for their specific binding to small cell lung cancer (SCLC) cells in human bone marrow, was used for detection of bone marrow metastases in 81 patients with diagnosed SCLC. This procedure was compared with two routine morphologic methods with regard to diagnostic efficiency and sensitivity. Bone marrow involvement was found in 26 patients (32%), one of which had limited disease according to conventional clinical criteria. Eight of the positive cases were exclusively diagnosed by immunocytochemistry, whereas the histologic and cytologic methods separately identified two patients each. Immunocytochemistry had a detection level of tumor cells in the mononuclear cell fraction of approximately 1-2%, whereas no patients with less than 10% immunocytologically detectable tumor cells were diagnosed by cytomorphologic examination of bone marrow aspirates. Evidence was obtained that the diagnostic efficiency of any method increased with the number of samples examined. Of the four MAbs used, the anti-NCAM antibody, MOC-1, labeled tumor cells in all immunologically positive patients, and in all but one of these patients all cytologically confirmed tumor cells were stained. The antibodies MOC-31, which recognize a cluster-2 antigen, and NrLu10 bound nearly all tumor cells in most cases, whereas MLuC1 only diagnosed tumor cells in a fraction of the patients. The results show that the immunocytochemical application of these antibodies is superior to morphologic techniques in detecting SCLC bone marrow metastases. Further use of the method might provide prognostically and therapeutically useful information.

The DNA content of rat bone marrow megakaryocytes (MK) was studied by Feulgen photometry following splenectomy and sham operation, respectively. The DNA measurements were preceded by acetylcholinesterase staining for identification of the 2N-8N MK. The number of 2N-8N MK decreased to minimum values, while the number of 16N-64N MK increased to maximum values about 4 days following both splenectomy and sham operation. However, the changes were somewhat more pronounced following splenectomy than sham operation. The total MK number did not change significantly. Platelet production, measured by 35S incorporation into platelets, increased during the first 2 days and remained high for 6-7 days, increasing the platelet counts. All values were about normal 30 days after surgery, except for a minor thrombocytosis following splenectomy. The early, highly significant thrombocytosis, following both splenectomy and general surgery, is caused by increased production of platelets due to the surgical trauma. This is caused by a direct action on bone marrow MK by transforming 2N-8N MK into higher ploidy classes. Lack of splenic platelet pooling may influence the grade and duration of the early thrombocytosis after splenectomy. The late, long-lasting, minor thrombocytosis, which occurs after splenectomy but not after sham operation, can be explained by the removal of the splenic platelet pool.