Is Adjuvant Radiochemotherapy Always Mandatory in Patients with Resected N2 Non-Small Cell Lung Cancer?

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), the pathologic union for international cancer control (UICC) stage IIIA is a heterogeneous entity, with different forms of N2-lymph node involvement representing different prognoses. Although a multimodality treatment approach, including surgery, systemic therapy, and/or radiotherapy, is almost always recommended, in this retrospective observational study, we sought to determine whether long-term survival might be possible in selected patients who are treated with complete surgical resection alone. METHODS: Between 2013 and 2018, we retrospectively identified 24 patients with NSCLC (16 men and 8 women), who were found to have pathologic N2-lymph node involvement, and were treated with complete surgical lung resection and systematic mediastinal and hilar lymph node dissection but no neoadjuvant or adjuvant treatment. RESULTS: The most frequent reason (n = 14) for forgoing adjuvant treatment was patient refusal. The mean overall survival (OS) was 34.5 months (interquartile range [IQR]: 15.5-53.5 months). The mean disease-free survival (DFS) was 18 months (IQR: 4.75-46.75 months). We identified five patients who survived at least 5 years without recurrence (21%). In each of these cases, the nodal metastases were restricted to a single level and no extracapsular lymph node involvement were detected. Additionally, worse DFS was associated with pT3/4 (vs. a lower T-stage), as well as microscopic lymphovascular invasion. CONCLUSION: Although the small sample size precludes any definitive conclusions, it was possible to demonstrate that long-term survival without neoadjuvant and adjuvant treatment is possible in some patients if complete tumor and nodal resection is performed.

Extracapsular extension of pN2 lymph node metastases is not prognostically significant in surgically resected patients with non-small cell lung cancer.

Objectives: In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N2 is a heterogeneous entity, with different degrees of lymph node involvement representing different prognoses. It is speculated whether extra capsular nodal extension may help to define a subgroup with implications on long-term survival. Methods: We retrospectively identified 118 patients with non-small cell lung cancer (65 men, 53 women), who were treated between 2013 and 2018 and found to have pathologic N2 lymph node involvement. In all patients lung resection with systematic mediastinal and hilar lymph node dissection was performed with curative intent. In N2 lymph node metastases capsules of affected lymph nodes were examined microscopically as to whether extracapsular extension was present. Results: 51 patients (43 %) had extracapsular extension (ENE). Most of these patients (n=35) only had ENE in a single lymph node (69 %). The overall 5-year survival rate was 24.6 % and progression-free survival rate 17.8 %. In the multivariate analysis OS was worse for patients with multiple affected pN2 stations, concurrent N1 metastases, increasing age, and larger tumor size. For the percentage of lymph nodes affected with ENE (of total examined) only a non-significant trend towards worse OS could be observed (p=0.06). Conclusions: Although we could not demonstrate significant prognostic differences between N2 extra capsular nodal involvement within our patient population, other analyses may yield different results. However, clinicians should continue performing thorough lymph nodes dissections in order to achieve local complete resection even in patients with extra capsular tumor spread.

Diffuse Alveolar Hemorrhage Associated with Epithelioid Angiosarcoma of the Lung: A Challenging Diagnosis.

A 68-year-old patient presented with persistent hemoptysis and weight loss. A CT scan showing diffuse bilateral ground-glass opacities and nodules was followed by bronchoscopy. While diffuse alveolar hemorrhage (DAH) could be seen, specimens obtained during bronchoscopy did not provide conclusive histological findings. The decision was made to conduct video-assisted wedge resection, after which histological examinations revealed the diagnosis of bifocal nodular manifestation of an epithelioid angiosarcoma in the lung. Being a rare entity even among sarcomas, these kinds of tumors can be primary lung tissue angiosarcomas or metastatic lesions with primaries in places like the skin, breast, and heart. Treatment usually includes chemotherapy, but prognosis remains grim. This case highlights that in DAH, uncommon causes should be considered, and sufficient probe gathering is the key to early diagnosis and treatment.

Value of 18F FDG-PET/CT parameters on long term follow-up for patients with non-small cell lung cancer.

Objectives: The purpose of this study was to investigate the value of PET/CT in the preoperative staging of non-small cell lung cancer in predicting long-term survival and diagnostic performance, validated by histopathology following surgical resection. Methods: Between 02/2009 and 08/2011, 255 patients with non-small cell lung cancer were included in this single-center prospective study. All underwent 18F FDG-PET/CT for pre-operative staging, and in 243 patients complete surgical resection was possible. Regarding lymph node involvement and extrathoracic metastases, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the histopathological staging as reference. Median follow-up for censored patients was 9.1 years. Results: Overall 5-year survival rate of all patients was 55.6%, and of patients who had complete surgical resection it was 58.2%. In multivariate analysis of all surgically resected patients lymph node involvement (p=0.029) and age >61 years (p=<0.001) were significant independent prognostic factors. SUVmax and SUVmean cut-offs between SUV 2 and 11, however, were not associated with better or ;worse survival. The PET-CT sensitivity, specificity, positive predictive value and negative predictive value for predicting lymph node involvement were 57, 95, 88, and 76%, respectively. Furthermore, sensitivity, specificity, positive predictive value, and negative predictive value for detecting extrathoracic metastases were 100, 58, 98, and 100%, respectively. Conclusions: In this study, tumor 18F FDG-uptake values did not provide additional prognostic information. Age>61 years and lymph node metastasis were associated with worse long-term survival in surgically resected patients. 18F FDG-PET/CT scans allow for improved patient selection. However, in staging mediastinal lymph nodes, there is a high rate of false positives and false negatives, suggesting that tissue biopsy is still indicated in many cases.

Trends in age- and sex-specific lung cancer mortality in Europe and Northern America: Analysis of vital registration data from the WHO Mortality Database between 2000 and 2017.

BACKGROUND: In the context of new targeted therapies and immunotherapy as well as screening modalities for lung cancer patients, detailed mortality trends in Europe and Northern America are unknown. METHODS: Time-trend analysis using vital registration data of Northern America and Europe from the WHO Mortality Database (years 2000/2017). To assess improvements in lung cancer mortality, we performed a population-averaged Poisson autoregressive analysis. The average annual percent change (AAPC) was used as a summary measure of overall and country-specific trends in mortality. Second, we studied time trends of lung cancer incidence and smoking prevalence rates. FINDINGS: In the total population of 872·5 million people between 2015 and 2017, the average annual age-standardised mortality from lung cancer was 54·6 deaths per 100 000, with substantial differences across countries. Lung cancer was reported as the primary cause of death in 5·4 cases per 100 deaths. The age-standardised mortality rate decreased constantly (AAPC -1·5%) between 2000 and 2017. While mortality in men dropped annually by an average of -2·3%, mortality in women decreased by an average of -0·3%. This slight decline was driven exclusively by the USA. In contrast, 21 out of 31 countries registered a significant increase in female lung cancer mortality between 2000 and 2017, with Spain (AAPC 4·1%) and France (AAPC 3·6%) leading the list. INTERPRETATION: Despite overall decreases in lung cancer mortality trends, female mortality remained unchanged or increased significantly in all countries except the USA. National mortality outcomes reflect variabilities in tobacco control, screening, therapeutic advances, and access to health care.

Implication of FDG-PET/CT in patients with potentially operable colorectal lung metastases.

OBJECTIVES: This prospective study assessed the role of F-18-FDG-PET/CT in clinical staging for patients with colorectal cancer planned for pulmonary metastasectomy by thoracotomy or video-assisted surgery. PATIENTS AND METHODS: In addition to conventional imaging, we performed 86 F-18-FDG-PET/CT studies in 76 patients with potentially resectable metastatic colorectal lung metastases. We then investigated the effect that PET/CT had on further clinical management. Based on the results from the 47 thoracotomies performed, we compared the number of pulmonary metastases discovered after histologic examination with the number predicted by the conventional computed tomography (CT) as an independent part of the F-18-FDG-PET/CT examination and by the F-18-FDG-PET component. RESULTS: F-18-FDG-PET/CT led to changes in treatment regime and diagnostic planning in many patients. In five patients PET/CT revealed previously undetected local recurrence of the primary colorectal cancer, in four patients hepatic metastases, in three patients bone metastases, in two patients soft-tissue metastases, and in three patients histologically preoperatively proven N2 or N3 station lymph node involvement. These all constituted exclusion criteria, and consequently the previously planned pulmonary metastasectomy was not performed. The sensitivity and positive predictive value (PPV) for detection of pulmonary metastases were 84.2% and 36.4% for CT and 75.0% and 61.6% for F-18-FDG-PET study. The calculated sensitivity, specificity, PPV, and NPV of F-18-FDG-PET/CT for detecting thoracic lymph node involvement were 85.7%, 93.0%, 66.7%, and 97.5%, respectively. Furthermore, we found that F-18-FDG-PET/CT may predict thoracic lymph node involvement based on the SUV of pulmonary nodules. CONCLUSIONS: F-18-FDG-PET/CT has a clear role in the diagnostic workup for pulmonary metastatic colorectal cancer and may save patients from futile surgery. It cannot, however, be relied on to detect all possible pulmonary and nodal metastases, which surgeons must always consider when making treatment decisions.

Risk-Adjusted Mortality Rates as a Quality Proxy Outperform Volume in Surgical Oncology-A New Perspective on Hospital Centralization Using National Population-Based Data.

PURPOSE: Despite a long-known association between annual hospital volume and outcome, little progress has been made in shifting high-risk surgery to safer hospitals. This study investigates whether the risk-standardized mortality rate (RSMR) could serve as a stronger proxy for surgical quality than volume. METHODS: We included all patients who underwent complex oncologic surgeries in Germany between 2010 and 2018 for any of five major cancer types, splitting the data into training (2010-2015) and validation sets (2016-2018). For each surgical group, we calculated annual volume and RSMR quintiles in the training set and applied these thresholds to the validation set. We studied the overlap between the two systems, modeled a market exit of low-performing hospitals, and compared effectiveness and efficiency of volume- and RSMR-based rankings. We compared travel distance or time that would be required to reallocate patients to the nearest hospital with low-mortality ranking for the specific procedure. RESULTS: Between 2016 and 2018, 158,079 patients were treated in 974 hospitals. At least 50% of high-volume hospitals were not ranked in the low-mortality group according to RSMR grouping. In an RSMR centralization model, an average of 32 patients undergoing complex oncologic surgery would need to relocate to a low-mortality hospital to save one life, whereas 47 would need to relocate to a high-volume hospital. Mean difference in travel times between the nearest hospital to the hospital that performed surgery ranged from 10 minutes for colorectal cancer to 24 minutes for pancreatic cancer. Centralization on the basis of RSMR compared with volume would ensure lower median travel times for all cancer types, and these times would be lower than those observed. CONCLUSION: RSMR is a promising proxy for measuring surgical quality. It outperforms volume in effectiveness, efficiency, and hospital availability for patients.

Depression and Anxiety Management in Parkinson Disease.

ABSTRACT: BACKGROUND: Depression and anxiety are common but underrecognized and undertreated nonmotor symptoms of Parkinson disease (PD) due to their diagnostic criteria overlapping with other PD symptoms, limited randomized controlled studies in this specific population, and the need for multidisciplinary expertise. The purpose of this article is to offer evidence-based solutions for managing comorbid depression and anxiety in patients with PD through a case study analysis. CASE STUDY: A case study is used to illustrate the somatic manifestations of anxiety in PD that leads to diagnostic challenge and multidisciplinary management. MANAGEMENT CONSIDERATIONS: The appropriate use of screening tools, pharmacological and nonpharmacological management, and education are important interventions to consider when treating depression and anxiety in PD. CONCLUSION: Effective management requires accurate assessments, individualized treatment modalities, and patient education. Nurses who are knowledgeable about the effects and management of mood disorders in PD can play an integral role in the multidisciplinary team approach for assessment, patient and caregiver education, and treatment plan implementation.

Validation of the T Descriptor (TNM-8) in T3N0 Non-Small-Cell Lung Cancer Patients; a Bicentric Cohort Analysis with Arguments for Redefinition.

The current pT3N0 category represents a heterogeneous subgroup involving tumor size, separate tumor nodes in one lobe, and locoregional growth pattern. We aim to validate outcomes according to the eighth edition of the TNM staging classification. A total of 281 patients who had undergone curative lung cancer surgery staged with TNM-7 in two German centers were retrospectively analyzed. The subtypes tumor size >7 cm and multiple nodules were grouped as T3a, and the subtypes parietal pleura invasion and mixed were grouped as T3b. We stratified survival by subtype and investigated the relative benefit of adjuvant chemotherapy according to subtype. The 5-year overall survival (OS) rates differed between the different subtypes tumor diameter >7 cm (71.5%), multiple nodules in one lobe (71.0%) (grouped as T3a), parietal pleura invasion (59.%), and mixed subtype (5-year OS 50.3%) (grouped as T3b), respectively. The cohort as a whole did not gain significant OS benefit from adjuvant chemotherapy. In contrast, adjuvant chemotherapy significantly improved OS in the T3b subgroup (logrank p = 0.03). This multicenter cohort analysis of pT3N0 patients identifies a new prognostic mixed subtype. Tumors >7 cm should not be moved to pT4. Patients with T3b tumors have significantly worse survival than patients with T3a tumors.

Validation of the 8th lung cancer TNM classification and clinical staging system in a German cohort of surgically resected patients.

OBJECTIVES: The updated 8th edition of the tumor, node, metastases (TNM) classification system for non-small cell lung cancer (NSCLC) attempts to improve on the previous 7th edition in predicting outcomes and guiding management decisions. This study sought to determine whether the 8th edition was more accurate in predicting long-term survival in a European population of surgically treated NSCLC patients. METHODS: We scanned the archives of the Heckeshorn Lung Clinic for patients with preoperative clinical stages of IIIA or lower (based on the 7th edition), who received surgery for NSCLC between 2009 and 2014. We used pathologists' reports and data on tumor size and location to reassign tumor stages according to the 8th edition. We then analyzed stage specific survival and compared the accuracy of the two systems in predicting long-term survival. We excluded patients with neoadjuvant treatment, incomplete follow-up data, tumor histologies other than NSCLC, or death within 30 days of surgery. RESULTS: The final analysis included 1,013 patients. Overall five-year survival was 47.3%. The median overall survival (OS) was 63 months (range 1-222), and the median disease-free survival (DFS) was 50 months (0-122). The median follow-up time for non-censored patients was 84 months (range 60-122). CONCLUSIONS: We found significant survival differences between the newly defined stages 1A1, 1A2 and 1A3 (previously 1A). We also found that the 8th edition of TMN classification was a significantly better predictor of long-term survival, compared to the 7th edition.

Prognostic significance of the pattern of pathological N1 lymph node metastases for non-small cell lung cancer.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N1 is a heterogeneous entity, and different forms of lymph node involvement may represent different prognoses. For methodological reasons, the 8th edition of the TNM staging system for NSCLC makes no official changes to the N descriptor. However, there is evidence that different subforms of N1 disease are associated with different prognoses, and it is now recommended that clinicians record the number of affected lymph nodes and nodal stations for further analyses. In this investigation we sought to determine whether patients with different levels and types of N1 lymph node involvement had significantly different 5-year survival rates. METHODS: We retrospectively identified 90 patients with NSCLC (61 men, 29 women), who were treated between 2008 and 2012 and found to have pathologic N1 lymph node involvement and tumor sizes corresponding to T1 or T2. All patients were treated in curative intent with surgical lung resection and systematic mediastinal and hilar lymph node dissection. RESULTS: The overall 5-year survival rate was 56.3%. In the univariate analysis, lower tumor stage and tumor histology other than large-cell carcinoma were significantly associated with better long-term survival. Patients with solitary lymph node metastases also had longer disease-free survival than those with multiple nodal metastases. In the multivariate analysis, large-cell carcinoma and Union for International Cancer Control (UICC) stage IIB were independently associated with worse survival, while pneumonectomy, compared to lobar or sublobar resection, was independently associated with better survival. CONCLUSIONS: Although we did not observe significant prognostic differences between N1 subcategories within our patient population, other analyses may yield different results. Therefore, these data highlight the need for large, well-designed multicenter studies to confirm the clinical significance of N1 subcategories.