Update on the management of elderly patients with colorectal cancer

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans (AU)

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Update on the management of elderly patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

A Comparison of Total Thoracoscopic and Robotic Surgery for Lung Cancer Lymphadenectomy.

BACKGROUND: Robotic-assisted thoracic surgery (RATS) is used increasingly frequently in major lung resection for early stage non-small-cell lung cancer (NSCLC) but has not yet been fully evaluated. The aim of this study was to compare the surgical outcomes of lymph node dissection (LND) performed via RATS with those from totally thoracoscopic (TT) four-port videothoracoscopy. METHODS: Clinical and pathological data were collected retrospectively from patients with clinical stage N0 NSCLC who underwent pulmonary resection in the form of lobectomy or segmental resection between June 2010 and November 2022. The assessment criteria were number of mediastinal lymph nodes and number of mediastinal stations dissected via the RATS approach compared with the four-port TT approach. RESULTS: A total of 246 pulmonary resections with LND for clinical stages I-II NSCLC were performed: 85 via TT and 161 via RATS. The clinical characteristics of the patients were similar in both groups. The number of mediastinal nodes dissected and mediastinal stations dissected was significantly higher in the RATS group (TT: mean ± SD, 10.72 ± 3.7; RATS, 14.74 ± 6.3 [p < 0.001]), except in the inferior mediastinal stations. There was no difference in terms of postoperative complications. CONCLUSIONS: In patients with early stage NSCLC undergoing major lung resection, the quality of hilomediastinal LND performed using RATS was superior to that performed using TT.

Prediction of serious complications in patients with pulmonary thromboembolism and solid cancer: Validation of the EPIPHANY Index in a prospective cohort of patients from the PERSEO study.

INTRODUCTION: There is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIPHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE. METHOD: The PERSEO Study prospectively recruited individuals with PE and active cancer or receiving antineoplastic therapy from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test. RESULTS: A total of 900 patients, who were diagnosed with PE between October 2017 and January 2020, were enrolled. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index was associated with overall survival (OS) in patients with different risk levels: median OS was 16.5, 14.4, and 4.4 months for those at low, intermediate, and high risk, respectively. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value = 0.037) episodes. Of the outpatients, serious complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases. CONCLUSION: We have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

The Influence of Preoperative Nutritional and Systemic Inflammatory Status on Perioperative Outcomes following Da Vinci Robot-Assisted Thoracic Lung Cancer Surgery.

Background: Nutrition is an important factor in the outcome of any disease process. We evaluated the relationship of nutritional status and inflammatory status of non-small cell lung cancer (NSCLC) patients undergoing robotic-assisted thoracic surgery (RATS) with postoperative complications. Methods: This prospective cohort study included 107 NSCLC patients undergoing surgical treatment, between 2019 and 2021. Nutritional status and inflammatory status were assessed before pulmonary resection using anthropometric assessment, blood tests, and body mass index (BMI). Results: The BMI was 27.5 ± 4.4. Based on BMI, 29% (n = 31) were classified as normal weight, 43% (n = 46) as overweight, and 28% (n = 30) as obese. The mean neutrophil/lymphocyte ratio (NLR) was 2.16 ± 0.85, the platelet/lymphocyte ratio (PLR) was 121.59 ± 44.21, and the lymphocyte/monocyte ratio (LMR) was 3.52 ± 1.17. There was no increase in the number of intraoperative complications or bleeding (p = 0.696), postoperative complications (p = 0.569), mean hospital stay (p = 0.258) or duration of chest drain (p = 0.369). Higher inflammatory status, with an NLR > 1.84, was associated with more overall postoperative complications (p = 0.028), only in univariate analysis, but this significance was not maintained on multivariate analysis. Conclusions: BMI was not a predictor of increased postoperative risk in this cohort; therefore, weight should not deter surgeons from using RATS for pulmonary resection.

Preoperative Omega-6/Omega-3 Fatty Acid Ratio Could Predict Postoperative Outcomes in Patients with Surgically Resected Non-Small-Cell Lung Cancer.

Introduction: The aim of this study was to determine whether preoperative nutritional status and inflammatory status, specifically polyunsaturated acids and the omega 6/3 ratio, would affect postoperative outcomes and complications in patients with lung cancer undergoing lung resection. Methods: This prospective observational study included 68 patients with early-stage non-small-cell lung cancer who were candidates for radical surgery. A complete nutritional assessment was performed. The primary study variable was postoperative complications and mortality in the first 30 days. Descriptive, bivariate, and logistic regression analyses were carried out. Results: A total of 50 men (73.53%) and 18 women (26.47%) underwent surgery, with a median age of 64.2 (±9.74) years. The mean omega 6/3 ratio was 17.39 (±9.45). A complication occurred in 39.7% of the study sample (n = 27), the most common being persistent air leak in 23.53% (n = 16). After performing the bivariate analysis, the only variable that remained significant was the omega 6/3 ratio; we observed that it had a prognostic value for persistent air leak (p = 0.001) independent of age, sex, comorbidity, preoperative respiratory function, and approach or type of surgery. The remaining nutritional and inflammatory markers did not have a statistically significant association (p > 0.05) with postoperative complications. However, this significance was not maintained in the multivariate analysis by a small margin (p = 0.052; 95% CI: 0.77-1.41). Conclusions: Omega 6/3 ratio may be a prognostic factor for air leak, independent of the patient's clinical and pathological characteristics.

The Role of Endoscopic Ultrasound in the Interventional Management of Mediastinal Collections: A Narrative Review.

The numerous causes underlying mediastinal lesions require different diagnostic and therapeutic approaches, including conservative, minimally invasive, and surgical interventions. Solid lesions of a malignant nature, mostly located in the anterior mediastinum, are properly treated with surgical resection either with or without adjuvant schemes. In contrast, a surveillance program is usually recommended with solid benign tumors, depending on their size and related symptomatology. In the management of mediastinal collections, when a drainage intervention is required (suspicion of infection and symptomatology), a minimally invasive nonsurgical procedure or thoracic surgery is considered. The minimally invasive nonsurgical procedures that can be available are percutaneous radiology-guided imaging (abdominal ultrasound (US) or computed tomography (CT) scan), complete single-aspiration guided by endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS), and transmural drainage guided by EUS. Surgical debridement is feasible to treat collections, but as this entails considerable risk of postoperative complications, it is chosen only when other minimally invasive therapies are not possible. The published literature related to the interventional endoscopic approach to mediastinal lesions is scarce. Nevertheless, reports in this field reveal that interventional EUS may have a role in both the diagnosis of and therapeutic approach to mediastinal lesions, mainly in the management of mediastinal collections.

Incidence, risk factors, and evolution of venous thromboembolic events in patients diagnosed with pancreatic carcinoma and treated with chemotherapy on an outpatient basis.

BACKGROUND: Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. PATIENTS AND METHODS: We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. RESULTS: With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p<0.001). CONCLUSIONS: Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.

Localización preoperatoria guiada por tomografía computada de nódulo pulmonar con verde de indocianina para resección toracoscópica uniportal asistida por robot. Reporte de caso

Introducción: El abordaje del nódulo pulmonar solitario tiene como objetivo la detección temprana del cáncer de pulmón en donde la resección quirúrgica es la piedra angular del tratamiento. La tecnología de imagen por fluorescencia combina un agente excitable en el espectro de luz cercano al infrarrojo y un sistema para visualizar selectivamente un tejido diana que permite su localización intraoperatoria. Caso clínico: Varón de 72 años fumador con un nódulo pulmonar de 9 milímetros con patrón en vidrio deslustrado en el lóbulo inferior derecho localizado bajo guía tomográfica con verde de indocianina y tratado mediante resección sublobar con linfadenectomía sistemática asistida por robot con abordaje uniportal. Conclusión: La técnica de marcaje preoperatorio con verde de indocianina y tecnología de imagen por fluorescencia es un método seguro y preciso que permite la identificación intraoperatoria de un nódulo pulmonar solitario durante la cirugía de mínima invasión. (provisto por Infomedic International)

Introduction: The solitary pulmonary nodule approach aims at early detection of lung cancer where surgical resection is the cornerstone of treatment. Fluorescence imaging technology combines an excitable agent in the near-infrared light spectrum and a system to selectively visualize a target tissue allowing its intraoperative localization. Case report: A 72-year-old male smoker with a 9-millimeter lung nodule with ground-glass pattern in the right lower lobe located under tomographic guidance with indocyanine green and treated by sublobar resection with robotic-assisted systematic lymphadenectomy with uniportal approach. Conclusion: The technique of preoperative labeling with indocyanine green and fluorescence imaging technology is a safe and accurate method that allows intraoperative identification of a solitary pulmonary nodule during minimally invasive surgery. (provided by Infomedic International)

Efficacy of hyperthermia pleurodesis: A comparative experimental study on serous membrane of abdominopelvic and thoracic cavities of rats.

BACKGROUND: Pleurodesis is a common technique for treating the accumulation of air or liquid in the pleural space caused by pneumothorax or pleural effusion, it is based on the bounding of pleural layers through induced inflammatory lesions. There are several pleurodesis procedures. OBJECTIVES: To test and describe the inflammatory effect of hyperthermia on the pleural and peritoneal mesothelia of rats, with the aim of testing the effectiveness of this process for inducing pleurodesis. METHODS: 35 Sprague-Dawley (male/female) rats were randomized into four treatment groups: Group A (Talc, 10 individuals); group B (control, 5 individuals); group C (hyperthermic isotonic saline, 10 individuals); and group D (filtrate air at 50°, 10 individuals). Inflammatory effect of hyperthermia was the primary outcome parameter. RESULTS: In the talc group, minimal adhesions between both pleural and peritoneal layers were observed in seven rats. Talc produced peritoneal mesothelium inflammation and fibrosis associated to foreign body giant cells in 80% (8/10) of the sample. Furthermore, clear evidence of a granulomatous foreign-body reaction was detected. No macroscopic and/or microscopic damage was registered in the remaining three groups (control, hyperthermic, and filtrate air). CONCLUSIONS: Talc is an excellent method for producing pleuro-peritoneal inflammatory lesions. On the contrary, hyperthermia apparently does not induce the macroscopic and microscopic damage that is required for efficient pleurodesis. Therefore, hyperthermia should not be used for pleurodesis procedures.

Molecular Nodal Restaging Based on CEACAM5, FGFR2b and PTPN11 Expression Adds No Relevant Clinical Information in Resected Non-Small Cell Lung Cancer.

BACKGROUND: The relapse rate in non-small cell lung cancer (NSCLC) is high, even in localized disease, suggesting that the current approach to pathological staging is insufficiently sensitive to detect occult micrometastases present in resected lymph nodes. Therefore, we aimed to determine the prognostic value of the expression of embryonic molecular markers in histologically-negative lymph nodes of completely-resected NSCLC. METHODS: 76 completely-resected NSCLC patients were included: 60 pN0 and 16 pN1. Primary tumors and 347 lymph node were studied. CEACAM5, FGFR2b, and PTPN11 expression levels were evaluated through mRNA analysis using real-time RT-qPCR assay. Statistical analyses included the Kruskal-Wallis test, Kaplan Meier curves, and log-rank tests. RESULTS: CEACAM5 expression levels were scored as high in of 90 lymph nodes (26%). The molecular-positive lymph nodes lead to the restaging of 37 (62%) pN0 patients as molecular N1 or N2 and 5 (31%) pN1 cases were reclassified as molecular-positive N2. Surprisingly, molecular-positive patients associated with a better OS (overall survival, p = 0,04). FGFR2b overexpression was observed in 41 (12%) lymph nodes leading to the restaging of 17 patients (22%). Again a trend was observed toward a better DFS (disease-free survival) in the restaged patients (p = 0,09). Accordingly, high expression levels of CEACAM5 or FGFR2b in the primary were related to better DFS (p = 0,06; p < 0,02, respectively). CONCLUSION: Molecular nodal restaging based on expression levels of CEACAM5 and/or FGFR2b, does not add relevant clinical information to pathological staging of NSCLC likely related to the better prognosis of their overexpression in primary tumors.

Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma.

BACKGROUND: There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. METHODS: We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. RESULTS: Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models evaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. CONCLUSIONS: Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.

Case-Control Analysis of the Impact of Anemia on Quality of Life in Patients with Cancer: A Qca Study Analysis.

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively; mean difference: -12.4, p < 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery.

BACKGROUND: The aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery. METHODS: We performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months. RESULTS: Two hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307-0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352-0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association. CONCLUSION: Preoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer.