Adjuvant Chemotherapy for T4 Non-Small Cell Lung Cancer with Additional Ipsilateral Lung Nodules.

BACKGROUND: Adjuvant chemotherapy is indicated for patients with resectable stage II and IIIa non-small cell lung cancer. With the revised definition of T4 tumors with nodules in a different ipsilateral lobe, the survival advantage imparted by adjuvant chemotherapy has yet to be defined. We evaluated the role of adjuvant chemotherapy in patients with T4 disease characterized by additional tumor nodules in a different ipsilateral lobe treated with surgical resection. METHODS: We identified patients with T4 disease and additional tumor nodules in a different ipsilateral lobe treated with surgical resection alone or with adjuvant chemotherapy in the National Cancer Database between 2010 and 2016. The primary outcome was 3-year overall survival (OS). RESULTS: A total of 920 patients with T4 tumors and additional tumor nodules in a different ipsilateral lobe were identified. We excluded patients with lymph node metastases, tumors 4 cm or greater, and local invasion. Of the remaining 373 patients, 152 received surgery and adjuvant multiagent chemotherapy whereas 221 received surgery alone. When adjusted for patient, tumor, and treatment factors, the use of adjuvant chemotherapy was associated with improved 3-year OS compared with surgery alone (hazard ratio = 0.572; 95% confidence interval, 0.348-0.940; P = .03). CONCLUSIONS: Adjuvant chemotherapy in patients with T4 non-small cell lung cancer with additional tumor nodules in a different ipsilateral lobe is associated with improved 3-year OS. Accurate identification of T4 disease is important to define patients in whom adjuvant chemotherapy should be considered. Further prospective study is needed to delineate further the use of adjuvant chemotherapy for this patient population.

The value of positron emission tomography computed tomography in predicting invasiveness of ground glass nodules: A protocol for systematic review and meta-analysis.

BACKGROUND: The study was conducted to investigate the value of Positron emission tomography computed tomography (PET/CT) in predicting invasiveness of ground glass nodule (GGN) by the method of meta-analysis. METHODS: Two researchers independently searched for published literature on PET/CT diagnosis of GGN as of November 30, 2020. After extracting the data, RevMan5.3 was used to evaluate the quality of the included literature. The Stata14 software was used to test the heterogeneity of the original study that met the inclusion criteria, to calculate the combined sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, the prior probability and posttest probability. The summary receiver operator characteristic curve was drawn and the area under the curve was calculated. Using Deeks funnel plot to evaluate publication bias. RESULTS: Five studies were finally included, including 298 GGN cases. The included studies had no obvious heterogeneity and publication bias. The combined sensitivity and specificity of PET/CT for predicting invasive adenocarcinoma presenting as GGN were 0.74 (95% confidence interval [CI]: 0.68-0.79), 0.82 (95% CI: 0.71-0.90), positive likelihood ratio and negative likelihood ratio were 4.1 (95% CI: 2.5-6.9), 0.32 (95% CI: 0.25-0.40), and the diagnostic odds ratio was 13 (95% CI: 7-26). The prior probability is 20%, the probability of GGN being invasive adenocarcinoma when PET/CT was negative was reduced to 7%, and the probability of GGN being invasive adenocarcinoma when PET/CT was positive was increased to 51%. The area under the curve of the summary receiver operator characteristic curve was 0.85. CONCLUSION: PET/CT has high diagnostic accuracy for invasive adenocarcinoma presenting as GGN.

Manejo de los nódulos pulmonares subsólidos: resultados quirúrgicos basados en algoritmo local / Pulmonary subsolid nodules: surgical outcomes based on institutional algorithm

INTRODUCCIÓN: en la actualidad no existe un consenso respecto al manejo de los nódulos pulmonares subsólidos (NPSS). OBJETIVO: describir los resultados del manejo quirúrgico de los NPSS, basados en un algoritmo local. MATERIAL Y MÉTODOS: estudio descriptivo de corte transversal. Se revisaron las fichas clínicas electrónicas de los pacientes operados por NPSS, sugerentes de ser malignos, a juicio de un equipo multidisciplinario, entre enero de 2014 y enero de 2018, en el Departamento de Cirugía de Adultos de Clínica Las Condes. RESULTADOS: se estudió un total de 35 pacientes. La edad promedio fue de 65,8 años. El tamaño promedio de los nódulos fue de 15 mm. Todos los pacientes fueron abordados por cirugía videotoracoscópica asistida. El 88,6% de las biopsias demostró la presencia de una neoplasia maligna. CONCLUSIONES: la adopción de un algoritmo local, instituido por un equipo multidisciplinario, es una alternativa para el manejo adecuado de los portadores de NPSS.

BACKGROUND: Nowadays, there is no consensus in the management of pulmonary subsolid nodules (SSNs). AIM: describe the results of surgical management of SSNs, based on institutional algorithm. MATERIAL AND METHODS: cross-sectional, descriptive study, with revision of clinical electronic records, that included all patients intervened for SSNs, suggestive of malignancy, by the judgment of a multi-disciplinary team, from January 2014 to January 2018 at the Department of Adult Surgery, Clinica Las Condes. RESULTS: 35 patients were studied. The average age was 65.8 years. The average size of the nodules was 15 mm. All patients were approached by video-assisted thoracoscopic surgery. 88.6% of biopsies turned out to be malignant neoplasm. CONCLUSIONS: the acquisition of a local algorithm established by a multidisciplinary team is an appropriate alternative for the management of the patients with SSNs.

Clinical significance of indeterminate pulmonary nodules on the survival of 364 patients with nonmetastatic, high-grade, localized osteosarcoma: A 12-year retrospective cohort study.

BACKGROUND AND OBJECTIVES: We investigated the clinical significance of indeterminate pulmonary nodules (IPNs) in patients diagnosed with nonmetastatic, high-grade localized osteosarcoma. METHODS: We retrospectively analyzed the clinical data of 364 patients with nonmetastatic, high-grade localized osteosarcoma. Based on pulmonary computed tomography findings at presentation, the patients were categorized into the no-nodules and the IPNs group and were further categorized into subgroups based on age (<18 and ≥18 years). We performed an intergroup comparison of event-free survival (EFS) and overall survival (OS). RESULTS: At presentation, 276 (75.8%) patients showed no nodules, and 88 (24.2%) patients showed IPNs. The EFS and OS were similar between adults with IPNs (n = 54 [30.5%]) and without nodules (n = 123 [69.5%]) (p = .200 and p = .609, respectively). No significant intergroup difference in OS was observed in pediatric patients (p = .093). However, pediatric patients with IPNs (n = 34 [18.2%]) had poorer EFS than those without nodules (n = 153 [81.8%]) (p = .016). Multivariate analyses confirmed that IPNs were independently associated with poorer EFS in pediatric patients (hazard ratio 1.788, 95% confidence interval 1.092-2.926, p = .021). CONCLUSIONS: This study showed that IPNs at presentation did not affect the survival of adults with nonmetastatic, high-grade localized osteosarcoma but were associated with poorer EFS in pediatric patients.

Augmented fluoroscopic bronchoscopy (AFB) versus percutaneous computed tomography-guided dye localization for thoracoscopic resection of small lung nodules: a propensity-matched study.

BACKGROUND: Dye localization is a useful method for the resection of unidentifiable small pulmonary lesions. This study compares the transbronchial route with augmented fluoroscopic bronchoscopy (AFB) and conventional transthoracic CT-guided methods for preoperative dye localization in thoracoscopic surgery. METHODS: Between April 2015 and March 2019, a total of 231 patients with small pulmonary lesions who received preoperative dye localization via AFB or percutaneous CT-guided technique were enrolled in the study. A propensity-matched analysis, incorporating preoperative variables, was used to compare localization and surgical outcomes between the two groups. RESULTS: After matching, a total of 90 patients in the AFB group (N = 30) and CT-guided group (N = 60) were selected for analysis. No significant difference was noted in the demographic data between both the groups. Dye localization was successfully performed in 29 patients (96.7%) and 57 patients (95%) with AFB and CT-guided method, respectively. The localization duration (24.1 ± 8.3 vs. 21.4 ± 12.5 min, p = 0.297) and equivalent dose of radiation exposure (3.1 ± 1.5 vs. 2.5 ± 2.0 mSv, p = 0.130) were comparable in both the groups. No major procedure-related complications occurred in either group; however, a higher rate of pneumothorax (0 vs. 16.7%, p = 0.029) and focal intrapulmonary hemorrhage (3.3 vs. 26.7%, p = 0.008) was noted in the CT-guided group. CONCLUSION: AFB dye marking is an effective alternative for the preoperative localization of small pulmonary lesions, with a lower risk of procedure-related complications than the conventional CT-guided method.

Follow-up of incidental pulmonary nodules and association with mortality in a safety-net cohort.

Background Though incidental pulmonary nodules are common, rates of guideline-recommended surveillance and associations between surveillance and mortality are unclear. In this study, we describe adherence (categorized as complete, partial, late and none) to guideline-recommended surveillance among patients with incidental 5-8 mm pulmonary nodules and assess associations between adherence and mortality. Methods This was a retrospective cohort study of 551 patients (≥35 years) with incidental pulmonary nodules conducted from September 1, 2008 to December 31, 2016, in an integrated safety-net health network. Results Of the 551 patients, 156 (28%) had complete, 87 (16%) had partial, 93 (17%) had late and 215 (39%) had no documented surveillance. Patients were followed for a median of 5.2 years [interquartile range (IQR), 3.6-6.7 years] and 82 (15%) died during follow-up. Adjusted all-cause mortality rates ranged from 2.24 [95% confidence interval (CI), 1.24-3.25] deaths per 100 person-years for complete follow-up to 3.30 (95% CI, 2.36-4.23) for no follow-up. In multivariable models, there were no statistically significant associations between the levels of surveillance and mortality (p > 0.16 for each comparison with complete surveillance). Compared with complete surveillance, adjusted mortality rates were non-significantly increased by 0.45 deaths per 100 person-years (95% CI, -1.10 to 2.01) for partial, 0.55 (95% CI, -1.08 to 2.17) for late and 1.05 (95% CI, -0.35 to 2.45) for no surveillance. Conclusions Although guideline-recommended surveillance of small incidental pulmonary nodules was incomplete or absent in most patients, gaps in surveillance were not associated with statistically significant increases in mortality in a safety-net population.

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group.

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.

Lung Adenocarcinomas Manifesting as Radiological Part-Solid Nodules Define a Special Clinical Subtype.

INTRODUCTION: The clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear. METHODS: We retrospectively compared the clinicopathologic features and survival times of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors treated with surgery at Fudan University Shanghai Cancer Center and evaluated the prognostic implications of consolidation-to-tumor ratio (CTR), solid component size, and tumor size for part-solid lung adenocarcinomas. RESULTS: A total of 911 patients and 988 pulmonary nodules (including 329 part-solid nodules [PSNs], 501 pGGNs, and 158 pure solid nodules) were analyzed. More female patients (p = 0.015) and nonsmokers (p = 0.003) were seen with PSNs than with pure solid nodules. The prevalence of lymphatic metastasis was lower in patients with PSNs than in those with pure solid tumors (2.2% versus 27% [p < 0.001]). The 5-year lung cancer-specific (LCS) recurrence-free survival and LCS overall survival of patients with PSNs were worse than those of patients with pGGNs (p < 0.001 and p = .042, respectively) but better than those of patients with pure solid tumors ([p < 0.001 and p < 0.0001, respectively]). CTR (OR = 12.90; 95% confidence interval [CI]: 1.85-90.04), solid component size (OR = 1.45; 95% CI: 1.28-1.64), and tumor size (OR = 1.23; 95% CI: 1.15-1.31) could predict pathologic invasive adenocarcinoma for patients with PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had prognoses comparable to those of patients receiving lobectomy (p = .178 for 5-year LCS recurrence-free survival and p = .319 for 5-year LCS overall survival). The prognostic differences between patients with systemic lymph node dissection and those without systemic lymph node dissection were statistically insignificant. CONCLUSIONS: Part-solid lung adenocarcinoma showed clinicopathologic features different from those of pure solid tumor. CTR, solid component size, and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype.

A Decision Analysis of Follow-up and Treatment Algorithms for Nonsolid Pulmonary Nodules.

Purpose To evaluate management strategies and treatment options for patients with ground-glass nodules (GGNs) by using decision-analysis models. Materials and Methods A simulation was developed for 1 000 000 hypothetical patients with GGNs undergoing follow-up per the Lung Imaging Reporting and Data System (Lung-RADS) recommendations. The initial age range was 55-75 years (mean, 64 years). Nodules could grow and develop solid components over time. Clinically significant malignancy rates were calibrated to data from the National Lung Screening Trial. Annual versus 3-year-interval follow-up of Lung-RADS category 2 nodules was compared, and different treatment strategies were tested (stereotactic body radiation therapy, surgery, and no therapy). Results Overall, 2.3% (22 584 of 1 000 000) of nodules were clinically significant malignancies; 6.3% (62 559 of 1 000 000) of nodules were treated. Only 30% (18 668 of 62 559) of Lung-RADS category 4B or 4X nodules were clinically significant malignancies. The risk of clinically significant malignancy for persistent nonsolid nodules after baseline was higher than Lung-RADS estimates for categories 2 and 3 (3% vs <1% and 1%-2%, respectively). Overall survival (OS) at 10 years was 72% (527 827 of 737 306; 95% confidence interval [CI]: 71%, 72%) with annual follow-up and 71% (526 507 of 737 306; 95% CI: 71%, 72%) with 3-year-interval follow-up (P < .01). At 10 years, OS among patients whose nodules progressed to Lung-RADS category 4B or 4X was 80% after radiation therapy (49 945 of 62 559; 95% CI: 80%, 80%), 79% after surgery (49 139 of 62 559; 95% CI: 78%, 79%), and 74% after no therapy (46 512 of 62 559; 95% CI: 74%, 75%) (P < .01). Conclusion Simulation modeling suggests that the follow-up interval for evaluating ground-glass nodules can be increased from 1 year to 3 years with minimal change in outcomes. Stereotactic body radiation therapy demonstrated the best outcomes compared with lobectomy and with no therapy for nonsolid nodules. © RSNA, 2018 Online supplemental material is available for this article.

Clinical Significance of Pulmonary Nodules in the Pretransplant Evaluation of Liver Transplant Recipients With Hepatocellular Carcinoma.

OBJECTIVES: Pulmonary nodules are common in patients with hepatocellular carcinoma who are being evaluated for a possible liver transplant. MATERIALS AND METHODS: In this retrospective study, we analyzed the records of liver transplant recipients at our institution with a primary diagnosis of hepatocellular carcinoma who received transplants between 2000 and 2015. All patients had magnetic resonance imaging-confirmed disease within Milan criteria and a concurrent staging chest computed tomography. Patient survival was estimated using Kaplan-Meier methods and compared between pulmonary nodule characteristic groups. A Cox proportional hazards model was constructed for adjusted analysis. RESULTS: Of the 197 liver transplant recipients who met our study inclusion criteria (median follow-up, 40 mo), 115 (58.4%) had a total of 231 pulmonary nodules, with 57 (49.6%) having multiple nodules and 108 (93.9%) having nodules ≤ 1 cm. The presence of pulmonary nodules did not negatively affect patient survival, per our univariate and multivariate analysis, nor did their presence affect their number, location, laterality, shape, edge, density, or the presence of calcifications (P ≥.05). However, pulmonary nodules ≥ 1 cm were associated with decreased overall survival. CONCLUSIONS: In our pretransplant evaluation of patients with hepatocellular carcinoma, pulmonary nodules ≤ 1 cm did not portend worse patient or graft survival posttransplant.

Controversies on lung cancers manifesting as part-solid nodules.

PURPOSE: Summarise survival of patients with resected lung cancers manifesting as part-solid nodules (PSNs). METHODS: PubMed/MEDLINE and EMBASE databases were searched for all studies/clinical trials on CT-detected lung cancer in English before 21 December 2015 to identify surgically resected lung cancers manifesting as PSNs. Outcome measures were lung cancer-specific survival (LCS), overall survival (OS), or disease-free survival (DFS). All PSNs were classified by the percentage of solid component to the entire nodule diameter into category PSNs <80% or category PSNs ≥80%. RESULTS: Twenty studies reported on PSNs <80%: 7 reported DFS and 2 OS of 100%, 6 DFS 96.3-98.7%, and 11 OS 94.7-98.9% (median DFS 100% and OS 97.5%). Twenty-seven studies reported on PSNs ≥80%: 1 DFS and 2 OS of 100%, 19 DFS 48.0%-98.0% (median 82.6%), and 16 reported OS 43.0%-98.0% (median DFS 82.6%, OS 85.5%). Both DFS and OS were always higher for PSNs <80%. CONCLUSION: A clear definition of the upper limit of solid component of a PSN is needed to avoid misclassification because cell-types and outcomes are different for PSN and solid nodules. The workup should be based on the size of the solid component. KEY POINTS: • Lung cancers manifesting as PSNs are slow growing with high cure rates. • Upper limits of the solid component are important for correct interpretation. • Consensus definition is important for the management of PSNs. • Median disease-free-survival (DFS) increased with decreasing size of the nodule.

Survival and risk factors for progression after resection of the dominant tumor in multifocal, lepidic-type pulmonary adenocarcinoma.

BACKGROUND: It remains unclear whether a dominant lung adenocarcinoma that presents with multifocal ground glass opacities (GGOs) should be treated by local therapy. We sought to address survival in this setting and to identify risk factors for progression of unresected GGOs. METHODS: Retrospective review of 70 patients who underwent resection of a pN0, lepidic adenocarcinoma, who harbored at least 1 additional GGO. Features associated with GGO progression were determined using logistic regression and survival was evaluated using the Kaplan-Meier method. RESULTS: Subjects harbored 1 to 7 GGOs beyond their dominant tumor (DT). Mean follow-up was 4.1 ± 2.8 years. At least 1 GGO progressed after DT resection in 21 patients (30%). In 11 patients (15.7%), this progression prompted resection (n = 5) or stereotactic radiotherapy (n = 6) at mean 2.8 ± 2.3 years. Several measures of the overall tumor burden were associated with GGO progression (all P values < .03) and with progression prompting intervention (all P values < .01). In logistic regression, greater DT size (odds ratio, 1.07; 95% confidence interval, 1.01-1.14) and an initial GGO > 1 cm (odds ratio, 4.98; 95% confidence interval, 1.15-21.28) were the only factors independently associated with GGO progression. Survival was not negatively influenced by GGO progression (100% with vs 80.7% without; P = .1) or by progression-prompting intervention (P = .4). CONCLUSIONS: At 4.1-year mean follow-up, 15.7% of patients with unresected GGOs after resection of a pN0 DT underwent subsequent intervention for a progressing GGO. Some features correlated with GGO growth, but neither growth, nor need for an intervention, negatively influenced survival. Thus, even those at highest risk for GGO progression should not be denied resection of a DT.

Surgery for malignant pulmonary nodules in patients with a history of oesophageal cancer.

Objectives: The objective of this study is to analyse the short- and long-term results of surgery for malignant pulmonary nodules in patients with a history of oesophageal cancer (EC) in order to assess the significance of surgery in these patients. Methods: The data of 28 consecutive patients with a history of EC who underwent pulmonary resection for malignant pulmonary nodules were reviewed. The perioperative and long-term results were analysed. Results: The histological type of oesophageal cancer was squamous cell carcinoma in all of the patients. The preceding treatments for EC were surgery with or without neoadjuvant therapy in 21, chemoradiotherapy in 4 and endoscopic resection in 3. The patients were smokers, with low body mass indices, and had high incidences of a history of malignancy besides EC and other comorbidities. Complete resection was achieved in 27 patients (96%). There was no perioperative mortality and 7 patients (25%) developed postoperative complications. Based on the pathological and clinical criteria, 14 patients (50%) were diagnosed with primary lung cancer, 10 patients (35%) with pulmonary metastases from EC and 4 patients (25%) with pulmonary metastasis from another cancer. The 5-year disease-free and overall survival rates of all patients were 48% and 60%, respectively. Conclusions: Surgery for malignant pulmonary nodules in patients with a history of EC can be performed with acceptable surgical risk despite the high rate of comorbid illness in these patients. Proactive surgical management should be considered for treating malignant pulmonary nodules in patients with a previous history of EC as this strategy provides favourable long-term results.

Surgical Management of Multifocal Ground-Glass Opacities of the Lung: Correlation of Clinicopathologic and Radiologic Findings.

Background We evaluated the clinicopathologic characteristics and oncologic outcome in patients who underwent surgical resection for multifocal ground-glass opacities (GGOs) of the lung. Methods We examined 131 patients who underwent surgical resections for multiple clinical-N0 lung cancers. Multifocal GGOs were defined as tumors showing GGO dominance with a consolidation/tumor ratio (CTR) < 0.5 for all, whereas solid lesions were defined as having at least one tumor that showed CTR ≥0.5. Results Multifocal GGOs were found in 53 (40.5%) patients. A significantly large number of GGOs with a median of 3 per patient (range 2-41) was observed in multifocal GGOs (p < 0.0001). A multivariate analysis demonstrated tumor size ≤ 20 mm (p = 0.0407) and multifocal GGOs (p = 0.0345) were significantly associated with the survival. Regarding surgical managements for multifocal GGOs, the 5-year overall survival (OS) of multiple synchronous or staged limited resection only (n = 26) versus anatomical resection with or without additional limited resection (n = 27) was not significantly different (100% and 91.9%, p = 0.2287). The total number of resected multifocal GGOs was 278, most of which revealed adenocarcinoma or precancerous lesions. Unresected or new GGOs developed in 19 (35.8%) patients, all of which remained pure-GGO of < 10 mm in size without any interventions. The 5-year OS of multifocal GGOs and solid lesions were 94.4% and 80.6% (p = 0.0096), with a median follow-up time of 60 months. Conclusion Surgical interventions combined with limited surgery or adequate follow-up management based on the findings on thin-section CT could provide acceptable oncologic outcomes for multifocal GGOs.

Lung Cancer Deaths in the National Lung Screening Trial Attributed to Nonsolid Nodules.

Purpose To validate the recommendation of performing annual follow-up of nonsolid nodules (NSNs) identified by computed tomographic (CT) screening for lung cancer, all cases of lung cancer manifesting as NSN in the National Lung Screening Trial (NLST) were reviewed. Materials and Methods Institutional review board and informed consent were waived for this study. The NLST database was searched to identify all participants with at least one NSN on CT scan with lung cancer as the cause of death (COD) documented by the NLST endpoint verification process. Among the 26 722 participants, 2534 (9.4%) had one or more NSNs, and lung cancer as the COD occurred for 48 participants. On review, 21 of the 48 patients had no NSN in the cancerous lobe, which left 27 patients whose CT scans were reviewed by four radiologists: Group A (n = 12) were cases of lung cancer as the COD because of adenocarcinoma, and group B (n = 15) were cases of lung cancer as the COD because of other cell types. Frequency of lung cancer as the COD because of NSN and the time from randomization to diagnosis within these groups was determined. Results Six of the 12 patients in group A had no NSN in the cancerous lobe whereas the remaining six patients had a dominant solid or part-solid nodule in the lobe that rapidly grew in four patients, was multifocal in one patient, and had a growing NSN in one patient in whom diagnosis was delayed for over 3 years. Five of the 15 patients in group B had no NSN, and for the remaining 10 patients, lung cancer as the COD was not because of NSN. Conclusion It seems unlikely that patients with lung cancer as the COD occurred with solitary or dominant NSN as long as annual follow-up was performed. This lends further support that lung cancers that manifest as NSNs have an indolent course and can be managed with annual follow-up. © RSNA, 2016.

Outcomes of lung cancers manifesting as nonsolid nodules.

This is a comprehensive review and re-analysis of available literature to assess the outcome of lung cancer presenting as nonsolid nodules (NSNs), a more indolent form of cancer. PubMed and EMBASE were searched for articles reporting on CT-detected lung cancers manifesting as NSNs published in English on or before July 17, 2015. Only studies including clinicopathologic data, lung cancer-specific survival, or overall survival were included. Data extraction was performed by three independent reviewers using prespecified criteria. Twenty-four articles from 5 countries met criteria and they included 704 subjects with 712 lung cancers manifesting as NSNs. Each article reported from 2 to 100 lung cancer cases with a median follow up of 18-51 months. All NSNs were Stage I adenocarcinoma without pathologic nodal involvement upon resection, except for one case in which the NSN progressed to become part-solid nodule after 6 years of follow-up. The five-year lung cancer-specific survival rate was 100%. These findings suggest an indolent course for lung cancers manifesting as NSNs.

Adjuvant Chemotherapy for T3 Non-Small Cell Lung Cancer with Additional Tumor Nodules in the Same Lobe.

INTRODUCTION: Adjuvant chemotherapy after surgical resection of non-small cell lung cancer is associated with a survival advantage in several staging scenarios. T3 tumors associated with a separate tumor nodule in the same lobe (formerly "satellite nodules") have a significant risk for systemic failure, yet the efficacy of adjuvant chemotherapy in this setting is unknown. The survival of patients with T3 tumors and additional tumor nodules in the same lobe treated with and without postoperative chemotherapy was evaluated to understand the role of adjuvant chemotherapy in this setting. METHODS: The National Cancer Data Base was queried for patients with T3 tumors with additional tumor nodules in the same lobe between 2010 and 2012. Primary outcomes were 3-year overall and relative survival (a surrogate of cancer-specific survival). RESULTS: A total of 1013 patients with T3 tumors and additional tumor nodules in the same lobe were identified; 56% received multiagent postoperative chemotherapy and 44% were treated with surgical resection only. The use of adjuvant chemotherapy versus resection alone was associated with improved 3-year overall survival (70% versus 59%, p < 0.001). A Cox model adjusting for patient, tumor, and treatment factors demonstrated that adjuvant chemotherapy was associated with a survival advantage compared with resection alone (hazard ratio = 0.544, p < 0.0001). Relative 3-year survival was also improved in the adjuvant chemotherapy subgroup (74% versus 64% for the surgery-only subgroup). CONCLUSIONS: Adjuvant chemotherapy is associated with increased overall survival among patients with T3 tumors with additional pulmonary nodules. Further study is warranted to clarify the role of adjuvant chemotherapy in this setting.

Surgical Therapy for Bilateral Multiple Primary Lung Cancer.

BACKGROUND: With the development of diagnostic techniques, the incidence of multiple pulmonary nodules has increased. The management of multiple primary lung cancer patients based on currently established criteria, however, remains controversial. METHODS: Patients who underwent curative operations for bilateral multiple primary lung cancer (BMPLC) based on the Martini-Melamed criterion between January 2001 and June 2014 were reviewed retrospectively. RESULTS: Bilateral lobectomies and lobectomies with contralateral sublobar resections were performed in 39 and 49 patients, respectively. Bilateral sublobar resections were performed in the remaining 13 cases. Overall survival at 3 and 5 years was 84.5% and 75.0%, respectively. The use of a limited resection procedure for the contralateral second nodule in cases with stage I BMPLC did not have a negative effect on the 5-year overall survival (p = 0.752). Postoperative pathologic diagnosis classified by the most advanced TNM stage appeared to present a good correlation with prognosis in patients with BMPLC. Cox multivariate analysis identified the most advanced TNM stage (p = 0.018) and the number of lesions (p = 0.001) as significant predictors of overall survival. CONCLUSIONS: The prognosis of patients after bilateral surgical treatment with curative intent for BMPLC was shown to be promising. The use of a limited resection procedure for the contralateral second nodule in cases with stage I BMPLC did not have a negative effect on the 5-year overall survival. Postoperative pathologic diagnosis classified by the most advanced TNM had a good correlation with prognosis in patients with BMPLC.

Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma: Imaging characteristics and clinical outcomes.

No guidelines exist for the management of pulmonary nodules in patients with hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation. The 172 patients with HCC who were listed for liver transplant at our institution received both pretransplant chest computed tomography (CT) and follow-up CT. Pulmonary nodules on CT were characterized and followed on subsequent scans by a blinded radiologist, with a consensus review with a second radiologist being performed for equivocal cases. Nodule characteristics and outcomes were examined with chi-square tests, and the posttransplant survival of patients with different nodule outcomes was compared. Cumulative probabilities of waiting-list removal for nontransplant patients and cumulative probabilities of undergoing transplantation for all patients were also compared between patients with and without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules represented HCC metastases, 1.0% represented other bronchopulmonary malignancies, and 2.7% represented infections. None of the malignant nodules exhibited a triangular/lentiform shape or calcifications. There were no statistically significant differences in pulmonary nodule outcomes between patients who underwent transplantation and those who did not undergo transplantation. No significant differences in posttransplant survival were found between patients with different nodule outcomes. There was also no significant difference between patients with and without nodules in the cumulative probabilities of waiting-list removal. However, the cumulative probability of undergoing liver transplantation was borderline significantly higher in patients without pulmonary nodules. In conclusion, despite the low prevalence of malignant nodules, all pulmonary nodules besides triangular/lentiform-shaped or calcified nodules should be followed with serial CT while the patient is on the transplant list, with biopsy performed for new and/or enlarged nodules. Both malignancy and active infection must be excluded when one is confronted with enlarged pulmonary nodules. Clinicians should also be aware of the possibility of reactivation of a granulomatous infection after transplantation.

Preoperative concurrent chemoradiotherapy followed by extrapleural pneumonectomy for patients with non-small cell lung cancer with malignant pleural effusion and/or pleural nodules: Ten-year results of a prematurely terminated single institute phase II trial.

BACKGROUND: Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-small cell lung cancer (NSCLC), which is currently classified as M1a-Stage IV disease. The role of surgery, especially extrapleural pneumonectomy (EPP) for local disease control and its impact on the survival of patients remains uncertain. PATIENTS AND METHODS: This single institute phase II trial was performed from March 1997 to March July 2004 to assess the effects of induction concurrent chemoradiotherapy (CRT) using a pro-drug of 5-FU, uracil-tegafur (UFT(®), Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), plus cisplatin concurrently with 40 Gy hemithorax radiation followed by EPP. Intraoperative hypotonic cisplatin treatment in the pleural cavity before resection of the pericardium and diaphragm was performed. The primary endpoint of this study was the overall survival (OS), and the secondary endpoint was the disease-free survival (DFS), safety, response to the induction CRT, local disease control period in the affected thorax and the type of disease recurrence. RESULTS: This trial was prematurely terminated because of the slow registration pace. During the study period, 11 patients were enrolled. There were five males and six females, with a median age of 55 (36-64) years. All patients had adenocarcinoma. All patients received the planned induction CRT. Five patients achieved a partial response and five achieved stable disease, and one patient could not be evaluated. One patient underwent exploratory thoracotomy due to unresectable chest wall invasion, and nine patients (81.8%) underwent EPP. No perioperative deaths were encountered. The median follow-up time was matured at 32.1 (range 15.0-100) months. The one-, three- and five-year DFS rates were 77.8% (95%CI: 50.6-100%), 11.1% and 11.1% (95%CI: 95%CI: 0-31.7%), respectively. The one-, three- and five-year OS rates were 100.0%, 33.3% (95%CI: 2.5-64.1%) and 22.2% (95%CI: 0.0-49.4%), respectively. Recurrence developed in eight of nine patients who underwent EPP (88.9%). All first recurrent sites were distant regions, and no ipsilateral local recurrence was identified. CONCLUSION: The trimodality treatment used in this trial appears to be a choice of treatment for highly selected patients. However, the impact on the survival of NSCLC patients with malignant pleural effusion and/or pleural nodules still remains uncertain given the small number of patients enrolled in the study.