Characteristics and Growth Rate of Lung Metastases in Patients With Primary Gastrointestinal Malignancies and Lung-dominant Metastatic Disease

442 Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course than metastatic disease occurring at other anatomic sites. We performed a retrospective analysis at a high-volume tertiary care center to evaluate host and tumor characteristics of this pt population, describe treatment approaches, and model patterns and rates of growth. Methods: Eligible pts were identified through Cancer Center registry data, provider recall, and electronic record review. Criteria included LM occurring either synchronously (SLM) or metachronously (MLM) w/primary cancer diagnosis; nodal, but not visceral or peritoneal, mets allowed. Data re: demographics, tumor characteristics, and rx modalities were collected. We reviewed all eligible CT +/- PET scan reports to gather data on #, location, and size of pulm mets, with all images subsequently reviewed by an independent radiologist. Up to 5 pulm mets were tracked through each pt’s clinical course. Growth rate was estimated using a linear mixed model analysis considering patients as the random. Results: Forty pts were identified between 9/2009 - 12/2019 (23 F/17 M; 28 white/7 Asian/5 other/multi; median age 62 y.o.; n = 15 w/tobacco hx). Tumor types: pancreatic (n = 18), colorectal (n = 12), hepatobiliary (n = 7), other (n = 3). SLM vs MLM:13/27; intact vs resected primary = 16/24. Median time from orig cancer dx to onset of MLM = 16 mos (range, 1 to 60 mos). No. of pulm mets at 1st appearance: 1 (n = 7); 2-5 (n = 17); 6-10 (n = 16). Median size of largest pulm met at 1st appearance = 6 mm (range, 0-39 mm); avg growth rate of largest pulm met = 0.18 mm/month (95% CI, 0.08-0.27). Avg growth rate of up to 5 largest lesions (sum) = 0.35 mm/month (95% CI, 0.07-0.64). Median f/u time prior to rx initiation for MLM = 172 days (range, 25-1547 days); 18 pts developed additional mets during their observation period. Rx modalities for LM: surg (n = 6), radiation (n = 18), systemic rx (n = 32). Addn details specific to cancer type, progression patterns, and pt outcomes will be presented at the meeting. Conclusions: The natural hx of LM varies across the spectrum of GI malignancies. Further larger-scale efforts to define patterns of growth of LM for different GI cancers, informed by size, #, and clinical/molecular features, are needed to guide appropriate timing and selection of rx as well as surveillance strategies.

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Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

Journal of Clinical Medicine ◽

10.3390/jcm10112340 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2340

Author(s):

Lucia Borriello ◽

John Condeelis ◽

David Entenberg ◽

Maja H. Oktay

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Metastatic Disease ◽

Breast Cancer Cells ◽

Lung Metastases ◽

Primary Tumors ◽

Metastatic Burden ◽

First Time ◽

Do So

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.

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Outcomes of metastatic adrenocortical carcinoma (ACC): A 16-year single institutional experience.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16088 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16088-e16088

Author(s):

Dwight Hall Owen ◽

Sandipkumar Patel ◽

John E Phay ◽

Lawrence Andrew Shirley ◽

Lawrence S Kirschner ◽

...

Keyword(s):

Metastatic Disease ◽

Systemic Therapy ◽

Lung Metastases ◽

Cox Proportional Hazards ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Second Line ◽

First Line ◽

First Line Therapy ◽

Line Therapy

e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C > G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.

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Surgical Management of Gastric Cancer: An Institutional Experience

Journal of Nepalgunj Medical College ◽

10.3126/jngmc.v17i2.31662 ◽

2019 ◽

Vol 17 (2) ◽

pp. 82-85

Author(s):

Anup Sharma ◽

Pradip Thapa

Keyword(s):

Gastric Cancer ◽

Metastatic Disease ◽

Stage Iv ◽

Radical Resection ◽

Stage Ii ◽

Stage Iii ◽

Gastrointestinal Malignancies ◽

Female Ratio ◽

Screening Programs ◽

The Common

Introduction: Gastric cancer (GC) is the second most common cause of cancer-related deaths causing about 800,000 deaths worldwide/year. In Nepal gastric cancer is the second common cancer among males after the lung cancer. Gastric cancer shows a wide variation in incidence worldwide, being highest in Korea and Japan. It is detected early due to the low threshold for upper gastrointestinal endoscopy and screening programs. In the rest of the world and particularly in developing countries, GC is advanced in most of the cases. Inspite of controversies in extent of resection and lymphadenectomy, surgery remains the gold standard treatment. The study was conducted to determine the outcome of the patients with gastric cancer. Methods: The study was conducted in the department of surgery at Nepalgunj Medical College and Teaching Hospital Kohalpur from November 2015 to Dec 2018. Patients diagnosed with GC were studied. The patients with resectable disease underwent radical resection followed by adjuvant chemo-radiation as indicated. Patient’s demography, clinical presentation, stage of disease, types of surgery performed and survival were analysed. Results: 58 patients were diagnosed with gastric cancer. The age ranged from 20-83 years with the mean of 61.26±11.28. Male to female ratio was 2.41: 1. The common clinical presentations were weight loss, anorexia and anemia, 17 (29.31%) had gastric outlet obstruction at initial presentation and 4 (6.89%) presented with perforation peritonitis. Antropyloric region was the commonest site of tumor location seen in 41 (70.68%). 7 (12.06%) patients had distant metastasis and 5 (8.62%) had ascites at presentation. Out of 58 patients, 43 (74.13%) were operated. Only 18 (41.86%) patients underwent R0 resection. 14 (24.13%) underwent palliative gastrojejunostomy. Two (3.44%) patients underwent primary repair for perforation and in 9 (15.51%) the procedure was abandoned due to and presence of metastasis. There was one post-operative mortality. The histology of gastric cancer was found to be adenocarcinoma in all patients. There was no patient in stage I. 3(16.66%) patients were in stage II and 15 (83.33%) in stage III. 17 (29.31%) had stage IV disease. Out of 43 operated patients, 13 lost follow up. All 17 resected patients and those with metastatic disease were followed up. There was no death and no local recurrence in stage II. In stage III, 78.57% were alive and in stage IV 35.29% were alive. Conclusion: Gastric cancer is one of the common gastrointestinal malignancies affecting predominantly male gender. Stage of the disease is one of the major prognostic factors related with the survival. Adenocarcinoma is the commonest histology. Radical resection followed by adjuvant chemotherapy is the standard of care. Palliative chemotherapy can prolong the overall survival in patients with metastatic disease.

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Translocation renal cell carcinomas: An evolving entity.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15078 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15078-e15078

Author(s):

Derek Gerard Power ◽

Jodie E Battley ◽

Aoife McCarthy ◽

Claire Brady ◽

John P. Sweeney ◽

...

Keyword(s):

Transcription Factor ◽

Metastatic Disease ◽

Renal Cell ◽

Renal Mass ◽

Lung Metastases ◽

Incidental Finding ◽

Renal Cell Carcinomas ◽

Fuhrman Grade ◽

Post Surgery ◽

First Case

e15078 Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.

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Phase II trial evaluating a 12-week regimen of interdigitating FOLFOX chemotherapy plus pelvic chemoradiation for the simultaneous treatment of primary and metastatic rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3629 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3629-3629

Author(s):

Michael Michael ◽

Joseph James McKendrick ◽

Mathias Bressel ◽

Trevor Leong ◽

Prasad Cooray ◽

...

Keyword(s):

Rectal Cancer ◽

Treatment Regimen ◽

Phase Ii ◽

Metastatic Disease ◽

Metabolic Response ◽

Lung Metastases ◽

Current Phase ◽

Intensive Chemotherapy ◽

Radical Radiotherapy ◽

Folfox Chemotherapy

3629 Background: Current chemotherapy regimens used during chemoradiation (CRT) are adequate for radiosensitization but suboptimal for systemic control. The aim of this study was to assess tolerability, and local/systemic benefits of new regimen delivering intensive chemotherapy and radical radiotherapy in an interdigitating manner. Methods: Phase II prospective study for patients (pts) with untreated simultaneous symptomatic primary and metastatic rectal cancer. The treatment regimen: 12 weeks long. FOLFOX chemotherapy (oxaliplatin 100mg/m2, leucovorin 200mg/m2, 5-FU 400mg/m2 bolus, all day 1, and 5FU continuous infusion [CI] 2.4 g/m2/46 hours) was given in weeks 1, 6, and 11. Pelvic CRT: 25.2 Gy in 3 weeks, 1.8 Gy/fr, with concurrent oxaliplatin 85mg/m2 day 1 and 5-FU CI 200mg/m2/day given in weeks 3-5, and 8-10. Pts received, in 12 weeks, 3 courses of FOLFOX and pelvic radiation 50.4 Gy with concurrent oxaliplatin/5-FU. All pt were staged with CT, MRI and FDG-PET before and post-treatment. Results: 26 pts treated. The mean age was 61 years, 69% male. Rectal primary MRI stage was T2 4%, T3 81% and T4 15%. Liver and lung metastases were present in 81%, and 35% of pts, respectively: 38% of patients had more than one site of metastatic disease. 24 pts (92%) completed the 12-week treatment regimen. All pts received the planned radiation dose. 65% of pts received the planned number of oxaliplatin courses with 88% of pts receiving at least 75% of the protocol oxaliplatin dose. In this 12-week period, grade 3 toxicities were neutropenia 23%, diarrhoea 15%, and radiation perineal skin reaction 12%. Only grade 4 toxicity was neutropenia: 15%. PET metabolic response (CR+PR) rate for rectal primary was 96%. Overall PET metabolic response rate for metastatic disease was 60% (CR rate 16%). Conclusions: It is thus feasible to deliver intensive chemotherapy and radical radiotherapy in an interdigitating manner to treat both primary and metastatic rectal cancer simultaneously. High completion and response rates are encouraging. This regimen is the subject of a current phase II neoadjuvant trial for resectable rectal cancer (TROG 09.01).

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Accuracy of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting node positivity and metastatic disease in patients with gastrointestinal malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.462 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 462-462

Author(s):

Matthew Doepker ◽

Kabisa Baughen ◽

Richard H. Brown ◽

Steven Kucera ◽

Justin Lee ◽

...

Keyword(s):

Metastatic Disease ◽

Predictive Value ◽

Advanced Disease ◽

Gastrointestinal Malignancies ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Before And After ◽

Clinicopathologic Parameters ◽

Complete Blood Counts ◽

Higher Sensitivity

462 Background: Accurate predictors of node positivity and metastatic disease for patients with gastrointestinal (GI) malignancies are currently lacking. Neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) have been introduced as a possible prognostic scoring system. We sought to evaluate the accuracy of NLR and PLR in predicting advanced disease in patients with GI malignancies. Methods: We queried a prospective GI oncology database to identify 116 patients. NLR and PLR were calculated from complete blood counts before and after neoadjuvant therapy (NT) and pre-operatively in patients not treated with NT. The associations between NLR and PLR and the clinicopathologic parameters were assessed via χ2 or Fisher’s exact tests where appropriate. All the tests were two-sided, and p < 0.05 was considered statistically significant. Results: We identified 49(42.2%) esophageal, 34 (29.3%) pancreatic, 14 (12.1%) colorectal, 13 (11.2%) gastric, and 6(5.2%) biliary cancers. There were 36 (31%) LN-, 52 (44.8%) LN+, and 28 (24.2%) patients with metastatic disease. The median NLR for LN – patients was 1.78 (0.2-4.5) and for LN + and metastatic patients was 4.48 (2.38-24.1) p < 0.00001. The median PLR for LN– patients was 123 (66-207) and for LN+ and metastatic patients was 212 (112-2185) p < 0.00001. The sensitivity (SENS), specificity (SPEC), positive predictive value (PPV) and negative predictive value (NPV) for a NLR > 2.25 was 98.8%, 72.2%, 89%, and 96% respectively with an overall accuracy of 91%. The SENS, SPEC, PPV, and NPV for PLR > 140 was 95%, 78%, 90%, and 88% respectively with an overall accuracy of 90%. Utilizing both NLR > 2.25 and PLR > 140 the SENS, SPEC, PPV and NPV was 95%, 89%, 95%, and 89% respectively and the overall accuracy was 93%. Conclusions: NLR and PLR can be used to identify patients with node positivity and metastatic disease. Individually, NLR has a higher sensitivity and NPV while PLR has a higher specificity and PPV. However, the combination of NLR and PLR has the highest accuracy of predicting advanced disease among all gastrointestinal malignancies.

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Tumor growth rate in metastatic adrenocortical carcinoma using two-dimensional computer tomography scan.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16125 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16125-e16125

Author(s):

Sarah N. Fuller ◽

Ahmad Shafiei ◽

Maran Ilanchezhian ◽

Mohammadhadi Bagheri ◽

Jaydira Del Rivero

Keyword(s):

Growth Rate ◽

Lymph Node ◽

Metastatic Disease ◽

Computer Tomography ◽

Adrenocortical Carcinoma ◽

Liver Lesions ◽

Two Dimensional ◽

Lung Lesions ◽

Metastatic Lesions ◽

Computer Tomography Scan

e16125 Background: Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5–2 per million people per year. It has a poor prognosis with an overall 5-year mortality of 75-80%. The treatment of choice for a localized primary or recurrent tumor is radical surgical resection. However, patients with recurrent or metastatic disease are infrequently cured by surgery alone and chemotherapy has limited benefits. Little is known about the growth rate of metastatic lesions or how disease burden varies among patients, which poses a considerable obstacle in patient care as 17–53% of patients present with distant metastases at the time of diagnosis. Most ACC metastases are found in the liver, lung, bone, and retroperitoneum. Methods: This study retrospectively analyzed the growth rate of metastatic ACC lesions in the lung, liver, lymph nodes, and adrenal bed using serial two-dimensional segmentation of computer tomography images from 10 patients seen at the National Institutes of Health. All patients were females (mean age of 61 years; range, 49–70 years) who had an ACC diagnosis for a mean of 7 years (range, 3–14 years). Only lesions that exhibited FGD-PET avidity were included with up to five lesions per organ recorded. Results: Of the 10 patients, 7 showed metastatic disease at primary diagnosis, although all patients developed recurrent and/or distant metastatic lesions throughout the course of their disease (3 patients had lung lesions, 6 had liver lesions, 8 had adrenal bed recurrence, and 5 had lymph node involvement). Compared over a 6-month period without treatment alteration (change in chemotherapy, surgical intervention, or ablation) lung lesions increased by 11.6%, liver lesions decreased by 17.9%, retroperitoneal lesions increased by 69.25%, and lymph node lesions increased by 9.2%. Conclusions: Treatment of metastatic lesions, particularly in the liver, can increase long-term survival. Understanding growth rates of metastatic tumors may lead to improved treatment of patients with ACC.

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The impact of metastasis location on overall survival among patients with renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.621 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 621-621

Author(s):

Devin Patel ◽

Fady Ghali ◽

Margaret Meagher ◽

Aaron Bradshaw ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Bone Metastases ◽

Cell Carcinoma ◽

Metastatic Disease ◽

Renal Cell ◽

Lung Metastases ◽

Univariate Analysis ◽

The Impact ◽

Disease Location

621 Background: Current staging guidelines define all patients with metastatic renal cell carcinoma (RCC) as a singular group. We sought to compare the impact of metastatic disease location on overall survival (OS) in patients with RCC. Methods: We queried our institutional database of consecutive patients with metastatic RCC. A confirmatory analysis was performed using the National Cancer Database (NCDB) for cases between 2010 to 2015. Only cases from which all metastatic disease location was known were used. Patients were grouped into having brain or bone metastases, liver or lung metastases or other metastases. From our institutional database, we performed a univariate analysis to determine the impact of metastasis location on OS. From the NCDB, univariable and multivariable Cox proportional hazards and Kaplan-Meier survival analysis with log-rank testing was performed. Multivariable models were adjusted for age, comorbidity, race, gender, and treatment with either palliative care, chemotherapy or immunotherapy. Results: A total of 95 patients were analyzed from our institutional database, with 30 (31.9%) having brain/bone metastases, 20 (21.3%) having lung/liver metastases, and 44 (46.8%) having other site metastases. On univariate analysis, patients with brain/bone metastases had significantly worse OS (HR 1.87; 95% CI 1.01-3.47). However, no significant difference was seen in patients with liver/lung metastases (HR 1.44; 95% CI 0.64-3.27). A total of 25,528 patients met inclusion for our NCDB analysis, of which 12,119 (47.5%) had brain/bone metastases, 10,004 (39.2%) had liver/lung metastases, and 3,405 (13.3%) had other site metastases. On univariate analysis, patients with lung/liver (HR 1.46; 95% CI 1.38-1.53) and patients with bone/brain (HR 1.69; 95% CI 1.60-1.77) had progressively worse OS with non-overlapping confidence intervals. Multivariable analysis again showed that patients with lung/liver disease (HR 1.51; 95% CI 1.43-1.59) and brain/bone disease (HR 1.66; 95% CI 1.60-1.75) had progressively worse OS. Conclusions: Our results highlight the heterogeneity of patients with metastatic renal cell carcinoma. Location of metastatic disease may drive differences in survival.

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Pulmonary Metastases

Chest Imaging ◽

10.1093/med/9780199858064.003.0051 ◽

2019 ◽

pp. 295-299

Author(s):

Tyler H. Ternes

Keyword(s):

Metastatic Disease ◽

Pulmonary Metastases ◽

Lung Metastases ◽

Lung Parenchyma ◽

Ground Glass Attenuation ◽

Common Causes ◽

Endobronchial Lesion ◽

Lymphangitic Carcinomatosis ◽

Lung And Kidney ◽

Interlobular Septal Thickening

Pulmonary metastases represent spread of malignancy to the lung parenchyma. Patients with metastatic disease may present with dyspnea, cough, or hemoptysis. Alternatively, affected patients may be asymptomatic. The lungs are a common site for metastatic disease. Relatively common primary malignancies (breast, colon, lung, and kidney cancers) are the most common causes of pulmonary metastases. However, less common primary malignancies (choriocarcinoma, testicular cancers, melanoma, and sarcomas) have a higher likelihood to produce lung metastases. The vast majority of pulmonary metastases spread via the bloodstream. Hematogenous metastases are typically basilar predominant lung nodules. Metastatic nodules may be very small (miliary, < 3mm), or very large (cannonball), and may rarely be solitary. The presence of surrounding ground-glass attenuation (CT-Halo sign) often indicates surrounding hemorrhage. Some metastases may be cavitary or calcified. Pulmonary metastases may spread via the lymphatics. Asymmetric smooth or nodular interlobular septal thickening should raise concern for lymphangitic carcinomatosis. An uncommon mechanism is spread within the airways, which may result in an endobronchial lesion or post obstructive atelectasis.

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