Indeterminate Pulmonary Nodules In Patients Research Articles

A prediction model for lung metastases in patients with indeterminate pulmonary nodules in newly diagnosed colorectal cancer

IntroductionMultidisciplinary teams treating patients with newly diagnosed Colorectal Cancer (CRC) often encounter the appearance of Indeterminate Pulmonary Nodules (IPNs) that warrants follow–up with repetitive medical imaging and anxiety for patients. We determined the incidence of IPNs in patients with newly diagnosed CRC and developed and validated a model for individualized risk prediction of IPNs being lung metastases. Material and methodsNewly diagnosed CRC who underwent surgery between November 2011 to June 2014 were included to create the risk model, developed using both clinical experience and statistical selection. Discrimination and calibration slopes of the risk score were evaluated in an independent temporal validation sample. A nomogram is presented to assist clinicians in estimating an individual risk score. ResultsOut of 2111 CRC patients staged with chest CT, 204 (9.6%) had IPNs and 54/204 (26%) had lung metastases. We identified 4 predictors: “location of primary tumour”, “pathological nodal stage”, “size of the largest nodule” and “extrapulmonary synchronous metastases at diagnosis”. Discrimination of the final model in the validation sample was demonstrated by the difference in mean predicted risk between progressed cases en non-progressed cases (49% versus 21%, p = <0.001). ConclusionA prediction model with 4 clinical risk factors can be used to assist multidisciplinary teams in the prediction of individualized risk of lung metastases and imaging strategy in patients with IPNs and newly diagnosed colorectal cancer. The model performed well in new patients not included in the model development.

Exploring the Diagnostic Dilemma of Indeterminate Pulmonary Nodules in Patients with Primary Sarcoma of Bone.

Bone sarcomas are known to have a predilection for pulmonary metastasis. Surveillance protocols are thus focused on periodic chest imaging, typically with CT scan. Pulmonary nodules can be easily identified with this modality, but smaller nodules are not readily biopsied and may not represent metastatic disease. These are called indeterminate. The natural history of indeterminate nodules in a bone sarcoma population and factors associated with progression to true metastatic disease are not clearly defined. All bone sarcoma patients treated at a single institution from 2010 to 2020 were eligible for inclusion. We treated 327 patients over this period; 119 were excluded for age less than 16 years, 31 were excluded for evident metastatic disease at presentation, and 60 were excluded for incomplete clinical follow-up or CT chest imaging either at staging or in surveillance. We assessed chest CT images for presence of pulmonary nodules and selected variables both at the staging and on surveillance images. Nodules were considered metastatic if proven histologically with a biopsy or by clinical interpretation by the multidisciplinary sarcoma team. Clinical and imaging factors were assessed for the association of indeterminate nodule progression to true metastatic disease. Seventy three of the 117 patients had indeterminate nodules on their staging CT scan; 41.1% of those patients progressed to metastatic disease compared to 43.2% of the patients that did not have indeterminate nodules on staging CT. Fifty eight of the 117 patients developed indeterminate nodules on surveillance chest CT, and 55.2% of those patients progressed to metastatic disease. There were no clinical or imaging factors that predicted the development of metastatic disease in the group that had indeterminate nodules at presentation; however, the number and size of nodules did correlate with progression to metastasis in those that developed indeterminate nodules on surveillance. Indeterminate pulmonary nodules are common on staging CT scans in patients with a bone sarcoma. The presence or absence of these indeterminate nodules was not predictive of progression to true metastatic disease in this cohort. However, the development of indeterminate nodules on surveillance imaging was associated with progression to metastatic disease with the size and number of nodules being important factors.

Indeterminate pulmonary nodules and prior malignancy: survival and recurrence after surgery in newly diagnosed stage I non-small cell lung cancer.

Surgical excision biopsy remains the only reliable option in most cases of indeterminate pulmonary nodules, particularly in cancer survivors for whom surgery provides local control of pulmonary metastasis and the best chance of cure for early-stage lung cancer. Nevertheless, unnecessary surgeries remain a concern and the prognosis of newly diagnosed lung cancer might be influenced by the history of previous malignancy. We aimed to analyze the outcomes of resected indeterminate pulmonary nodules in patients with and without previous malignancy, and the impact of prior cancer history on survival and recurrence in stage I non-small cell lung cancer (NSCLC) patients. We retrospectively studied 176 resected indeterminate pulmonary nodules from 169 patients (58% with and 42% without previous cancer). Recurrence and overall survival (OS) were analyzed in newly diagnosed stage I NSCLC using the Kaplan-Meier method and Cox proportional hazard models. The rate of benign lesions was 15.3% (9.6% in the previous cancer group and 23.6% in the no previous cancer group). In stage I NSCLC patients (n=86), previous malignancy was associated with recurrence (P<0.001) but not OS (P=0.23). Chronic obstructive pulmonary disease and visceral pleural invasion were associated with impaired OS and recurrence. Mediastinal lymph node removal was associated with better OS. The rate of benign resections among indeterminate pulmonary nodules in the no-previous cancer group more than doubled that of the previous cancer group and, in newly diagnosed stage I NSCLC patients, recurrence was independently associated with prior cancer. Therefore, in this setting, a history of previous malignancy should be taken into consideration when identifying patients at risk of tumor recurrence.

Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16status (p<.0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p>.0005 and p=.046, respectively). Negative or unknown p16status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

P-248 Clinical factors associated with the risk of malignancy in indeterminate pulmonary nodules in patients with head and neck cancer

P-248 Clinical factors associated with the risk of malignancy in indeterminate pulmonary nodules in patients with head and neck cancer

Indeterminate nodules in osteosarcoma: what\u2019s the follow-up?

Background:Indeterminate pulmonary nodules in patients diagnosed with osteosarcoma present a challenge for accurate staging and prognosis. The aim of this study was to explore the significance of this finding.Methods:A retrospective cohort study of 120 patients with osteosarcoma was performed in the North East of England. Chest computed tomographies (CTs) at presentation were reviewed and the incidence of ‘indeterminate’ nodules recorded. Follow-up scans were reviewed and survival as well as prognostic features were analysed.Results:25% of our cohort presented with indeterminate nodules. Of these, 33% were subsequently confirmed as metastases, the majority within a year. Kaplan–Meier survival analysis showed that patients with indeterminate nodules fared better than those with frank metastatic disease, and similar to those who presented with a normal chest CT. We found no radiographic features that predicted survival.Conclusions:Indeterminate nodules remain a clinical and diagnostic dilemma. Close monitoring of patients is advised during the first year from presentation, and there is potential for indeterminate nodules to develop into frank metastases later than five years from presentation.

Clinical destiny of indeterminate pulmonary nodules in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

297 Background: Perioperative risks and significant quality of life concerns following radical cystectomy (RC) render accurate pre-operative staging paramount, since metastatic patients are unlikely to benefit from extirpation. Yet, incidental indeterminate pulmonary nodules (IPNs) are a common pre-operative finding in clinical practice, thus representing a significant management challenge. As such, we sought to evaluate the natural history of IPNs in a large institutional cohort that underwent RC. Methods: We reviewed our institutional database for patients who underwent RC from 2000 through 2014 for urothelial carcinoma (UCC) of the bladder and had at least 1 identifiable pulmonary lesion on preoperative staging imaging measuring &lt;2cm in any axis. Patients who were M1 at surgery, had gynecologic, colorectal, or missing pathology, or non-urothelial histology were excluded. We sought to determine the natural history of these pulmonary lesions and evaluated predictors of metastatic etiology. Results: During the study period, 681 RC were performed at our institution. We identified 73 patients with an identifiable preoperative IPN who met inclusion criteria and underwent RC. In this subset, 23.3% were female, 21.9% were active smokers, and 54.8% former smokers. The median age at surgery was 70±8.6 years. Nearly half (49.3%) received neoadjuvant chemotherapy. 61.6% of RC were performed using the traditional open approach, while 38.4% were performed robotically. Final pathologic staging included 16.4% pT0N0Mx, 19.2% pTa/Tis/T1N0Mx, 42.5% pT2-4N0Mx, and 21.9% pTanyN+Mx. Median IPN size was 0.7±0.3cm. At median follow up of 23.5±21.9 months, 93% (68/73) of IPNs in our cohort were clinically benign, with metastatic urothelial cancer confirmed in only 4 patients, and a primary lung malignancy diagnosed in 1 patient. Conclusions: The majority of IPNs in patients who proceeded to RC for UCC of the bladder were stable upon follow-up and rarely represented malignancy. As such, in appropriately screened UCC patients, IPNs should not be a barrier to proceeding with extirpative surgical therapy.

Predicting pulmonary metastases among patients with indeterminate pulmonary nodules with renal cell carcinoma.

505 Background: Indeterminate pulmonary nodules (IPN) are of uncertain significance in renal cell carcinoma (RCC) patients. We sought to determine the natural history of IPN in patients undergoing radical nephrectomy and to identify clinical variables associated with the development of lung metastases. Methods: We reviewed all radical nephrectomy patients at a single institution from 2005 – 2009 who had ≥1 IPN on chest computed tomography (CT) within 6 months prior to surgery and no evidence of distant metastates. All chest CTs were re-reviewed by a radiologist who was blinded to outcomes to independently determine number, size, location of nodules and whether the IPN appeared concerning for metastases based on nodule size, tissue density, and morphology. Univariate and multivariate Cox regression was used to assess associated predictive factors. Results: Of 258 patients with IPN, 73 (28%) developed pulmonary metastases. Median follow−up was similar in the groups at 36 months. Patients who developed pulmonary metastases had significantly poorer survival compared to those who did not (3-year DSS 54.5 versus 86.5 months, p&lt;0.001), and 39 (53%) developed pulmonary metastases at the same location as the largest IPN. On univariate analysis, larger renal tumor diameter (HR 1.12, p&lt;0.001), number of pulmonary nodules CT (HR 1.12, p 0.001), presence of hilar lymphadenopathy on chest CT were associated with both lung metastasis development and cancer-specific mortality. After adjusting for age, performance status, comorbidities, histology, and smoking status, higher tumor grade (HR 5.11, p 0.007), presence of tumor thrombus above the diaphragm (HR 4.38, p 0.013), perinephric (HR 4.29, p 0.002) or renal sinus (HR 2.16, p 0.045) fat invasion, and a chest CT concerning for metastasis by the radiologist (HR 2.91, p&lt;0.001) were associated with development of pulmonary metastases. Conclusions: RCC patients with IPN who develop pulmonary metastases have a significantly poorer outcome. Independent predictors of developing lung metastases include tumor grade, presence of tumor thrombus above the diaphragm, perinephric or renal sinus fat invasion, and a chest CT concerning for metastasis.

What is the Significance of Indeterminate Pulmonary Nodules in Patients Undergoing Resection for Pancreatic Adenocarcinoma?

ObjectiveThe significance of indeterminate pulmonary nodules (IPNs) in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) is unknown. We sought to define the prevalence and impact of IPN in such patients. MethodsWe studied all patients who underwent surgical resection of PDAC between 1980 and 2013. IPN was defined as ≥1 well-defined lung nodule(s) less than 3 cm in diameter. Survival was assessed using univariate and multivariate Cox models. ResultsOf the 2306 resected patients, 374 (16.2 %) had a preoperative chest computed tomography (CT) scan. Of these patients, 183 (49 %) had ≥1 IPN. Demographic and clinicopathological characteristics were similar among patients with or without IPN (all P > 0.05). Median survival was comparable among patients who did (15.6 months) or did not (18.0 months) have IPN (P = 0.66). Of the 183 patients with IPN, 29 (16 %) progressed to clinically recognizable metastatic lung disease compared to 13 % without IPN (P = 0.38). The presence of >1 IPN was associated with the development of lung metastasis (relative risk 1.58, 95 % CI 1.03–2.4; P = 0.05). However, lung metastasis was not associated with survival (P = 0.24). ConclusionsAn IPN proved to be a lung metastasis in only one of six patients with PDAC undergoing surgical resection in this study. Survival was not impacted, even among patients who developed lung metastasis. Patients with PDAC who have IPN should not be precluded from surgical consideration.

Clinical significance of indeterminate pulmonary nodules in patients with locally advanced head and neck squamous cell carcinoma

The purpose of this study was to determine whether indeterminate pulmonary nodules (IPNs) at staging are predictive of lung metastasis, primary lung carcinoma, or survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). One hundred ten patients with IPN at staging who had follow-up imaging and 100 patients without IPN were identified from an HNSCC database. The primary endpoints were lung progression-free survival (PFS) and overall survival (OS). Two-year lung PFS for the IPN and No-IPN cohorts were 66% versus 61% (p = .92) and the OS for these cohorts were 71% versus 68% (p = .77). Within the IPN cohort, level IV/V lymph node involvement (odds ratio = 4.34; p = .03), hypopharynx primary (odds ratio = 21.5; p = .005), and race (odds ratio = 9.29; p = .001) were independent predictors of developing lung malignancy. IPNs at staging in patients with HNSCC do not affect prognosis and should neither influence initial treatment planning nor the frequency of posttreatment surveillance.

The natural history of preoperative indeterminate pulmonary nodules in patients with resectable pancreatic adenocarcinoma.

161 Background: Preoperative abdominal imaging often detects indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma. The natural history of IPN in this setting is not well characterized. Methods: Patients with adenocarcinoma of the head of the pancreas who underwent pancreaticoduodenectomy (PD) were queried from a prospectively maintained database. Pre- and postoperative imaging was reviewed and IPN characterized and analyzed for associations with nodule progression and overall survival (OS). Results: 463 patients underwent PD for adenocarcinoma of the head of the pancreas from 2000-2010. Of these, 329 (71%) had reviewable pre-operative imaging. 48 patients (15%) had pre-operative IPN (non-calcified) identified with follow-up imaging available for review. The only pre-operative factor associated with the presence of IPN was increasing age (68 v. 64 years; p=0.003). 8 patients (12%) had new or enlarging nodules, of whom 5 (7%) had confirmed pulmonary metastatic adenocarcinoma. There was no difference in OS between patients with or without pre-operative IPN (2-year OS 41% v. 38%, respectively; p=0.37). Further, no radiographic criteria of IPN (including # of, size of, bilateral, calcified, solid, spiculated, smooth, lobular, or ground-glass nodules) was associated with OS. On follow-up, new or enlarging nodules were not associated with OS. Conclusions: IPN are often found in patients undergoing PD for pancreatic adenocarcinoma. The majority of IPN remain stable on post-operative imaging. Neither the presence of IPN nor nodule characteristics was associated with OS. These data do not support the routine additional workup of pre-operative IPN in patients with resectable adenocarcinoma of the head of the pancreas; however, larger studies are needed to further characterize the significance of IPN in the preoperative evaluation of patients with pancreatic adenocarcinoma.

The Frequency and Significance of Radiologically Detected Indeterminate Pulmonary Nodules in Patients with Colorectal Cancer

Objective: To investigate the frequency and significance of pulmonary nodules in patients with colorectal cancer (CRC). Subjects and Methods: Medical records of 1,344 patients with CRC who underwent thoracic computerized tomography scans between January 2003 and December 2009 were reviewed. Those with any distant metastatic disease or who were already known to have pulmonary malignancies were excluded. Number, size, shape and location of the nodules were evaluated. A multivariate analysis was performed to determine the predictive factors for evidence of metastases. Results: Of the 1,344 patients, 55 (4.09%) had nodules that met the criteria of an indeterminate pulmonary nodule. The mean follow-up time was 25 ± 17.9 months and the mean time to develop pulmonary metastasis was 15.5 ± 6.4 months. The nodules of 17 (30.9%) patients showed progression at follow-up; 8 had metastasized. Multivariate analysis showed multiple indeterminate pulmonary nodules (p = 0.006) of parenchymal localization (p = 0.016) with an irregular border (p = 0.002), which is predictive of metastatic disease. Conclusion: Our study has shown that multiple indeterminate pulmonary nodules with an irregular border in a parenchymal location were more likely to represent metastatic disease. However, the frequency of the occurrence of indeterminate pulmonary metastases of CRC was low.

Indeterminate Pulmonary Nodules in Patients with Sarcoma Affect Survival

We prospectively studied 331 sarcoma patients treated between April 1999 and December 2004 to see if small, indeterminate pulmonary nodules are of prognostic significance. Seventy-one (21%) had indeterminate pulmonary nodules on initial spiral CCT. Twenty of 71 (28%) patients with indeterminate nodules progressed with metastatic disease. Metastatic disease developed in 18/20 (90%) in the area of the original indeterminate nodule. The presence of tiny (<5 mm) indeterminate nodules was not a prognostic variable, however, the presence of nodules > or =5 mm was associated with worse 3 year disease-free survival compared to those with no nodules or tiny nodules (81% versus 49%) but better than those with definite metastatic disease at presentation (49% versus 5%). Because patients with pulmonary nodules > or =5 mm are at increased risk for metastatic disease compared to patients with normal CCT or those with <5 mm nodules but better survival than patients with Stage IV disease, we believe a new staging system of these patients should be considered and recommend careful followup.

Mucinous Cystadenocarcinoma - An Extremely Rare Tumor in a Young Patient

We report on an extremely rare case of pulmonary mucinous cystadenocarcinoma. A 29-year-old male patient was admitted because of progressive enlargement of a right lower lobe mass over a period of 10 years. Right lower lobectomy was performed after a malignant mucinous cystadenocarcinoma was diagnosed by intraoperative frozen section. PET and CT scans did not detect metastatic disease. This case is the youngest patient reported so far with a malignant pulmonary mucinous cystadenocarcinoma and highlights the importance of close follow-up of indeterminate pulmonary nodules in patients with unremarkable history.