Lung-only Metastases Research Articles

The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma.

Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status. Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between 2004-2020. Primary tumor resection status (Adrenalectomy vs no-adrenalectomy). Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only). Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naïve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9). The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.

Assessing Surgical Benefits and Creating a Prognostic Model for Breast Cancer with Lung-only Metastasis: An Analysis of the National Cancer Database.

The decision to perform surgery on breast cancer patients with lung-only metastasis is a subject of ongoing debate. Our investigation seeks to assess the survival rates following surgical intervention among individuals diagnosed with breast cancer experiencing isolated metastasis to the lungs. Additionally, we endeavor to devise a predictive nomogram aimed at forecasting the long-term survival. We analyzed patients diagnosed with primary lung metastases from breast cancer between 2010 and 2015, utilizing datasets obtained from the National Cancer Database (NCDB). We employed the Cox proportional hazards regression model and the Kaplan-Meier method to analyze survival data. Additionally, we constructed nomograms to forecast survival outcomes. The study comprised 2403 patients, with 1058 (44.0%) undergoing breast-specific surgery and 1345 (56.0%) not receiving surgical treatment. The group that underwent surgical procedures exhibited a significantly enhanced overall survival (OS) compared to the non-surgery group (multivariate analysis: hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.54-0.75; p < 0.001). Surgical intervention consistently improved survival across nearly all patient subgroups. The research successfully established a predictive nomogram designed to calculate the likelihood of long-term survival, attaining a concordance index (C-index) of approximately 0.7 in both validation and training cohorts. By integrating multiple clinicopathological variables, the nomogram efficiently classified patients into categories reflecting different survival forecasts. The findings of this investigation support the notion that surgical treatment can enhance the overall survival of patients with initial lung-only metastasis from breast cancer. The investigation further introduces a nomogram demonstrating reasonable accuracy in forecasting long-term survival of patients in this cohort.

The impact of metastatic sites on survival Rates and predictors of extended survival in patients with metastatic pancreatic cancer

Background objectivesThe aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. MethodsWe examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016–2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. ResultsMedian overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). ConclusionWhile synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

A phase 2 study evaluating response and biomarkers in patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) treated with nivolumab/relatlimab.

3554 Background: Lymphocyte-activation gene 3 (LAG-3) is an immunosuppressive signal, impairing T effector (Teff) activation. Pre-clinical studies suggest LAG-3 inhibition promotes anti-tumor immunity by enhancing Teff function. Correlative studies linked increased LAG-3 levels with reduced overall survival (OS) in CRC. These data prompted optimism that combined LAG-3/PD-1 inhibition might promote anti-tumor responses in MSS CRC. Methods: We conducted a phase 2 study of nivolumab (Nivo) (aPD1)/relatlimab (Rela) (aLAG3) in patients with previously treated advanced MSS CRC. This study enrolled patients onto 1 of 3 arms. Arms A and B used a Composite PD-L1 and acellular Mucin (CPM) score to define patients as CPM(+) in Arm A (CPM≥ 15%) and CPM(-) in Arm B (CPM&lt; 15%). Patients in Arm A and B received Nivo 480mg/Rela 160mg IV q4 weeks. Arm C enrolled patients without biomarker selection who received Nivo 480mg/Rela 960mg or Rela 480mg/Nivo 480mg. The primary endpoint was objective response, and each arm was powered to detect an objective response rate (ORR) of ≥20%. Results: Fifty nine evaluable patients were enrolled (Arm A: 12, Arm B: 15, Arm C: 32). Patient characteristics and responses are outlined. Treatment was well tolerated with no new safety signals over aPD1 alone. Three (5%) patients achieved a partial response (PR), 6 (10%) stable disease (SD), and 50 with progression of disease (PD) as best response. The median progression-free survival was (Arm A: 2.2 mo., Arm B: 2.8 mo., Arm C: 2.6 mo.) while median OS was (Arm A: 4.3 mo., Arm B: 14.2 mo., Arm C: 12.4 mo.). In N=6 patients with lung-only metastases, 2 (33%) experienced a PR, and 1 (17%) a SD, for a clinical benefit rate of 50%. The trial incorporated translational correlates. We will report mass cytometry on PBMCs, RNAseq on baseline biopsies, and imaging mass cytometry on pre- and on-treatment biopsies. Conclusions: This combination did not meet the primary endpoint of 20% ORR for any of the 3 cohorts, but there was intriguing possible activity in patients with lung only metastases, consistent with emerging data. Clinical trial information: NCT03642067 .

Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.

Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN. This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN. Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN (n = 217) as well as PDAC (n = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes. Invasive IPMN was significantly smaller in size (p < 0.001) and of a lower tumor grade (p < 0.001), with fewer lymph node metastases (p < 0.001), lymphangiosis (p < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN. Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.

Use of Natural Language Processing to Infer Sites of Metastatic Disease From Radiology Reports at Scale.

To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports. A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports. The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P < .001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P < .001). We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score‑matched SEER database analysis.

Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma

ObjectivesLung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). MethodsThe study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. ResultsThe study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. ConclusionMost ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

Abstract A115: Collective invasion facilitates liver metastasis in pancreatic ductal adenocarcinoma

Abstract Fifty percent of PDAC patients present with distant metastasis and face a dismal prognosis of 8 to 11 months. However, patients with lung metastases have better prognosis than patients with metastatic spread to other sites. In our PDAC metastasis cohort, patients with lung-only metastasis survived longer than patients with liver metastasis, despite sharing the same tumor subtype. To understand features of the primary tumor linked to metastatic site, we generated a novel gene signature for primary organotropism (pORG) that distinguishes primary tumors that developed liver metastasis from those that developed lung metastasis, independent of known tumor subtypes. Our pORG signature predicts survival independently of transcriptional subtype, genetic alterations and clinicopathological variables and in a validation cohort consisting of TCGA pancreatic cancer. Primary tumors with high pORG scores, i.e., liver-tropic primaries, have increased transcriptomic signatures of proliferation and replication stress whereas low pORG tumors have increased lymphocyte gene expression. To validate our findings, we generated cyclic immunofluorescence multiplex imaging data from 34 primary tumors. As anticipated, single cell image analysis revealed high B and T cell infiltration in low-pORG tumors, and increased proliferation and replication stress foci in high-pORG tumors. Intriguingly, malignant cells from high pORG tumors had an increased fraction KRT19-high tumor cells relative to low pORG tumors and were distinctly epithelial in appearance. To reconcile the metastatic behavior of high pORG tumors with their apparent enrichment for epithelial-state cells, we hypothesized that liver-tropism was associated with a partial epithelial-to-mesenchymal transition (EMT) state and metastasis via collective invasion. Bulk transcriptional analysis of 200 PDAC primary tumors revealed a distinct subset of high pORG tumors have increased expression of markers linked to partial EMT and collective invasion, including RAB11a, Rho-like GTPases, and proteases MMP7 and KLK7. Our results support a model of E-cadherin internalization facilitating partial EMT and collective invasion. Current efforts include in-vitro characterization of migration modes in patient-derived cell lines and organoids. Our work suggests unique and targetable tumor intrinsic features linked to organotropism in PDAC. Citation Format: Jennifer R. Eng, Carl Pelz, Koei Chin, Sam Sivagnanam, Link M. Jason, Dove Keith, Lisa Coussens, Rosalie C. Sears. Collective invasion facilitates liver metastasis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A115.

Immunotherapy response in microsatellite stable metastatic colorectal cancer is influenced by site of metastases

BackgroundPrior studies indicate that colorectal cancer patients with liver metastases did not benefit from regorafenib, nivolumab (REGONIVO) or regorafenib, ipilimumab, nivolumab (RIN) treatments, while those without liver metastases showed significant response. This study explores the impact of metastatic sites on treatment outcomes. MethodsChemotherapy-refractory colorectal cancer patients treated with REGONIVO or RIN were evaluated, focusing on 2-month organ-specific response, ORR, PFS and OS based on metastatic sites. ResultsOf the 96 patients analyzed (58 REGONIVO, 38 RIN), liver or peritoneal metastases led to poor outcomes, with 0 % ORR, and median PFS of 2.0 and 1.5 months respectively. In contrast, lung-only metastases had an ORR of 56.3 % and a PFS of 14 months. The presence of concurrent LN or other extrahepatic metastatic disease in patients with lung metastatic disease diminished but did not prohibit responses. The 2-month response assessment revealed activity in the lungs, soft tissues, and distant lymph nodes. ConclusionsREGONIVO and RIN were most active in lung-only metastases. Liver and peritoneal metastases were resistant. Future checkpoint inhibitor trials in MSS colorectal cancer should stratify patients based on metastatic locations.

Progression before local control in osteosarcoma: Outcome and prognosis-predictive factors.

The prognosis and impact of early disease progression in patients with osteosarcoma prior to local control (LC), and the potential therapeutic benefits of ifosfamide/etoposide (IE) remain underexplored in the medical literature. A retrospective study was conducted on pediatric patients (≤18years) with osteosarcoma who presented to King Hussein Cancer Center between June 2006 and March 2022. We studied patients with disease progression before LC. Among 195 patients, 31 (17males) exhibited disease progression before LC. The median age at diagnosis was 14.1years, and patients were followed for a median of 23.1months (range: 5.8-94.7). The majority of tumors were located in the extremities (n=28). Ten patients (48%) had lung-only metastasis. Twenty-five patients showed progression at the local site only, and six showed progression both at local/metastatic sites. For the 25 patients with local-site-only progression, the decision for 24 was immediate LC via LSS (n=9), amputation (n=10), hemimandibulectomy (n=1), and radiation therapy (n=1). Three families refused amputation. Among the six patients with combined local/metastatic site progression, the decision was for two to intensify chemotherapy by adding IE, while the other four were recommended immediate LC. However, two of them refused surgery. In total, five patients received IE as intensification for progression, all of whom subsequently progressed. The 5-year event-free survival and overall survival were 27.2% and 31.3%, respectively. Our findings suggest that early disease progression before LC in patients with osteosarcoma is associated with poor prognosis. However, patients initially diagnosed with localized disease and who later exhibited local-disease-only progression appeared to have better outcomes. The potential role of IE in the treatment of patients exhibiting early progression merits further investigation in a larger study cohort.

Outcomes of lung oligometastasis in pancreatic cancer.

Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases. Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model. A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P=0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3months, P=0.527) and polymetastasis (17.9 vs. 16.7months, P=0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7months. Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival.

Disparate Outcomes, Biologic and Therapeutic Differences in Pediatric versus Adult Patients with Ewing Sarcoma

Introduction: Ewing sarcoma (ES) is a small blue round cell sarcoma affecting a wide age spectrum. Clinical advances predominately stem from pediatric research consortia clinical trials. In most series, adults have poorer outcomes when compared to children. The aim of this study was to perform a detailed evaluation of factors potentially accounting for this difference. Methods: A single institution retrospective chart review was conducted on patients with ES diagnosed from 2005 to 2015, identified using a free-text search engine with the keywords “Ewing sarcoma” as well as a corresponding pathologic database. Data were analyzed based on age, pediatric (age <18) and adult (age >18 years), using a multivariate analysis model. Results: Eighty-eight ES patients (34 pediatric, 54 adult) were identified with a median age of 13 (range 3–18) and 31 (range 19–70) in their respective cohorts. Five-year overall survival (OS) was higher in pediatric patients (73.5% vs. 48.1%, p = 0.0213). By stage, 5-year OS in pediatric versus adult patients was 65% versus 20% (p = 0.0530) in metastatic (n = 32) and 68.1% versus 58.8% (p = 0.278) in localized (n = 56) patients. Lung-only metastases were present in 83% of metastatic pediatric patients versus 35% of adult metastatic patients. Pediatric patients received more cycles of first-line chemotherapy (13.8 vs. 11.4, p = 0.001), independent of stage. More cycles of chemotherapy correlated with improved OS (HR: 0.864, CI: 0.773–0.967) and progression-free survival (HR: 0.897, CI: 0.808–0.996). Conclusions: Outcome differences were most notable in patients with metastatic disease, although not statistically significant. Our series found differences in presentation between pediatric and adult populations with adult patients receiving fewer cycles of chemotherapy. This may suggest that both variations in underlying disease biology and potentially differences in treatment may account for outcome disparities.

The efficacy and safety in radioactive iodine refractory thyroid cancer patients treated with sorafenib.

Sorafenib included in Chinese medical insurance is the earliest targeted drug for radioactive iodine refractory differentiated thyroid cancer (RR-DTC). This study is to further demonstrate the clinical efficacy and safety of sorafenib used in Zhujiang Hospital of Southern Medical University. RR-DTC patients treated at our Department of Nuclear Medicine in Zhujiang Hospital of Southern Medical University (October 2017-May 2020) were retrospectively analyzed. Treatment effects, progression-free survival (PFS), and adverse effects (AEs) during medication were evaluated. Of the 31 patients included, 26 patients were evaluated for efficacy with a median follow-up time of 17.5 months (4.0-51.0 months). The disease control rate (DCR) was 57.7% (n = 15) and the objective response rate (ORR) was 26.9% (n= 7). Most patients with disease control had thyroglobulin decreases of more than 60% (p = 0.004), ORRs were favorable in patients with lung metastasis and lung-only metastasis (p = 0.010 and 0.001, respectively). The PFS of the 26 patients analyzed was 16.5 months (95%CI: 14.41 -23.90 months). In the subgroup analysis, female, patients with lung-only metastasis, hand-foot skin syndrome (HFS), and thyroglobulin response ≥ 60% observed longer PFS (p = 0.038, 0.045, 0.035, and 0.000, respectively), while patients with bone metastasis had lower PFS (p = 0.035). The most common toxicity profile was HFS (93.5%), followed by diarrhea (83.9%), alopecia (74.2%). All the side effects were mainly grade 1-2. Grade 3-4 adverse reactions were more common in diarrhea and HFS. Sorafenib has promising efficacy in RR-DTC, especially in patients with lung metastasis and lung-only metastasis. The AEs of sorafenib were generally mild, and the main AE was HFS.

Variations in the approach to lung metastases in osteosarcoma among pediatric and adult patients.

11528 Background: Osteosarcoma (OS) is most common in the pediatric (ped) and young adult population but can occur at any age. Amongst other factors, older age confers a worse prognosis, and it is uncertain whether this is due to inherent biologic differences or treatment approaches. Lung-only metastases (mets) is common, and metastasectomy is performed frequently to improve overall survival. Little is known about the differences in lung-only metastatic OS and approaches to metastasectomies between ped and adult populations. Methods: A single-institution retrospective chart review using a free-text search engine and keywords “osteosarcoma, “lung mets” and “pulmonary mets”, generated 206 patients(pts) diagnosed from 2006-2021. Eligible pts had a diagnosis of lung-only metastatic disease, resection performed at the institution and at least one year of follow-up data. Data was analyzed in two cohorts based on age at OS diagnosis: ped (age&lt;18) and adult (age &gt; 18 years), as well as with age as a continuous predictor. Results: Fifty pts (27F/23M) with lung only mets were eligible for analysis with a median follow up of 10.4 years. Median age was 23 yrs (range 6-77); 20 pts (40% were ≤18 years old); 31 pts (16 ped, 15 adult) had an extremity primary site. Rates of metachronous (67% vs 60%) and bilateral (50% vs 40%) lung mets were similar in ped vs. adult pts, respectively. The median number of lung mets was 2 (range 1 to &gt; 25) with 50% of patients (35) having 2-6 metastases (8 ped, 20 adult). The median size of lung metastasis was 1.2 cm (range 0.1-4.0 cm). 15 ped pts (75%) underwent metastasectomy, compared to 19 adult (63.3%) (OR 1.74, p = 0.39). Probability of metastasectomy decreased with age when used as a continuous predictor (p = 0.11). Ped pts were more likely to have an open procedure as compared to thoracoscopic (OR 12.75, p &lt; 0.01). There was no significant difference in relapse-free survival between ped and adult pts who underwent metastatectomy (p = 0.84). Median overall survival following lung metastasis detection was 5.8 years for ped pts compared to 3 years for adult pts (p = 0.15 from Cox model). Conclusions: Multiple tumor and patient-specific factors affect the decision to undergo metastatectomy in lung-only OS. In our single-center study we learned that timing, pattern, and number of lung mets in ped vs. adult pts were similar, but younger pts were more likely to undergo an open procedure. Our data trended towards a lower chance of undergoing metastatectomy with older age. Larger studies are required to further understand decision-making and therapeutic outcome and a randomized study of open vs. thoracoscopic metastatecomy for lung-only OS mets is underway. In this small study, many patients with lung-only metastatic OS had long-term survival. We showed that relapse-free survival post-metastatecomy was similar in ped and adult patients.

O149 The utility of chest computed tomography in the staging of pancreatic cancer: a retrospective observational study

Abstract Background Almost 50% of patients with pancreatic cancer initially present with metastatic disease. Current NICE guidelines recommend chest, abdomen and pelvis computed tomography (CT) for all patients with a diagnosis of pancreatic cancer. This study aimed to determine the incidence of lung metastases and the clinical utility of completion chest CT in this group. Methods Electronic healthcare records were retrospective reviewed at a regional hepatopancreaticobiliary centre to identify patients diagnosed with pancreatic cancer between 2010-2019 inclusive. Patient demographics, tumour characteristics, metastatic pattern and management outcomes such as surgery and chemotherapy were assessed for all patients. Kaplan Meier survival analysis were used to assess survival outcomes stratified by pattern of metastatic disease and treatment strategy. Results Of the 1293 patients who met the inclusion criteria 69.1%(n=863) had metastatic disease at diagnosis. Only 2.6% (32/1293) of the entire cohort presented with lung-only metastasis, with the liver being the commonest site of metastases (17.7%, 221/1293). Detection of lung metastases in the absence of intra-abdominal metastatic disease precluded surgery. However, lung metastases synchronous with intra-abdominal metastases did not alter management – chemotherapy or best supportive care. Patients with isolated lung metastasis had marginally improved median (IQR) survival [134 (48-347 days] compared with isolated liver [88 (36-221) days] and synchronous lung and liver metastases [88 (29-185) days, p&amp;lt;0.0001]. Conclusion For potential surgical candidates, a chest CT would be recommended as detection of lung metastasis would alter management. However, for patients with unresectable disease, a chest CT confers no additional benefit as management strategy would remain unchanged.

O147 The incidence and impact of pattern of metastases on treatment strategy and outcomes for patients with pancreatic cancer

Abstract Background Pancreatic cancer is a major cause of cancer mortality with dismal survival outcomes. At the time of diagnosis, 15% of patients with pancreatic cancer have resectable disease, 35% present with locally advanced pancreatic cancer and 50% of patients present with metastatic disease. This study aimed to determine the pattern of metastatic disease in patients with pancreatic cancer and evaluate their influence on survival outcomes. Methods Electronic healthcare records were retrospectively reviewed at a regional hepatopancreaticobiliary centre to identify patients diagnosed with pancreatic cancer between 2010-2019 inclusive. Patient demographics, tumour characteristics, metastatic pattern and management were recorded and compared. Kaplan Meier survival analysis were used to assess survival outcomes stratified by sex, metastatic pattern, and treatment strategy. Results Of the 1293 patients who met the inclusion criteria, metastatic disease was present in 863 (69.1%) at diagnosis. The commonest site of metastases was liver only [25.6% (221/863], followed by disseminated metastases [24.1% (208/863)] and regional lymph nodes [22.9% (198/863)]. Only 3.7% (32/863) of patients with metastases had lung-only metastases. Detection of lung metastases synchronous with intra-abdominal metastases did not alter management. The surgical resection rate was only 15% and the 5-year survival for those who underwent surgery was 9.8% compared with 0.8% for those with unresectable disease (p&amp;lt;0.0001). Conclusion A large proportion of patients with pancreatic cancer were diagnosed with metastatic disease with the liver being the commonest site. Metastases reduce resectability rates and consequently lead to poor 5-year survival outcomes.

Inflammatory biomarkers predict outcomes of patients with radioactive iodine refractory thyroid cancer treated with sorafenib.

The objective of this multicenter, retrospective cohort study was to evaluate the ability of inflammatory biomarkers representing the host immune system to predict outcomes in 70 patients with progressive radioactive iodine (RAI)-refractory thyroid cancer who were treated with sorafenib. Patients were divided into low and high inflammatory biomarker groups based on median values. Progression-free survival (PFS) and overall survival (OS) were assessed based on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The median LMR, NLR, and PLR values were 3.4, 2.2, and 140.1, respectively. No significant differences were observed in baseline characteristics of high and low LMR, NLR and PLR groups. Median PFS values were 6.6 and 19.5 months in the low and high LMR groups, respectively (P < 0.001). Compared with the high NLR and PLR groups, PFS was significantly prolonged in the low NLR and PLR groups (P = 0.003 and P = 0.041 respectively). In the multivariate analysis, low LMR and high NLR were associated with poor PFS after adjusting for multiple confounding factors including age, sex, pathology, disease-related symptoms, serum thyroglobulin level, lung-only metastasis, cumulative RAI dose, time from diagnosis, and longer diameter of the target lesion (hazard ratio, HR = 2.42; 95% confidence interval, CI 1.25-4.71; P = 0.009, and HR = 2.09; CI, 1.06-4.14; P = 0.033, respectively). High LMR, low NLR, and low PLR were significantly associated with prolonged OS (P = 0.011, P = 0.023, and P = 0.007, respectively). Patients with at least one risk factors for inflammatory biomarkers presented a significantly lower PFS (HR 2.29; CI, 1.36-3.84; P = 0.003) and OS (HR 2.95; CI, 1.49-5.81; P = 0.006) than patients without any risk factor. Baseline inflammatory biomarkers successfully predicted PFS and OS in patients with progressive RAI-refractory thyroid cancer treated with sorafenib. These prognostic biomarkers might help arrive at appropriate clinical decisions regarding the use of sorafenib.

Rhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases. Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test. Compared with patients with other metastatic sites (n=373), patients with lung-only metastases (n=55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p<.0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p<.0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%). With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms.

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.