Metastatic Lung Disease Research Articles

Metastatic lung disease in children with solid tumors: a historical excursion

The review article provides information about metastases of solid tumors in the lungs: from pathogenesis and the first experience of metastasectomy to a combined local method of therapeutic treatment. According to the literature, lung metastasectomy is part of the standard treatment for adults, but information about the surgical treatment of metastatic lesions in children remains poorly understood. As a rule, metastatic lesion accompanies the progression of the tumor process. Since the 1960s, methods of isolated lung perfusion have been developed, the results of which are reflected in a few articles, but most of the studies are aimed at exploring the possibilities of use and at the direct results of the implementation of this technique.

Small cell lung cancer presenting with hoarseness

A 61-year-old man presented with a 2-year history of progressive hoarseness. He has a 30 pack-year of smoking history. The stroboscopic examination revealed paralysed left vocal cord with asymmetrical motion...

Management of malignant airway obstruction

Malignant central airway obstruction (MCAO) is an important manifestation of advanced primary lung cancer or metastatic disease and has a significant impact on both morbidity and mortality. Several minimally invasive endobronchial techniques exist which can provide rapid recanalization of the airway and improve a patient’s quality of life and potentially overall survival by improving candidacy for systemic or surgical therapies. Modalities for the management of MCAO include thermal ablative techniques, non-thermal techniques, mechanical debulking, and airway stent placement. These therapies are not without complications and as such, the risks and benefits of each intervention should be weighed and individualized to a patient’s particular need. Though large randomized trials are lacking, data show that in experienced hands, multimodality therapy in MCAO can provide significant overall symptom palliation.

Lung Stereotactic Body Radiation Therapy: Is There a Difference in Outcome Based on Respiratory Gating?

Stereotactic body radiation therapy (SBRT) is being increasingly used for the treatment of both primary lung cancer and pulmonary oligometastases. Tumor motion during the breathing cycle can be accounted for with respiratory motion management with gating for example, which is employed in our institution if tumor excursion is greater than 5mm in any direction. There is evidence that there is a greater risk of target miss and loss of local control with gating as compared to contouring with the maximal intensity projection (MIP). Herein we compare lesion outcomes in groups of patients who required gating versus those who did not. A retrospective case control study was carried out on 244 pulmonary lesions in both primary and metastatic lung disease in patients treated with SBRT from 2008-2014. Lesion motion was assessed on 4D-CT and motion limited in a gating window if >5mm in any direction. Target failure-free survival (TPFS) and progression-free survival (PFS) were calculated for lesions which were gated and lesions which were not and compared with Kaplan-Meier and log-rank methods. Univariate and multivariate Cox regression analyses were performed on factors predictive of outcomes. T-test and Chi-squared analysis with done on demographic data between groups. Median age at first SBRT was 70.1 years and median follow-up was 28.4 months (range: 0-74 months). Lobe distribution waas 139 upper lobe lesions, 16 in the middle lobe, and 98 in the lower lobes. Of lower lobe lesions, 77.6% were gated, 43.8% of middle lobe lesions, and 38.8% of upper lobe lesions were gated (p<0.001). Tumor size was not associated with likelihood of requiring gating. The median lesion excursion for gated lesions was 10mm vs 3mm for non-gated lesions p<0.001. The median maximum excursion in the treatment window was 4mm for gated lesions vs 3mm for non-gated lesions p=0.003. Two- and 3-year TPFS for the whole cohort were 89.1% and 86.2%, respectively. Target control was not statistically different at 2 and 3 years depending on gating use; non-gated 94.5% and 90.4% vs. 86.3% and 84.4%, p=0.136. Despite differential utilization of gating depending on lesion location, local control appeared to be similar, as can be seen in the table below. Middle lobe lesions were excluded from target control analysis because of small numbers. Maximum magnitude of lesion excursion in the treatment window did not impact TPFS (HR 1.393, 95%CI 0.153-12.681; p=0.769).Abstract TU_28_3598; Table 12/3-year TPFSUpper LobeLower LobeGated90.4%/86.1%86.7%/86.7%Non-gated95.6%/90.1%94.7%/94.7%p0.6020.439 Open table in a new tab The data suggest that the use of respiratory gating does not negatively impact local control and did not result in deterioration in expected outcomes. A gated approach may result in smaller amounts of normal tissue irradiated. Gating should be considered to reduce the potential toxicity of larger margins used in non-gated SBRT treatments verses the use of a maximum intensity projection.

A UNIQUE PRESENTATION OF EOSINOPHILIC GRANULOMA IN THE LUNG

SESSION TITLE: Diffuse Lung Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Langerhans Cell Histiocytosis is characterized by granuloma formation in various organs. Pulmonary Langerhans Cell Histiocytosis (PLCH) is a more localized, rare disease. We present a case of a rapidly progressive interstitial lung disease. CASE PRESENTATION: A 58-year-old female, active smoker, with a history of chronic obstructive pulmonary disease (COPD) was referred to the pulmonology clinic for an incidental finding of lung nodules on chest imaging. She presented with upper respiratory tract symptoms to an urgent care center where a chest X-ray was done and showed pulmonary nodules. A CT of the chest then revealed multiple bilateral pulmonary nodules in the upper and middle lung zones, with the largest nodule measuring 12 x 10 mm without associated lymphadenopathy. Of note, these nodules were absent on CT imaging three months prior. She denied dyspnea, cough, fever, night sweats, weight loss, recent travel, exposure to tuberculosis, birds or chemicals. Vital signs and physical exam were unremarkable. Antinuclear antibodies, Cryptococcal antigen and Fungitell assay were negative. Position Emission Tomography was done and showed mild tracer uptake in the largest nodule (left lower lobe). An Interventional Radiology guided biopsy was done and histopathology showed bronchoalveolar tissue infiltrated with Langerhans cells and eosinophils. These Langerhans cells were highlighted by immunohistochemical stains of CD1a and S100, consistent with histiocytosis. She was advised to stop smoking with close follow up. DISCUSSION: Pulmonary Langerhans Cell Histiocytosis (PLCH) is rare and at least 90% of PLCH patients are active smokers [1].PLCH may present with pulmonary symptoms such as dyspnea or non-productive cough; extra-pulmonary manifestations such as bone pain, rash, diabetes insipidus, lymphadenopathy, and weight loss; or patients can be asymptomatic as seen in this case [3]. Diagnosis is by findings on high-resolution CT imaging, and biopsy proven histology with positive immunohistochemical staining for CD1a and S100.PLCH typically affects upper and middle lung zones with sparing of the costophrenic angles and the progression is insidious. However, it was interesting that this patient’s nodules involved bilateral lower lobes and progressed rapidly in size and number over a short interval of three-months.Treatment is individualized as little is known about the pathophysiology of the disease. Data on other treatment modalities is controversial; however smoking cessation has been shown to improve outcomes [2]. CONCLUSIONS: PLCH in elderly smokers may be mistaken for metastatic lung disease. Definitive diagnosis is by histopathology. Therefore, it is important to keep PLCH in the differential diagnosis in patients with diffuse pulmonary nodules, especially because it can be reversed with smoking cessation. Also, missing the diagnosis and delays in treatment can lead to lung fibrosis. Reference #1: Elia D, Torre O, Cassandro R, Caminati A, Harari S. Pulmonary Langerhans Cell Histiocytosis: A comprehensive analysis of 40 patients and literature review. Eur J Intern Med. 2015;26(5):351-356. Reference #2: Wolters PJ, Elicker BM. Subacute onset of Pulmonary Langerhans Cell Histiocytosis with resolution after smoking cessation. Am J Respir Crit Care Med. 2014;190(11):e64. Reference #3: Juvet SC, Hwang D, Downey GP. Rare lung diseases III: Pulmonary Langerhans Cell Histiocytosis. Can Respir J. 2010;17(3):e55-62. DISCLOSURES: No relevant relationships by Gunjan Gupta, source=Web Response no disclosure on file for Lirim Krveshi; No relevant relationships by QUOC NGUYEN, source=Web Response No relevant relationships by Rahila Ogunnaike, source=Web Response No relevant relationships by Aashutosh Ramakar, source=Web Response no disclosure on file for Sakshi Sethi

Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population-based analysis.

PurposePrevious studies have reported that psychological and social distresses associated with a cancer diagnosis have led to an increase in suicides compared to the general population. We sought to explore lung cancer-associated suicide rates in a large national database compared to the general population, and to the three most prevalent non-skin cancers [breast, prostate and colorectal cancer (CRC)].MethodsThe Surveillance, Epidemiology and End Results (SEER) database (1973–2013) was retrospectively reviewed to identify cancer-associated suicide deaths in all cancers combined, as well as for each of lung, prostate, breast or CRCs. Suicide incidence and standardised mortality ratio (SMR) were estimated using SEER*Stat-8.3.2 program. Suicidal trends over time and timing from cancer diagnosis to suicide were estimated for each cancer type.ResultsAmong 3,640,229 cancer patients, 6,661 committed suicide. The cancer-associated suicide rate was 27.5/100,000 person years (SMR = 1.57). The highest suicide risk was observed in patients with lung cancer (SMR = 4.17) followed by CRC (SMR = 1.41), breast cancer (SMR = 1.40) and prostate cancer (SMR = 1.18).Median time to suicide was 7 months in lung cancer, 56 months in prostate cancer, 52 months in breast cancer and 37 months in CRC (p < 0.001).We noticed a decreasing trend in suicide SMR over time, which is most notable for lung cancer compared to the other three cancers. In lung cancer, suicide SMR was higher in elderly patients (70–75 years; SMR = 12), males (SMR = 8.8), Asians (SMR = 13.7), widowed patients (SMR = 11.6), undifferentiated tumours (SMR = 8.6), small-cell lung cancer (SMR = 11.2) or metastatic disease (SMR = 13.9) and in patients who refused surgery (SMR = 13).ConclusionThe cancer-associated suicide rate is nearly twice that of the general population of the United States of America. The suicide risk is highest among the patients with lung cancer, particularly elderly, widowed, male patients and patients with unfavourable tumour characteristics. The identification of high-risk patients is of extreme importance to provide proper psychological assessment, support and counselling to reduce these rates.

Wednesday, September 26, 2018 2:00 PM – 3:00 PM Improving Quality of Life for Patients with Tumors: 82. Implication of biomarker mutations for predicting survival in patients with metastatic lung disease to the spine

BACKGROUND CONTEXT Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication. PURPOSE The aim of this study was to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine. PATIENT SAMPLE We identified every consecutive patient at our institution with metastatic lung cancer who underwent surgery for spinal metastases from 2011 to 2017. Inclusion criteria were the availability of genetic mutational data through chart review, and the existence of any known metastatic lesion in the body and spine at the time of presentation. OUTCOME MEASURES Median overall survival (OS) was recorded following both diagnosis and surgical treatment. METHODS Genetic mutations in ALK, MET, ROS1, EGFR, and KRAS were chosen a priori for study based on availability by standard SNaPshot Lung Tumor Genotyping Analysis. Survival time was the duration between treatment for spinal metastases and death. Kaplan-Meier methods and the log-rank test were applied to characterize survival data. RESULTS Twenty-six patients met criteria for inclusion. Median survival following surgery was 0.67 years. Median overall survival (OS) following diagnosis was 2.7 years. The presence of molecular abnormalities in patients with spinal metastases was significantly associated with increased OS(HR 0.38, 95% CI 0.12-1.22, P=.03). CONCLUSIONS Molecular phenotyping may provide prognostic insight in patients undergoing surgery for spinal metastases. This is the first study to demonstrate an association between genetic mutational data and OS in this patient population. It also represents the largest published series of such patients (n=26) for which genetic mutational data are reported. Future models estimating survival for patients with spinal metastases may be enhanced by incorporation of molecular criteria. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Abstract 5545: Heterodimeric interleukin 15 (hetIL-15) treatment decreases primary breast cancer 4T1 tumors and alleviates the metastatic burden

Abstract Introduction: In this preclinical study, we tried to model the therapeutic strategies often used in the clinic to treat breast cancer patients. We analyzed the role of hetIL 15 immunotherapy alone and in combination with chemotherapy and surgery using the 4T1, a triple-negative breast cancer cell line, murine breast cancer model. Experimental Procedures: We evaluated the therapeutic potential of combining surgery, chemotherapy (doxorubicin) and immunotherapy (hetIL-15) in the murine 4T1 breast cancer model. Cancer cells were orthotopically implanted into the mammary fat pad of Balb/c mice, and the efficacy of hetIL-15 in combination with doxorubicin on the growth of primary tumors and metastatic disease was assessed. In addition, we monitored the impact of surgery alone in the development of metastatic disease, and, finally, we evaluated the effects on the metastatic burden of the three different approaches combined. Results: hetIL-15 monotherapy and combination of doxorubicin chemotherapy with hetIL-15 immunotherapy inhibited the growth of primary tumors. Interrogating the role of these treatments on lung metastatic disease, the results were unexpected. Doxorubicin alone did not affect the numbers of the metastatic lesions in the lungs. In contrast, hetIL-15 monotherapy reduced the metastatic burden. The combination strategy did not show advantage as compared to hetIL-15 monotherapy. Surgical removal of the growing tumor also decreased metastatic burden, especially when performed at an early point. Chemotherapy with doxorubicin prior to and post-surgery had no impact on the metastatic disease. In contrast, hetIL-15 treatment strongly diminished or eliminated the metastatic burden. Conclusion: Our data strongly suggest that treatment with hetIL-15 as an adjuvant therapy after surgery, or as a neoadjuvant agent before surgery, significantly impacts metastatic disease. Citation Format: Dimitris Stellas, Konstantinos Dimas, Bethany A. Nagy, Antonio Valentin, Barbara K. Felber, George N. Pavlakis. Heterodimeric interleukin 15 (hetIL-15) treatment decreases primary breast cancer 4T1 tumors and alleviates the metastatic burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5545.

SUBSTANTIATION OF THE MODEL FOR CALCULATING THE INDIVIDUAL DOSE OF CYTOSTATICS USING CT VOLUMETRY FOR ISOLATED LUNG CHEMIOPERFUSION WITH METASTASECTOMY

In order to create conditions for increasing the effectiveness of treatment of patients with metastatic lung disease a new method for calculating the dose of antitumor drug for performing isolated chemo-perfusion of the lung with metasta-sectomy taking into account the anatomical features of patients and previous operations on the lung was developed. The study consisted of three stages. As a result of the first stage of the study the effectiveness of the software package was measured in the volume of lung patients based on the presence of a strong positive correlation between the volumes of left lungs (Rs = 0.91, p

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

Quantitative Primary Tumor Indocyanine Green Measurements Predict Osteosarcoma Metastatic Lung Burden in a Mouse Model.

Current preclinical osteosarcoma (OS) models largely focus on quantifying primary tumor burden. However, most fatalities from OS are caused by metastatic disease. The quantification of metastatic OS currently relies on CT, which is limited by motion artifact, requires intravenous contrast, and can be technically demanding in the preclinical setting. We describe the ability for indocyanine green (ICG) fluorescence angiography to quantify primary and metastatic OS in a previously validated orthotopic, immunocompetent mouse model. (1) Can near-infrared ICG fluorescence be used to attach a comparable, quantitative value to the primary OS tumor in our experimental mouse model? (2) Will primary tumor fluorescence differ in mice that go on to develop metastatic lung disease? (3) Does primary tumor fluorescence correlate with tumor volume measured with CT? Six groups of 4- to 6-week-old immunocompetent Balb/c mice (n = 6 per group) received paraphyseal injections into their left hindlimb proximal tibia consisting of variable numbers of K7M2 mouse OS cells. A hindlimb transfemoral amputation was performed 4 weeks after injection with euthanasia and lung extraction performed 10 weeks after injection. Histologic examination of lung and primary tumor specimens confirmed ICG localization only within the tumor bed. Mice with visible or palpable tumor growth had greater hindlimb fluorescence (3.5 ± 2.3 arbitrary perfusion units [APU], defined as the fluorescence pixel return normalized by the detector) compared with those with a negative examination (0.71 ± 0.38 APU, -2.7 ± 0.5 mean difference, 95% confidence interval -3.7 to -1.8, p < 0.001). A strong linear trend (r = 0.81, p < 0.01) was observed between primary tumor and lung fluorescence, suggesting that quantitative ICG tumor fluorescence is directly related to eventual metastatic burden. We did not find a correlation (r = 0.04, p = 0.45) between normalized primary tumor fluorescence and CT volumetric measurements. We demonstrate a novel methodology for quantifying primary and metastatic OS in a previously validated, immunocompetent, orthotopic mouse model. Quantitative fluorescence of the primary tumor with ICG angiography is linearly related to metastatic burden, a relationship that does not exist with respect to clinical tumor size. This highlights the potential utility of ICG near-infrared fluorescence imaging as a valuable preclinical proof-of-concept modality. Future experimental work will use this model to evaluate the efficacy of novel OS small molecule inhibitors. Given the histologic localization of ICG to only the tumor bed, we envision the clinical use of ICG angiography as an intraoperative margin and tumor detector. Such a tool may be used as an alternative to intraoperative histology to confirm negative primary tumor margins or as a valuable tool for debulking surgeries in vulnerable anatomic locations. Because we have demonstrated the successful preservation of ICG in frozen tumor samples, future work will focus on blinded validation of this modality in observational human trials, comparing the ICG fluorescence of harvested tissue samples with fresh frozen pathology.

Characterization of Pulmonary Metastases in Children With Hepatoblastoma Treated on Children's Oncology Group Protocol AHEP0731 (The Treatment of Children With All Stages of Hepatoblastoma): A Report From the Children's Oncology Group.

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those < 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis.

Malignant central airway obstruction.

This review comprehensively describes recent advances in the management of malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and devastating manifestation of primary lung cancer or metastatic disease. A variety of diagnostic modalities are available to provide valuable information to plan a therapeutic intervention. Clinical heterogeneity in the presentation of malignant CAO provides opportunities to adapt and utilize endoscopic technology and tools in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents are methods and instruments used to rapidly restore airway patency. Delayed bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can also be utilized in specific non-emergent situations to establish airway patency. Although data regarding the success and complications of therapeutic interventions are retrospective and characterized by clinical and outcome measure variability, the symptoms of malignant CAO can often be successfully palliated. Assessment of risks and benefits of interventions in each individual patient during the decision-making process forms the critical foundation of the management of malignant CAO.

PPARGC1A is upregulated and facilitates lung cancer metastasis

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.

Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment.

Osteosarcoma (OS) is a rare primary malignant bone tumour arising from primitive bone-forming mesenchymal cells, with high incidence in children and young adults, accounting for approximately 60% of all malignant bone tumours. Currently, long-term disease-free survival can be achieved by surgical treatment plus chemotherapy in approximately 60% of patients with localized extremity disease, and in 20–30% of patients with metastatic lung or bone disease. Diagnosis of primary lesions and recurrences is achieved by using radiological investigations and standard tissue biopsy, the latter being costly, painful and hardly repeatable for patients. Therefore, despite some recent advances, novel biomarkers for OS diagnosis, prediction of response to therapy, disease progression and chemoresistance, are urgently needed. Biological fluids such as blood represent a rich source of non-invasive cancer biomarkers, which allow to understand what is really happening inside the tumour, either at diagnosis or during disease progression. In this regard, liquid biopsy potentially represents an alternative and non-invasive method to detect tumour onset, progression and response to therapy. In this review, we will summarize the state of the art in this novel area, illustrating recent studies on OS. Although the data reported in literature seem preliminary, liquid biopsy represents a promising tool with the potential to be rapidly translated in the clinical practice.

Survival of patients with lung cancer and diabetes mellitus.

Diabetes mellitus (DM) and lung cancer are two highly globally prevalent diseases. The current study aimed to determine the prognostic significance of DM comorbidity in patients with lung cancer. All patients diagnosed at Tsukuba Medical Center Hospital and Mito Medical Center, (University of Tsukuba, Ibaraki, Japan) between April 1999 and March 2012 were followed up to 2015 and were retrospectively analyzed. DM was defined as a fasting plasma glucose (FPG) level ≥126 mg/dl, a non-FPG level ≥200 mg/dl, or a hemoglobin (Hb) A1c level ≥6.5%. Additionally, patients taking medication for diabetes and those with a history of using such medications were also classified as having DM. During the study period, 1,798 patients with lung cancer were diagnosed. Within this cohort, 338 (18.8%) were classed as having lung cancer and DM. In univariate and multivariate analyses, smoking status, poorer performance status, small cell lung cancer pathology, metastatic disease and supportive care were the only unfavorable prognostic factors (all P=0.001). Additionally, multivariate analysis revealed that existing DM was an unfavorable disease-modifying factor (P=0.03612). Therefore, DM comorbidity adversely affects lung cancer outcomes. To provide prolonged quality of survival, appropriate pre-evaluation of lung cancer, as well as the patient's medical condition, including DM, is required.

Orbito-maxillofacial mesenchymal chondrosarcoma with intracranial invasion and lung metastasis

We report on a patient who presented with swelling to the left side of the face accompanied by exophthalmos. Imaging studies revealed a large expansive heterogeneous mass encroaching on the sinonasal region. Following intravenous contrast administration revealed a lesion with moderate enhancement and involvement of the ipsilateral orbital cavity with intracranial invasion. The patient underwent tumor resection and a biopsy confirmed the presence of a mesenchymal chondrosarcoma. Additional treatment included radiation therapy and the patient is currently receiving palliative and supportive care for advanced metastatic lung disease.

P2.04-027 Targeting Adenosine A2B Receptor for Modulation of Tumor Microenvironment, Primary Tumor Growth, and Lung Metastasis: Topic: Esophageal Cancer and Other Malignancies

Our work addresses two poorly understood areas of tumor metastases; the first is how tumor-conditioned immune cells initiate and drive premetastatic niche evolution and secondary tumor establishment and secondly, how the tumor microenvironment (TME) conditions shape the tumor immune response and function. We have developed a model that is fully capable of addressing these biological questions through in vivo EPR monitoring of the primary TME that allows simultaneous measurements of tumor pO2, pH, and inorganic phosphate (Pi) levels, which are parameters implicated in tumor metastasis and demonstrates how the TME contributes to metastasis. In combination, we employ an in vivo immune/tumor cell imaging platform in which mice are fitted with cutaneous window chambers containing syngeneic lung tissue transplant to create a lung metastatic site in which differentially-labeled tumor and immune subsets will be imaged via multiphoton microscopy. Our EPR methodology accurately monitors TME changes that occur with tumor growth as well as their modulation by pharmacological inhibition of the A2B adenosine receptor, giving reason to the use of specific A2B receptor inhibitors as anti-tumor and anti-metastatic therapeutics. A2B inhibition prevented the accumulation of Pi in the tumor interstitial space for every tumor model tested, which includes lung adenocarcinoma, breast adenocarcinoma, colon carcinoma, and melanoma. The exact role this plays in tumor initiation and progression is not completely elucidated but correlates with the reduction of tumor lung metastases and tumor growth. Secondly, our window chamber model enables spatiotemporal analysis of pre-metastatic niche enrichment, individual tumor cell recruitment, and subsequent secondary tumor growth with specific focus on metastatic lung disease. To our knowledge, no model exists capable of unifying these aspects of tumor biology and immunity. The project will lead to understanding a key process of metastasis and thus allow targeted immunotherapies to block metastasis and thus eliminate, or greatly reduce, the lethal aspect of cancer. Future work will also examine the potential anti-tumor therapeutic strategy of using specific A2B adenosine receptor antagonists for TME modulation. Of which, PBF-1129 is undergoing pre-clinical and IND-enabling studies and demonstrates high anti-tumor efficacy, suggesting the possibility for clinical trials with A2B antagonists for cancer therapy in the nearest future. Lastly, our methodology is targeting a glaring hole in the understanding of tumor metastasis, meaning the forthcoming information from our work holds great promise to identify novel therapeutic strategies aimed at greatly diminishing the chief cause of cancer morbidity.

488P - Survival after resection of colorectal cancer with synchronous metastases – a Danish population based historical cohort study

Conflicting data exist on the optimal treatment for resectable synchronous metastatic disease in liver and/or lungs in patients with colorectal cancer (CRC). We examined the long term survival of a large national cohort of patients resected for CRC and timing of treatment for synchronous metastasectomies. From 2000-2013 we included all patients from the Danish Cancer Registry and the Danish National Patient Registry recorded with CRC surgery for adenocarcinoma We also obtained data from the Danish National Patient Registry for patients operated for liver and/or lung metastases synchronously (<90days ) from the date of CRC surgery. A total of 35.993 patients had surgery for colon (n = 24.206) or rectal cancer (n = 11.787) (46,4% females (n = 16.711) and 53,6% males (n = 19.282)). 2.625 patients (7,3%) were surgically treated for metastatic disease with liver and/or lung surgery. 117 patients (0,3%) had liver surgery prior to CRC surgery while 1.458 patients (4,1%) underwent liver surgery following resection of the primary tumour. 106 patients (0,3%) were operated for lung metastases before and 944 patients (2,6%) after the CRC surgery. The 1 and 5 year overall survival for the entire cohort of patients were 84,1% (83,8%-84,5%) and 56,7% (56,1%-57,2%) respectively. For the subset of patients undergoing synchronous metastasectomy the 1 and 5 year survival were 88,0% (85,3%-90,2%) and 41,4% (36,9%-45,9%). We found a 5 year survival of 41,4 % in patients treated for synchronous metastatic disease with liver and/or lung surgery

Evaluation and management of aerodigestive conditions

More than 250,000 people in the United States are diagnosed with tumors involving the aerodigestive systems yearly. The majority of these malignancies arise from lung cancer, esophageal cancer, and metastatic disease. Unfortunately, these patients frequently present in later stages of their disease due to lack of symptoms in early stages. Consequently, the prognosis is often poor and treatment does not include surgical resection. These patients are often gravely ill and their tumors are life threatening conditions. In the case of esophageal cancer malnutrition and dehydration are common symptoms. In the case of lung cancer or metastatic disease to the airway severe symptoms including respiratory failure, hemoptysis, and obstructive pneumonia frequently occur. Management of these patients is frequently challenging but can be rewarding. Successful management allows for increased treatment options as well as prolonging and improving quality of life. In this manuscript the authors describe management options, various tools and outcomes associated with aerodigestive conditions.