Search

A 50-year-old woman was referred to rheumatology for new onset polyarthralgia and headache. She had a history of metastatic lung adenocarcinoma and was started on treatment with the programmed death 1 receptor (PD-1) antagonist pembrolizumab 2 months prior. Examination revealed left temporal artery tenderness and hand synovitis. Investigations revealed enlarged temporal artery on ultrasound imaging. On steroid treatment, she had resolution of symptoms, but due to significant steroid side effects required methotrexate and her PD-1 antagonist therapy was continued in consultation with her oncologist. Her malignant disease has remained stable, and she has improved functional status.

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient's preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission.

Objective: To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of KRASG12C, KRASother, and next-generation sequencing (NGS) panel negative patients. Methods: NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant KRAS followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, KRASG12C, and KRASother groups were compared. Results: In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) KRAS mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) KRASother, and 25 (16.7%) KRASG12C. Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group ( p = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival ( p = 0.56) or progression-free survival ( p = 0.71) among NGS panel negative, KRASother, and KRASG12C patients. Conclusion: There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, KRASG12C, or KRASother metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.

Uncommon mutations account for 10–15% of epidermal growth factor receptor (EGFR) mutations in patients with non-small-cell lung cancer (NSCLC). However, in spite of the wealth of knowledge of the clinical significance and tyrosine kinase inhibitor (TKI) sensitivity of these mutations, acquisition of deeper insights is limited by the paucity of case reports and cohort studies of the exceptionally rare mutations, including compound mutations. In the present case, we describe the clinical efficacy of icotinib and osimertinib in a metastatic lung adenocarcinoma patient carrying a highly uncommon EGFR L858R/D761Y compound mutation. The progression-free survival (PFS) with osimertinib treatment was much longer than that with icotinib (19 mo vs 8.2 mo), and the overall survival (OS) has currently exceeded three years. To the best of our knowledge, this is the first report of durable osimertinib response in an NSCLC patient with a rare EGFR L858R/D761Y mutation.

Lung adenocarcinoma (LUAD) is a highly malignant cancer. Although competing endogenous RNA (ceRNA)‐based profiling has been investigated in patients with LUAD, it has not been specifically used to study metastasis in LUAD. We found 130 differentially expressed (DE) lncRNAs, 32 DE miRNAs and 981 DE mRNAs from patients with LUAD in The Cancer Genome Atlas (TCGA) database. We analysed the functions and pathways of 981 DE mRNAs using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Based on the target DE mRNAs and DE lncRNAs of DE miRNAs, we established an lncRNA‐miRNA‐mRNA ceRNA network, comprising 37 DE lncRNAs, 22 DE miRNAs and 212 DE mRNAs. Subsequently, we constructed a protein‐protein interaction network of DE mRNAs in the ceRNA network. Among all, DE RNAs, 5 DE lncRNAs, 5 DE miRNAs and 45 DE mRNAs were confirmed found to be associated with clinical prognosis. Moreover, 3 DE lncRNAs, 4 DE miRNAs and 9 DE mRNAs in the ceRNA network were associated with clinical prognosis. We further screened 3 DE lncRNAs, 3 DE miRNAs and 3 DE mRNAs using clinical samples. These DE lncRNAs, DE miRNAs and DE mRNAs in ceRNA network may serve as independent biomarkers of LUAD metastasis.

The classically affected cranial nerve from intracranial hypertension is the sixth nerve. Carcinomatous meningitis can cause persistent or progressive cranial nerve palsies by infiltrating them in the subarachnoid space. Here we present a rare case of episodic, short-lasting, and unilateral oculomotor nerve palsy associated with carcinomatous meningitis and intracranial hypertension in a 44-year-old woman diagnosed with metastatic lung adenocarcinoma. As the survival rates enhance for metastatic cancers, neurologists should expect more perplexing neurologic presentations and consider leptomeningeal metastasis and intracranial hypertension in patients who have cancer and present with short episodes of diplopia and unilateral third nerve palsy.

PURPOSE Broad-panel sequencing of tumors facilitates routine care of people with cancer as well as clinical trial matching for novel genome-directed therapies. We sought to extend the use of broad-panel sequencing results to survival stratification and clinical outcome prediction. METHODS By using sequencing results from a cohort of 1,054 patients with advanced lung adenocarcinomas, we developed OncoCast, a machine learning tool for survival risk stratification and biomarker identification. RESULTS With OncoCast, we stratified this patient cohort into four risk groups on the basis of tumor genomic profile. Patients whose tumors harbored a high-risk profile had a median survival of 7.3 months (95% CI, 5.5 to 10.9 months) compared with a low-risk group with a median survival of 32.8 months (95% CI, 26.3 to 38.5 months) with a hazard ratio of 4.6 ( P < .001), far superior to any individual gene predictor or standard clinical characteristics. We found that comutations of both STK11 and KEAP1 are strong determinants of unfavorable prognosis with currently available therapies. In patients with targetable oncogenes (eg, EGFR, ALK, ROS1) who received targeted therapies, the tumor genetic background additionally differentiated survival with mutations in TP53 and ARID1A, which contributed to a higher risk score for shorter survival. CONCLUSION A mutational profile derived from broad-panel sequencing presents an effective genomic stratification for patient survival in advanced lung adenocarcinoma. OncoCast is available as a public resource that facilitates the incorporation of mutational data to predict individual patient prognosis and compare risk characteristics of patient populations.

Brain metastasis (BM) is common in patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. However, the brain surveillance strategy during treatment in advanced lung cancer patients varies, and the impact on clinical outcome is unclear. Here we aimed to evaluate the effect of different brain surveillance strategies on the clinical characteristics and treatment outcome in patients with EGFR-mutant lung adenocarcinoma treated with first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs).This is a retrospective observational study conducted in a medical center in an area with high prevalence of EGFR mutation. Patients with initially diagnosed stage IV EGFR-mutant lung adenocarcinoma were included. Patients undergoing regular brain magnetic resonance imaging (MRI) every 3-6 months were categorized in the regular follow-up (RFU) group, and the rest were categorized in the liberal follow-up (LFU) group. Clinical outcomes were collected and analyzed.A total of 310 patients were included, and 43.5% initially had brain metastases. Patients in the LFU group were significantly older than those in the RFU group (median age: 67 vs 62, p 0.001). The overall survival and time-to-treatment failure of patients with initial EGFR-TKIs treatment showed no statistical difference between the two groups. However, the intracranial progression free survival was significantly shorter in the RFU group than in the LFU group (p = 0.009). The risk of mortality was similar in the LFU and RFU groups. There was no difference in the intracranial progression patterns and cause of death between the two groups.For EGFR-mutant lung adenocarcinoma patients who used EGFR-TKIs as the frontline therapy, regular or liberal brain MRI follow-up showed no significant impact on the outcome, irrespective of initial brain metastasis.

Intratumoral metastasis is rare, and in the brain, meningiomas are the most common type of primary brain tumors to harbor metastases. We report a case of angiomatous microcystic meningioma associated with intratumoral metastatic lung adenocarcinoma in a patient with no prior history of malignancy, in which the pronounced atypia of the meningioma potentially mimics or masks the minute focus of metastatic cancer. A meticulous search for intratumoral metastasis within the meningioma is recommended if metastasis is clinically suspected. A formal ethical approval for the single case report is waived by the Institutional Review Board of National University Health System, Singapore.

Several double ALK fusions coexisting in one patient have been reported. However, few studies have reported the clinical efficacy of ALK inhibitors in rare double ALK fusions. Here, we described a rare PDK1-ALK, STRN-ALK double-fusion variant in a patient with metastatic lung adenocarcinoma. The patient responded well to alectinib (600 mg) twice daily. This case shows a promising treatment option for patients with rare ALK double-fusion variants.

Background: Paraneoplastic hyper-eosinophilia associated with metastatic lung adenocarcinoma is a rare finding and has been associated with a poor prognosis when present. Early hyper-eosinophilia appearing following non-small cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICI) has been previously reported with contradictory outcomes. Case summary: We present the case of an elderly man with newly diagnosed metastatic lung adenocarcinoma and baseline hyper-eosinophilia, treated with pembrolizumab, and showing evidence of significant and rapid disease progression suggestive of hyper-progressive disease, worsening baseline hyper-eosinophilia, and a fatal outcome within 1 month of therapy initiation. Conclusion: Pre-treatment hyper-eosinophilia could represent a predictive factor of an unfavorable response to ICI treatment in cases of NSCLC. Additional similar cases are needed to draw a more conclusive relationship.

Increased cancer risk in patients with inflammatory and infectious diseases has been reported in many studies and lung cancer‐associated empyema in

Upper gastrointestinal bleeding as a result of gastrointestinal metastases from lung cancer is extremely rare. We report two cases of patients with duodenal metastases from lung adenocarcinoma presented with recurrent melena. Histopathological examination and immunohistochemical staining of the duodenal biopsies supported the diagnosis of metastatic lung adenocarcinoma.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the preferred frontline therapy for EGFR-mutant advanced NSCLC. However, despite its high initial response rates, multiple EGFR-independent mechanisms of resistance have been reported in patients receiving osimertinib. One such mechanism is the emergence of acquired, targetable oncogenic fusion events. It has been documented in other case reports that combination therapies can be efficacious in these scenarios. In our case report, we present a patient with EGFR-mutant advanced NSCLC who developed an acquired EML4-ALK rearrangement mediating resistance to osimertinib, which was overcome by using a combination of osimertinib with the ALK tyrosine kinase inhibitor alectinib.

Cutaneous metastases are unusual presenting symptoms of lung cancer. Therefore, they are prone to be misdiagnosed and missed. The report describes a case of a forty-nine-year-old female with painful zosteriform rashes showing multiple vesicle-like papules localized on the left breast for 10 days. The patient had been diagnosed as lung adenocarcinoma at the department of oncology one year ago. Skin biopsy revealed blue nodular lesions in the dermis, composed of clustered heterogeneous tumor cells with glandular formation. Immunohistochemical stains confirmed the diagnosis of metastatic lung adenocarcinoma.

Lung cancer metastases to soft tissues are rarely reported in the literature. In this report, we discuss a case of a 59-year-old female who presented with worsening shortness of breath for over five months. A CT scan of the chest revealed right upper lobe mass and ipsilateral mediastinal adenopathy. An endo-bronchial ultrasound (EBUS)-guided biopsy of the involved lymph nodes revealed cellular features consistent with lung adenocarcinoma. MRI of the brain was negative for metastases; however, a positron emission testing (PET) scan showed fluorodeoxyglucose (FDG)-avid nodules in the soft tissues of the bilateral buttocks. Tissue biopsy of the buttock lesions confirmed metastases of lung origin. To the best of our knowledge, this is the first case report of metastatic lung adenocarcinoma with occult involvement of the gluteal muscles as the sole site of distant metastasis.

In recent years, serious changes have been observed in the treatment algorithms of especially lung cancer patients. The start-up phase of treatment planning of metastatic lung adenocarcinoma patients is comprised of driver mutation research. Among the pretreatment options of patients diagnosed with EML4-ALK rearrangement, is crizotinib. The group disgnosed with EML4-ALK rearrangement, composes a little part of metastatic non-small cell lung cancer. In this case presented, I will focus on the start of crizotinib treatment and 53-month follow-up in remission in a patient, who has been operated twice and received cisplatin-based adjuvant chemotherapy twice, and relapsed for the second time as Stage-4.

The geriatric nutritional risk index (GNRI) is a simplified nutritional assessment. This study aimed to evaluate the prognostic value of the pretreatment GNRI in geriatric patients with metastatic lung adenocarcinoma (MLA). The clinicopathological characteristics of 144 geriatric patients with MLA were analyzed. The receiver operating characteristic curve was used to determine the best cutoff value of GNRI for predicting overall survival (OS). The Cox regression was used to identify variables associated with OS in the whole group, the non-sensitizing

We present a patient with erythrodermic Darier disease occurring in temporal association with diagnosis of metastatic lung adenocarcinoma. The patient presented with eroded and crusted keratotic papules and plaques over greater than 90% body surface area with extensive secondary impetiginization. Given a longstanding history of pruritic eruption, this presentation represents a paraneoplastic flare of an underlying genodermatosis. Near total resolution was achieved with chemotherapy and topical corticosteroids.

Lung cancer is the leading cause of cancer-related death worldwide. The majority of these cancers are non–small-cell lung cancer, of which adenocarcinoma is the most common histologic subtype. Most patients are diagnosed at advanced stages when systemic treatment is needed. Whereas prognosis has improved for patients with targetable driver mutations, the majority of patients do not possess tumors with such molecular mutations. Platinum-based chemotherapy has traditionally been the mainstay of treatment, although in recent years immunotherapy has emerged as a treatment option and can result in robust and durable treatment responses in a subset of patients. Recent clinical trials on novel immunotherapy combinations and immunochemotherapy combinations may broaden the number of patients that may benefit from checkpoint inhibitors and elicit responses in those who otherwise may not have experienced a response to monotherapy with an immunotherapy drug. This review will outline the currently available therapies for the first-line treatment of metastatic adenocarcinoma that do not possess a driver mutation and provide a recommended approach and algorithm by which to select the best first-line therapy.

Following diagnosis of primary malignancies, subsequent workup includes evaluation for metastasis. Each malignancy, both location and histologic features, have statistically common and less common metastatic patterns. Metastatic lung adenocarcinoma typically involves lymph nodes, liver, brain, and bone. Very rarely can it involve the reproductive tract. Specifically, in females, multiple reported cases include ovarian metastasis. Even rarer, endometrial metastasis, such as this case report, has been reported. Even with usual staging utility of PET/CT, common things remain common; knowledge of common metastatic patterns can bias overall interpretation. This case is a reminder that despite our tendencies to focus on frequent patterns, even the rarest of metastatic patterns are still possible. Keywords: Endometrial metastasis, Lung adenocarcinoma

Lung cancer is number one cause of cancer mortality in United States both in men and women. Lung cancer is uncommon in patients younger than 35 years with no smoking and family history. Malignancy from lung nodule depends on size, growth rate, borders, calcification and location. Appropriate follow up for lung nodules in older patient with risk factors has been well described in literature based on various researches. However there is very limited data regarding follow up and management of lung nodule in younger patient with risk factors. We describe a patient who was 30 year old when he presented with acute appendicitis and incidentally found to have lung nodule of 1.2 cm. It was decided that patient should follow up as an outpatient for lung nodule. As patient was uninsured with poor socioeconomic he never followed up as outpatient. After 2 years patient was diagnosed with stage IV lung adenocarcinoma and died shortly after. Guidelines should be used in the proper clinical context as a tool to help with patient management, though exceptions always exist. Some expert believe lung nodule between 8-30 mm in patient with poor follow-up due to socioeconomic status, psychological issues, or young age should get complete resection of nodule.

Background Ovarian metastatic tumors from lung adenocarcinoma are rare, and a serial study of these tumors is lacking to date. Additionally, a better understanding of the clinicopathological and molecular characteristics of metastatic tumors is needed. Methods Seven cases of ovarian metastasis from lung adenocarcinoma from 2013 to 2017 at our institute were investigated. The results were combined with those found in literature review. A total of 16 cases were analyzed in the present study. We examined clinicopathological and immunohistochemical characteristics, further detected ALK rearrangement by FISH (fluorescence in situ hybridization), and assessed EGFR and KRAS mutations using Sanger sequencing or the amplification refractory mutation system (ARMS). Results The mean age of the patients was 44.6 years (range, 33–56 years). Eleven of sixteen patients developed ovarian tumors within a mean time of 18.5 months (range, 5–48 months) from the initial diagnosis of lung adenocarcinoma; 5 patients had lung tumors and ovarian masses simultaneously. Five tumors (5/16, 31%) occurred in the bilateral ovaries, and the others were unilateral ovarian tumors (11/16, 69%). All seven cases from our institute were positive for TTF-1 and Napsin A but negative for PAX8. In four cases, ALK (D5F3) was diffusely and strongly expressed, with ALK rearrangements (4/7, 57%). Overall, ALK rearrangement was found by FISH or immunohistochemistry in 11/16 (69%) cases. In two cases, EGFR mutations in exons 19 and 21, respectively, were found. One patient did not detected EGFR or ALK mutation in the metastatic tumor, but the primary lung adenocarcinoma did harbor an EGFR mutation. Two cases had no alterations in three genes above. Although the mean survival time of the patients with ALK rearrangement was longer than those without (mean survival time 25 m vs. 20 m), no statistical significance of the difference was found. Conclusions As the largest case series of ovarian metastasis from lung adenocarcinoma, our findings indicate that ALK rearrangement is the most common molecular alteration. Although patients with ALK rearrangement appear to have a better prognosis than do those without ALK rearrangement, more cases with longer follow-up and multivariant analysis are needed to clarify this point.

Miliary mottling on imaging is usually infectious in etiology and is less commonly seen with metastatic cancers. The cancers that are reported to cause miliary metastases include secondaries from cancers of the thyroid, kidney, trophoblasts, etc. Here, we report a case of a 63-year-old female who presented with prolonged cough and shortness of breath and whose imaging showed diffuse bilateral miliary nodules. Bronchoscopy with a transbronchial biopsy confirmed the diagnosis as adenocarcinoma of the lung with intrapulmonary miliary metastasis. Treatment with a combination of pemetrexed and carboplatin was not helpful and cancer had spread diffusely across the lung on repeat imaging after three months. It is essential to consider this clinical presentation as a separate subtype, with specific treatment protocols as compared to primary adenocarcinoma of the lung.

Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist’s differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist’s differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.