- Brain metastases from adenocarcinoma of the lung with truly cystic magnetic resonance imaging appearance. [Journal Article]
- CIClin Imaging 2018 Aug 08; 52:203-207
- Metastatic disease represents over half of all malignancies in brain parenchyma, and carcinoma when metastatic will often spread to the brain, with lung and breast tumors being the most common culpri...
Metastatic disease represents over half of all malignancies in brain parenchyma, and carcinoma when metastatic will often spread to the brain, with lung and breast tumors being the most common culprits. The suggestive features of metastatic disease on magnetic resonance imaging include peritumoral, vasogenic edema and avid postcontrast enhancement. We present the case of a 50-year-old male with an established diagnosis of metastatic adenocarcinoma of the lung treated with erlotinib who developed multiple cystic brain lesions on surveillance MRI. These cysts demonstrated T2 prolongation, suppressed completely on FLAIR, lacked surrounding edema, and featured a complete lack of enhancement. Due to the ambiguous imaging findings, brain biopsy was performed to establish the diagnosis. The pathology revealed a single layer of malignant cells lining brain parenchyma and focal areas of glandular growth. The intracranial lesions responded well to total brain radiation. This case is unique for the imaging findings most characteristic of simple cysts in biopsy-proven metastatic disease and may relate to the effects of erlotinib on metastatic brain tumors.
- Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. [Journal Article]
- JCJ Clin Oncol 2018 Aug 20; :JCO2018790006
- Purpose Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids...
Purpose Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation. Methods We identified patients who were PD-(L)1-naïve with advanced non-small-cell lung cancer from two institutions-Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center-who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression. Results Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P < .001). Conclusion Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non-small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended.
- Isolation of circulating tumor cells in a preclinical model of osteosarcoma: Effect of chemotherapy. [Journal Article]
- JBJ Bone Oncol 2018; 12:83-90
- Osteosarcoma is a rare primary bone tumor, which mainly affects children and adolescents and has a poor prognosis, especially for patients with metastatic disease. A poor therapeutic response to the ...
Osteosarcoma is a rare primary bone tumor, which mainly affects children and adolescents and has a poor prognosis, especially for patients with metastatic disease. A poor therapeutic response to the conventional chemotherapy is observed with the development of lung metastases, highlighting the need for improving the current regimens and the identification of early markers of the recurrent and metastatic disease. Circulating Tumour Cells (CTCs) play a key role in the metastatic process and could be powerful biomarkers of the progressive disease. The present study aimed to isolate CTCs by using a pre-clinical model of human osteosarcoma and to monitor their kinetic of release and their modulation by ifosfamide. CTCs were detectable into the bloodstream before any palpable primary tumors. Ifosfamide increased CTCs count and in contrast decreased the number of lung tumor nodules. On established tumors, ifosfamide slowed down the tumour growth and did not modulate CTC count that could be explained by a release of cancer cells from the primary tumour with reduced properties for inducing lung metastases. This report highlights the biological interest of CTCs in osteosarcoma.
- C-X-C Motif Ligand 1 (CXCL1) from melanoma cells down-regulates the invasion of their metastatic melanoma cells. [Journal Article]
- OOncotarget 2018 Jul 24; 9(57):31090-31097
- The surgical resection of a primary melanoma is sometimes followed by the immediate development of distant metastases, suggesting that the primary melanoma might control the metastatic process. We hy...
The surgical resection of a primary melanoma is sometimes followed by the immediate development of distant metastases, suggesting that the primary melanoma might control the metastatic process. We hypothesized that a paracrine factor(s) from primary melanoma cells might regulate the progression of metastasizing melanoma cells. Here we attempted to identify the factor(s) from primary melanoma cells that regulate the invasion ability of metastatic melanoma cells. We used two mouse melanoma cell lines, B16 and B16/BL6, that latter of which is a subline of B16 melanoma and shows high metastatic potential to lung. We investigated the interaction between the parent B16 cells and daughter B16/BL6 cells by invasion assay, cell morphology, cytokine array, RT-PCR, and gelatin-zymography. The conditioned medium (CM) from B16 significantly (p=0.02) inhibited the invasion ability of B16/BL6 cells. The morphology of the B16/BL6 cells was changed from bipolar shape to a multipolar shape following the addition of the CM from B16. The B16 cells produced high levels of C-X-C motif ligand 1 (CXCL1), CXCL10, and M-CSF compared to the B16/BL6 cells. CXCL1 significantly (p=0.01) decreased the invasion ability of B16/BL6 cells, but CXCL10 and M-CSF did not. The invasion-inhibitory activity of the CM from B16 was significantly (p=0.046) suppressed following the addition of a neutralizing anti-CXCL1 antibody. The CM of B16 and CXCL1 increased the E-cadherin mRNA level and decreased MMP2 activity of B16/BL6 cells. These findings suggested that primary melanoma cells might down-regulate the invasion activity of metastatic melanoma cells through CXCL1 signaling.
- 'Malignant' hypertension from hyperaldosteronism: a case report. [Journal Article]
- PAPan Afr Med J 2018; 30:10
- Adrenocortical carcinomas (ACC) are rare with an incidence of 0.7-2 per million population per year and account for only 0.05%-2% of all malignant tumors. While majority of the functional ACC present...
Adrenocortical carcinomas (ACC) are rare with an incidence of 0.7-2 per million population per year and account for only 0.05%-2% of all malignant tumors. While majority of the functional ACC present as Cushing syndrome, recurrent hyperaldosteronism from metastatic ACC is exceedingly rare. We describe a 67-year old female presented with hypertensive urgency & hypokalemia as a result of hyperaldosteronism from an 8-cm right ACC. She underwent a radical right nephrectomy with adrenalectomy that normalized her blood pressure. However, a few years later she presented again with resistant hypertension from hyperaldosteronism, raising the suspicion of recurrence of ACC. A contrast-enhanced CT scan showed a normal left adrenal gland but revealed pulmonary metastases of ACC based on a lung biopsy. Chemotherapy was complicated with side effects leading to refusal of further chemotherapy, henceforth requiring high dose of spironolactone for blood pressure control. Despite curative surgery, metastatic functional ACC should be considered in patients presenting with secondary hypertension from recurrent hyperaldosteronism, due to its high recurrence rate. Besides standard cancer surveillance after a curative surgery, meticulous monitoring of blood pressure is a simple yet crucial way to detect cancer recurrence early.
- The pattern of bone involvement, management, and outcomes in patients with nonsmall cell lung cancer: A retrospective study. [Journal Article]
- ATAnn Thorac Med 2018 Jul-Sep; 13(3):150-155
- CONCLUSIONS: Metastatic bone disease is considered a huge burden on patients, clinicians, and the society. The majority of bone metastasis patients will experience SREs. Most SREs predict poor prognosis. Supportive therapy to overcome the reasons for poor prognosis may improve patients' survival and quality of life.
- Bone metastasis predicts poor prognosis of patients with brain metastases from colorectal carcinoma post aggressive treatment. [Journal Article]
- CMCancer Manag Res 2018; 10:2467-2474
- CONCLUSIONS: Although the prognosis of CRC patients having BM is frequently very poor, those with good performance status and few brain lesions responded to aggressive treatment, while those with bone metastasis at the time of diagnosis of BM had relatively dismal survival rates, even when treated aggressively.
- Staging Uveal Melanoma with Whole-Body Positron-Emission Tomography/Computed Tomography and Abdominal Ultrasound: Low Incidence of Metastatic Disease, High Incidence of Second Primary Cancers. [Journal Article]
- MEMiddle East Afr J Ophthalmol 2018 Apr-Jun; 25(2):91-95
- CONCLUSIONS: Whole-body PET/CT and abdominal ultrasound complement each other in the staging of uveal melanoma. Benign hepatic abnormalities found using ultrasound is common. Of importance, a second asymptomatic primary malignancy associated with uveal melanoma was detected almost one in 10 patients.
- Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin. [Journal Article]
- MEMiddle East Afr J Ophthalmol 2018 Apr-Jun; 25(2):81-90
- CONCLUSIONS: In a tertiary referral service, uveal metastasis originates from cancer in the breast, lung, kidney, GI tract, cutaneous melanoma, or others. Overall prognosis is poor with 5-year survival at 23% and worst survival with pancreatic metastasis whereas best survival with lung carcinoid metastasis.
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- Functioning of Proteasomes in Lymphogenic Metastasizing of Non-Small-Cell Lung Cancer. [Journal Article]
- BEBull Exp Biol Med 2018 Aug 18
- Chymotrypsin- and caspase-like activities and expression of the total proteasome pool subunits (α1α2α3α5α6α7) were studied in patients with non-small-cell lung cancer. Proteasome activities were high...
Chymotrypsin- and caspase-like activities and expression of the total proteasome pool subunits (α1α2α3α5α6α7) were studied in patients with non-small-cell lung cancer. Proteasome activities were higher in the primary tumors and lymphogenic metastases than in corresponding adjacent lung tissue. The content of α1α2α3α5α6α7 subunits decreased in metastases and remained unchanged in primary tumor tissue. The development of metastatic process in non-small-cell lung cancer was associated with nonlinear changes in proteasome activities and content in primary tumor tissue and lymphogenic metastases.