SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Disseminated disease

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Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumor. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multi-region sequencing showed significant discrepancy within the primary tumor and between the primary tumor and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, pilot analysis of cfDNA sequencing demonstrated the feasibility of detecting genomic amplifications not detected in primary tumor sampling. Lastly, we profiled paired primary, metastatic tumors and cfDNA from patients enrolled in the PANGEA trial of targeted therapies in GEA, and found that genomic biomarkers were recurrently discrepant between the primary tumor and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.

Concepts: Cancer, Metastasis, Oncology, Lung cancer, Extracellular matrix, Ovarian cancer, Disseminated disease

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Pneumothorax is a well-described complication of osteosarcoma. Conversely, the presence of a pneumomediastinum to our knowledge has been reported just once in a patient with osteosarcoma, and never without detectable lung metastasis. We report the case of an 18-year-old male with a localized, distal femur osteosarcoma who was found to have an asymptomatic pneumomediastinum and pneumatocele at diagnosis, and then 16 months later experienced a pulmonary relapse. Our case suggests that these findings may represent the presence of occult metastatic disease and cautions providers to treat appropriately and provide surveillance with a high index of suspicion for pulmonary recurrence.

Concepts: Cancer, Metastasis, Pulmonology, Lung cancer, Medical terms, Pulmonary contusion, Disseminated disease

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Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal neoplastic process, largely due to the presence of disseminated disease at presentation. As such, evidence-based management of metastatic disease is integral to patient care in such circumstances. This review aimed to summarize the current state of knowledge regarding the potential effectiveness of liver metastasectomy in the setting of PDAC.

Concepts: Cancer, Metastasis, Oncology, Lung cancer, Ovarian cancer, Jaundice, Disseminated disease

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Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of patients who present with localized disease and up to 90% of those who present with metastases experience a metastatic disease recurrence, highlighting the inability to identify patients with residual disease at the end of therapy. Up to 95% of Ewing sarcomas carry a driving EWS-ETS translocation that has an intronic breakpoint that is specific to each tumor, and the authors developed a system to quantitatively detect the specific breakpoint DNA fragment in patient plasma.

Concepts: Cancer, Metastasis, Oncology, Patient, Disseminated disease

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Abdominal leiomyosarcoma arising from the mesentery is a rare malignancy. It is an aggressive entity with an overall 5 year survival rate between 20 and 30 %. Surgical resection is the cornerstone of primary treatment and may be curative for localized disease. However, patients often develop intra-abdominal relapse and/or metastatic disease. If surgical resection is not feasible, palliative chemotherapy is the treatment of choice. However, there are no clear guidelines regarding chemotherapy; neither in the adjuvant nor advanced setting.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Medical terms, Chemotherapy, Melanoma, Disseminated disease

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Ewing sarcoma (EWS) is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. Our goal was to identify novel predictive biomarkers for these patients, focusing on chemokines, specifically genes involved in the CXCR4-pathway because of their established role in metastasis and tumour growth.

Concepts: Gene expression, Cancer, Metastasis, Oncology, Lung cancer, Medical terms, Chemokine, Disseminated disease

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Pancreatic neuroendocrine tumors (pNETs) are a rare and heterogeneous group of neoplasia. Presentation of these tumors can vary widely. Current treatment modalities range from potentially curative surgical interventions in localized disease to the use of varied hormonal analogues, cytotoxic agents and targeted therapy for the management of locally advanced and metastatic disease. With such a wide variety of therapeutic modalities, clinicians are faced with the task of building an effective and comprehensive treatment strategy for their patients.

Concepts: Medicine, Cancer, Oncology, Hospital, Chemotherapy, Therapy, Neuroendocrine tumor, Disseminated disease

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Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS) for pediatric patients with metastatic disease over the last 40 years.

Concepts: Cancer, Oncology, Disseminated disease

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Neuroendocrine neoplasms (NEN) in children are rare. In Germany, children with NEN of the gastroenteropancreatic system are prospectively registered since 1997. The objective of this study was to evaluate diagnostics, treatment and outcome in children with extra-appendiceal NEN.Clinical data of 39 patients with NEN registered in the GPOH-MET 97 trial from 1997 to 2012 were analyzed. Children with NEN of the appendix were excluded.14 patients with pancreatic, 12 patients with bronchial, 6 patients with gastrointestinal, 2 patients with nasopharyngeal and 5 patients with NEN of unknown primary were registered. About half of the patients had localized disease and rather low grade tumors, including all bronchial NEN, 5 of 14 pancreatic and 2 of 6 gastrointestinal tumors. Metastatic disease and high grade tumors were stated in cases with nasopharyngeal tumors, NEN of unknown -primary and in part of pancreatic and gastrointestinal NEN. Complete surgical resection was performed in patients with localized NEN with an overall survival of 100%. In contrast, overall survival in metastatic disease was 26%.Outcome in children with low grade NEN and localized disease is excellent. Management of high grade tumors and metastatic disease remains challenging. Establishing international registries is inevitable for further improvements.

Concepts: Cancer, Metastasis, Oncology, Lung cancer, Disseminated disease

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Objective: A systematic review of the literature was performed to clarify the natural history and treatment expected outcomes of upper aerodigestive tract metastases from cutaneous melanoma. Data Sources: Included data obtained from review of MEDLINE database Review Methods: A search of the MEDLINE database was undertaken from 1950 to 2013. Article inclusion required cases with documentation of previous cutaneous melanoma primary lesions, adequate survival data, and description of metastatic treatment. Individual patient data was extracted from source articles for analysis of survival outcomes. Results: Systematic search revealed 34 relevant articles with 37 cases for inclusion. Metastases were identified throughout the upper aerodigestive tract with a predilection for the oropharynx, larynx, and oral cavity. Treatment outcomes were estimated with the Kaplan-Maier method with survival of 37% and 16% at one and five years. As expected from previous reports, 73% presented with disseminated disease burden with almost universal poor prognosis despite locoregional or systemic therapy. Conversely, a group of patients with limited metastatic burden had improved treatment response with a one year survival of 90%, denoting a hazard ratio of 9.7332 (95% CI 4.5-21.1) for disseminated disease in comparison. Conclusion: Upper aerodigestive tract metastases of melanoma are rare clinical entities which in general present in the setting of disseminated disease and evidently necessitate a focus on palliation. In contrast, for those with a limited metastatic burden, aggressive multimodality therapy including complete metastatectomy can produce a significant survival advantage.

Concepts: Medicine, Cancer, Metastasis, Oncology, Lung cancer, Chemotherapy, Melanoma, Disseminated disease