European Organization for Research and Treatment of Cancer

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM 84% of cases were men with an average age of 607 years EC was located in the lower third in 65% Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60% Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%) The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 535% and multiple in 465% The overall survival rate was 102 months Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies These critical data are the cornerstone of optimal cancer approach and treatment

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Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review.

Background Dermatofibrosarcoma protuberans (DFSP) is rare, infiltrating dermal neoplasm, characterized by indolent growth and low probability of metastases. The first effective systemic therapy in DFSP introduced into clinical practice was imatinib, demonstrating high activity in advanced cases. The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in routine clinical practice with long-term follow-up. Patients and methods We analyzed the data of 31 Caucasian patients (14 male, 17 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP who started therapy with imatinib at initial dose 800 mg daily between 12/2004 and 07/2014. All diagnoses were confirmed cytogenetically for the presence of specific COL1A1-PDGFB fusion. Median follow-up time was 5.3 years. Results Metastases were present in 15 cases (8 – lungs, 5 – soft tissue, 2 – lymph nodes). Fibrosarcomatous transformation (FS-DFSP) was confirmed in 16 patients (52%). 5-year progression-free survival (PFS) rate was 58% (median 6.8 years), 5-year overall survival (OS) rate was 64% (median time for OS was not reached). The shorter PFS and OS correlated with FS-DFSP and presence of metastatic disease. 5-year PFS rate was 93% for classic DFSP and 33% for FS-DFSP. The best overall responses were: 21 partial responses (68%, including 8 FS-DFSP, but the responses were shorter than for classic DFSP), 6 stable disease (19%) and 4 progressive diseases (13%). Thirteen patients (47%) underwent resection of residual disease and nine of them remained free of disease, although imatinib was discontinued. Median survival after progression on imatinib was 19 months, and longer survival were observed only in cases were rescue surgery/radiotherapy was possible. Conclusions Our results indicate the long-term activity of imatinib in therapy of inoperable and/or metastatic cases of DFSP, including FS-DFSP. Some DFSP patients initially evaluated as unresectable/metastatic or necessitating mutilating surgery turned resectable after imatinib therapy and this rational approach leading to complete remission maybe potentially curative.

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Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate - The impact of fibrosarcomatous transformation.

https://pureadmin.qub.ac.uk/ws/files/200618291/NovelApproach.pdf

A novel next generation sequencing approach to improve sarcoma diagnosis.

Introduction Oral tyrosine kinase inhibitors targeting the chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) in non-small cell lung cancer (NSCLC) were associated with superior clinical outcome. Tyrosine Kinase inhibitors (TKIs) are known to have peculiar toxicity profile, hence, increasing awareness to the safety profile of ALK inhibitors is essential. Methods A comprehensive systematic review of literature has been conducted to include prospective trials that used the ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib and Lorlatinib in patients with advanced NSCLC and have available efficacy and toxicity results. Results A total of 14 studies including 2793 patients were considered eligible for our review and included two phase IB, seven phase II and five phase III studies. The most common adverse events (AEs) observed with ALK inhibitors were gastrointestinal (GI) toxicities as nausea (up to 83%), vomiting (up to 67%) and diarrhea (up to 86%), elevation of liver enzymes occurred in up to 60% and fatigue (up to 43%). There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib. Most of the AEs were low grade and treatment-related deaths were associated with ALK inhibitors in 0–1% of patients. Conclusion Most of adverse effects of ALKi can be managed efficiently via dose modifications or interruptions. Timely identification of each ALKi pattern of toxicity can prevent treatment-related morbidity and mortality in this palliative setting.

Safety issues with the ALK inhibitors in the treatment of NSCLC: A systematic review.

Successful treatment of crizotinib-induced dysgeusia by switching to alectinib in ALK-positive non-small cell lung cancer.

We herein encountered a case of abdominal wall dermatofibrosarcoma protuberans (DFSP) that developed pulmonary and pancreatic metastases 5 years after complete resection. Because specific rearrangements of the platelet-derived growth factor beta (PDGFB) locus by a novel fluorescence in situ hybridization method was detected, the patient was treated with imatinib mesylate at 400 mg/day. A partial response was achieved by imatinib without any specific toxicity. Although metastatic DFSP is an extremely rare disease, an evaluation of PDGFB fusion is essential and imatinib mesylate should be considered as an optimal therapeutic choice in patients with metastatic or locally advanced DFSP.

Effectiveness of Imatinib Mesylate Treatment in a Patient with Dermatofibrosarcoma Protuberans with Pulmonary and Pancreatic Metastases.

A 75-year-old man was referred to the Department of Ophthalmology at our hospital due to pain in his left eye. An ophthalmologic examination revealed a tumor on the surface of the left iris at 3 o’clock (Picture 1), suggesting a metastatic malignant disease. F-Fluorodeoxy glucose positron emission tomography (FDG-PET) revealed abnormal uptake in the esophagus, liver, and lymph nodes as well as a lesion in the left eye (Picture 2). An endoscopic examination revealed type I advanced esophageal cancer 35 cm from the dental arches (Picture 3), and the histological findings indicated squamous cell carcinoma. Based on these findings, we diagnosed the patient with iris metastasis of esophageal cancer and the patient received radiotherapy for the left eye and esophagus. The tumor in the left eye reduced in size and the pain was also alleviated after radiotherapy, however, the patient’s vision failed to improve. Metastasis of the iris in patients with esophageal cancer is extremely rare (1, 2).

Iris Metastasis of Esophageal Cancer.

A 58-year-old Japanese man was diagnosed with differentiated adenocarcinoma of the stomach. Histological findings of the resected specimen revealed well- to moderately-differentiated tubular adenocarcinoma (tub1, tub2), 13 mm in diameter, which invaded into the submucosa (SM1, 300 μm) and lymphovascular lumen (ly1). Serum antibody against Helicobacter pylori (Hp) and the (13)C-urea breath test were negative, and there were no atrophic changes in the tumor-adjacent mucosa. The immunohistochemical analysis showed that gastric mucin (MUC5AC) was strongly positive and intestinal mucin (MUC2) was weakly and partially positive. According to these results, the final diagnosis of Hp-negative well-differentiated early gastric cancer was made.

Toshiharu Tatai

Papers

Successful treatment of crizotinib-induced dysgeusia by switching to alectinib in ALK-positive non-small cell lung cancer.

Effectiveness of Imatinib Mesylate Treatment in a Patient with Dermatofibrosarcoma Protuberans with Pulmonary and Pancreatic Metastases.

Iris Metastasis of Esophageal Cancer.

Helicobacter pylori-negative Differentiated Adenocarcinoma of the Stomach.