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   Table of Contents - Current issue
January-March 2023
Volume 10 | Issue 1
Page Nos. 1-43

Online since Friday, March 10, 2023

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Role of wnt ligand secretion mediator signaling in cancer development p. 1
Kai-Ting Chuang, Li-Ting Wang, Shih-Hsien Hsu
Objective: The Wnt signaling pathway is among the crucial cascades that regulate development and homeostasis of tissue. Data Sources: Further, it is closely associated with different types of cancer, which includes glioma, breast, colorectal, lung, and prostate cancer, and hepatocellular carcinoma (HCC). The deviant activation or inhibition of Wnt signaling regulates cancer progression, thereby exerting oncogenic or tumorsuppressive effects that control the invasion, metastasis, and metabolism of cancer cell. Study Selection: In the Wnt secretory pathway, lipidmodified Wnt molecules interact with Wnt ligand secretion mediator (WLS), a Wnt cargo receptor. Moreover, they are directed to the plasma membrane and then secreted. Results: Loss of WLS function leads to the accumulation of Wnt in the endoplasmic reticulum (ER), leading to retrograde Golgi–ER transport and ER stress associated with the pathogenesis of several conditions, including early embryonic death, and developmental defects related to lymphopoiesis, neurogenesis, and osteogenesis in adults. Although there is substantial evidence, the regulatory mechanisms through which WLS controls cellular functions are not fully elucidated. Conclusion: Therefore, the current study aimed to identify the underlying mechanism of the effects of WLS on the development of human diseases.
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Anti-tumor efficacy of a bevacizumab preconditioning followed by etoposide and cisplatin regimen in human epidermal growth factor receptor-2-positive breast cancer brain metastasis refractory to whole brain radiotherapy p. 11
Tom Wei-Wu Chen, Ching-Hung Lin, Dah-Cherng Yeh, Ling-Ming Tseng, Kun-Ming Rau, Bang-Bin Chen, Ta-Chung Chao, Shu-Min Huang, Dwan-Ying Chang, I-Chun Chen, Ann-Lii Cheng, Yen-Shen Lu
Background: For human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC), treating brain metastasis (BM) remains challenging. We have previously demonstrated that administering bevacizumab 1 day before etoposide and cisplatin (BEEP) can significantly improve antitumor efficacy in cases of breast cancer with BM. Herein, we report the antimetastatic brain tumor efficacy of BEEP in an HER2-positive subpopulation. Materials and Methods: Thirty-five MBC patients with BM were enrolled from January 2011 to January 2013. BEEP was given in 21 day cycles: bevacizumab 15 mg/kg on day 1, etoposide 70 mg/m2/day from days 2 to 4, and cisplatin 70 mg/m2 on day 2. The primary endpoint was composite central nervous system (CNS) volumetric objective response rate (ORR). Anti-HER2 treatments were not permitted during the clinical trial. Results: A total of 23 patients were HER2-positive, 9 ER-positive, and 14 ER-negative. All had been exposed to trastuzumab; 11 (47.8%) had received lapatinib treatment, and 6 (26.1%) of them had received both lapatinib and capecitabine treatment. Of these, 16 patients (69.6%, 95% confidence interval [CI] 47.1–86.8) achieved CNS-ORR, including 7 (30.4%) with ≥80% and 9 (39.1%) with 50%–80% CNS volumetric reduction. A further 5 patients (21.7%) had 20%–50% CNS volumetric reduction. Median CNS-specific progression-free survival and overall survival were 7.4 (95% CI 5.8–9.0) and 11.8 (95% CI 8.7–14.9) months, respectively. Toxicities were tolerated with granulocyte-colony stimulating factor support. Conclusion: The BEEP regimen had a significant antitumor effect in cases of BM of HER2-positive breast cancer that progressed following whole brain radiotherapy.
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Real-world evidence of daratumumab-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: A single-center experience in Taiwan focusing on efficacy p. 19
Ling-Jung Chiu, Chin-Yuan Kuo, Ming-Chun Ma, Chun-Kai Liao, Hung-Lin Liu, Ming-Chung Wang
Background: Daratumumab (DARA) introduced in the multiple myeloma (MM) treatment strategy, producing a direct antitumor activity and immunomodulatory effects in phase I-II trial GEN501. In the POLLUX trial, the combination of DARA with lenalidomide and dexamethasone (DRd) reported impressive response rates. In Taiwan, the Dara-based regimen was supported by National Health Insurance recently, but there were no real-world data in Taiwan. Materials and Methods: We described a heavily pretreated group of 31 patients with MM who had received one or more lines of therapy to receive DRd therapy after Taiwan Food and Drug Administration approval. The primary end point was progression-free survival (PFS). Results: After a median follow-up of 22.87 (95% confidence interval [CI]: 16–29.73) months, the median time to first response was 59 days (95% CI: 24.8–81.6). Median PFS was 24.082 months (95% CI: 14–33) in patients who received DRd therapy. Twelve-month PFS showed 80.7% in the DRd group. Patients who achieved at least very good partial response (VGPR) had longer median PFS (39.8 months) than those who achieved partial response (7.35 months). The complete response rate and VGPR were 35.5% and 29%, respectively. About 22.6% of patients had a partial response. The average treatment duration was 11.48 ± 7 months. Patient experienced biological relapse at 5.88 months after discontinuing DRd treatment. Conclusion: After DRd treatment for 11.48 months, most of the patients showed biological relapse at 5.88 months, suggesting the good efficacy; however, the need of a longer maintenance treatment of DARA. The median PFS in real-world setting was consistent with the POLLUX trial regardless of more patients with high cytogenetic risks. Patient who could achieve deep response above VGPR had better PFS than those who did not.
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Ewing's sarcoma of the small intestine with liver metastasis mimicking gastrointestinal stromal tumor p. 24
Po-Yi Chen, Wan-Ting Li, Chih-Hung Hsu, Tom Wei-Wu Chen
Ewing's sarcoma (ES) is the second most common primary bone malignancy of childhood, whereas extraosseous ES (EES) is more common in older patients. EES of the small intestine is an extremely rare disease. We present a case of ES of the small intestine with liver metastasis mimicking a gastrointestinal stromal tumor. The diagnosis of ES requires a combination of histological, immunohistochemical, and molecular techniques. Further studies to investigate whether multimodality treatments can improve the survival of metastatic EES are needed.
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Fumarate hydratase-deficient renal cell carcinoma: A case report and literature review p. 28
Yi-Hsuan Huang, Nan-Haw Chow, Yu-Ting Yu, Wen-Pin Su
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare but aggressive subtype of renal cancer associated with germline or somatic mutations of the FH gene. The histology demonstrates a broad range of morphologic patterns with loss of FH immunostaining. There is no standard therapy approved for FH-deficient RCC, and treatment is often extrapolated from other subtypes of RCC. With a better understanding of the molecular mechanism and pathogenesis, more studies including this population are ongoing. We reported a 33-year-old man with no relevant family history diagnosed with locally advanced FH-deficient RCC and who later developed distant metastasis. He received erlotinib-bevacizumab combination therapy and achieved a partial response. We also performed a literature review of FH-deficient RCC.
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Immune-related giant cell myocarditis after immune checkpoint inhibitor therapy in a patient with urothelial carcinoma and myasthenia gravis p. 31
Chun-Chih Chiu, Jhe-Cyuan Guo
Immune-related adverse events (irAEs) have drawn global attention after the extended use of immune checkpoint inhibitors (ICIs) in the past decade. These inflammatory side effects hinder cancer treatment and potentially have a negative impact on the prognosis. Myocarditis is an infrequent but often life-threatening irAE, and the pathogenesis remains unclear owing to its rarity and fulminant nature. We present a case of immune-related giant cell myocarditis after pembrolizumab treatment for unresectable urothelial carcinoma of the bladder in a patient with underlying invasive thymoma and myasthenia gravis. This unusual presentation highlights the complexity of immune crosstalk in patients with autoimmune diseases who receive ICI therapy. Further, investigations and individualized treatment for this population are warranted to minimize toxicity.
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Frontline autologous stem cell transplantation in POEMS syndrome with pulmonary arterial hypertension p. 34
Po-Hsien Li, Hsin-Chen Lin
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome is a rare para-neoplastic syndrome related to plasma cell disorder. Pulmonary arterial hypertension (PAH) is a cardiovascular comorbidity caused by underlying plasma cell disorder. Targeted therapy aimed at plasma cells may be more beneficial than treating POEMS syndrome with conventional PAH therapy. We present the case of a 47-year-old woman who was diagnosed with POEMS syndrome complicated with PAH and treated with myeloma-like therapy followed by autologous stem cell transplantation (ASCT). This case highlights that targeted therapy against plasma cells and frontline ASCT may be beneficial with regards to the clinical outcomes.
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Multiple immunosuppressants for immune-related acholia in a patient with metastatic colorectal cancer p. 38
Ching-Tso Chen, Yi-Hsin Liang, Chien-Wen Hung, Kun-Huei Yeh
Immunotherapy-related adverse events (irAEs) such as hepatitis or cholestasis have been well recognized. In contrast, acholia was not previously reported as an irAE with a lack of standard treatment. We presented a case of a 68-year-old man with metastatic colon cancer that progressed after several chemotherapy sessions with targeted agents. He received nivolumab plus regorafenib (REGONIVO) as salvage treatment. However, he reported clay-colored stools and jaundice after 3 months of REGONIVO treatment. Computed tomography (CT) revealed no significant biliary tract dilation. Laboratory tests ruled out viral hepatitis or autoimmune hepatitis. Endoscopic retrograde cholangiopancreatography showed multiple filling defects of blood clot formation, and endoscopic retrograde biliary drainage was ineffective. An irAE presenting as acholia and hyperbilirubinemia was diagnosed. Subsequently, the patient was initially administered a corticosteroid only, with an equivalent dose of prednisone (1 mg/kg/day); however, this treatment had only limited effect. After the addition of multiple immunosuppressants, including mycophenolate mofetil and tacrolimus, the severity of hyperbilirubinemia declined and acholia was resolved. This case demonstrated that irAEs can present as acholia and hyperbilirubinemia without significant biliary obstruction. Although the mechanism of such an unusual irAE remains unclear, it seems to be refractory to corticosteroid treatment alone. A more aggressive strategy, such as multiple immunosuppressants, may be advisable.
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