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   Table of Contents - Current issue
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October-December 2020
Volume 7 | Issue 4
Page Nos. 139-183

Online since Tuesday, December 1, 2020

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REVIEW ARTICLES  

Dual therapeutic strategy targeting tumor cells and tumor microenvironment in triple-negative breast cancer p. 139
Pamungkas Bagus Satriyo, Chi- Tai Yeh, Jia- Hong Chen, Teguh Aryandono, Sofia Mubarika Haryana, Tsu- Yi Chao
DOI:10.4103/JCRP.JCRP_13_20  
Objective: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Only 30% of TNBC patients show a pathologic complete response, and the other 70% of patients exhibit a less pronounced response followed by relapse and metastasis to distant organs after neoadjuvant chemotherapy. Achievements of immunotherapy targeting programmed cell death 1 ligand 1 (PD-L1) in clinical trials for treating melanoma, nonsmall-cell lung cancer, renal cell carcinoma, and TNBC suggest that targeting the interaction of tumor cells with tumor microenvironment is highly beneficial for cancer treatment. Finding a novel dual-targeting therapy against tumor cells and the tumor microenvironment (TME) may provide options for improved responses in TNBC patients. Data Sources: We searched the potential targeted therapy candidates that regulate tumor cells as well as the TME of cancer diseases, including TNBC, based on our previous and recent other publications. Study Selection: We selected the potential targeted therapies supported by relevance clinical data, in vitro and in vivo studies. Results: In this review, we found the KDM5B, Cadherin 11, β-catenin, CDK2, signal peptide CUB-EGF domain-containing protein 2, and PDL1 regulate the tumor cells and TME of TNBC cells. In addition, we also highlighted the Antrocin, Ovatodiolide, and Pterostilbene as natural small compound possess anti-cancer through the disruption of tumor cell–TME interactions. Conclusion: The new therapy approach targeting tumor cells-TME interaction may improve the response and survival rate of TNBC patients. Later, natural small compounds could provide alternative therapy options for TNBC patients.
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Neoadjuvant chemotherapy for bladder cancer p. 149
RB Nerli, Manas Sharma, Shridhar C Ghagane, Shashank D Patil, Pulkit Gupta, Neeraj S Dixit, Murigendra B Hiremath
DOI:10.4103/JCRP.JCRP_18_20  
Background: Muscle invasive bladder cancer (MIBC) is an aggressive malignancy, with 5-year survival rates ranging from 36% to 48% for pT3-4/pN+ tumors. Radical cystectomy (RC) remains the gold-standard treatment for the management of MIBC. Perioperative treatment can improve overall survival (OS), with more robust evidence favoring neoadjuvant chemotherapy (NAC). Objective: This review aims to discuss the historical perspectives, recent advances, experimental therapies, and current evidence for the use of various chemotherapeutic drugs in a neo-adjuvant setting for the treatment of MIBC. Data Sources: We searched and analyzed research articles, reviews, clinical trials, and meta-analyses addressing NAC in the management of MIBC. Results: The advantages of NAC in MIBC include the delivery of chemotherapy at the earliest time point when the micrometastatic burden is presumed to be the lowest. It has improved patient compliance and better tolerability in preoperative period with more number of patients completing the therapy. It reflects in vivo chemosensitivity of urothelial cancer along with favorable pathological outcomes in individual showing response. Delay in RC in nonresponders and overtreatment in low-stage disease are the potential disadvantages. Conclusion: NAC in MIBC is associated with improved OS. Cisplatin-based NAC is the current standard of care in eligible patients.
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ORIGINAL ARTICLES Top

A retrospective cohort study of 304 patients with gastrointestinal stromal tumors in mackay memorial hospital p. 156
Po- Chun Wang, Pao- Shu Wu
DOI:10.4103/JCRP.JCRP_10_20  
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs often occur in middle-aged and older individuals. The main morphologic type of GISTs is the spindle cell type. Immunohistochemistry and genotyping can help to identify GISTs from other subgroups of sarcoma. Materials and Methods: This retrospective study collected 304 patients over a 10-year period (from January 2009 to June 2019) who were diagnosed with GISTs based on the pathological database of our hospital. We retrospectively analyzed the clinical manifestations and treatment strategies. Results: Anemia or gastrointestinal bleeding was the most common symptom (36.5%), followed by gastrointestinal discomfort (32.6%) and incidental findings (21.4%). Ruptured tumors with hollow organ perforation increased the mortality risk. Liver metastasis and peritoneal seeding were the most two common patterns of recurrence. GISTs arising in adults are characterized by the near-universal expression of CD117/KIT antigen. Early surgery with margin-free resection is the best strategy for GISTs without metastasis. Routine lymph node dissection is not recommended. Laparoscopic surgery is feasible and safe for GISTs in the gastrointestinal tract. Endoscopic submucosal dissection to treat GISTs is suitable for small tumors with very low-to-intermediate risk in the stomach. Postoperative treatment with tyrosine kinase inhibitors can prolong recurrence-free survival after surgery. Conclusion: Surgical resection is the preferred treatment for patients without metastasis. Administration of tyrosine kinase inhibitors such as imatinib is recommended for unresectable, metastatic, or recurrent GISTs. Postoperative follow-up by computed tomography to detect early recurrence is recommended.
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Outcome and prognostic analysis of salvage esophagectomy for clinical T4b esophageal squamous cell carcinoma after definite chemoradiotherapy p. 160
Yu Chen, Chien- Ming Lo, Yu- Ming Wang, Li- Chun Chen, Shau- Hsuan Li, Hung- I Lu
DOI:10.4103/JCRP.JCRP_19_20  
Background: Definite chemoradiotherapy (dCRT) followed by surgery is a treatment option for clinical T4b esophageal squamous cell carcinoma (ESCC). However, the feasibility and safety of salvage esophagectomy for clinical T4b patients after dCRT remains unclear. This study aimed to analyze the outcomes and prognostic factors of salvage esophagectomy for cT4b ESCC after dCRT. Materials and Methods: From 2008 to 2017, a total of 21 patients who underwent salvage esophagectomy after dCRT for initially unresectable disease at the author's institution were assessed. The study retrospectively reviewed the baseline characteristics of these cases and evaluated the prognostic factors and surgical outcomes. Results: Among the study group, R0 resection was achieved in 9 patients (43%). The rate of major complications classified as Clavien-Dindo classification (CDc) Grade IIIb or higher was 24.0%. The overall survival (OS) and disease-free survival (DFS) rates were 46% and 25% at 3 years, respectively. Univariate analysis showed that the patients who had R0 resection had a significantly better OS (P = 0.012, 78% vs. 25%) and DFS (P = 0.025, 39% vs. 18%) compared to those with R1/2 resection. The patients with minor complications (CDc ≤ IIIa) had a better OS (P = 0.002, 61% vs. 0%) compared to the group with major complications (CDc ≥ IIIb). The pathological results with earlier T (ypT0-2) were better than with advanced T (ypT3-4) for 3-year OS (P = 0.042, 83% vs. 30%) and 3-year DFS (P = 0.018, 53% vs. 13%). In multivariate analysis, R0 resection (P = 0.042, 95% confidence interval [CI] 1.051–15.617) and CDc ≤ IIIa (P = 0.019, 95% CI 1.286–16.023) were associated with a significantly better prognosis with regards to 3-year OS, and R0 resection was associated with a significantly better prognosis with regards to 3-year DFS (P = 0.0339, 95% CI 1.108–13.136). Conclusion: The results showed that in salvage esophagectomy for T4b ESCC patients after dCRT, R0 resection and CDc ≤ IIIa were favorable prognostic factors. The surgical complications were still high, but this was acceptable in view of the potential long-term survival after salvage esophagectomy. Carefully selecting candidates remains an important issue before surgery.
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CASE REPORTS Top

Successful treatment with continuous high-dose 5-fluorouracil infusion, followed by oral capecitabine in a patient with advanced gastric cancer with bone marrow metastasis and microangiopathic hemolytic anemia p. 167
Hsiu- Tzu Wang, Su- Peng Yeh
DOI:10.4103/JCRP.JCRP_20_20  
A 61-year-old male with a history of Stage 1A gastric body adenocarcinoma and s/p radical subtotal gastrectomy + B-II reconstruction 5 years previously presented with general malaise and bone pain. A hemogram revealed severe anemia and thrombocytopenia, which were refractory to blood transfusion. A peripheral blood smear showed marked thrombocytopenia with numerous fragmented red blood cells and normoblasts. A bone marrow biopsy showed metastatic adenocarcinoma of gastric origin. Therefore, he was diagnosed with cancer-associated microangiopathic hemolytic anemia (MAHA). In addition to aggressive transfusion support, high-dose continuous 5-fluorouracil infusion was administered, and the MAHA and thrombocytopenia dramatically resolved. Capecitabine was subsequently administered orally at the outpatient clinic, and his disease was well controlled without the recurrence of MAHA or thrombocytopenia for 1 year. Although most chemotherapies may aggravate cytopenia, our case illustrates that effective chemotherapy can not only control cancer-associated MAHA but also restore cytopenia to normal.
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Infliximab treatment in immune-related pneumonitis with respiratory failure after high-dose steroids: A patient with metastatic gastric cancer p. 170
Fu- Ming Cheng, Chi- Ching Chen
DOI:10.4103/JCRP.JCRP_22_20  
Patients treated with immune checkpoint inhibitors sometimes have immune-related adverse events (IRAEs). Immune-related pneumonitis (IRP) is an uncommon but potentially fatal IRAE. We report a 69-year-old man with metastatic gastric cancer who received paclitaxel and nivolumab after failure with oxaliplatin and capecitabine. After his third dose of nivolumab, he had progressive shortness of breath and was diagnosed as having IRP with respiratory failure. He received high-dose methylprednisolone for 2 days, however, the response was not satisfactory. Thus, we added infliximab 5 mg/kg to high-dose methylprednisolone. With the combination of infliximab and high-dose methylprednisolone, the IRP greatly improved. Moreover, he had nearly complete remission of gastric cancer and was progression free for 3 months without any further anticancer treatment.
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Durable response to tamoxifen and metronomic cyclophosphamide in a patient with metastatic estrogen receptor-positive uterine leiomyosarcoma p. 174
Tsung- Che Wu, Hsiang- Wei Hu, Tom Wei-Wu Chen
DOI:10.4103/JCRP.JCRP_23_20  
Uterine leiomyosarcoma is a rare uterine malignancy, but the most common type of uterine sarcoma, in which a considerable proportion of tumors express estrogen/progesterone hormone receptors. We report a case of estrogen receptor-positive uterine leiomyosarcoma with a durable response to a combination of tamoxifen and metronomic cyclophosphamide. The current landscape and potential systemic treatment for uterine leiomyosarcoma were also briefly reviewed.
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Parapharyngeal inflammatory myofibroblastic tumor harboring fibronectin 1- ros protooncogene 1 fusion responded to crizotinib p. 179
Yu- Ju Kuo, Jen- Chieh Lee, Chun- Nan Chen, Tom Wei-Wu Chen
DOI:10.4103/JCRP.JCRP_25_20  
Inflammatory myofibroblastic tumor (IMT) is a rare tumor type usually arising in the thoracic or abdominal cavity. Despite its rarity, IMT commonly harbors driver gene rearrangements involving anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), and neurotrophic tropomyosin-related kinase. We present a rare case of the parapharyngeal IMT with convoluted diagnostic test results in determining driver gene rearrangement. The immunohistochemical stains were ALK-negative and ROS1 positive, but the result of ROS1 fluorescence in situ hybridization was equivocal. Amplicon-based targeted next-generation sequencing (NGS) did not detect any ROS1 rearrangement, but hybridization capture-based NGS revealed a rare fibronectin 1 (FN1)-ROS1 fusion. Eventually, the patient started crizotinib and had a tumor response with tolerable toxicity. This case highlights the importance of appropriate molecular testing of IMTs to guide the proper targeted therapy.
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