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Zhou Y, Dong L, Dai L, Hu S, Sun Y, Wu Y, Pan T, Li X. Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review. Front Surg 2023; 10:1133335. [PMID: 37065996 PMCID: PMC10098014 DOI: 10.3389/fsurg.2023.1133335] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/13/2023] [Indexed: 04/18/2023] Open
Abstract
Background Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy. Case Description A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up. Conclusions We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.
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Affiliation(s)
- Yunxiang Zhou
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
| | - Linping Dong
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Department of Surgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Linyun Dai
- Department of Surgery, Haiyan People's Hospital, Jiaxing, Zhejiang, China
| | - Sien Hu
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Yongji Sun
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Yulian Wu
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Department of Surgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Tao Pan
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Correspondence: Tao Pan Xiawei Li
| | - Xiawei Li
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Correspondence: Tao Pan Xiawei Li
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Ricco G, Andrini E, Siepe G, Mosconi C, Ambrosini V, Ricci C, Casadei R, Campana D, Lamberti G. Multimodal Strategy in Localized Merkel Cell Carcinoma: Where Are We and Where Are We Heading? Int J Mol Sci 2021; 22:ijms221910629. [PMID: 34638968 PMCID: PMC8508588 DOI: 10.3390/ijms221910629] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 02/07/2023] Open
Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence is rising. Multimodal treatment is crucial in the non-metastatic, potentially curable setting. However, the optimal management of patients with non-metastatic MCC is still unclear. In addition, novel insights into tumor biology and newly developed treatments (e.g., immune checkpoint inhibitors) that dramatically improved outcomes in the advanced setting are being investigated in earlier stages with promising results. Nevertheless, the combination of new strategies with consolidated ones needs to be clarified. We reviewed available evidence supporting the current treatment recommendations of localized MCC with a focus on potentially ground-breaking future strategies. Advantages and disadvantages of the different treatment modalities, including surgery, radiotherapy, chemotherapy, and immunotherapy in the non-metastatic setting, are analyzed, as well as those of different treatment modalities (adjuvant as opposed to neoadjuvant). Lastly, we provide an outlook of remarkable ongoing studies and of promising agents and strategies in the treatment of patients with non-metastatic MCC.
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Affiliation(s)
- Gianluca Ricco
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy; (G.R.); (E.A.); (V.A.); (G.L.)
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
| | - Elisa Andrini
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy; (G.R.); (E.A.); (V.A.); (G.L.)
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
| | - Giambattista Siepe
- Radiation Oncology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy;
| | - Cristina Mosconi
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- Department of Radiology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
| | - Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy; (G.R.); (E.A.); (V.A.); (G.L.)
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40139 Bologna, Italy
| | - Claudio Ricci
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40139 Bologna, Italy
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Riccardo Casadei
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40139 Bologna, Italy
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy; (G.R.); (E.A.); (V.A.); (G.L.)
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
- Correspondence: ; Tel.: +39-051-2142886
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy; (G.R.); (E.A.); (V.A.); (G.L.)
- NET Team Bologna—ENETS Center of Excellence, 40138 Bologna, Italy; (C.M.); (C.R.); (R.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy
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Abstract
Purpose of Review The therapeutic landscape for non-melanoma skin cancer (NMSC) has recently expanded with the development of effective and targeted immunotherapy. Here, we provide an overview of the role of immunotherapy in the management of advanced cutaneous carcinomas. Recent Findings Several agents were recently U.S. Food and Drug Administration (FDA)-approved for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma, Merkel cell carcinoma, and basal cell carcinoma. However, recent approvals in tissue-agnostic indications may also benefit other NMSCs including cutaneous adnexal solid tumors with high tumor mutation burdens or microsatellite instability. Furthermore, while FDA-approved indications will likely continue to expand, continued studies are needed to support the role of immunotherapy in the neoadjuvant, adjuvant, and refractory settings. Summary Immunotherapy is emerging as the standard of care for several advanced NMSCs not amenable to surgery and radiation. Ongoing evaluation of the clinical trial landscape is needed to optimize enrollment and ensure continued innovation.
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Leão I, Marinho J, Costa T. Long-term response to avelumab and management of oligoprogression in Merkel cell carcinoma: A case report. World J Clin Cases 2021; 9:4829-4836. [PMID: 34222455 PMCID: PMC8223835 DOI: 10.12998/wjcc.v9.i18.4829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/04/2021] [Accepted: 05/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasia, with high risk of recurrence and metastasis and poor survival. Immune checkpoint inhibitors, like the anti-programmed death-ligand 1 agent avelumab, were recently approved for the treatment of advanced MCC. We, herein, report the first case of advanced MCC with oligoprogression managed with avelumab and local radical treatment.
CASE SUMMARY A 61-year-old man was presented to the hospital with sporadic fever and an exudative malodorous mass (10 cm of diameter), located on the right gluteal region. The final diagnosis was MCC, cT4N3M1c (AJCC, TNM staging 8th edition, 2017), with invasion of adjacent muscle, in-transit metastasis, and bone lesions. Patient started chemotherapy (cisplatin and etoposide), and after six cycles, the main tumor increased, evidencing disease progression. Two months later, the patient started second line treatment with avelumab (under an early access program). After two cycles of treatment, the lesion started to decrease, achieving a major response. Local progression was documented after 16 cycles. However, as the tumor became resectable, salvage surgery was performed, while keeping the systemic treatment with avelumab. Since the patient developed bilateral pneumonia, immunotherapy was suspended. More than 2.5 years after surgery (last 19 mo without systemic therapy), the patient maintains complete local response and stable bone lesions.
CONCLUSION This report highlights the efficacy and long-term response of avelumab on the management of a chemotherapy resistant advanced MCC, with evidence of oligoprogression, in combination with local radical treatment.
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Affiliation(s)
- Inês Leão
- Department of Oncology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia 4434-502, Portugal
| | - Joana Marinho
- Department of Oncology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia 4434-502, Portugal
| | - Telma Costa
- Department of Oncology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia 4434-502, Portugal
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Babadzhanov M, Doudican N, Wilken R, Stevenson M, Pavlick A, Carucci J. Current concepts and approaches to merkel cell carcinoma. Arch Dermatol Res 2020; 313:129-138. [PMID: 32666149 DOI: 10.1007/s00403-020-02107-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/26/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023]
Abstract
Merkel cell carcinoma (MCC) is an aggressive and rare cutaneous cancer of the mechanoreceptor unit of the skin with a neuroendocrine origin. MCC incidence has been on the rise over the past two decades. Risk factors include old age, chronic UV exposure, and immunosuppression. Although MCC is a cutaneous malignancy that is often misdiagnosed as a benign nodule at the time of diagnosis, it has an aggressive disease course due to its high recurrence and metastatic potential. The PD-1/PD-L1 checkpoint blockade has recently shown promising results in the management of advanced MCC. Avelumab and pembrolizumab are considered the new standard of care for metastatic MCC. Despite advances in the field, studies are needed to elucidate the role of immunotherapy for patients who are resistant to treatment. Most ongoing clinical trials aim to assess the efficacy of checkpoint inhibitor combination therapies. This article reviews the most current literature on the surgical and medical management of MCC.
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Affiliation(s)
| | | | - Reason Wilken
- Dermatology, NYU Langone Med Center, New York, NY, USA
| | | | - Anna Pavlick
- Dermatology, NYU Langone Med Center, New York, NY, USA
| | - John Carucci
- Dermatology, NYU Langone Med Center, New York, NY, USA.
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