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   Table of Contents - Current issue
January-March 2020
Volume 3 | Issue 1
Page Nos. 1-47

Online since Friday, February 21, 2020

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Cancer immunotherapy for immunocompromised patients: An often ignored, yet vital puzzle p. 1
Jyoti Bajpai
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Immune checkpoint blockade in gastrointestinal cancers: The current status and emerging paradigms p. 3
Mihailo Miljanic, Anna Capasso, Todd A Triplett, S Gail Eckhardt, Kyaw L Aung
Immunotherapy is a rapidly evolving treatment paradigm that holds promise to provide long-lasting survival benefits for patients with cancer. This promise, however, remains unfulfilled for the majority of patients with gastrointestinal (GI) cancers, as significant limitations in efficacy exist with immune checkpoint inhibitors (ICIs) in this disease group. A plethora of novel combination treatment strategies are currently being investigated in various clinical trials to make them more efficacious as our understanding of molecular mechanisms mediating resistance to immunotherapy advances. In this article, we summarize the current status of immune checkpoint blockade in GI cancers and discuss the biological rationales that underlie the emerging treatment strategies being tested in ongoing clinical trials in combination with ICIs. We also highlight the promising early results from these strategies and provide future perspectives on enhancing response to immunotherapy for patients with GI cancers.
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Bromodomain and extra-terminal (BET) domain protein inhibitors for solid tumor cancers p. 16
Martin V Nguyen, Lydia Loof, Gerald S Falchook
The bromodomain and extraterminal (BET) domain protein family is involved in the process of transcription of genetic information. The BET protein family includes BRD2, BRD3, BRD4, and bromodomain testis-specific protein. BET protein alterations are associated with some solid tumor cancers, including nuclear protein in testis midline carcinoma. BET protein has a role in carcinogenesis and in the regulation of the cell cycle. A number of BET inhibitors have entered clinical trials. This review discusses the results of BET inhibitor clinical trials in solid tumor cancers.
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Ramucirumab and docetaxel in patients with metastatic urothelial carcinoma harboring fibroblast growth factor receptor alterations: A case series and literature review p. 23
Katherine Emilie Rhoades Smith, Emilie Elise Hitron, Greta A Russler, Deborah A Baumgarten, Mehmet Asim Bilen
Metastatic urothelial carcinoma (mUC) has a poor prognosis with a 5-year survival probability of 4.8%. The mainstay of first-line treatment is platinum-based chemotherapy. Second-line therapy involves immune checkpoint inhibitors or a fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, for patients harboring selected FGFR alterations. Several additional agents are under development for the treatment of mUC. Recent studies demonstrate that ramucirumab and docetaxel have clinical activity in mUC. We report two patients with metastatic upper tract urothelial cancer (mUTUC) with FGFR alterations who were heavily pretreated with FGFR inhibitors that later showed response to ramucirumab and docetaxel. Preclinical studies indicate that FGF and VEGF pathways work synergistically, which could explain the observations in our patients. Our findings may represent another treatment option for patients with mUC and FGFR alterations who have progressed on multiple lines of therapy.
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Pneumocystis infection in two patients treated with both immune checkpoint inhibitor and corticoids p. 27
Maroun Sadek, Angela Loizidou, Annie Drowart, Sigi Van den Wijngaert, Maria Gomez-Galdon, Sandrine Aspeslagh
The introduction of immune checkpoint inhibitor (ICI) targeting cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death receptor 1 has dramatically improved clinical outcome for cancer patients. Nevertheless, this treatment can be associated with immune-related adverse events (irAEs) which sometimes need management with prolonged immune suppression. In order to analyze the risk of Pneumocystis jiroveci pneumonia (PJP) in this population, all PJP cases at our oncological hospital between 2004 and 2019 were searched. Only two cases were found in patients treated with ICI (480 patients received ICI during that period). The first was treated with both ipilimumab and nivolumab for metastatic melanoma and required long-term corticosteroids plus infliximab for immune-related colitis. The second received both pembrolizumab and brentuximab for Hodgkin's lymphoma and received corticosteroids for macrophage-activating syndrome. These two cases illustrate that PJP is rare but might be severe in the ICI population and should be differentiated from tumor progression or irAE.
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A case report of a cutaneous mucinous reaction associated with erlotinib therapy used in the treatment of metastatic tonsillar sinus squamous cell carcinoma p. 31
Benjamin D Freemyer, Carlos A Torres-Cabala, Anisha B Patel
Cutaneous mucinoses are a diverse group of diseases that are occasionally seen in the context of an adverse drug reaction. We report the case of a 59-year-old male who presented with an asymptomatic, acneiform rash on his forehead, scalp, nose, upper chest, and upper back that had developed after treatment with erlotinib therapy used in the treatment of metastatic tonsillar sinus squamous cell carcinoma. Biopsy of these lesions demonstrated atypical histology that had features of both follicular mucinosis and myxedema. This histologic phenomenon is a rare drug reaction that has not previously been described in association with erlotinib.
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Highlights on the management of oligometastatic disease Highly accessed article p. 34
Salem M Alshehri, Khaled Alkattan, Ahmed Abdelwarith, Hussain Alhussain, Shaker Shaker, Majed Alghamdi, Hossam Alassaf, Ali Albargawi, Manal Al Naimi, Ameen Alomair, Saif Althaqfi, Adnan Alhebshi, Majid Alothman, AbdulRahman Jazieh
Purpose: The understanding of oligometastatic disease (OMD) is rapidly evolving and with this comes the ability to utilize a number of modalities that excel in the localized control of disease. It has been identified that there are no clear guidelines based on high-level evidence to standardized approaches toward the management of OMD. These highlights have been developed to provide a road map for all health-care professionals who are involved in the management of OMD to support standardized patient care. Methods: The Saudi Lung Cancer Guidelines Committee is a part of the Saudi Lung Cancer Association which, in turn, is part of the Saudi Thoracic Society. Considering that lung cancer constitutes a major proportion of OMD prevalence, the committee took the initiative to develop national highlights to support the management of OMD within Saudi Arabia. The committee members are national clinical leaders who collaborated with international expertise to establish these highlights to serve as a general clinical pathway in the management of OMD. Results: Standardization of the indications to diagnose oligometastases and patient selection criteria including ineligibility criteria for treatment are the basis of the highlights. Treatment approaches including surgical and the variety of radiotherapeutical options are discussed in relation to specific oligometastatic sites. Acceptable measurements for response to treatment and the future for the treatment of OMD conclude the development of the highlights. Conclusion: These are the first national highlights addressing this important disease in oncology. The implementation of these highlights as guidelines requires a robust multidisciplinary team and access to specific technology and expertise. These highlights are based on the most recent findings within the literature but will require repeated review and updating due to this rapidly evolving field in disease management.
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Introducing the 3rd Annual PARP and DNA Damage Response Inhibitors Summit p. 45

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IO360° speaker interview: Q and A with Dr. Crystal Mackall p. 46

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Finding T-Cure: A CEO's vision for the future of adoptive cell immunotherapy p. 47

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