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Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Hao Hu, Qian Zhu, Xian Shi Luo, Xiong Wen Yang, Hai Dong Wang, Chang Ying Guo
Background: Programmed cell death 1 (PD-1) and programmed cell death-ligand 1(PD-L1) inhibitors have captured our attention as new therapeutic options for several tumor types. Nonetheless, the differences in efficacy between PD-1/PD-L1 inhibitors and conventional treatments (chemotherapy or targeted therapy) in pretreated advanced cancer patients remain unclear. Materials and Methods: A systematic literature search was conducted to identify phase III randomized controlled trials (RCTs)-based investigations of PD-1(nivolumab, pembrolizumab)/PD-L1 inhibitors (atezolizumab) against pretreated advanced cancer...
February 20, 2018: Oncotarget
Georges Al-Helou, Nardos Temesgen, Jonathan Gwizdala, Jalil Ahari
Our patient is a 69-year-old man who presented to the emergency department with left-sided hemiparesis that started 4 hours prior to presentation. Brain CT showed right basal ganglia and internal capsule haemorrhagic strokes. MRI revealed multiple brain lesions suspicious for metastases. Further workup revealed a 5 cm lung mass and a 1 cm pancreatic nodule. Biopsy of both pulmonary and pancreatic lesions was consistent with melanoma and was similar histologically. The patient underwent cyberknife stereotactic radiosurgery to the brain metastases followed by immunotherapy with pembrolizumab, and then by nivolumab and ipilimumab...
March 15, 2018: BMJ Case Reports
Charles S Fuchs, Toshihiko Doi, Raymond W Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia I Jalal, Manish A Shah, Jean-Phillipe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A Wainberg, Daniel V Catenacci, Atsushi Ohtsu, Kohei Shitara, Ravit Geva, Jonathan Bleeker, Andrew H Ko, Geoffrey Ku, Philip Philip, Peter C Enzinger, Yung-Jue Bang, Diane Levitan, Jiangdian Wang, Minori Rosales, Rita P Dalal, Harry H Yoon
Importance: Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. Objective: To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. Design, Setting, and Participants: In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016...
March 15, 2018: JAMA Oncology
Benjamin L Solomon, Ignacio Garrido-Laguna
The advent of immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4) has resulted in unprecedented long-term remissions of unresectable cancers. The efficacy of checkpoint inhibitors was recently demonstrated in gastrointestinal malignancies with mismatch repair deficiencies (dMMR). Pembrolizumab became the first tissue-agnostic US FDA-approved drug based on the presence of the predictive biomarker dMMR. In addition, the FDA in 2017 approved pembrolizumab for PD-L1-positive advanced gastric cancer in third-line and second-line hepatocellular therapy...
March 15, 2018: Future Oncology
Shrujal Baxi, Annie Yang, Renee L Gennarelli, Niloufer Khan, Ziwei Wang, Lindsay Boyce, Deborah Korenstein
OBJECTIVE: To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials...
March 14, 2018: BMJ: British Medical Journal
Jad Chahoud, Miao Zhang, Amishi Shah, Sue-Hwa Lin, Louis L Pisters, Shi-Ming Tu
PURPOSE OF REVIEW: In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs). RECENT FINDINGS: Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs, with recent evidence showing that the adverse health outcomes of etoposide and cisplatin for four cycles in comparison to bleomycin, etoposide, and cisplatin for three cycles appear to be similar. Recent data showed that multidisciplinary clinic approach and management in experienced academic centers were associated with improved overall survival in GCT patients...
March 13, 2018: Current Opinion in Oncology
Andrea Bianco, Umberto Malapelle, Danilo Rocco, Fabio Perrotta, Gennaro Mazzarella
Cancers have the ability to disrupt immune response by interfering with adaptive immunity. Blocking checkpoint pathways has become a target for pharmacological research in lung cancer with particular focus on peptides PD-1 and CTLA-4. A number of immune check-point inhibitors (ICIs) targeting both PD-1 and CTLA-4 pathways are under investigation within clinical trials, of which Nivolumab, Pembrolizumab and Atezolizumab have already been approved for lung cancer treatment by both FDA and EMA. Employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC) ICIs have exhibited advantages in terms of overall survival and response rate with some responses being durable...
March 8, 2018: Current Opinion in Pharmacology
Dmitry Ratner, Jochen K Lennerz
No abstract text is available yet for this article.
March 9, 2018: Oncologist
Lionel Kankeu Fonkoua, Nelson S Yee
Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively...
March 9, 2018: Biomedicines
Y Taniguchi, A Tamiya, S Ishii, S Atagi
No abstract text is available yet for this article.
March 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
M Alsharedi, R Srivastava, N Elmsherghi
Immunotherapy has revolutionized cancer care in the modern era of oncology. Research in immunotherapy has led to important advances in the treatment of melanoma, non-small cell lung cancer and other malignancies using checkpoint inhibition. Multiple systemic immunotherapies have been approved or are currently being investigated for the management of urothelial malignancies (1). Five antibodies targeting the programmed cell death protein 1--programmed cell death 1 ligand 1 (PD-1--PD-L1) pathway have been approved by the U...
December 2017: Drugs of Today
Ghina Fakhri, Reem Akel, Ziad Salem, Ayman Tawil, Arafat Tfayli
Background: Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported. Case Presentation: We report the case of a 74-year-old male patient diagnosed with stage IIIA programmed death-ligand 1-positive non-small cell lung adenocarcinoma treated with 4 cycles of carboplatin/pemetrexed plus pembrolizumab combination therapy followed by 2 cycles of pembrolizumab treatment...
September 2017: Case Reports in Oncology
Marzia Del Re, Riccardo Marconcini, Giulia Pasquini, Eleonora Rofi, Caterina Vivaldi, Francesco Bloise, Giuliana Restante, Elena Arrigoni, Chiara Caparello, Maria Grazia Bianco, Stefania Crucitta, Iacopo Petrini, Enrico Vasile, Alfredo Falcone, Romano Danesi
BACKGROUND: PD-L1 expression in tumour tissues is widely used to select patients to receive anti-PD-1/PD-L1 antibodies, but data are lacking on the correlation of plasma PD-L1 levels with the effect of treatments. METHODS: To investigate the association between PD-L1 mRNA in plasma-derived exosomes and response to nivolumab and pembrolizumab in patients with melanoma (n=18) and NSCLC (n=8), blood was obtained at time point 0 and after 2 months. Exosomal PD-L1 mRNA was measured by digital droplet PCR...
March 6, 2018: British Journal of Cancer
Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, Mark Evers, Susanne Arnold, Lowell Anthony
This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors. Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series. Design: Case series and review of literature. Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab). Main Outcomes and Measuress: Life expectancy, quality of life, disease progression...
February 6, 2018: Oncotarget
Dean R Cugley, Samuel J Roberts-Thomson, Alan A McNab, Zelda Pick
Merkel cell carcinoma is a rare neuroendocrine tumor of subspecialized dermal mechanoreceptors, associated with immunosuppression. The usual ophthalmic presentation is an eyelid lesion. The authors present a case of biopsy-proven orbital metastatic Merkel cell carcinoma in the absence of any eyelid lesion, in an immunosuppressed patient with a history of multiple cancers. There are to the authors' knowledge only 2 other case reports of presumed metastatic Merkel cell carcinoma to the orbit, though neither were biopsied...
March 2, 2018: Ophthalmic Plastic and Reconstructive Surgery
Qu-Knafo Lise, Auregan-Giocanti Audrey
Purpose: To report a case of bilateral panuveitis with multifocal choroiditis associated with a systemic sarcoidosis unmasked by pembrolizumab. Case report: A 68-years old woman with a history of metastatic melanoma treated by pembrolizumab consulted for bilateral blurred vision. The ophthalmologic examination revealed a bilateral anterior uveitis with cells in the anterior chamber and granulomatous keratic precipitates, vitreous cells and multifocal choroiditis confirmed by indocyanine green angiography...
April 2017: American Journal of Ophthalmology Case Reports
Danielle Benedict Sacdalan, Josephine Anne Lucero, Dennis Lee Sacdalan
Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients...
2018: OncoTargets and Therapy
Marlana Orloff
The incidence of cutaneous melanoma in the elderly continues to rise. Immunotherapies such as the immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have shown great promise in the management of this disease. There are growing data, mostly out of clinical trial experience, that shows the efficacy and tolerability of these agents across all ages, including those older than 75 years. Though at first glance immunotherapy for melanoma may appear to be a one-size fits all when it comes to age, a rationale is evolving for why this approach may warrant additional personalization in the older patient...
March 2, 2018: Current Oncology Reports
Paul J Bröckelmann, Stephanie Sasse, Andreas Engert
With defined chemo- and radiotherapy and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in the majority of patients. A major current goal is hence to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease, i.e. limited stage without risk factors (RFs), are frequently treated with two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (2xABVD) followed by 20Gy involved-field or -site radiotherapy (IF/IS-RT)...
March 2, 2018: Blood
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