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1.
AGA Technical Review on Systemic Therapies for Hepatocellular Carcinoma.
Altayar, O, Shah, R, Chang, CY, Falck-Ytter, Y, Muir, AJ
Gastroenterology. 2022;(3):937-951
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2.
Appendiceal tumors with glandular and neuroendocrine features exhibiting peritoneal metastases - Critical evaluation of outcome following cytoreductive surgery with perioperative chemotherapy.
Barrak, D, Desale, S, Yoon, JJ, Dugan, MM, Kodavanti, PP, Sampah, ME, Sugarbaker, PH
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(6):1278-1285
Abstract
BACKGROUND A rare appendiceal malignancy is characterized by both glandular and neuroendocrine histology. It often presents with dissemination of the perforated tumor to peritoneal surfaces. Current treatments involve systemic chemotherapy, cytoreductive surgery and perioperative intraperitoneal chemotherapy. METHODS The impact of clinical, histological and treatment-related characteristics on survival were evaluated and subjected to univariate statistical analyses. All patients had stage IV disease and were treated by a uniform treatment strategy. Survival was determined from onset of disease until death or most recent follow-up. RESULTS There were 47 patients available for study of whom 17 were male. Median age was 48 with a range of 27-65. None or a single symptom vs. 2 or more symptoms had a significant effect on survival. Median survival of the entire cohort was 45 months and 34.88% and 8.72% of patients survived 5 and 10 years, respectively. The use of neoadjuvant chemotherapy showed no impact on survival. Patients with a peritoneal cancer index (PCI) of 0-20 as compared to PCI > 20 survived longer (p = 0.012). The survival of patients able to have a complete resection as compared to an incomplete resection of disease was significant (p = 0.0087). The type of perioperative chemotherapy did not alter survival. CONCLUSIONS These data show that patients with a lesser extent of disease with a complete cytoreduction had an improved prognosis. No benefit from systemic or perioperative regional chemotherapy was apparent. With long-term follow-up, patients with the combined glandular and neuroendocrine histology exhibiting peritoneal metastases have a guarded prognosis.
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3.
Future Directions in Chronic Phase CML Treatment.
Javidi-Sharifi, N, Hobbs, G
Current hematologic malignancy reports. 2021;(6):500-508
Abstract
PURPOSE OF REVIEW This review will focus on recent and emerging treatment paradigms in chronic phase CML. The discussion of each novel treatment or drug combination will include a brief overview of scientific rational and pre-clinical data, followed by recently published or ongoing clinical trial efforts. The review will be divided into three focus areas in CML treatment: new frontline approaches and approaches to deepen remission, second treatment-free remission studies, and the treatment of refractory disease. RECENT FINDINGS The section on new frontline approaches will highlight several strategies of combination therapy. These can be grouped into immunomodulatory approaches with interferons and immune checkpoint inhibitors, targeting of leukemia stem cells with compounds such as venetoclax and pioglitazone, and BCR-ABL1-intrinsic combination therapy with asciminib. The chance at a second treatment-free remission is an important emerging clinical trial concept, and again combination approaches are under investigation. Lastly, in advanced disease, the development of novel tyrosine kinase inhibitors remains a major focus. This review will provide an overview and perspective of treatment strategies on the horizon for chronic phase CML. Despite the already excellent clinical outcomes for most patients, challenges remain with regard to deepening initial responses, prolonging treatment-free remission, and providing efficacious and tolerable options for patients with refractory disease and resistance mutations.
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4.
Metastatic Acinar Cell Carcinoma of the Pancreas: A Retrospective Cohort Study on Systemic Chemotherapy and Review of the Literature.
Busch, E, Werft, W, Bougatf, N, Hackert, T, Jäger, D, Springfeld, C, Berger, AK
Pancreas. 2021;(3):300-305
Abstract
OBJECTIVES Acinar cell carcinoma of the pancreas (pACC) forms a rare subgroup of pancreatic tumors. We report on our institutional experience with systemic first- and further-line therapy in patients with metastatic pACC and embed our findings in a review of the literature. METHODS Patients with stage IV pACC who started systemic treatment between 2008 and 2019 at our institution were identified via our institutional database. Clinical data were extracted from the patients' electronic data records. Survival times were calculated by the Kaplan-Meier method. RESULTS Six patients received a fluoropyrimidine- and oxaliplatin-containing first-line treatment, and 4 patients were started on gemcitabine-based protocols. Median progression-free survival was 4.8 months [95% confidence interval (CI), 3.3 to not available (n.a.)], and median overall survival was 15.3 months (95% CI, 10.1 to n.a.). Residual survival for second-line treatment was 2.1 months (95% CI, 1.3 to n.a.), although 1 patient experienced almost complete remission under targeted therapy. CONCLUSIONS The most encouraging and deep responses result from poly-chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), which seems to be the appropriate choice in fit patients. Gemcitabine monotherapy seems without substantial activity in pACC. Whenever possible, patients with pACC should be screened for targetable mutations.
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5.
Acute promyelocytic leukemia current treatment algorithms.
Yilmaz, M, Kantarjian, H, Ravandi, F
Blood cancer journal. 2021;(6):123
Abstract
In 1957, Hillestad et al. defined acute promyelocytic leukemia (APL) for the first time in the literature as a distinct type of acute myeloid leukemia (AML) with a "rapid downhill course" characterized with a severe bleeding tendency. APL, accounting for 10-15% of the newly diagnosed AML cases, results from a balanced translocation, t(15;17) (q22;q12-21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. The PML-RARA fusion oncoprotein induces leukemia by blocking normal myeloid differentiation. Before using anthracyclines in APL therapy in 1973, no effective treatment was available. In the mid-1980s, all-trans retinoic acid (ATRA) monotherapy was used with high response rates, but response durations were short. Later, the development of ATRA, chemotherapy, and arsenic trioxide combinations turned APL into a highly curable malignancy. In this review, we summarize the evolution of APL therapy, focusing on key milestones that led to the standard-of-care APL therapy available today and discuss treatment algorithms and management tips to minimize induction mortality.
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6.
Oxaliplatin-induced Immune Thrombocytopenia: A Case Report and Literature Review.
Stack, A, Khanal, R, Denlinger, CS
Clinical colorectal cancer. 2021;(1):e1-e4
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Abstract
Oxaliplatin-induced immune thrombocytopenia is a rare manifestation of oxaliplatin hypersensitivity, presenting as an acute onset of severe thrombocytopenia after oxaliplatin administration. No standard therapeutic approach outside of permanent discontinuation of oxaliplatin exists. Here, we present a case of oxaliplatin-induced immune thrombocytopenia occurring after oxaliplatin retreatment for metastatic colon cancer. Possible mechanisms of disease and approach to treatment are discussed.
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7.
Acute promyelocytic leukemia with myelofibrosis: A case report and literature review.
Xiao, M, Qin, L, Niu, X, Zhou, P, Niu, J, Wei, S, Li, D, Dou, L, Zhang, W, Zhang, L, et al
Medicine. 2021;(13):e24567
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Abstract
RATIONALE Acute promyelocytic leukemia (APL) with myelofibrosis (MF) is rare, and only 14 cases have been reported in the literature to date. PATIENT CONCERNS A 42-year-old woman was admitted to the hospital with easy bruising and excessive bleeding. With the remission of the primary disease during treatment, the degree of fibrosis did not decrease, but worsened progressively. DIAGNOSIS The woman was diagnosed with acute promyelocytic leukemia with secondary myelofibrosis. INTERVENTIONS All-trans retinoic acid (ATRA) was discontinued after 6 months of complete remission of APL. Arsenic trioxide (ATO) was discontinued because of supraventricular tachycardia 9 months after complete remission of APL. OUTCOMES After withdrawal of ATRA for 2 months, the degree of fibrosis was significantly alleviated, and after withdrawal of ATRA for 8 months and ATO for 5 months, bone marrow biopsy showed no reticular fiber deposition. LESSONS In this case report and review of an additional 14 cases of APL with MF, we highlighted the importance of the degree of MF to be evaluated by bone marrow biopsy at the time of bone marrow aspiration when APL is suspected. If MF is present, the type of MF should be determined in a timely manner, and appropriate intervention measures should be taken accordingly.
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Efficacy and safety of sorafenib plus hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.
Regmi, P, Hu, HJ, Lv, TR, Paudyal, A, Sah, RB, Ma, WJ, Jin, YW, Li, FY
Surgical oncology. 2021;:101663
Abstract
BACKGROUND Sorafenib is the standard treatment for patients with advanced HCC with improvement in survival and radiologic progression of the disease. Recently, few studies have advocated the Sorafenib + HAIC combination therapy results in better overall survival and progression-free survival than Sorafenib monotherapy in patients with advanced HCC. Herein, we aim to identify the best possible treatment option among the above two lines of therapy for patients with advanced HCC. METHODS The fixed effects and a random-effects model were used to perform a meta-analysis for overall response rate overall survival, and adverse events. Subgroup analysis of the data of univariate analysis in each included trial was performed to identify the specific patient population who could be benefitted from the combination therapy. RESULTS Four RCTs containing 609 patients were included in the final analysis. The overall response rate (OR: 3.81; 95% CI 1.01 to 14.42; P = 0.05) and overall survival (HR: 0.70; 95% CI 0.40 to 1.24; P > 0.05) were comparable. Subgroup analysis of OS showed that patients with Child-Pugh score B (HR: 0.30; 95% CI 0.13 to 0.72; P < 0.05) and AFP <400 ng/ml (HR: 0.72; 95% CI 0.52 to 0.99; P < 0.05) were associated with significantly improved survival in the Sorafenib + HAIC group. Bone marrow suppression (OR: 3.76; 95% CI 2.58 to 5.48; P < 0.001) was significantly higher in the Sorafenib + HAIC group, but hepatic function impairment, constitutional symptoms, gastrointestinal events, and dermatological events were comparable (p > 0.05). CONCLUSIONS Patients with Child-Pugh score B and AFP <400 ng/ml may be benefited most from Sorafenib + HAIC combination therapy.
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Current strategies for intratumoural immunotherapy - Beyond immune checkpoint inhibition.
Yuan, J, Khilnani, A, Brody, J, Andtbacka, RHI, Hu-Lieskovan, S, Luke, JJ, Diab, A, Marabelle, A, Snyder, A, Cao, ZA, et al
European journal of cancer (Oxford, England : 1990). 2021;:493-510
Abstract
Immunotherapy has revolutionised cancer treatment through restoration of host antitumour immune response. Immune checkpoint inhibitors (ICIs) confer durable responses in only a subset of patients. Mechanisms of ICI resistance to improve durable response rates and overall survival are an area of intense clinical research. Robust clinical development is ongoing to evaluate novel combination therapies to overcome ICI resistance, including targeting immunoregulatory pathways in the tumour microenvironment. Intratumoural (IT) immunotherapies such as toll-like receptor agonists, stimulator of interferon-induced gene agonists, retinoic-inducible gene I-like receptor agonists and oncolytic viruses may represent potential combination treatment options to overcome ICI resistance. Use of IT immunotherapies in combination with ICIs may alter the tumour microenvironment to address resistance mechanisms and improve antitumour response. Optimisation of IT immunotherapy clinical trials will elucidate resistance mechanisms, facilitate clinical trial design, define pharmacodynamic predictors that identify patients who may most benefit and inform clinical development of combination immunotherapy regimens. Here we provide an overview of IT immunotherapy principles, mechanisms of action, categories of IT immunotherapeutics, emerging data, clinical development strategies, response assessment, dose and schedule determination, clinical trial design and translational study design.
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Biliary cancer: gateway to comprehensive molecular profiling.
Sardar, M, Shroff, RT
Clinical advances in hematology & oncology : H&O. 2021;(1):27-34
Abstract
Cholangiocarcinoma is a rare malignancy with a poor prognosis. The majority of tumors present at an advanced stage, and relapse often occurs after surgery conducted with curative intent. In both of these cases, standard treatment is a combination of cisplatin and gemcitabine. The use of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) in second-line treatment improves survival, but outcomes remain dismal. Studies have shown that cholangiocarcinoma possesses a wide spectrum of genetic aberrations. Clinical trials evaluating targeted therapies in patients with FGFR2 fusions, IDH1 mutations, and BRAF mutations have yielded very promising results, and the agents were generally well tolerated. Several FGFR2 fusion-targeted agents have achieved response rates between 20.7% and 35.5%, with disease stability rates ranging between 76% and 82%. Agents targeting FGFR2 fusions also have produced median progression-free survival (PFS) ranging from 5.7 to 6.9 months and median overall survival (OS) ranging from 12.5 to 21.1 months. Ivosidenib in patients with an IDH1/2 mutation has produced a response rate of 2% and a disease stability rate of 51%, with median PFS of 2.7 months and median OS of 10.8 months. In patients with a BRAF mutation, a combination of dabrafenib and trametinib led to an overall response rate of 51% and disease stability in another 40% of patients. Median PFS and OS were 9 and 14 months, respectively. Patients should be encouraged to participate in clinical trials.