Abstract

Pancreatic cancer is the fourth leading cause of cancer-related death in both sexes in the United States. In 2013, it is expected to account for 7% of all female cancer deaths and 6% of all male cancer deaths in the USA. Late presentation of the disease and poor prognosis even after complete operative resection, justify the necessity for early detection of pancreatic cancer as well as identifying high-risk individuals (screening). Herein, the authors summarize the data presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting regarding screening and early detection of pancreatic cancer (Abstracts #4045 and #4052).

Abstract

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are potentially malignant intraductal epithelial neoplasms which consist of columnar, mucin-containing cells and arise from the epithelium of the main pancreatic duct or its branches. IPMNs as well as pancreatic intraepithelial neoplasias (PanINs) and mucinous cystic neoplasms represent noninvasive precursors of invasive ductal adenocarcinoma of the pancreas. The diagnosis of IPMNs includes radiographic (CT scanning, MRI, MRCP) and endoscopic evaluation (ERCP, EUS), PET, as well as serum tumor markers and molecular markers. The Sendai Consensus Guidelines help guide surgical resection for patients with IPMN. The follow-up of these patients, as well as of those who do not undergo surgical resection, is of great importance, since patients with IPMN appear to be at risk for other malignancies. Herein, the authors summarize the data presented at the 2013 ASCO Gastrointestinal Cancers Symposium regarding incidence and clinicopathological characteristics of IPMN (Abstracts #324, #187 and #179).

Abstract

Introduction: The emergence of molecularly targeted agents and immune checkpoint inhibitors has positively revolutionized the management and prognosis of BRAF-mutant metastatic melanoma. However, the availability of both therapeutic options, with their pros and cons, rationally triggered clinical considerations for the optimum frontline and subsequent treatment decisions. Areas covered: Here, we debate all approved therapies in patients with BRAF-mutant metastatic melanoma evaluating their efficacy and safety based on their pivotal trials. With prospective randomized data pending, retrospective comparisons of BRAF/MEK versus immune checkpoint inhibitors are reviewed to recognize any advantage between these two alternatives and to optimize their implementation. Preclinical and early clinical results of combining concurrently or sequentially targeted therapy and immunotherapy are also discussed. Expert opinion: BRAF/MEK inhibitors produce rapid and deep responses and should be included in first-line approaches, particularly in cases with aggressive and bulky disease, while single or double checkpoint inhibition lead to more durable responses and could be involved either in frontline treatment of BRAF-mutant melanoma with less unfavorable characteristics or in maintenance after initial targeted induction or in future immune/targeted regimens for high-risk groups. Data from ongoing trials directly comparing or combining these strategies are expected to update their role in a more individualized basis.

Abstract

In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this therapeutic panel. Among the ICPIs-treated cases with prior viral hepatitis, we focus further on those experienced HBV or HCV reactivation and discuss their host, tumor and serological risk factors, their antiviral and immunological management as well as their hepatitis and tumor outcome. Based on a low level of evidence, immunotherapy in these specific cancer cases seems to be associated with no inferior efficacy and with a relevantly low reactivation rate. However, hepatitis reactivation and subsequent irreversible complications appeared to have poor response to deferred antiviral treatment. While, the prophylactic use of modern antiviral drugs could eliminate or diminish up front the viral load in most cases, leading to cure or long-term hepatitis control. Taking together the clinical significance of preventive therapy, the low but existing reactivation risk and the potential immune-related hepatotoxicity, a comprehensive baseline assessment of liver status, including viral hepatitis screening, before the onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.

Abstract

The management and prognosis of BRAF-mutant metastatic melanoma have changed drastically following the introduction of immune checkpoint inhibitors and molecularly targeted agents. These treatment options present different mechanisms of action and toxicities but also totally distinct kinetics of their response, including a "relatively" short-lasting benefit in subsets of patients treated with BRAF/MEK inhibitors and a lower response rate in patients treated with immune checkpoint inhibitors. BRAF/MEK inhibitors, when administered prior to or concurrently with immune checkpoint inhibitors, at least transiently alter some immunosuppressive parameters of the tumor microenvironment and theoretically improve sensitivity to immunotherapy. Preclinical data from mouse models with oncogene-addicted melanoma confirmed this beneficial immune/targeted synergy and supported the clinical testing of combinations of BRAF/MEK inhibitors and immune checkpoint inhibitors to improve the activity of upfront anti-melanoma therapies. The first positive phase III results were published in 2020, and triggered the discussion about the benefits, the limitations, as well as the possible implications of combining or sequencing targeted therapies with immune checkpoint inhibitors in everyday practice. Beginning from the interplay of immune/targeted agents within the melanoma microenvironment, this review outlines available information from the retrospective experience up to the late- stage randomized evidence on combinatorial treatments. Many clinical trials are currently underway exploring open questions about optimal timing, new immune biomarkers, and eligible patient subsets for these immune/targeted regimens. Awaiting these results, decision making in the first- line setting for BRAF-mutant melanoma is still guided by the patients' characteristics and the biological aspects of melanoma.

Abstract

BACKGROUND Persistent air leak following pulmonary lobectomy can be very difficult to treat and results in prolonged hospitalization. We aimed to evaluate the efficacy of a new method of postoperative air leak management using intrapleurally infused fresh frozen plasma via the chest tube. MATERIAL AND METHODS Between June 2008 and June 2014, we retrospectively reviewed 98 consecutive patients who underwent lobectomy for lung cancer and postoperatively developed persistent air leak treated with intrapleural instillation of fresh frozen plasma. RESULTS The study identified 89 men and 9 women, with a median age of 65.5 years (range 48-77 years), with persistent postoperative air leak. Intrapleural infusion of fresh frozen plasma was successful in stopping air leaks in 90 patients (92%) within 24 hours, and in 96 patients (98%) within 48 hours, following resumption of the procedure. In the remaining 2, air leak ceased at 14 and 19 days. CONCLUSIONS Intrapleural infusion of fresh frozen plasma is a safe, inexpensive, and remarkably effective method for treatment of persistent air leak following lobectomy for lung cancer.

Abstract

Background/aim: The treatment of patients with solitary hematogenous metastases from non-small cell lung cancer (NSCLC) remains controversial, although numerous retrospective studies have reported favorable results for patients offered combined surgical therapy. Our aim was to determine the role of surgical resection in the management of NSCLC with solitary extrapulmonary metastases and to investigate for possible prognostic factors. Patients and methods: Between January 2004 and December 2012, 12 patients with NSCLC, from two Institutions, underwent metastasectomy for their solitary metastatic lesion. Sites of metastases included brain (n=3), adrenal gland (n=6), thoracic wall (n=2) and diaphragm (n=1). All patients had undergone pulmonary resections for their primary NSCLC. Results: Median survival for the entire cohort was 24.1 months, whereas 1- and 5-year survival rates were 73% and 39%, respectively. Patients with stage III intrathoracic disease had significantly worse survival than those with lower tumor stage. A tendency for adenocarcinomatous histology to positively affect survival was recognized, although it was proven not to be statistically significant. Conclusion: Despite the retrospective nature of our study and the small cohort size, it is emerging that combined surgical resection might offer patients with NSCLC with solitary hematogenous metastases a survival benefit. Limited intrathoracic disease and adenocarcinomatous histology might be associated with better outcomes.

Abstract

Case report A 44-year-old white man presented with a 3-month history of dry cough and weakness. He had already been treated with antibiotics without any relief. He did not report dyspnea, fever, or expectoration. The patient's medical history was significant for mild arterial hypertension and autoimmune thyroiditis with normal thyroid hormone levels. He was a nonsmoker and had been in excellent health until symptom onset.

Abstract

Purpose: Stage IV disease at initial presentation accounts for approximately 41% of newly diagnosed cases with non-small cell lung cancer (NSCLC). Although the majority of these patients have disseminated metastatic disease at diagnosis, a small percentage of them are found to have a solitary site of extrathoracic metastasis. In addition, patients who have received surgical or multimodality treatment with curative intent may experience metachronous solitary distant recurrences during the natural course of their disease. Our aim was to review the possible role of surgical resection in the management of NSCLC with solitary hematogenous metastasis. Methods: We performed electronic literature search of PubMed, EMBASE and the Cochrane Library for articles in English using a number of key words. Results: All identified studies reported survival benefit for patients operated for their single metastatic lesion. Patients with metachronous disease had slightly better prognosis than those with synchronous metastatic lesions. We found no prospective randomized trials comparing surgical and non-surgical treatment modalities for NSCLC with solitary hematogenous metastasis. Conclusions: Available evidence supports the presumption that in highly selected patients with isolated synchronous or metachronous hematogenous metastasis surgical resection as part of an aggressive approach positively affects patients' survival. Factors that are in favor of a satisfactory outcome include control of primary site, confirmed solitary metastatic disease, good performance status (PS), metachronous lesions and longer disease-free interval (DFI). Prospective randomized trials are necessary to provide stronger evidence. Finally, it is worth investigating the biology of these tumors presenting with single-site distant metastasis.