Lung cancer and immunotherapy: a real-life experience from second line and beyond.

Aim: This study assessed the efficacy of anti-PD-1/PD-L1 agents in real life when used in second line or beyond. Materials & methods: Patients with advanced non-small-cell lung cancer progressing after standard chemotherapy and receiving immunotherapy in the second line or beyond were included. Results: One hundred and ten patients were included with PD-L1 expression above 50%, between 1-49 and <1% in 38.6, 27.3 and 34.1% of patients, respectively. Checkpoint inhibitors were used as second, third and fourth line in 74.7, 21.8 and 3.5%, respectively. Partial response was observed in 25.6% of patients. Median progression-free survival was 4 months and median overall survival was 8.1 months. Conclusion: Immunotherapies are emerging as important tools in the oncologic field with good responses in real-life practice.

Paraneoplastic syndromes in cancers of unknown primary: An unknown field for oncologists.

Paraneoplastic syndromes are signs or symptoms that result from tissue damage at locations remote from tumour sites. Paraneoplastic syndromes associated with cancer of unknown primary (CUP) are not well recognized as they are rarely reported. These syndromes can impair various organ functions and include endocrine, neurologic, dermatologic, rheumatologic, hematologic and several other system alterations. To our knowledge, the association between the histological CUP type and the paraneoplastic syndrome has never been assessed. In some instances, paraneoplastic syndromes can become the major clinical problems determining survival. However, they can also herald earlier the occurrence of CUP in patients with asymptomatic tumors. In this article, we review the available literature of CUP patients presenting paraneoplastic syndromes by trying to collect all available published cases during the last three decades. One additional goal of this article is to make practicing oncologists aware of the coexistence of paraneoplastic syndromes in patients with CUP.

Comparison of second-line treatments of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

AIM: The literature lacks direct evidence comparing the different regimens evaluated in the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: We conducted a network meta-analysis (NMA) of the randomized controlled Phase III trials reporting on the second-line drug treatment options in R/M SCCHN. RESULTS: The eligible trials included 11 regimens among which six targeted therapies, two immune checkpoint inhibitors and three chemotherapy regimens. Only nivolumab has shown statistically significant superiority over methotrexate in terms of overall survival (HR: 0.64; 95% CI: 0.43-0.96) and objective response rate (OR: 2.51; 95% CI: 1.07-5.86). CONCLUSION: Based on the efficacy and safety outcomes of this network meta-analysis, nivolumab seems the most favorable regimen inthe management of R/M SCCHN.

Comparative Efficacy of Anti-TNF Therapies For The Prevention of Postoperative Recurrence of Crohn's Disease: A Systematic Review and Network Meta-Analysis of Prospective Trials.

INTRODUCTION: There is a lack of studies on the optimal anti-tumor necrosis factor (anti-TNF) agent for postoperative prophylaxis of Crohn's disease (CD) recurrence. Therefore, we conducted a network meta-analysis (NMA) of prospective trials to compare the efficacy of anti-TNF agents in the prevention of postoperative endoscopic and clinical recurrence of CD following ileocolonic resection. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and recent American gastroenterology association (AGA) meeting abstracts through August 2017. We selected prospective studies comparing anti-TNF agents among each other or to other agents in the setting of postoperative prevention of CD recurrence. We performed a NMA using a frequentist approach with generalized pairwise modeling and inverse variance heterogeneity method. RESULTS: We identified 9 studies, including 571 patients and 5 treatment agents, among which 2 anti-TNF drugs (adalimumab and infliximab). Compared with infliximab, our NMA yielded the following results for endoscopic recurrence: adalimumab [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.18-4.75], thiopurines (OR, 4.11; 95% CI, 0.68-24.78), placebo (OR, 4.39; 95% CI, 0.70-27.68), and Mesalamine (OR, 37.84; 95% CI, 3.77-379.42). For clinical recurrence: adalimumab (OR, 1.03; 95% CI, 0.17-6.03), thiopurines (OR, 1.40; 95% CI, 0.20-10.02), placebo (OR, 1.77; 95% CI, 1.01-3.10), and mesalamine (OR, 16.54; 95% CI, 1.55-176.24). CONCLUSIONS: On the basis of a NMA combining direct and indirect evidence either adalimumab or infliximab may be used in the postoperative prophylaxis of CD recurrence. There is currently a lack of evidence on the use of other anti-TNF agents in this setting.

Factors associated with the time to first palliative care consultation in Lebanese cancer patients.

INTRODUCTION: Early palliative care is recommended for cancer patients. However, palliative care consults (PCC) are often delayed in Lebanon. The aim of this study was to identify the factors associated with timing of PCC and their impact on the place of death. METHODS: This is a retrospective, single institution, study conducted at Hotel Dieu de France University Hospital in Lebanon. The clinical and demographic characteristics of oncology patients who received PCC were obtained. Cox and logistic regression models were used to evaluate the factors determining the time to first PCC and location of death, respectively. RESULTS: Two hundred and ten patients were included in our analyses with a median age of 69 years (range 22-92 years). The median survival times were: overall survival 18.7 months, time to first PCC 17.9 months, and survival post-PCC 0.6 months. Among patients who were followed-up at home, the median time spent at home was 0.6 months. Late PCC were associated with a childless status (HR = 0.57, 95%CI = 0.37-0.86, p = 0.007), awareness of the diagnosis (HR = 0.64, 95%CI = 0.45-0.91, p = 0.013), and lack of palliative home care (HR = 0.42, 95%CI = 0.25-0.65, p < 0.001). Older patients (OR = 1.03, 95%CI = 1.01-1.05, p = 0.026) and those who had been followed up at home during the PCC (OR = 160.56, 95%CI = 21.39-1205.50, p < 0.001) were significantly more likely to have died at home as opposed to the hospital. DISCUSSION: Cancer patients often receive PCC only shortly before their death. PCC for Lebanese cancer patients were found to be significantly delayed in patients that are childless, knowledgeable of their diagnosis, and lack home palliative care.

A comprehensive review of the current evidence for trabectedin in advanced myxoid liposarcoma.

Myxoid liposarcoma (MLS) is a rare mesenchymal tumor that constitutes 10-20% of all liposarcomas. MLS is a translocation-related sarcoma (TRS) related to the chromosomal translocation t(12:16) (q13:p11), producing the FUS-CHOP oncoprotein that constitutes one of the main targets of trabectedin in MLS patients. It is known to be chemosensitive namely to trabectedin in contrast to other soft tissue sarcomas. The efficacy of this agent in MLS have been demonstrated in different settings including treatment-naïve and pre-treated patients with both locally advanced and metastatic disease. However, the benefits of trabectedin in MLS are shadowed by the limited activity of this drug in other subtypes of sarcomas that are enrolled within the same trials. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of trabectedin in MLS. In this review, we will summarize the available evidence for the applicability of trabectedin in MLS.

Second-line Treatments of Advanced Hepatocellular Carcinoma: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) constitutes the second leading cause of cancer-related deaths. First-line therapy is either sorafenib or lenvatinib. Several treatment options have been recently added to the second-line treatment of advanced HCC. The aim of this network meta-analysis of randomized controlled trials was to compare the second-line treatments of advanced HCC. METHODS: Network meta-analyses were computed for overall survival (OS), progression-free survival, rates of grade 3 to 5 adverse events, and for treatment discontinuation due to adverse events. OS was considered to be the primary outcome of this study, and everolimus was chosen to be the common comparator for efficacy analyses and placebo for safety analyses. Subgroup analyses were computed for OS in patients with hepatitis B, patients with hepatitis C, Asian patients, patients with macrovascular invasion, and patients with extrahepatic metastases. RESULTS: Thirteen randomized controlled trials including 5076 patients and evaluating 11 agents were found to be eligible. Regorafenib [hazard ratio (HR)=0.60, 95% confidence interval (CI)=0.44-0.81] and cabozantinib (HR=0.72, 95% CI=0.55-0.95) were found to significantly prolong OS compared with everolimus. The effect of regorafenib on OS tended to be conserved across patient subgroups. Regorafenib was also found to significantly prolong progression-free survival (HR=0.46, 95% CI=0.35-0.62) and significantly increase the rates of grade 3 to 5 adverse events (odds ratios=3.18, 95% CI=2.22-4.54) and treatment discontinuation due to adverse events (odds ratios=2.67, 95% CI=1.21-5.87). CONCLUSIONS: This network meta-analysis concludes that, based on current evidence, regorafenib could be the agent of choice in the second-line treatment of HCC, with cabozantinib as a possible alternative for sorafenib-intolerant patients.

Liquid biopsy: a new diagnostic, predictive and prognostic window in cancers of unknown primary.

Cancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers characterised by early dissemination of metastases in the absence of any identifiable primary site. Most patients with CUP have poor prognosis with the traditional diagnostic and treatment modalities. Recognising the putative primary tumour is hypothesised to ameliorate the prognosis of patients with CUP by guiding treatment decisions. The active efforts in molecular oncology have shown that gene expression profiling is able to identify the primary tumour site and to determine targetable mutations. In this regard, liquid biopsy opens a new diagnostic, predictive and prognostic window in CUP that may lead to substantial improvement in the management of patients with CUP.

Efficacy and safety of everolimus in hormone receptor positive breast cancer in a developing country: Real-life single institutional experience.

INTRODUCTION: Breast cancer is the second leading cause of cancer-related mortality despite the staggering improvement in cancer therapeutics. So far, published data illustrate endocrine therapy as the cornerstone treatment for patients with hormone receptor-positive metastatic breast cancer. Unfortunately, most patients eventually develop resistance to this treatment. METHODS: The purpose of this study is to evaluate the efficacy of mammalian target of rapamycin inhibition in reversing hormone resistance in the Lebanese breast cancer patients. Efficacy of the intervention according to the independent factors and notable side effects encountered were the primary points of the evaluation. RESULTS: In total, fifty patients received the combination of everolimus and exemestane. The mean age of the study population was 61 ± 11 years. Sensitivity to hormonal therapy before the start of the combination treatment was estimated at 64%. Response rate was 14%, and all patients were partial responders. After regular interval evaluation, the median progression-free survival was 5.2 months since the initiation of therapy. The main toxicities associated with the combination were stomatitis (22%), myalgia (22%), skin toxicity (8%), and hyperglycemia (4%), all Grades 1 and 2. CONCLUSION: Everolimus has been shown to be effective in overcoming hormonal resistance in Lebanese breast cancer patients with results inferior to those reported in the BOLERO-2 population. The particular differences in molecular and pathological aspects of breast cancer in our region should stimulate the extensive research for a better understanding of the particular pattern of the disease.

Prognostic utility of neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio in predicting biochemical recurrence post robotic prostatectomy.

AIM: Utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting biochemical recurrence (BCR) in patients with localized prostate cancer. MATERIALS & METHODS: Retrospective analysis of patients operated by robot-assisted radical prostatectomy. Variables included were: NLR, PLR pre-operative prostate specific antigen, pathological Gleason score, surgical margins status, extracapsular extension, seminal vesical invasion, and lymph node status. RESULTS: Out of 321 patients, no association between NLR or PLR and BCR was detected. Predictors of BCR were pathological Gleason score, extracapsular extension and positive surgical margins. On multivariate analysis, the Gleason Score, extracapsular extension and positive surgical margins remained the only predictors of BCR. CONCLUSION: Neither elevated NLR nor PLR predicted an increased risk of BCR.

Toxicities Associated with Docetaxel-Based Regimens in the Adjuvant Treatment of Early-Stage Breast Cancer: A Multicenter Prospective Real-Life Experience.

BACKGROUND: The present study reports on the efficacy and safety of adjuvant docetaxel in real-life patients with early-stage breast cancer. METHODS: This is a prospective, multicenter, post-marketing study that evaluates the efficacy and safety of docetaxel-based regimens in patients with early breast cancer treated between 2007 and 2012. RESULTS: A total of 698 female breast cancer patients receiving adjuvant docetaxel-based regimens were included in this study. Docetaxel monotherapy was administered in 4.2%, whilst most patients received polychemotherapy. Non-hematological adverse events included skin reactions in 32.7% of the subjects. Multiple adverse events were reported and most commonly included asthenia (66.5%), alopecia (43.4%), and diarrhea (24.2%). It is noteworthy that no fatal toxicities occurred. Several hematological adverse events were reported during treatment, with anemia being the most common. CONCLUSION: The results of this real-life experience, characterized by a relatively large sample size and long follow-up, confirm that docetaxel is effective and well tolerated in early-stage breast cancer patients.

Non-small cell lung cancer brain metastases and the immune system: From brain metastases development to treatment.

Brain metastases (BM) are diagnosed frequently in non-small cell lung cancer (NSCLC) patients. Despite the high incidence of BM (up to 40% in unselected patients), patients with untreated and/or unstable BM were excluded from pivotal immune checkpoint inhibitors (ICI) NSCLC trials. Percentage of patients with stable and treated BM in these trials ranged from 9.1 to 14.7% and ICI benefit over chemotherapy was not always demonstrated. Only small trials have been completed that demonstrated ICI efficacy in locally untreated, selected BM patients. With 33%, cranial objective response rate (ORR) was comparable to extracranial ORR and responses were often durable. With the promising survival benefits of ICI, in daily practice also unstable and/or untreated BM patients will often receive treatment with ICI and extrapolating clinical trial data to these patients can be challenging. In this review, we will summarize the preclinical rationale and potential concerns for the use of ICI in BM patients. Furthermore, we will summarize BM subgroup data from the pivotal NSCLC trials, retrospective series, the NSCLC BM specific ICI trials and the use of cranial radiation and ICI. Last, we provide an overview of response measurement criteria and future directions.

CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

The current evidence for a biomarker-based approach in cancer of unknown primary.

Cancer of unknown primary (CUP) accounts for the seventh to eighth most frequently diagnosed cancer yet its prognosis remains poor with conventional chemotherapy. The spectrum of therapeutic management includes both locoregional and systemic therapy and should intend to offer optimal benefit to favorable CUP patients and palliative care to unfavorable cases. The recent molecular advances have revolutionized the armamentarium of cancer treatments though a biomarker-based approach. Unfortunately, solid data in CUP is lacking in the absence of a CUP-specific driver molecular signature. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of the biomarker-based approach in CUP patients. In this review, we will summarize the available evidence for the applicability of targeted therapies in CUP.