Is there a role for the platelet-to-lymphocyte ratio in chronic lymphocytic leukemia?

AIM: The rationale for platelet-to-lymphocyte ratio (PLR) in chronic lymphocytic leukemia (CLL) is that both the platelet and lymphocyte counts are affected by the CLL pathogenesis and could influence treatment decision-making. METHODS: Demographic and clinical data of CLL patients diagnosed at our institution between 1989 and 2013 were collected. Cox regression models were used to evaluate the role of PLR in the duration of watchful waiting, postdiagnosis survival and postchemotherapy survival. RESULTS: The data of 100 patients with CLL were reviewed for this study. The PLR correlated only to watchful waiting in the univariable analysis (Hazard ratio = 0.48 [0.32-0.73]; p = 0.018). In the multivariable analysis, the duration of watchful waiting was determined by Binet staging and lymphocyte count (p < 0.001). The postdiagnosis survival was determined by age (p = 0.002) and lymphocyte count (p = 0.010). CONCLUSION: The PLR did not seem to act as a prognostic biomarker for CLL.

A comprehensive review of the role of immune checkpoint inhibitors in brain metastasis of renal cell carcinoma origin.

The contribution of renal cell carcinoma (RCC) to brain metastases (BM) reaches 7-13%. These patients have limited survival with local control and targeted therapies. Immune checkpoint inhibitors (ICI) revolutionized the treatment landscape of RCC but commonly excluded BM patients from their pivotal trials. The daily clinical practice often imposes the use of ICI in RCC patients with BM in view of the promising survival times and durations of response. Only small prospective trials have included BM patients but rarely reported on the efficacy or safety of ICI in this subgroup. The available data is limited to small retrospective and prospective series that have shown comparable efficacy to that of the pivotal trials. In this review, we will discuss the biological rationale and potential concerns for the use of ICI in BM RCC. Furthermore, we will summarize BM subgroup data from the prospective and retrospective series of ICI in RCC as well as the use of cranial radiation and ICI.

The current state of immune checkpoint inhibitors in the first-line treatment of renal cancer.

Until recently, tyrosine kinase inhibitors (TKI) were the only approved drugs for the first-line treatment of metastatic renal cell carcinoma (mRCC). Emerging trials of immune checkpoint inhibitors (ICI)-based regimens have shown survival benefits over the standard TKI. These studies challenge a paradigm shift in the management of mRCC concerning the identification of the subgroup of patients that would benefit from ICI in treatment-naive mRCC, the possibility of treatment discontinuation between TKI and ICI, and the sequencing of surgery and systemic treatment. This paper reviews the currently available data and discusses the paradigm shift concerning first-line treatments of mRCC.

Do immune checkpoint inhibitors perform identically in patients with weight extremes?

The interaction between the two recent hallmarks of carcinogenesis, the immune system and energetic metabolism, has not been well investigated. The limited literature available on this topic describes a correlation between the efficacy and safety of immune checkpoint inhibitors with body mass index. A key knowledge gap is the understanding of this correlation as outcomes are strongly affected highlighting the need to prospective studies in this regard. This paper evaluates the rationale to these correlations at weight extremes and suggests the evaluation patient's weights and associated inflammatory profile before the initiation of immune checkpoint inhibition in cancer patients.

A network meta-analysis of the PD(L)-1 inhibitors in the salvage treatment of urothelial bladder cancer.

AIM: To determine which of the approved immune checkpoint inhibitors is the optimal treatment in metastatic urothelial bladder cancer. METHODS & MATERIALS: Only the pivotal Phase III trials of second-line metastatic urothelial bladder cancer were included in this network meta-analysis. RESULTS: This NMA included three pooled trials (NCT00315237, NCT02256436 and NCT02302807) of 1125 participants. Pembrolizumab was the only treatment with positive effect on overall survival compared with the best supportive care. The treatment discontinuation rates due to adverse events of the pembrolizumab and atezolizumab did not differ from that of the best supportive care. C onclusion: Our results confirmed the superiority of pembrolizumab in the management of metastatic urothelial bladder cancer.

A prospective clinical study of the implications of IL-8 in the diagnosis, aggressiveness and prognosis of prostate cancer.

AIM: We evaluated the relationship between IL-8 and prostate cancer (PCa) with emphasis on diagnosis, aggressiveness and prognosis. MATERIALS & METHODS: Prostate-specific antigen (PSA) and serum IL-8 were collected from patients undergoing prostate biopsy. IL-8 expression was evaluated on immunohistochemistry with IL-8 labeling index. Complete follow-up of this cohort was achieved over a period of up to 6 years with continuous follow-up of PSA levels. RESULTS: Among 135 patients, serum IL-8 level did not correlate to the diagnosis or aggressiveness of PCa. In 52 radical prostatectomy specimens, a higher IL-8 labeling index was detected in the tumor areas (0.4 ± 0.2 vs 0.33 ± 0.2; p = 0,007) but did not correlate to any of the prognostic markers: D'Amico classification (p = 0.52), Gleason score (p = 0.45), perineural (p = 0.83) and capsular invasion (p = 0.75). No correlation was found to PSA biochemical-free failure. CONCLUSION: IL-8 serum level was not a significant predictor of diagnosis, aggressiveness or prognosis of PCa.

Management of stage III non-small cell lung cancer.

Optimal management of patients with locally advanced non-small cell lung cancer remains challenging in the context of this heterogeneous disease. Despite aggressive therapeutic approaches, survival benefits are still unsatisfactory for what might be viewed as a localized malignancy. A combined modality approach offers patients superior outcomes, especially because technological advances and refined surgical procedures now provide better results with fewer complications. Nevertheless, several features of therapy remain controversial and lack formal prospective data. Traditional cytotoxic chemoradiation therapy may have reached a plateau and future perspectives opting to integrate molecularly targeted agents and immunotherapy might be the way to improve outcomes in this disease subset.

Advances in urothelial bladder cancer immunotherapy, dawn of a new age of treatment.

Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy. Despite the great success, there are still some unanswered questions and ongoing trials that are in progress to define the role of combination therapy and sequencing strategies. The objective of our manuscript is to summarize the most recent data on immunotherapy in advanced urothelial cancer. Current challenges and future perspectives of immunotherapy as a monotherapy or in combination strategies will also be analyzed.

Diffuse edema suggestive of cytokine release syndrome in a metastatic lung carcinoma patient treated with pembrolizumab.

Immune checkpoint inhibitors (ICIs) are actually being indicated more commonly in the management of chemoresistant cancer patients in view of their favorable toxicity profile in comparison to cytotoxic chemotherapy. In this paper, we report, to our knowledge, the first case suggestive of cytokine release syndrome secondary to pembrolizumab in a patient with metastatic lung squamous cell carcinoma. In view of the quick approvals of ICI and the absence of sufficient knowledge of the corresponding toxicity profile, the occurrence of any clinical or biological sign or symptom in patients receiving ICI requires further investigation.

Untreated chronic lymphocytic leukemia in Lebanese patients: an observational study using standard karyotyping and FISH.

AIM: We aimed to understand the biology of chronic lymphocytic leukemia (CLL) patients in Lebanon. MATERIALS & METHODS: We applied conventional cytogenetic and FISH studies on Lebanese patients diagnosed with CLL and undergoing a watch and wait approach. RESULTS: Our study disclosed 53.6% of patients with aberrant karyotypes among which 26.7% were complex karyotypes. Genetic aberrations included del(13q14) 46.4%, 14q32 translocation in 25%, trisomy 12 in 14.3%, del(17p13) and del(11q22) in 7.1% each. The deletion of 6q21/6q23 was not found in any of our patients. CONCLUSION: The higher prevalence of del(13q14) as a sole abnormality could be the primary event in inducing CLL. The del(17p13) and del(11q22) followed as potential drivers for progression in CLL patients with a watch and wait approach.

Immune checkpoint inhibitors renal side effects and management.

The choice of immunotherapy in the treatment of cancer has improved the prognosis of many patients affected by various malignancies. The high expectations foreseen with immunotherapy have led to fast approvals despite the incomplete understanding of the toxicity profiles in the different organs, including the kidneys. The high prevalence of chronic kidney disease in cancer patients complicates the issue further and requires a better knowledge of the renal safety profile to ensure an optimal safe treatment. This review summarizes the present knowledge of renal adverse events secondary to immune checkpoint inhibitors and discusses their pathophysiology, clinical presentation and adequate management. We also advocate the need for a multidisciplinary approach in patients with immune-related toxic adverse events.

Characteristics of Incident Testicular Cancer in Lebanon - 1990-2015 Single Institutional Experience.

BACKGROUND: Despite the fact that testicular cancer is a major health issue with its increasing incidence, very few studies have described its characteristics in the Middle East, particularly in Lebanon. MATERIALS AND METHODS: We report in this paper a retrospective pilot study of the characteristics of testicular cancer in Lebanon. The demographic, epidemiologic and survival characteristics of 178 patients diagnosed between 1990 and 2015 at an oncology clinic affiliated to Hotel Dieu de France Hospital were analyzed. RESULTS: The mean age at diagnosis was 32 ±10 years. The most prevalent testicular tumor was the germ cell type (GCT) (95.2%) of which non-seminomatous tumors (NST) were the commonest (64.7%). Most of our patients were diagnosed at an early stage. Lymph node spread affected most commonly the retroperitoneal region and distant visceral metastases occurred in 14.6%. All patients underwent orchiectomy with 67% receiving adjuvant treatment, mainly chemotherapy. After a median follow up of 2,248 days (75.9 months) 16 patients were reported dead. Two, five and ten-year overall survival rates were 96%, 94% and 89% respectively. The median overall survival rate was not reached. CONCLUSIONS: Despite being part of the developing world, demographic, epidemiologic and survival analyses of testicular cancer reported in our study are in line with those reported from developed countries and would allow us to extrapolate management plans from these populations.

Acquired factor inhibitor in a patient with monoclonal gammopathy of undetermined significance responding to rituximab.

Bleeding diathesis is a rare manifestation of monoclonal gammopathies that is often attributed to a dysfunction of the coagulation pathway. Patients usually present with a severe bleeding disorder attributed to an acquired factor inhibitor, most commonly factor VIII inhibitor. Data are sparse concerning this disease, and subsequently the best course of action is not yet defined in such clinical instances. In this article, we report the case of a patient, known to have a monoclonal gammopathy of unknown significance, who was followed for over two decades for a bleeding disorder attributed to an acquired thrombin inhibitor. We describe also the different modalities used as maintenance and event treatments as the patient presented repetitive cataclysmic bleedings.