Immunotherapy: last bullet in platinum refractory germ cell testicular cancer.

Testicular germ cell tumors are chemosensitive with very high cure-rates even in the metastatic setting. However, patients with platinum-refractory and relapsing tumors after autologous stem cell transplant have very poor outcomes despite salvage treatments, and with no effective alternative therapies. Immunotherapy, notably with PD-1 inhibitors, has proven to be very effective in treating various solid tumors. This review summarizes the experience with anti-PD-1 agents (pembrolizumab, nivolumab) in the treatment of testicular germ cell tumor relapsing after multiple lines of treatment, and exposes future trials evaluating newer checkpoint inhibitors in this setting.

The merit of tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma: a meta-analysis.

AIM: As no meta-analyses have evaluated tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate the benefit of sunitinib and pazopanib in the adjuvant setting. METHODS: This meta-analysis included all Phase III randomized controlled trials evaluating adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and placebo. RESULTS: There was a tendency for significant overall effect of both sunitinib and pazopanib on DFS (hazard ratio: 0.85; 95% confidence interval: 0.72-1.01; p = 0.06). There was no significant difference between the effect of sunitinib and pazopanib on DFS (p = 0.51;  I2 = 0%). CONCLUSION: Pazopanib and sunitinib could prolong DFS in the adjuvant treatment of high-risk RCC and seem equally effective in this setting.

Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer in a Lebanese experience: in all aspects.

BACKGROUND: Bladder cancer (BC) is the most common malignant tumor of the urinary tract and the 11th most frequent cancer worldwide. BC is the 2nd most common cancer in Lebanon in men and women. MATERIALS AND METHODS: After searching for patients records in the pathology and oncology database, we identified those who underwent a cystectomy between 2017 and 2019 in our hospital, Hotel Dieu de France - Beirut. We selected for the study the patients who have undergone a cystectomy for MIBC. We excluded patients who initially had a pelvic tumor, or a prostate cancer invading the bladder, and patients with absent medical record from the study. We also noted the gender of the patients, if they are smokers and the number of pack years at the time of diagnosis, as well as their age, the histological type of the tumor, its stage according to the TNM classification and its grade. We also noted whether neoadjuvant chemotherapy was taken by the study 's subjects. RESULTS: The total number of patients who met the inclusion and exclusion criteria was 38. The median age of the population was 66 (± 10) years and the median number of pack years at diagnosis was 60 (± 36). 79% of study 's patients were males and 21% were females. Regarding the tumor 's histological type, the urothelial type predominated with 92% while the remaining 8% were of the squamous type. Regarding treatment modalities, only 20% of patients in the study received neoadjuvant chemotherapy before cystectomy. 80% of patients underwent a cystectomy directly without neoadjuvant and/or adjuvant chemotherapy. No patient received adjuvant chemotherapy. Among the 7 patients, 2 patients (29%) presented a pathological complete response (pCR; equivalent to pT0N0M0). 14% had a pT3 stage post-neoadjuvant chemotherapy and 43% had a pT4 stage. DISCUSSION AND CONCLUSIONS: We can note a reluctance of urologists at our institution to prescribe neoadjuvant chemotherapy. It would therefore be interesting to extend the study to the national level with a larger number of patients, as well as to evaluate survival in patients who received neoadjuvant chemotherapy, especially in those presenting a pCR. Our study can serve as a point of change in the practice of urologists in Lebanon regarding BC.

Increased psychomotor retardation and tension as short-term neuropsychiatric adverse events of immune checkpoint inhibitors: A prospective cohort study.

Introduction: Patients undergoing cancer treatment as well as cancer survivors commonly describe behavioral alterations. As a matter of fact, neuropsychiatric adverse events (NPAEs) have been extensively described with older immunotherapies, especially with interferon alfa. However, there are little data investigating the NPAEs of immune checkpoint inhibitors (ICIs). Therefore, the aim of this study is to evaluate the safety profile of ICI in terms of NPAEs. Materials and Methods: This is a prospective, interventional, self-controlled study. Participants receiving ICIs as unique therapy, between February and December 2019, were evaluated at the beginning of their treatment protocol, at 1 month and finally at 3 months. During the three evaluations, disease and patients' characteristics were assessed, as well as NPAEs using the Brief Psychiatric Rating Scale (BPRS) questionnaire, the psychological stress due to cancer's burden using the Herth hope index, and the performance status (PS) using the Eastern Cooperative Oncology Group (ECOG) score. Results: Forty-four patients were enrolled, of whom 24 patients completed their three evaluation visits. No changes in BPRS total score were found throughout the study period. However, two subscores of the BPRS, "motor retardation" (P = 0.008) and "tension" or "nervousness" (P = 0.002), increased starting the 1st month of treatment. Moreover, age (r = 0.426, P = 0.038) and the baseline PS (P = 0.027) were the main risk factors of such manifestations. Conclusion: This study suggests that ICI could be responsible for motor retardation and increased tension starting the 1st month of treatment, with higher ECOG score and older age being the main risk factors.

HER2 in metastatic colorectal cancer: a new to target to remember.

Metastatic colorectal cancer is the second most common cause of cancer death. Standard chemotherapy in combination with targeted therapies represent the backbone for the treatment of advanced disease. However, options are limited for patients progressing on these regimens. Genetic testing can offer patients the opportunity to benefit from novel therapies, namely immune checkpoint inhibitors in microsatellite instability-positive tumors. HER2 overexpression has recently emerged as a potentially targetable tumor marker in colorectal cancer (CRC). Despite the absence of approvals for anti-HER2 therapies in CRC, many agents such as trastuzumab and pertuzumab were tested and demonstrated significant antitumor activity, even in heavily pretreated patients. Early trials are also evaluating lapatinib, T-DM1, tucatinib and other anti-HER2 agents in patients with metastatic CRC, with promising results.

An unusual case of chronic lymphocytic leukemia with trisomy 12 and t(14;18) and a favorable response to ibrutinib.

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. Chromosomal abnormalities are reported to play important roles in CLL pathogenesis and evolution, including deletions of 11q, 13q, 17p, and trisomy12, that are frequently observed and have a known prognostic value. Furthermore, the mutational status of the IGHV gene was reported as an independent prognostic marker in CLL impacting the choice of therapy. We herein, report an unusual presentation of a Lebanese CLL patient with two cytogenetic abnormalities: trisomy 12 and t(14;18)(q32;q21), along with an unmutated IGHV, displaying a favorable response to ibrutinib with a maintained complete remission.

Molecular profiling of basal cell carcinomas in young patients.

BACKGROUND: Basal cell carcinoma (BCC) represents by far the most common non-melanoma skin cancer (NMSC) in the world with an increasing incidence of 3% to 10% per year, especially in patients under the age of 40. While variants in the sonic Hedgehog and cell cycle regulation pathways account for the majority of BCC cases in adults, the molecular etiology of BCC in young patients is unelucidated yet. This study aims to investigate the molecular profile of BCC in the young population. METHODS: 28 tumors belonging to 25 Lebanese patients under the age of 40, presenting different stages of BCC and diagnosed at Hôtel Dieu de France-Saint Joseph University Medical Center were included in this study. A selected panel of 150 genes involved in cancer was analyzed by Next Generation Sequencing (NGS) in the 28 included tumors. RESULTS: Genetic variants detected in more than 5% of the reads, with a sequencing depth ≥ 50x, were selected. Two hundred and two genetic variants in 48 different genes were detected, with an overall average sequencing depth of 1069x. Among the 28 studied tumors, 18 (64.3%) show variations in the PTCH1 gene, 6 (21.4%) in TP53 and 3 (10.7%) in SMO. CONCLUSIONS: This is the first study reporting NGS-based analysis of BCC in a cohort of young patients. Our results highlight the involvement of the hedgehog and cell cycle regulation pathways in the genesis of BCC in the general population. The inclusion of a larger cohort of young patients is needed to confirm our findings.

Cancer Patients in the Era of Coronavirus: What to Fear Most?

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to a worldwide medical crisis, affecting mostly immunocompromised patients, such as cancer patients. Various cancer societies have issued recommendations regarding patients care, but few studies addressed the perception of cancer patients regarding this pandemic. OBJECTIVE: The aim of the study was to assess the perception of cancer patients regarding their health risks during this pandemic and the preventive measures taken. MATERIALS AND METHODS: An anonymous survey was conducted among cancer patients presenting for their treatment, during 10 consecutive working days, at the one-day clinic of Hotel-Dieu de France University hospital in Beirut. We evaluated their state of disease, comorbidities, precautions taken, and their concerns regarding the virus spread. RESULTS: A total of 216 patients responded with a mean age of 60 years. The majority had a good performance status (performance status = 0-1 in 79.6%), 51.4% had metastatic disease, and chemotherapy was the main therapy used (65.7%). A total of 52.3% of patients considered themselves to be at increased risk of contracting the virus. A total of 55.1% were more worried about the coronavirus rather than their disease. The priority was for the treatment of their cancer in 47.7% of the total patients studied. Of note, only 2.8% of planned one-day clinic reservations were canceled or postponed to avoid COVID-19 exposure. CONCLUSIONS: Although cancer is a disease with a high mortality rate, many patients are more concerned about the actual pandemic rather than their disease. Nevertheless, the absenteeism from their treatment sessions during the COVID-19 atmosphere was minimal.

Poly-(ADP-ribose) polymerase inhibitors: paradigm shift in the first-line treatment of newly diagnosed advanced ovarian cancer.

Debulking surgery associated with chemotherapy represent the backbone of ovarian cancer therapy. Adding bevacizumab has improved survival. Recently, PARP inhibitors were added in the first line as maintenance treatment for the patients who achieve a complete or partial response. These drugs act by blocking the activity of the PARP enzyme responsible for base-excision repair, and have shown positive responses when used for tumors lacking homologous recombination. Olaparib, niraparib and veliparib were evaluated and showed an increase in the duration of progression-free survival: 22.1 months (hazard ratio [HR] = 0.59), 13.8 (HR = 0.62) and 23.5 (HR = 0.68) with olaparib, niraparib and veliparib, respectively. This review describes the benefit of PARP inhibitors as maintenance therapy and discusses the efficacy according to breast cancer gene and homologous recombination status.

PARP inhibitors: a tsunami of indications in different malignancies.

The evolution of precision medicine in the field of oncology has led to a radical change in the course of malignancies. PARP inhibitors are drugs that block the activity of the PARP enzyme responsible for base excision repair and have shown significant positive response when used for tumors lacking homologous recombination, namely high efficacy among BRCA-mutated tumors. Since 2014, when olaparib received an accelerated US FDA approval in ovarian cancer, we witnessed many other FDA approvals for olaparib, rucaparib, niraparib and talazoparib. Additionally, many Phase I, II and III trials were published presenting revolutionizing results. Other ongoing trials combined PARP inhibitors with checkpoint inhibitors. We aimed in this review to state the FDA approvals for PARP inhibitors in breast, ovarian, fallopian tube and primary peritoneal cancers, report the major published trials in high impact medical journals, and mention the ongoing trials combining these drugs with checkpoint inhibitors.

The Opinion of Oncologists on the Practice of Hypnosis among Cancer Patients in Lebanon.

INTRODUCTION: Medical hypnosis has received an increasing attention during the past decades. Various applications of hypnosis can be incorporated into the oncology field. This study aims to assess the knowledge of Lebanese medical oncologists on the use of hypnosis in the management of cancer patients. MATERIAL AND METHODS: An anonymous questionnaire was sent to all Lebanese medical oncologists to assess their knowledge, opinion and understanding of hypnosis and its use in oncology, as well as the obstacles facing its application in Lebanon. RESULTS: Hundred and three Lebanese medical oncologists responded to the survey, with a response rate of 65%. The findings revealed that most oncologists had little or no knowledge about hypnosis, but recommended it due to the benefits they believed it provided for the patients in improving chronic pain, invasive procedures, chemotherapy-induced nausea and anxiety. Around 40% of participants were interested in receiving a training in hypnosis. Lebanese oncologists also described many obstacles to the practice of hypnosis, mainly the lack of training for this technique and the lack of financial resources. CONCLUSION: Despite all obstacles, the majority of Lebanese oncologists would recommend hypnosis to their patients in order to improve their quality of life.

A rare case of acute myeloid leukemia with t(12;19)(q13;q13).

Acute myeloid leukemia (AML) is characterized by chromosomal abnormalities affecting both prognosis and course of treatment. While most AML patients have well described chromosomal aberrations, around 10% present with rare chromosomal abnormalities. We herein, report a rare balanced translocation t(12;19)(q13;q13) in a 66-year old M5-AML patient identified by Conventional cytogenetic analysis and confirmed by SNP array. We suggest that t(12;19) as a sole chromosomal abnormality could be associated with a poor prognosis. Further studies are needed to understand the molecular basis of this translocation in AML.

The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review.

The use of immune checkpoint inhibitors has been approved in the advanced and metastatic setting for many types of solid tumors. Nonetheless, their role in the adjuvant setting is limited to the treatment of surgically resected melanoma. Ipilimumab was the first immune checkpoint inhibitor approved for this indication, followed by nivolumab and pembrolizumab. Many ongoing trials are evaluating these molecules in the postoperative setting, alone or in combination with other therapies. Preliminary results are promising regarding the treatment of other cutaneous tumors, lung cancers, head and neck squamous cell carcinomas, bladder cancer and renal cell carcinomas. Some data assessing their use for the adjuvant treatment of esophageal, colorectal, ovarian cancer and other solid tumors are similarly emerging.