Maintenance Oral Etoposide After High-Dose Chemotherapy (HDCT) for Patients With Relapsed Metastatic Germ-Cell Tumors (mGCT).

BACKGROUND: HDCT and peripheral-blood stem-cell transplant (PBSCT) can cure up to 60% of pts with relapsed mGCT. Maintenance daily oral etoposide after salvage therapy has demonstrated potential clinical benefit. We now evaluate the potential role of maintenance etoposide versus observation post HDCT+PBSCT in this nonrandomized retrospective analysis. METHODS: The prospectively maintained Indiana University testicular cancer database was interrogated. Patients with relapsed non-seminoma who completed HDCT+PBSCT and achieved complete serologic remission and hematologic recovery were evaluated. Outcomes of pts who received maintenance etoposide (N = 141) were compared to pts who were observed (N = 242). In this retrospective study, Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Univariable and multivariable cox regression models were used to determine variables associated with PFS. We also performed an additional analysis to compare the survival outcomes in the platinum-refractory patients' subgroup based on maintenance etoposide treatment. RESULTS: Two-year PFS in the maintenance etoposide vs observation group was 55% vs. 46% (P = .028). Two-year OS was 61% vs 54% (P = .04). A multivariable analysis was performed, including the factors: primary tumor site (testis vs. mediastinum), IGCCCG risk, platinum refractory, HDCT line of therapy (2nd vs ≥3rd), tumor marker amplitude at HDCT initiation, and receipt of maintenance etoposide post HDCT vs. observation. Maintenance etoposide was confirmed as an independent predictor of improved PFS with HR 0.51 [95% CI, 0.37-0.70] (P < .001). Two-year OS and PFS for platinum-refractory patients who received maintenance etoposide vs. observation group were 50.2% vs. 26.1% (P < .0001) and 44.2% vs.. 23.1% (P = .0003), respectively. There was no statistically significant difference in 2-year OS and PFS between the platinum-sensitive patients who received maintenance etoposide and those who were observed. CONCLUSION: Daily oral etoposide therapy produced encouraging efficacy results in patients with relapsed non-seminoma GCT (NSGCT) who completed HDCT and PBSCT and achieved complete serologic remission and hematologic recovery. Patients with platinum-refractory disease and poor prognostic features are potential candidates for daily maintenance oral etoposide post HDCT. These data have led to an ongoing randomized phase II clinical trial (NCT04804007).

Two Patients Experience Same-Day Analgesic Effect of Methadone on Trigeminal Neuralgia Secondary to Malignancy: A Case Report.

Trigeminal neuralgia (TN) secondary to malignancy leads to significant distress and subsequently impacts a patient's quality of life. Use of methadone as a first-line opioid analgesic in this subset of oncology patients is uncommon and is rarely initiated after traditional first-line therapies have failed. We report two patients with TN secondary to tumor burden who experienced significant analgesia within 24 hours of methadone initiation.

Innovation in Resident Core Oncology Education: Switching from an Inpatient Ward Rotation to a Hybrid Model of Inpatient Consultations and Outpatient Clinics.

Interest in an oncology career has decreased among internal medicine residents completing an inpatient hematology-oncology rotation. Over years, our institutional data at Indiana University School of Medicine reflected lower satisfaction with the oncology inpatient ward rotation as compared to other rotations. We hypothesized that a switch from an inpatient ward rotation to a hybrid model of inpatient consultations and outpatient clinics would improve resident satisfaction with their educational experience in oncology. Over the 6-month periods preceding and following the change in rotation format, residents were asked to complete anonymous rotation evaluations and rate their experiences on a 5-point Likert scale (poor 1 to excellent 5). Areas assessed included patient load, educational value of patient mix, quality of didactics and teaching, quality of patient care delivery, adequacy of time for reading, and overall rotation quality. The hybrid oncology rotation was rated as significantly superior to the traditional ward format in six out of eight areas including patient load, educational value of patient mix, time for study, teaching quality, relevance of material, and overall rating. Improvements in the perceived quality of patient care delivery (p = 0.139) and quality of didactics (p = 0.058) were also observed without reaching statistical significance. The balance of inpatient and outpatient experiences with the hybrid rotation was highly rated (4.5 ± 0.5). The implementation of a hybrid oncology rotation was associated with perceived improvement in educational value, patient mix, and time for reflection and study without apparent compromise in the quality of patient care delivery.

Prevalence of programmed death ligand-1 in patients diagnosed with non-small cell lung cancer in Lebanon.

INTRODUCTION: Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking. This study examines the prevalence and the clinical, demographic and pathological predictors of programmed death ligand-1 expression in patients diagnosed with non-small cell lung cancer in Lebanon. METHODS: Medical records of 180 patients diagnosed with primary non-small cell lung cancer at our institution and tested for programmed death ligand-1 expression were reviewed. Clinical, demographic and pathological information were collected and correlated with programmed death ligand-1 expression using the chi-square test and logistic regression. RESULTS: One hundred eleven of the 180 non-small cell lung cancer tumor samples tested positive for programmed death ligand-1 expression (61.7%). 27.2% of those tumor samples expressed programmed death ligand-1 in 1%-49% of tumor cells, while 34.4% of tumor samples expressed programmed death ligand-1 in 50% or more of their cells. Squamous histology and advanced stage were significant predictors of programmed death ligand-1 expression (odds ratio = 2.79, 95% confidence interval [1.13-6.90], p = 0.012 and odds ratio = 2.48, 95% confidence interval [1.23-4.99], p = 0.044, respectively). CONCLUSION: Similar to reports from other populations, our results suggest that programmed death ligand-1 expression in non-small cell lung cancer is highly prevalent in the Lebanese population, especially in patients with advanced stage at diagnosis or squamous cell carcinoma histology. Because of the small sample size, while more that 60% of the patients are Lebanese, the results of this article cannot be extrapolated to the Middle Eastern and the Levantine population.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Deep targeted sequencing analysis of hot spot mutations in non-small cell lung cancer patients from the Middle Eastern population.

BACKGROUND: The overall 5-year survival of lung cancer remains dismal despite the current treatment regimens. Testing for driver mutations has become routine practice for oncologists due to the presence of targeted therapy readily available for patients. Deep targeted sequencing through next generation sequencing (NGS) is an adequate methodology to detect mutations at multi-genetic levels. The molecular pathology of non-small cell lung cancer (NSCLC) is poorly understood in the Middle East and, to date, no other reports have been published on deep targeted sequencing of lung adenocarcinoma (LUAD) tissues. METHODS: Deep targeted sequencing using TruSeq Amplicon Cancer panel of 48 genes was performed on 85 formalin-fixed paraffin-embedded tissues from patients with LUAD who were treatment-naive at the time of the collection. Variants with an allele frequency higher than 10% were retained. RESULTS: Variant calling identified a total of 2,455 variants of which missense mutations were the most frequent (75.6%). All of our samples showed at least one mutation in one of the 10 most commonly mutated genes with FLT3 being the gene with the highest mutation rate (67%). TP53, KRAS and STK11 were the second, third and fourth most commonly mutated genes, respectively while EGFR mutation rate reached 22.4%. CONCLUSIONS: To the best of our knowledge, this is the first hot spot profiling study on patients from this area. The frequencies of mutated genes presented in our study showed similarity to other reported outcomes. At least one mutation was detected in our cohort of LUAD.

Burnout among Lebanese Oncologists: Prevalence and Risk Factors

Background: Burnout syndrome (BOS) is defined as a work-related psychological state characterized by emotional exhaustion, depersonalization, and low sense of personal accomplishment. Despite the extensive data on physician burnout, studies assessing the prevalence of burnout among oncologists in the Middle East and especially Lebanon are lacking. Our main objective was to determine this prevalence as well as identify potential factors associated with the development of burnout. Methods: This was a cross-sectional study conducted among medical, surgical, and radiation oncologists attending several Continuing Medical Education (CME) activities in Lebanon over the course of a three month period. Participants were asked to complete a self-administered questionnaire composed of socio-demographic and work characteristics, as well as the Maslach Burnout Inventory- Human Service Survey (MBI-HSS). Results: A total of 51 oncologists completed the survey. Medical oncologists constituted the majority (84.3%), followed by surgical oncologists (9.8%) and radiation oncologists (5.9%). Approximately 47.1% of our sample had a high burnout level in at least one of the domains. 33.3% of oncologists exhibited high emotional exhaustion (EE) scores, 19.6% demonstrated low personal accomplishment (PA) scores, and 13.7% displayed high depersonalization (DP) scores. There was no statistically significant association between overall burnout level and any of the demographic or work characteristics. However, age was significantly associated with EE (p=0.03), while DP scores were significantly associated with the number of patients seen daily (p=0.028). Conclusion: Burnout is common among cancer professionals in Lebanon. Future research is needed to explore the problem in depth and suggest effective preventive approaches.

Concordance between Immunohistochemistry and Microarray Gene Expression Profiling for Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Statuses in Breast Cancer Patients in Lebanon.

INTRODUCTION: Accurate evaluation of estrogen and progesterone receptors and HER2 is critical when diagnosing invasive breast cancer for optimal treatment. The current evaluation method is via immunohistochemistry (IHC). In this paper, we compared results of ER, PR, and HER2 from microarray gene expression to IHC in 81 fresh breast cancer specimens. METHODS: Gene expression profiling was performed using the GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix Inc). Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 status was performed using standard methods at a CAP-accredited pathology laboratory. Concordance rates, agreement measures, and kappa scores were calculated for both methods. RESULTS: For ER, Kappa score was 0.918 (95% CI, 0.77.3-1.000) and concordance rate was 97.5% (95% CI, 91.4%-99.7%). For PR, Kappa score was 0.652 (95% CI, 0.405-0.849) and concordance rate was 86.4% (95% CI, 77%-93%). For HER2, Kappa score was 0.709 (95% CI, 0.428-0.916) and concordance rate was 97.5% (95% CI, 91.4%-99.7%). CONCLUSION: Our results are in line with the available evidence with the concordance rate being the lowest for the progesterone receptor. In general, microarray gene expression and IHC proved to have high concordance rates. Several factors can increase the discordance rate such as differences in sample processing.

Paraneoplastic Pemphigus as a First Manifestation of an Intra-Abdominal Follicular Dendritic Cell Sarcoma: Rare Case and Review of the Literature.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is an extremely rare malignant tumor caused by proliferation of antigen-presenting follicular dendritic cells. The tumor most commonly arises in lymph nodes, with fewer than 30% of cases originating in extranodal sites. CASE PRESENTATION: We report the case of a 39-year-old previously healthy male patient who presented with paraneoplastic pemphigus in the setting of a large intraperitoneal mass with no associated lymphadenopathy. The biopsy results showed a cellular proliferation of mildly to moderately atypical oval-to-spindle-shaped cells admixed with a variably dense lymphoplasmacytic infiltrate suggestive of FDCS versus inflammatory myofibroblastic tumor. A pathology review following total resection of the abdominal mass confirmed the diagnosis of FDCS. The tumor cells showed positivity for CD35, CD21, CD45, and CD68, negative ALK staining, and limited smooth muscle actin immunoreactivity. The surgery was complicated by severe pneumonia and acidosis, resulting in a prolonged ICU stay and death. CONCLUSION: It is essential to maintain a high index of suspicion for FDCS and include it in the differential diagnosis of a spindle cell neoplasm, especially in the setting of paraneoplastic pemphigus. The histological and immunohistochemical features should be sufficient to confirm the diagnosis of FDCS.

Cancer-Related Pain: Prevalence, Severity and Management in a Tertiary Care Center in the Middle East

Background: Despite pain awareness and the development of treatment guidelines, cancer-related pain assessment and management remain suboptimal. Our objectives were to estimate the prevalence and severity of pain and its interference with daily activities, and evaluate adequacy of treatment in cancer patients in Lebanon. Methods: A total of 400 cancer patients aged 18 and above were interviewed at the American University of Beirut Medical Center surgical and medical oncology floors, outpatient clinics and chemotherapy units from March 2016-February 2017. The subjects covered were socio-demographics, clinical data, and presence of pain in the past month with use of the Brief Pain Inventory questionnaire. Descriptive statistics were conducted using t-test, chi-square and Fischer's exact tests. Pearson's correlation coefficients were used to examine relationships between pain severity and pain interference. Logistic regression was employed to determine risk factors for pain. Results: The majority of participants were Lebanese (76.0%), females (62.7%), married (80.2%), of Muslim faith (64.2%), of urban residence (85.8%), and with insurance plans (81.3%). Most had breast cancer (38.8%), were stage 4 (52.7%) and underwent a combination of surgery and systemic therapy (55.1%). The prevalence of pain in the past month was 29.8%. Among patients with pain, the highest proportion had moderate pain (37.8%) and around 46% received inadequate treatment. Conclusion: More awareness about cancer-related pain is needed to improve pain management and encourage referral to palliative care and pain specialists early-on in diagnosis of disease.

Anxiety, Depression and Quality of Life in Breast Cancer Patients in the Levant

Background: Limited data are currently available regarding the psychological well-being and quality of life of breast cancer patients after active treatment in Lebanon and the Arab region in general. The objective of this study was to determine the prevalence of anxiety and depression among Arab breast cancer patients and assess the quality of life with reference to socio-demographic and clinical characteristics. Methods: This cross-sectional study was conducted among female breast cancer patients diagnosed between January 2009 and March 2014, who were recruited from the outpatient clinics of Naef K. Basile Cancer Institute at the American University of Beirut Medical Center (AUBMC) from November 2015 till December 2016. An interview was conducted utilizing two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Socio-demographic and clinical characteristics that might predict patient quality of life were collected and summarized. Results: A total of 150 patients were interviewed (median age 53.5±10.4 years). Most were assessed 3 to 5 years (68.7%) after initial diagnosis and had undergone surgery, chemotherapy, radiation, or hormonal therapy (97.3%, 79.3%, 80.7% and 86.0%, respectively). The median total HADS score was 10.0 ± 8.0, with approximately 41.3% of study participants having abnormal scores on the anxiety subscale and 24.7% on the depression subscale. Significant predictors of total HADS score were nationality and level of education (p=0.001, p=0.001 respectively; R2=0.181). Participants who were Iraqi, had stage IV disease, had a household monthly income below 1000 USD, or had received chemotherapy exhibited significantly lower total FACT-B scores, these being highly negatively correlated with total HADS scores (rs= -0.73, p=0.001). Conclusion: There is a vital need for the development of individualized interventions and psychosocial support programs tailored to the physical and psychological well-being of breast cancer patients in the Levant region.

Prevalence and Correlates of Complementary and Alternative Medicine Use among Patients with Lung Cancer: A Cross-Sectional Study in Beirut, Lebanon.

Patients with lung cancer are increasingly seeking complementary and alternative medicine (CAM) to improve their physiological and psychological well-being. This study aimed to assess CAM use among lung cancer patients in Lebanon. Using a cross-sectional design, 150 lung cancer patients attending the Basile Cancer Institute at the American University of Beirut Medical Center were interviewed. Participants completed a questionnaire addressing sociodemographic characteristics, lung cancer condition, and use of CAM. The main outcome of interest was "use of any CAM therapy since diagnosis." Prevalence of CAM use was 41%. The most commonly used CAM modality among study participants was "dietary supplements/special foods." Results of the multiple logistic regression analyses showed that CAM use was positively associated with Lebanese nationality and paying for treatment out of pocket and was negatively associated with unemployment and having other chronic diseases. About 10% of patients used CAM on an alternative base, 58% did not disclose CAM use to their physician, and only 2% cited health professionals as influencing their choice of CAM. This study revealed a prevalent CAM use among lung cancer patients in Lebanon, with a marginal role for physicians in guiding this use. Promoting an open-communication and a patient-centered approach regarding CAM use is warranted.

Late-Onset Inflammatory Bowel Disease-Like Syndrome after Ipilimumab Therapy: A Case Report.

BACKGROUND: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis. CASE PRESENTATION: We report the case of a 71-year-old male patient diagnosed with BRAF wild-type metastatic melanoma treated with three cycles of ipilimumab, after which he developed grade 3 enteritis. The patient improved on treatment with steroids, and ipilimumab was permanently discontinued at this point. Three years later, the patient's diarrhea returned and colonoscopy revealed active chronic colitis with ulceration resembling inflammatory bowel disease. He was started on Asacol (mesalamine). The patient did not report extraintestinal symptoms typically associated with inflammatory bowel disease, nor did he have a personal or family history of bowel disorders. Moreover, his presentation was not typical of inflammatory bowel disease in the elderly. CONCLUSION: Our findings suggest a link between ipilimumab-induced grade 3 enteritis and late-onset inflammatory bowel disease-like syndrome. To our knowledge, the case is the first in the literature to report late-onset inflammatory bowel disease-like syndrome years after discontinuation of ipilimumab treatment.

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report.

BACKGROUND: Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported. CASE PRESENTATION: We report the case of a 74-year-old male patient diagnosed with stage IIIA programmed death-ligand 1-positive non-small cell lung adenocarcinoma treated with 4 cycles of carboplatin/pemetrexed plus pembrolizumab combination therapy followed by 2 cycles of pembrolizumab treatment. Follow-up PET-CT scanning showed a very good response at the level of the tumor but new-onset activity in bilateral hilar and mediastinal lymph nodes. Biopsy of these lymph nodes revealed a benign pathology with noncaseating granulomas consistent with immune-mediated sarcoidosis. CONCLUSION: The pathogenesis of immunotherapy-induced sarcoidosis is not yet known but has been reported in different cancers and using different checkpoint inhibitors. To our knowledge, this case is the first in the literature displaying pulmonary sarcoidosis in a patient with NSCLC 4 months after having initiated chemotherapy plus pembrolizumab combination therapy.