Beyond clinical trials: real-world impact of immunotherapy on NSCLC in Jordan.

Background: This study aims to evaluate real-world (rw) outcomes of immunotherapy (IO) for advanced stage NSCLC at King Hussein Cancer Center (KHCC) in Jordan. Methods: Advanced stage NSCLC patients who received IO at KHCC between 2017 and 2022 were included. The data were retrospectively collected. PFS and OS were estimated for patients with ECOG performance status (ECOG PS) 0-1. Cox regression analyzed predictors of OS in first-line (1L) IO, regardless of performance status. Results: The total number of patients included was 244. Out of those, 160 (65%), 67 (28%), and 17 (7%) patients received IO as 1L, second-line (2L), or third-line or beyond (3L or beyond), respectively. The median age for all patients was 59 years. Male were 88%, and 77% were smokers. The median follow-up time was 12.5 months. The median PFS and OS for 1L IO were 7 [95% CI 5.8 - 10.3] and 11.8 [95% CI 8.8 - 14.4], months, respectively. In the first 3 months after starting 1L IO, 34/160 (21%) patients had died. For those who survived beyond 3 months after starting 1L IO, the median PFS and OS were 11.3 [95% CI 8.3 - 16.5] and 15.4 [95% CI 13.2 - 21] months, respectively. In the Cox regression model of 1L IO patients with any performance status, ECOG PS 2 was predictive of worse OS compared to ECOG PS 0-1 (p= 0.005). Conclusion: This real-world study of advanced-stage NSCLC patients treated with immunotherapy at KHCC reveals outcomes that fall short of those anticipated from clinical trials. The inclusion of Middle Eastern patients in lung cancer trials is essential to ensure adequate representation of various ethnicities in clinical research.

FDG-PET in Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy Toxicity: A Systematic Review.

The utilization of chimeric antigen receptor (CAR) T-cell therapy to target cluster of differentiation (CD)19 in cancer immunotherapy has been a recent and significant advancement. Although this approach is highly specific and selective, it is not without complications. Therefore, a systematic review was conducted to assess the current state of positron emission tomography (PET) in evaluating the adverse effects induced by CAR T-cell therapy. A thorough search of relevant articles was performed in databases such as PubMed, Scopus, and Web of Science up until March 2024. Two reviewers independently selected articles and extracted data, which was then organized and categorized using Microsoft Excel. The risk of bias and methodological quality was assessed. In total, 18 articles were examined, involving a total of 753 patients, in this study. A wide range of utilities were analyzed, including predictive, correlative, and diagnostic utilities. While positive outcomes were observed in all the mentioned areas, quantitative analysis of the included studies was hindered by their heterogeneity and use of varying PET-derived parameters. This study offers a pioneering exploration of this promising field, with the goal of encouraging further and more focused research in upcoming clinical trials.

PET/CT in leukemia: utility and future directions.

2-Deoxy-2-[18F]fluoro-d-glucose PET/computed tomography ([18F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [18F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [18F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [18F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [18F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients.

Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non-small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.

Definition of bulky disease in early stage diffuse large B-cell lymphoma in computed tomography on coronal and transverse planes.

Background: In early stage diffuse large B-cell lymphoma (ESDLBL), tumor bulkiness is an important determinant of treatment and prognosis. Tumor bulk is usually measured on transverse computed tomography (CT) plane and variably defined from 5 to 10 cm. Objectives: Our study aims to investigate the prognostic significance of bulky disease measured on CT coronal and transverse planes and to evaluate the outcome of patients with bulky disease. Methods: Patients with ESDLBL and treated with rituximab, cyclophosphamide, doxorubicin, and prednisolone (RCHOP) with or without radiotherapy were included. Receiver Operating Characteristic (ROC) analysis was used to identify the optimal tumor dimension that correlated with progression, relapse, or death. Correlation between different variables and progression-free survival (PFS) and overall survival (OS) were analyzed using log-rank (Mantel-Cox) test and Cox proportional hazard models. Results: A total of 127 patients with a median age of 47 (range: 18-90) years were included. Eighty-two (64.6%) patients treated with combined modality treatment (CMT) [RCHOP + radiotherapy]. After a median follow-up of 40 (range: 2-114) months, 3-year PFS and OS were 83.9% (95% CI: 76.759%-89.981%), and 80.6% (95% CI: 72.499%-87.531%), respectively. Tumor dimension of >7.5 cm measured on either CT plane was the optimal cutoff point to define bulky disease. Three-year PFS and OS were inferior in the group of patients with no bulky disease on transvers plane (n = 84) but had bulky disease on coronal plane (n = 9,10.7%); (94.2% vs. 75%, p = 0.017 and 90.5% vs. 56.3%, p = 0.002), as well as in patients with no bulky disease on coronal plane (n = 89), but had bulky disease on transverse plane (n = 14, 15.7%); (94.1% vs. 62.3%, p < 0.001, and 90.4% vs. 63.5%, p = 0.002). Compared to RCHOP alone, 3-year PFS and OS were better in patients with bulky disease treated with CMT (78% vs. 52.5%, p = 0.018 and 81.8% vs. 38.7%, p = 0.003) but not in patients with non-bulky disease (96.2% vs. 93%, p = 0.691 and 87.6% vs. 91.5%, p = 0.477). Conclusion: In ESDLBL, measurement of tumor mass on transverse and coronal CT planes may help in better identification of patients with bulky disease. The use of CMT was associated with better survival outcomes in patients with bulky disease.

Long-Term Survival Analysis and Prognostic Factors of Arabic Patients with Differentiated Thyroid Carcinoma: A 20-Year Observational Study at the King Hussein Cancer Center (KHCC) Involving 528 Patients.

DTC accounts for the majority of endocrine tumors. While the incidence of thyroid cancer has been increasing globally over the past few decades, papillary thyroid carcinoma (PTC) generally shows an excellent prognosis, except in cases with aggressive clinicopathological features. This study aimed to assess the 5- and 10-year overall survival (OS) and progression-free survival (PFS) of 528 Arabic patients diagnosed with primary DTC from 1998 to 2021. Additionally, the study aimed to analyze the impact of various factors on both OS and PFS. An univariable survival analysis was conducted using Kaplan-Meier curves. The 5- and 10-year OS for patients with DTC have exceeded 95%. Additionally, PFS showed very good rates (ranging between 96.5 and 85% at 5 and 10 years, respectively). Age, male gender, risk of recurrence, and distant metastasis were identified as the main negative prognostic factors for both OS and PFS, while RAI treatment was found to be a significant factor in improving OS. Moreover, adherence to the King Hussein Cancer Center's (KHCC) CPG demonstrated significant improvement in PFS. These findings highlight common prognostic factors and favorable outcomes in Arabic patients with DTC treated at a tertiary cancer center using standard of care approaches.

FDG-PET/CT in the Monitoring of Lymphoma Immunotherapy Response: Current Status and Future Prospects.

Cancer immunotherapy has been extensively investigated in lymphoma over the last three decades. This new treatment modality is now established as a way to manage and maintain several stages and subtypes of lymphoma. The establishment of this novel therapy has necessitated the development of new imaging response criteria to evaluate and follow up with cancer patients. Several FDG PET/CT-based response criteria have emerged to address and encompass the various most commonly observed response patterns. Many of the proposed response criteria are currently being used to evaluate and predict responses. The purpose of this review is to address the efficacy and side effects of cancer immunotherapy and to correlate this with the proposed criteria and relevant patterns of FDG PET/CT in lymphoma immunotherapy as applicable. The latest updates and future prospects in lymphoma immunotherapy, as well as PET/CT potentials, will be discussed.

The Impact COVID-19 Infection on Cancer Patients: A Tertiary Cancer Center Experience in Jordan.

BACKGROUND: Cancer patients are at higher risk of serious complications of COVID-19. Few studies evaluated the impact of COVID-19 on cancer patients in low- and middle-income countries. Our study aims to evaluate the outcomes of COVID-19 infection in cancer patients treated at our institution.  Methods: Medical records of patients with a positive COVID-19 polymerase chain reaction (PCR) between April 2020 and October 2020 were reviewed. Fisher's exact test and logistic regression analysis were employed to correlate various variables with mortality. Survival estimates were generated using the Kaplan-Meier method. RESULTS: A total of 317 patients were included, with a median age was 55 years (range: 19-88). 82 (25.9%) had hematological neoplasms while the remainder had solid cancers. At the time of infection, 220 (69.4%) had active cancer, and 99 (31.2%) had received systemic anticancer treatment (SACT) within four weeks. Hospitalization was required for 101 (31.8%), 17 (5.3%) were admitted to the ICU and 50 (15.8%) died. Among patients with active cancer, SACT was delayed or discontinued in 140 (63.6%) patients.  In the entire patient cohort, low albumin (p=<0.001) and leucocytosis (p=<0.001) correlated with mortality within six months of COVID-19 infection. The six-month mortality rate in patients with active cancer was significantly higher in patients with hypertension (p=0.024), no recent SACT (0.017), hematological cancer (p=0.029), low albumin (p=<0.001), leucocytosis (p=0.002) and lymphocyte count of less than 500/µL (p=0.004). Recent chemotherapy was associated with better 6-month survival rates (78.8% vs 89.9%, p=0.012) in patients with active cancer, patients with solid cancers (95.9% vs 82.2%, p=0.006) and was non-inferior in patient with hematological neoplasms (72% vs 65.4%, p=0.519).  Conclusion: COVID-19 infection in our cancer patients was associated with significant morbidity and mortality and adversely affected their treatment. The decision to delay or discontinue SACT should be individualized, considering other risk factors for mortality.

Analysis of FLT3-Activating Mutations in Patients With Acute Myelogenous Leukemia in Jordan: Association With FAB Subtypes and Identification of Subgroups With Poor Prognosis.

BACKGROUND: FLT3 mutations are common in acute myeloid leukemia (AML), particularly in French-American-British M2 subtype AML and in cytogenetically normal (CN) AML; however, its incidence in Jordan is poorly studied. An FLT3 mutation implies poor prognosis in AML patients. We aimed to assess the incidence and prognostic value of FLT3 mutations in AML in Jordan. PATIENTS AND METHODS: One hundred thirty-two newly diagnosed unselected AML patients were included. Patient data were collected, including demographics as well as morphologic, cytogenetic, and molecular testing results. FLT3 mutations were detected by real-time reverse transcriptase PCR, next-generation sequencing, or both. Survival analysis and comparisons of incidence, remission rate, relapse, and survival outcomes between FLT3-mutated and wild-type groups were done and prognostic factors identified. RESULTS: FLT3 mutation was detected in 40% of AML patients. The highest incidence was associated with M2 subtype AML (47%) and CN-AML (50%). There was a significant negative association between FLT3 mutations and overall survival (OS), as well as a trend toward improved relapse-free survival, with 3-year OS being 19.17% vs 34.16% (P < .0001) and 33.6% vs 71.0% (P = .085), respectively. Patients with FLT3 mutation had a significantly better complete remission rate after induction (67.9% vs 63.3%, P = .001). Also, OS improved in patients with complete remission (P = .0015) and who then continued to allogeneic hematopoietic cell transplantation compared to FLT3 wild-type patients (P < .001). CONCLUSION: FLT3 mutation is common in Jordanian AML patients, with the highest incidence occurring in patients with M2 or CN disease. It implies a poor prognosis, with poor OS and relapse-free survival, which may be abrogated by early allogeneic transplantation and/or peritransplantation provision of FLT3 inhibitors.

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.

Unusual presentation of non-small cell lung cancer with clival metastases: Case report.

A 37-year-old female with unusual presentation of metastatic non-small cell lung cancer (NSCLC), as she presented with symptoms related to clival bone metastases. This case highlights the unpredictable presentations and the variety of metastatic sites of which metastatic NSCLC could be presented.

Second-Line Chemotherapy for Metastatic Urothelial Carcinoma: Importance of Lymph Node-Only Metastasis as a Prognostic Factor and Construction of a Prognostic Model.

BACKGROUND: A prognostic model for patients with metastatic urothelial carcinoma (UC) progressing after platinum-based therapy was constructed from data from the phase III vinflunine trial. However, prognostic information for patients treated with other regimens is limited. MATERIALS AND METHODS: We pooled individual patient data from 7 second-line studies and analyzed the influence of factors of interest on overall survival (OS) through univariate and multivariate analysis. A prognostic model was constructed, and data from an independent series were used for validation. RESULTS: The data from 193 patients were pooled. The second-line chemotherapy regimen was single-agent taxane in 54 patients (28%), a platinum-based combination in 47 (24%), and a non-platinum combination in 92 (48%). On multivariate analysis, Eastern Cooperative Oncology Group performance status ≥ 1, hemoglobin < 10 g/dL, and metastatic patterns other than lymph node-only metastasis emerged as independent adverse prognostic factors. Patients with all 3 factors (poor risk), 1 to 2 factors (intermediate risk), and no factors (good risk) had a median OS of 3.1, 8.7, and 16.5 months, respectively (P < .0001). The corresponding median OS for the validation series (n = 44) was 3.3, 8.1, and 13.3 months (P = .023). Furthermore, platinum-based regimens were independently associated with an OS benefit compared with other regimens (hazard ratio, 0.31; 95% confidence interval, 0.18-0.53; P < .0001). CONCLUSION: We have proposed and validated a prognostic model for patients with metastatic UC who were eligible for second-line therapy. The proposed model could prove helpful for risk stratification. Furthermore, our data suggest that testing second-line platinum-based regimens in randomized trials is warranted.

Spontaneous subdural hematoma in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia with normal platelet count after dasatinib treatment.

Dasatinib, which is an inhibitor of BCR-ABL and SRC family tyrosine kinases, is used for the treatment of patients with Philadelphia chromosome (Ph) positive leukemia, especially for those who develop resistance or who are intolerant to imatinib. The most common adverse effects attributed to its use are: myelosuppression, nausea, diarrhea, and peripheral edema. Hemorrhage, which could be gastrointestinal, genitourinary or central nervous system, is a less frequent adverse effect. In this case, we report a patient affected by precursor B-cell acute lymphoblastic leukemia (ALL) positive for the Ph chromosome translocation treated with the tyrosine kinase inhibitor (TKI) dasatinib. During the treatment with dasatinib the patient developed subdural hematoma (SDH). She did not have any head trauma, thrombocytopenia, coagulopathy or meningeal involvement, making dasatinib-induced platelet dysfunction the most likely cause of SDH.