Quality Measures for Multidisciplinary Tumor Boards and Their Role in Improving Cancer Care.

While multidisciplinary tumor boards (MTBs) are widely used in managing patients with cancer, their impact on patient care and outcome is not routinely measured in different settings. The authors conducted a literature review in Medline, Google Scholar, Embase, and Web of Science using the following keywords: cancer, multidisciplinary, tumor board, quality performance indicator, lung cancer, and lymphoma. Standards from various accreditation and professional organizations were reviewed to compile relevant standards for MTB. A list of quality performance indicators that can be used to improve MTBs' performance and impact was compiled. Specific examples for non-Hodgkin lymphoma and lung cancer MTBs were presented. Guidance was provided to help MTB team members select implement the appropriate quality measures. The functions and impact of MTBs should be monitored and evaluated by a set of measures that help guide MTBs to improve their performance and provide better care to their patients.

Relapsed Waldenstrom's Macroglobulinemia and Therapy-Related Myelodysplastic Syndrome with Complex Cytogenetics: A Treatment Dilemma.

Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M as defined by the World Health Organization Classification of hematological malignancies. Historically, the treatment options for WM were limited to alkylating agents and purine analogs. The introduction of immune therapy, including CD20 targeted therapy, proteasome inhibitors, and immune modulators, has provided benefit to those patients and has now become the standard of care. As WM patients become long-term survivors, treatment's late toxicities have become more apparent. Here, we report a case of a 74-year-old female who presented to the hospital with fatigue and was diagnosed with WM. She was treated with bortezomib, doxorubicin, and bendamustine, followed by rituximab. After a remission period of 15 years, the patient had a relapse of WM, and bone marrow biopsy findings were consistent with intermediate-risk t-MDS with complex cytogenetics, presenting us with a treatment dilemma. We decided to treat WM, and the patient went into VGPR with residual lymphoma cells. Despite having dysplasia and complex cytogenetics, she did not have any cytopenia. Currently, she is under observation anticipating the progression of her MDS, given her intermediate I risk status. This case features the occurrence of t-MDS after therapy with bendamustine, cladribine, and doxorubicin. This highlights the need for closer monitoring and consideration of long-term adverse effects when treating patients with indolent lymphomas, especially WM. Late complications need to be considered, and risk versus benefit analysis needs to be carefully evaluated, especially in younger patients with WM.

Incidence and Predictors of Recurrence and Mortality Following First Venous Thromboembolism Among the Saudi Population: Single-Center Cohort Study.

Background: Little is written about recurrence and mortality rates after a first episode of venous thromboembolism (VTE) among Saudi population. Aim: Determine incidence rates and assess predictors of recurrence and mortality following the first VTE event. Patients and Methods: A total of 1124 patients aged ≥18 years with symptomatic VTE confirmed by imaging tests were evaluated. The incidence of VTE recurrence and mortality were assessed. The association between patient characteristics, and VTE recurrence and mortality was explored by estimating the hazard ratio (HR) and 95% confidence interval (CI). The difference between cancer-related, provoked and unprovoked VTE in terms of recurrence and mortality was explored using Kaplan-Meier curves. Results: The annual incidence rate of the first VTE was 1.7 per 1000 patients. Of 1124 patients with first VTE, 214 (19%) developed recurrent VTE, and 192 (17%) died with overall incidence rates of 15.8 per 100 person-years (95% CI, 13.8-18.0) and 10.0 per 100 person-years (95% CI, 8.7-11.5). Intensive care unit (ICU) admission (HR, 2.15; 95% CI, 1.67-3.10), presence of active cancer (HR, 2.97; 95% CI, 1.87-3.95), immobilization (HR, 2.52; 95% CI, 1.79-3.67), infection (HR, 2.32; 95% CI, 1.94-3.45), and pulmonary embolism ± deep venous thrombosis (HR, 2.22; 95% CI, 1.56-3.16) were found to be independent predictors of recurrent VTE. Recurrence carries a high hazard of mortality (HR, 5.21; 95% CI, 3.61-7.51). The estimated median time to VTE recurrence was lower in cancer-related VTE (18.7 months) compared with provoked (29.0 months) and unprovoked VTE (28.4 months). The estimated survival median time was lower in cancer-related VTE (21.8 months) compared with provoked (30.5 months) and unprovoked VTE (29.8 months). Conclusion: Immobilization and presence of active cancer, infection, and PE ± DVT were significant predictors of recurrent VTE. Patients who developed recurrent VTE had a 5.2-fold higher hazard of mortality compared with patients with no VTE recurrence.

Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis.

The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 109/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.

The trends of cancer patients' perceptions on the causes and risk factors of cancer over time.

OBJECTIVES: To evaluate patients' perceptions on the causes and outcomes of cancer and the changes observed over a decade (2006-2016) at King Abdulaziz Medical City, Riyadh, Saudi Arabia. METHODS: Patients diagnosed with cancer and treated at King Abdulaziz Medical City, Riyadh, Saudi Arabia, were enrolled in a cross-sectional study. The patients were enrolled in 2 cohorts: cohort 1 from 2006-2008 and cohort 2 from 2016-2018. The trends of the perceptions related to the causes and outcomes of cancer were compared between the 2 cohorts. RESULTS: In total, 1416 patients were enrolled in the 2 cohorts: cohort 1 included 464 patients and cohort 2 included 952 patients. The patients in cohort 2 had a higher level of education, higher unemployment rate, and more solid tumors. There was a significant increase in the belief of the "evil eye" as a cause of cancer from 1.3-33.1% between cohort one and cohort 2. A higher proportion (23.5%) of cohort 2 reported scientific causes for cancer, compared to 13.6% in cohort 1 (p<0.0001). Younger age, male gender, having a job, and being in cohort 2 were significantly associated with providing a scientific answer in a multivariate analysis (modeling scientific cause). CONCLUSION: In this study, a frequent misperception related to the causes of cancer was revealed. To tackle this issue, a systematic approach towards education for patients and the public is required to minimize the potential detrimental effects on patient care and patient outcomes.

Promising remissions in relapsed refractory classical Hodgkin lymphoma patients requiring multiple salvage regimens before transplantation in the brentuximab vedotin era.

Relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients refractory to first line salvage have poor outcomes. Herein we report the outcome of R/R cHL patients requiring ≥two vs. one line in the era of chemo-immunotherapy. Among 55 R/R cHL patients, 33 (60%) required one, 22 (40%) required ≥two lines. At 2 years, the estimated PFS and OS for patients requiring one vs. ≥two lines was 71.2% (50.1-84.7) vs. 51.9% (27.6-71.6), p= 0.16 and 84.6% (63-94) vs. 84% (58-95), p= 0.88, respectively. Patients requiring ≥two salvage lines prior to HCT can achieve comparable outcomes to those requiring one, possibly due to brentuximab vedotin leading to higher CMR rates.

Electronic early notification of sepsis in hospitalized ward patients: a study protocol for a stepped-wedge cluster randomized controlled trial.

BACKGROUND: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality. METHODS: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of "possible sepsis alert" to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days. DISCUSSION: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019.

A Drug Repositioning Approach Identifies a Combination of Compounds as a Potential Regimen for Chronic Lymphocytic Leukemia Treatment.

Drug repositioning is a promising and powerful innovative strategy in the field of drug discovery. In this study, we screened a compound-library containing 800 Food and Drug Administration approved drugs for their anti-leukemic effect. All screening activities made use of human peripheral blood mononuclear cells (PBMCs), isolated from healthy or leukemic donors. Compounds with confirmed cytotoxicity were selected and classified in three groups: i) anti-neoplastic compounds which are drugs used in leukemia treatment, ii) compounds known to have an anti-cancer effect and iii) compounds demonstrating an anti-leukemic potential for the first time. The latter group was the most interesting from a drug repositioning perspective and yielded a single compound, namely Isoprenaline which is a non-selective ß-adrenergic agonist. Analysis of the cytotoxic effect of this drug indicated that it induces sustainable intracellular ATP depletion leading, over time, to necrotic cell death. We exploited the Isoprenaline-induced intracellular ATP depletion to sensitize primary leukemic cells to fludarabine (purine analogue) and Ibrutinib (Bruton's tyrosine kinase inhibitor) treatment. In-vitro treatment of primary leukemic cells with a combination of Isoprenaline/fludarabine or Isoprenaline/Ibrutinib showed a very high synergistic effect. These combinations could constitute a new efficient regimen for CLL treatment following successful evaluation in animal models and clinical trials.

The trends of complementary alternative medicine use among cancer patients.

BACKGROUND: The use of complementary and alternative medicine (CAM) is common among cancer patients and it may reflect the individual and societal beliefs on cancer therapy. Our study aimed to evaluate the trends of CAM use among patients with cancer between 2006 and 2018. METHODS: We included 2 Cohorts of patients with cancer who were recruited for Cohort 1 between 2006 and 2008 and for Cohort 2 between 2016 and 2018. The study is a cross-sectional study obtaining demographic and clinical information and inquiring about the types of CAM used, the reasons to use them and the perceived benefits. We compared the changes in the patterns of CAM use and other variables between the two cohorts. RESULTS: A total of 1416 patients were included in the study, with 464 patients in Cohort 1 and 952 patients in Cohort 2. Patients in Cohort 2 used less CAM (78.9%) than Cohort 1 (96.8%). Cohort 1 was more likely to use CAM to treat cancer compared to Cohort 2 (84.4% vs. 73%, respectively, p < 0.0001,); while Cohort 2 used CAM for symptom management such as pain control and improving appetite among others. Disclosure of CAM use did not change significantly over time and remains low (31.6% in Cohort 1 and 35.7% for Cohort 2). However, physicians were more likely to express an opposing opinion against CAM use in Cohort 2 compared to Cohort 1 (48.7% vs. 19.1%, p < 0.001, respectively). CONCLUSION: There is a significant change in CAM use among cancer patients over the decade, which reflects major societal and cultural changes in this population. Further studies and interventions are needed to improve the disclosure to physicians and to improve other aspects of care to these patients.

Impact of cluster of differentiation 20 expression and rituximab therapy in classical Hodgkin lymphoma: Real world experience.

The prognostic impact of CD20 expression and rituximab therapy in classical Hodgkin lymphoma (cHL) is unclear. Among 310 patients, CD20 was expressed in 66 (22%) cases. The 3-year PFS was 75.1% for CD20+and 70% for CD20- (p = 0.36). The 3-year PFS was 84.7% for the rituximab group and 67.8% for the no rituximab group (p = 0.23). Only constitutional symptoms and positive interim PET/CT were significantly associated with worse outcome, HR 3.2 (1.14-9.01; p = 0.028) and 4.3 (2.27-8.1; p < 0.0001), respectively. Neither CD20 expression nor rituximab use significantly impacted outcome.

Outcome of Middle East Respiratory Syndrome (MERS) in hematology and oncology patients: A case series in Saudi Arabia.

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is associated with a high fatality rate (34%), which is higher in the presence of co-morbidities. The aim of the current study was to assess the clinical course and the outcome in hematological or oncological malignancy cases, diagnosed with MERS-CoV. METHODS: This is a case series of hematological /oncological cases, diagnosed with MERS-CoV, in a tertiary care setting in 2015. The cases were identified based on the World Health Organization (WHO) MERS-CoV case definition. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic health records. RESULTS: In total, nine hematological or oncological cases were identified, diagnosed with MERS-CoV. The baseline malignant condition was hematological malignancy in seven patients, as well as colon cancer and osteosarcoma in one patient each. Six (67%) patients were male. The median age was 65 years (range 16-80 years). Co-morbidities included chronic kidney disease (n = 3.33%), diabetes mellitus (n = 3.33%), and hypertension (n = 2.22%). The presenting symptoms were shortness of breath (n = 6.66%), fever (n = 5.55%), cough (n = 2.22%), and diarrhea (n = 2.22%). Chest x-rays indicated bilateral infiltrates in 6 patients (66%). The PCR (polymerase chain reaction) test was repeated in six patients to confirm the diagnosis. The mortality rate was 100%, and the median time to death was 26 days (range 15-77 days). CONCLUSION: MERS-CoV infection in this small cohort of hematology or oncology patients has a 100% mortality rate, regardless of the status of the underlying disease. The confirmation of the diagnosis may require repeated testing. Additional studies are required to verify the findings and to elucidate the disease pathogenesis in cancer patients.

Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis.

Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.

Reactivation of tuberculosis following ruxolitinib therapy for primary myelofibrosis: Case series and literature review.

Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. The only and curative option for PMF is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is highly effective in reducing constitutional symptoms and spleen volume, and has been found to improve survival. Ruxolitinib decreases the activity of type I T-helper cells, leading to decreased release of cytokines including tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, interferon-γ, and production of IL-12, which can be a risk factor for opportunistic infections. In this report, we describe three cases of tuberculosis reactivation shortly after initiation of ruxolitinib therapy followed by a literature review.

Impact of age and induction therapy on outcome of 180 adult patients with acute myeloid leukemia; retrospective analysis and literature review.

The prognosis of acute myeloid leukemia (AML) remains poor. Among 180 patients, the median age was 53 (14-88) years. The overall 2-year disease free survival (DFS) was 28.6% (+/- 3.4), 47.7% (+/- 6.6%) for ≤ 40, 23.6% (+/- 5.8%) for 41-60 and 11.7% (+/- 4.2%) for ≥61 (p< 0.0001). The overall 2-year survival (OS) was 45.3% (+/- 3.8%), 78.6% (+/- 5.5%) for ≤40, 43.5% (+/- 6.9%) for 41-60 and 15.8% (+/- 4.8%) for ≥61 (p< 0.0001). Induction outcome of ≥61 was best in high dose chemotherapy (HDC) group (p < 0.0001). Only those ≤40 had durable DFS and OS. HDC appears to improve the outcome of older AML patients.

Venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory multiple myeloma harboring t(11,14)(q13;q32): two case reports and a review of the literature.

BACKGROUND: Multiple myeloma has witnessed significant advances due to the approval of many novel agents. However, in spite of all these new developments, multiple myeloma remains an incurable disease with inevitable relapse in the majority of patients. Venetoclax is a selective antiapoptotic protein B-cell lymphoma 2 inhibitor that induces cell death in multiple myeloma cells, particularly in those harboring t(11,14)(q13;q32). We report two cases of patients with multiple myeloma with t(11,14)(q13;q32) who were treated with venetoclax/carfilzomib/dexamethasone with rapid initial response; however, the response was short-lived. CASES PRESENTATION: Patient 1 was a 50-year-old Saudi man with International Staging System stage III kappa light chain multiple myeloma with normal karyotype diagnosed in May 2013. He received bortezomib/thalidomide/dexamethasone treatment and underwent autologous hematopoietic stem cell transplant. Three years later, he presented with disease progression and received multiple lines of chemotherapy, including carfilzomib/lenalidomide/dexamethasone. Venetoclax/carfilzomib/dexamethasone was started after acquiring t(11,14)(q13;q32) 5 years into his disease course. He achieved complete remission, with disease progression after cycle 6. Patient 2 was a 48-year-old Saudi man with International Staging System stage III immunoglobulin G kappa multiple myeloma with t(11,14)(q13;q32) diagnosed in May 2017. He received bortezomib/thalidomide/dexamethasone treatment and underwent autologous hematopoietic stem cell transplant. Eighteen months later, he had disease progression, and he received multiple lines of chemotherapy, including carfilzomib/dexamethasone. He was shifted to venetoclax/carfilzomib/dexamethasone in April 2019 and had an initial clinical response; two months later, he progressed to plasma cell leukemia with rapid deterioration to multiorgan failure. CONCLUSIONS: Acquired t(11;14)(q13;q32) is unreported in the multiple myeloma literature. In the era of targeted therapy, it is essential to repeat the cytogenetic and multiple myeloma fluorescence in situ hybridization panel with each disease progression. Multiple myeloma remains a challenging hematological malignancy despite advances in personalized/precision medicine.

The causes of lymphadenopathy in the central region of Saudi Arabia: a clinicopathological analysis of 475 cases.

Lymphadenopathy (LAP) is a common working diagnosis in the primary care setting; although the underlying etiology of this condition can be self-limiting, serious causes need to be ruled out. A clear understanding of lymph node (LN) location and patient demographics and exposure is vital in identifying which cases require rapid and extensive workup. The incidence of tuberculous (TB) lymphadenitis in the Central Region of Saudi Arabia (CRSA) has been reported to be 37.8%. In this study, we aimed to investigate the causes of LAP in this region. This was a retrospective study evaluating all patients who underwent LN biopsy at King Abdulaziz Medical City, Riyadh between 2007 and 2017. A total of 475 patients met the eligibility criteria. The mean age was 40.9 ± 25.5 years; 203 (42.7%) were females and 447 (94.1%) were Saudis. The causes of LAP were malignant in 240 (50.5%) and benign in 235 cases (49.4%). Forty two (8.8%) cases had TB lymphadenitis, but only 17 (40.5%) of those presented with systemic symptoms. Malignant causes were more common in adults compared to children, at 209 cases (55.4%) and 31 cases (31.6%), respectively (P = 0.0001). Patients who presented with generalized LAP were more likely to have a malignancy (P = 0.0000). Of the 234 who presented with systemic symptoms, 138 (59%) were diagnosed with cancer (P = 0.0000). Although less prevalent than before, TB lymphadenitis remains a significant medical problem in the CRSA. Malignancy must be ruled out, especially in those who present with generalized LAP and those with associated systemic symptoms.

The use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in Saudi Arabia.

BACKGROUND: A significant proportion of cancer patients use complementary and alternative medicine (CAM) along with conventional therapies (CT), whereas a smaller proportion delay or defer CT in favor of CAM. Previous studies exploring CAM use among cancer patients in the Middle East region have shown discrepant results. This study investigates the prevalence and pattern of CAM use by Saudi cancer patients. It also discusses the possible benefits and harm related to CAM use by cancer patients, and it explores the beliefs patients hold and their transparency with health care providers regarding their CAM use. METHODS: A cross-sectional study was conducted in oncology wards and outpatient clinics by using face-to-face interviews with the participants. RESULTS: A total of 156 patients with a median age of 50 years (18-84) participated in the study. The prevalence of CAM use was 69.9%; the most prominent types of CAM were those of a religious nature, such as supplication (95.4%), Quran recitation (88.1%), consuming Zamzam water (84.4%), and water upon which the Quran has been read (63.3%). Drinking camel milk was reported by 24.1% of CAM users, whereas camel urine was consumed by 15.7%. A variety of reasons were given for CAM use: 75% reported that they were using CAM to treat cancer, enhance mood (18.3%),control pain (11.9%), enhance the immune system (11%),increase physical fitness (6.4%), and improve appetite (4.6%). Thirty percent of CAM users had discussed the issue with their doctors; only 7.7% had done so with their nurses. CONCLUSIONS: The use of CAM, including camel products, is highly prevalent among cancer patients in the Middle East, but these patients do not necessarily divulge their CAM use to their treating physicians and nurses. Although CAM use can be beneficial, some can be very harmful, especially for cancer patients. Association is known between camel products and brucellosis and Middle East respiratory syndrome coronavirus (MERS-CoV). Both can lead to tremendous morbidity in immune-compromised patients. Doctor-patient communication regarding CAM use is of paramount importance in cancer care.