The Outcomes of Diffuse Large B-cell Lymphoma Patients with Synchronous and Early Central Nervous System Involvement: A Single-Center Experience.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is the most commonly diagnosed subtype of non-Hodgkin's lymphoma (NHL). R-CHOP has significantly improved clinical outcomes in patients with DLBCL, however, its indication in the prevention of CNS relapse and recurrence is still inconsistent. Moreover, prophylactic methotrexate and/or cytarabine have been used prophylactically for DLBCL patients is at high risk of CNS relapse and to treat CNS DLBCL, however, their efficacy remains unclear. METHODS: The aim of our retrospective study was to determine the incidence of CNS in-volvement in patients with DLBCL and to describe its risk factors and survival outcomes. RESULTS: A total of 406 patients with DLBCL were identified, and 17 (4.2%) of DLBCL patients had CNS involvement i.e. 9 (2.2 %) at diagnosis and 8 (~2%) at relapse. The patients were younger, had advanced stage, high CNS-IPI, and had extra nodal involvement. Seven out of the 17 patients who survived received chemotherapy and a prophylactic methotrexate. Considering the CNS-IPI, of the 146 patients with high CNS-IPI at presentation, 18 received the prophylactic HDMTX and 3 (16.7%) of them had CNS relapse. Two (1.6%) out of 128 who did not receive the prophylactic HDMTX had CNS relapse. On the other hand, of the 223 patients with intermediate CNS-IPI, 25 received the prophylactic HDMTX and 2 (8%) of them had CNS relapse and in 198 patients who did not receive the prophylactic HDMTX, 2 (1.01%) had CNS relapse. The 5-year progression-free survival and overall survival rates for the entire cohort were 73% and 84%, respectively. The median OS for those who had CNS involvement was 17 months and the 2-year OS was 40%. CONCLUSION: CNS involvement in DLBCL has a poor prognosis, thus, aggressive CNS-directed therapy should be considered, especially in young patients.

Outcomes of high­dose methotrexate for CNS prophylaxis in diffuse large B­cell lymphoma with an intermediate or high CNS­International Prognostic Index: A single­center retrospective cohort study.

Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is rare (2-5% of cases), but is a devastating complication with a poor survival rate. The administration of high-dose methotrexate (HDMTX) for CNS prophylaxis in patients with DLBCL is controversial and variable in the literature. The present study aimed to evaluate the clinical outcomes of HDMTX CNS prophylaxis in patients with intermediate and high CNS-International Prognostic Index (IPI) DLBCL using real-world data. An observational retrospective cohort study was conducted of all patients with intermediate and high CNS-IPI DLBCL treated at Princess Noorah Oncology Center (King Abdulaziz Medical City, Jeddah, Saudi Arabia) between January 2010 and December 2020. Patients were treated with HDMTX either intravenously or intrathecally, according to the physician's evaluation of the patient. Data on patient clinical characteristics, CNS relapses, risk factors and survival rates were obtained from hospital records. Data were analyzed using Student's unpaired t-test and the χ2 test to compare the two subgroups, the Kaplan-Meier survival method with log-rank test to calculate and compare the survival rates, and regression analysis to determine the risk factors for CNS relapse and death. The study included 358 patients (n=32 with HDMTX CNS prophylaxis and n=326 without CNS prophylaxis). Patients in the CNS prophylaxis group had a significantly higher CNS relapse rate than those in the non-CNS prophylaxis group (12.5% vs. 1.8%; P=0.008). Patients who received CNS prophylaxis were younger and had an advanced stage of disease, with extranodal involvement and a high serum lactate dehydrogenase level at presentation. CNS prophylaxis was significantly associated with CNS relapse, while relapsed disease was associated with the risk of death (all P<0.05). In conclusion, the present study found that patients with intermediate and high CNS-IPI who received HDMTX CNS prophylaxis did not have fewer CNS relapses; however, those without CNS relapse had higher survival rates. In addition to CNS prophylaxis, Stage of DLBCL and IPI were significantly associated with CNS relapse. Future randomized control trials are needed to evaluate the efficacy of HDMTX CNS prophylaxis in patients with DLBCL.

Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study.

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9-20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum.Clinical trial registration: NCT03327571.

Treatment Landscape of Relapsed/Refractory Mantle Cell Lymphoma: An Updated Review.

Mantle cell lymphoma (MCL) accounts for nearly 2-6% of all non-Hodgkin lymphoma (NHL) cases, with a steady incidence increase over the past few decades. Although many patients achieve an adequate response to the upfront treatment, the short duration of remission with rapid relapse is challenging during MCL management. In this regard, there is no consensus on the best treatment options for relapsed/refractory (R/R) disease, and the international guidelines demonstrate wide variations in the recommended approaches. The last decade has witnessed the introduction of new agents in the treatment landscape of R/R MCL. Since the introduction of Bruton's tyrosine kinase (BTK) inhibitors, the treatment algorithm and response of R/R MCL patients have dramatically changed. Nevertheless, BTK resistance is common, necessitating further investigations to develop novel agents with a more durable response. Novel agents targeting the B-cell receptor (BCR) signaling have exhibited clinical activity and a well-tolerable safety profile. However, as the responses to these novel agents are still modest in most clinical trials, combination strategies were investigated in pre-clinical and early clinical settings to determine whether the combination of novel agents would exhibit a better durable response than single agents. In this report, we provide an updated literature review that covers recent clinical data about the safety and efficacy of novel therapies for the management of R/R MCL.

The Risk of Developing Lymphoma among Autoimmune Thyroid Disorder Patients: A Cross-Section Study.

Background: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the most common types of autoimmune thyroid diseases (AITD), and both are characterized by the infiltration of lymphocytes into the thyroid gland. Moreover, autoimmune diseases like HT have a higher risk of developing lymphoma. This study is aimed at assessing the prevalence and association of lymphoma in patients with AITD. Methods: This cross-sectional study was conducted in King Abdulaziz Medical City, Jeddah, Saudi Arabia. Data were gathered from the medical records of patients aged 18 years or older who developed AITD. A total number of 140 medical records were collected, and 72 patients were included after applying in exclusion criteria. Data on the subtype, clinical-stage, treatment modality, patient status, remission, and relapse were collected for patients who developed lymphoma. Results: Among 72 patients who developed AITD, HT was diagnosed in 58 (80.6%) patients and GD in 14 (19.4%). Five (7%) patients were diagnosed with lymphoma all of whom had a history of HT. The subtypes of lymphoma were diffuse large B-cell lymphoma (DLBCL 3; 4.2%), follicular lymphoma 1 (1.4%), and Hodgkin's lymphoma 1 (1.4%). Conclusion: The prevalence of PTL in patients with AITD, specifically HT, was 7%. Most patients developed NHL, with DLBCL being the most common subtype. The onset of lymphoma in this study was lower than reported in the literature. All patients with PTL had HT in their backgrounds. Further national studies are warranted to explore the relationship between the two diseases to provide more insight into the comprehension of this association.

Combination of palbociclib with adjuvant endocrine therapy for treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer: An experience at two cancer centers in Saudi Arabia.

The addition of palbociclib (a cyclin-dependent kinase 4/6 inhibitor) to endocrine therapy (ET) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) among patients with hormone receptor-positive (HR+) advanced breast cancer. The current study presents the local experience of using palbociclib at two cancer centers in Saudi Arabia. Electronic data of patients with metastatic HR+ and human epidermal growth factor receptor 2-negative breast cancer who progressed after prior ET and received at least one cycle of palbociclib plus ET, were retrospectively reviewed. A total of 97 patients were identified, and their data were included in the analysis. The median age of the patients was 55 years. Patients were heavily pretreated in the metastatic setting (55% received systemic chemotherapy and 49% received two or more lines of prior ET). In total, 29 (30%) and 50 (52%) patients achieved an objective response and clinical benefit, respectively. The median follow-up time was 31.0 months [95% confidence interval (CI), 16.9-44.9] and the median PFS time was 16.3 months (95% CI, 11.4-21.2), with 58% of patients remaining progression-free at 12 months. Upon multivariate regression analysis, liver involvement was the only significant independent variable that predicted a greater risk of progression or death (hazard ratio, 2.32; 95% CI, 1.22-4.40; P=0.010). The median OS time was 19.6 months (95% CI, 18.1-20.9), with 12- and 24-month OS rates of 75 and 30%, respectively. Overall, real-world data showed that administration of palbociclib in combination with ET in patients with advanced HR+ breast cancer achieved a favorable outcome that was comparable to that reported in clinical trials.

Mortality and morbidity of curative and palliative anticancer treatments during the COVID-19 pandemic: A multicenter population-based retrospective study.

Administration of effective anticancer treatments should continue during pandemics. However, the outcomes of curative and palliative anticancer treatments during the coronavirus disease (COVID-19) pandemic remain unclear. The present retrospective observational study aimed to determine the 30-day mortality and morbidity of curative and palliative anticancer treatments during the COVID-19 pandemic. Between March 1 and June 30, 2020, all adults (n=2,504) with solid and hematological malignancies irrespective of cancer stage and type of anticancer treatments at five large comprehensive cancer centers in Saudi Arabia were included. The 30-day mortality was 5.1% (n=127) for all patients receiving anticancer treatment, 1.8% (n=24) for curative intent, 8.6% (n=103) for palliative intent and 13.4% (n=12) for COVID-19 cases. The 30-day morbidity was 28.2% (n=705) for all patients, 17.9% (n=234) for curative intent, 39.3% (n=470) for palliative intent and 75% (n=77) for COVID-19 cases. The 30-day mortality was significantly increased with male sex [odds ratio (OR), 2.011; 95% confidence interval (CI), 1.141-3.546; P=0.016], body mass index (BMI) <25 (OR, 1.997; 95% CI, 1.292-3.087; P=0.002), hormone therapy (OR, 6.315; 95% CI, 0.074-2.068; P=0.001) and number of cycles (OR, 2.110; 95% CI, 0.830-0.948; P=0.001), but decreased with Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 (OR, 0.157; 95% CI, 0.098-0.256; P=0.001), stage I-II cancer (OR, 0.254; 95% CI, 0.069-0.934; P=0.039) and curative intent (OR, 0.217; 95% CI, 0.106-0.443; P=0.001). Furthermore, the 30-day morbidity significantly increased with age >65 years (OR, 1.420; 95% CI, 1.075-1.877; P=0.014), BMI <25 (OR, 1.484; 95% CI, 1.194-1.845; P=0.001), chemotherapy (OR, 1.397; 95% CI, 1.089-5.438; P=0.032), hormone therapy (OR, 1.527; 95% CI, 0.211-1.322; P=0.038) and immunotherapy (OR, 1.859; 95% CI, 0.648-4.287; P=0.038), but decreased with ECOG-PS of 0-1 (OR, 0.502; 95% CI, 0.399-0.632; P=0.001), breast cancer (OR, 0.569; 95% CI, 0.387-0.836; P=0.004) and curative intent (OR, 0.410; 95% CI, 0.296-0.586; P=0.001). The mortality risk was lowest with curative treatments. Therefore, such treatments should not be delayed. The morbidity risk doubled with palliative treatments and was highest among COVID-19 cases. Mortality appeared to be driven by male sex, BMI <25, hormonal therapy and number of cycles, while morbidity increased with age >65 years, BMI <25, chemotherapy, hormonal therapy and immunotherapy. Therefore, oncologists should select the most effective anticancer treatments based on the aforementioned factors.

Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon lymphoproliferative disorder, mainly associated with textured implants. The average time from the breast implants to the development of BIA-ALCL is about 7 to 10 years, and the median age at the time of diagnosis is in the mid-50s. The exact incidence and prevalence of BIA-ALCL are not known. The pathogenesis of BIA-ALCL remains unclear. Different theories have been postulated, including immune response to textured implants, subclinical bacterial infection, and genetic predisposition. However, none of those theories have yet been proven to be causal in the pathogenesis of BIA-ALCL. BIA-ALCL is histologically similar to but clinically distinct from other CD30-positive T-cell lymphomas such as anaplastic lymphoma kinase-positive, anaplastic lymphoma kinase-negative, and primary cutaneous ALCL. The revised World Health Organization classification of lymphoid neoplasm in 2016 recognized BIA-ALCL as a provisional entity. Suspected cases need proper evaluation and workup to confirm the diagnosis. Surgical resection should be considered for all the cases. However, adjuvant radiotherapy and anthracycline-based chemotherapy are warranted for locally advanced and advanced cases.

Energy and caloric restriction, and fasting and cancer: a narrative review.

Dietary interventions have a significant impact on body metabolism. The sensitivity of cancer cells to nutrient and energy deficiency is an evolving characteristic of cancer biology. Preclinical studies provided robust evidence that energy and caloric restrictions could hinder both cancer growth and progression, besides enhancing the efficacy of chemotherapy and radiation therapy. Moreover, several, albeit low-powered, clinical trials have demonstrated clinical benefits in cancer patients. Future research will inform and firmly establish the potential efficacy and safety of these dietary interventions. Here, we review the current evidence and ongoing research investigating the relationship between various dietary restriction approaches and cancer outcomes.

Saudi Lymphoma Group's Clinical Practice Guidelines for Diagnosis, Management and Follow-up of Patients with Various Types of Lymphoma during the Coronavirus Disease 2019 Pandemic.

The Saudi Lymphoma Group had previously published recommendations on the management of the major subtypes of lymphoma. However, the effect the currently ongoing coronavirus disease 2019 (COVID-19) pandemic has on the management of patients with lymphoma has been paramount. Therefore, the Saudi Lymphoma Group has decided to provide clinical practice guidelines for the diagnosis, management and follow-up of patients with various types of lymphoma during the COVID-19 pandemic.

Efficacy and safety of second-generation CAR T-cell therapy in diffuse large B-cell lymphoma: A meta-analysis.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma (NHL), representing 30% of all lymphoma cases. Within the first 2-3 years following immunochemotherapy, 30-40% of patients will experience a relapse or a refractory disease, thereby exhibiting a poor prognosis. High-dose immunotherapy followed by autologous stem cell transplantation is the standard care for relapsed/refractory (RR) patients with DLBCL. However, >60% of patients are ineligible for a transplant, presenting a therapeutic challenge. Chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in patients with DLBCL, including those with R/R disease. The present study conducted a meta-analysis that showed highly favorable outcomes [objective response rate (ORR): 69%; complete remission (CR): 49%] in B-cell NHL patients (n=419) who were treated with second-generation CAR T cells. The response rate varied in different types of B-cell NHL. In 306 patients with R/R DLBCL eligible for rate evaluation, the ORR and CR rate mean estimates were 68% [95% confidence interval (CI), 55-79%] and 46% (95% CI, 38-54%), respectively. Thus, the findings indicated that immunotherapy with CAR T cells has improved outcomes for patients with R/R DLBCL and other subtypes of B-cell NHL compared with standard chemotherapy regimens. The study revealed that grade ≥3 anemia (34%) and thrombocytopenia (30%) were the most common adverse effects of CAR T-cell therapy. Incidence of grade ≥3 cytokine release syndrome and neurotoxicity associated with CAR T-cell therapy was effectively managed.

Transformation of Grade I Follicular Lymphoma to Anaplastic Large Cell Lymphoma CD30+ ALK1- with Complete Response to Brentuximab Vedotin and High-Dose Methotrexate.

Lymphomas are a heterogeneous group of diseases that encompass malignant disorders of B-cells, T-cells, or natural killer cells. B-cell lymphomas represent approximately 80-85% of cases. Transformation of B-cell lymphomas from a low grade to a higher grade within the same lineage is a well-described phenomenon. The most common and well-known transformation is from follicular lymphoma to diffuse large B-cell lymphoma. However, the transformation of B-cell lymphomas to T-cell lymphomas is extremely rare. In this article, we report a case of grade I follicular lymphoma (B-cell lymphoma) that transformed into anaplastic large cell lymphoma CD30+ ALK1- (T-cell lymphoma). This article reported a case with a unique particular combination of morphology and immunophenotype in the same patient. In addition, we report a remarkable response with complete remission following treatment with Brentuximab vedotin (anti-CD30 antibody-drug conjugate) and high-dose methotrexate. The patient achieved this durable response despite the aggressive presentation.

Three-dimensional Virtual Reality as an Innovative Teaching and Learning Tool for Human Anatomy Courses in Medical Education: A Mixed Methods Study.

Introduction Poor knowledge retention is one reason for medical student attrition in learning and has been a huge concern in medical education. Three-dimensional virtual reality (3D-VR)-based teaching and learning in medical education has been promoted to improve student learning outcomes. This study aimed to determine the effectiveness of 3D-VR in knowledge retention in human anatomy courses as compared to traditional teaching methods among medical students. Methods A convergent mixed methods design was utilized to evaluate learning outcomes in terms of short- and long-term knowledge retention scores among students using 3D-VR and those using traditional models and to describe students' experiences and views of the use of 3D-VR as a teaching and learning tool. Results Male students who used the 3D-VR tool had significantly higher short- and long-term knowledge scores than males who used the traditional methods. Meanwhile, females who used traditional methods showed significantly higher short-term knowledge scores than females who used 3D-VR. Conclusion Medical students described 3D-VR as a learning tool with a great deal to offer for learning human anatomy as compared to traditional methods. Therefore, we recommend adding the use of 3D-VR in the anatomy curriculum. However, several 3D-VR limitations were also identified, which may hinder its utilization for teaching and learning. These concerns must be addressed before 3D-VR tools are considered for implementation in medical education human anatomy courses.

OSSMAR: An Observational Study to Describe the Use of Sunitinib in Real-Life Practice for the Treatment of Metastatic Renal Cell Carcinoma.

PURPOSE: Sunitinib offers improved efficacy for patients with metastatic renal cell carcinoma (mRCC). To provide better disease management in the Middle East, we studied its use in mRCC in real-life practice in this region. MATERIAL AND METHODS: Patients diagnosed with mRCC and started on sunitinib between 2006 and 2016 from 10 centers in Africa and the Middle East region were studied in this regional, multicenter, observational, retrospective trial to obtain routine clinical practice data on the usage patterns and outcomes of sunitinib in mRCC in real-life practice. RESULTS: A total of 289 patients were enrolled. Median age at diagnosis was 58.7 years. The patient characteristics were as follows: 73.6% of patients were males; 85.8% had clear-cell renal cell carcinoma (RCC); 97.5% had unilateral RCC; 66.3% had metastatic disease at initial diagnosis; 56.3% received previous treatment for RCC, among which 98.7% had undergone surgery; and 15.2% and 31.4% were classified in the favorable and poor-risk groups (expanded Memorial Sloan Kettering Cancer Center criteria), respectively. On treatment initiation, the mean total sunitinib dose was 48.1 mg, and 87.6% of patients were started on a sunitinib dose of 50 mg. The mean duration of sunitinib treatment was 9.6 months. Overall response rate was 20.8%, with a median duration of 8.2 months. Median time to progression was 5.7 months. Median follow-up time was 7.8 months. By months 12 and 24, 34.3% and 11.4% of patients, respectively, were still alive. Seventy-six patients (60.9%) experienced 314 adverse events. Twenty-three patients (8.0%) experienced 28 serious adverse events. Overall, 83 patients (28.7%) discontinued their sunitinib treatment. CONCLUSION: The results are indicative of the general treatment outcomes of patients with mRCC in the Middle East using sunitinib in routine clinical practice. Reported adverse events are similar to those described in the literature but at lower frequencies.