Mubarak Al-Mansour

Transformation to Aggressive Lymphoma in Nodular Lymphocyte-Predominant Hodgkin's Lymphoma

PURPOSE Prior observations suggest a higher risk of transformation of nodular lymphocyte-predominant Hodgkins lymphoma (NLPHL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), than in classical Hodgkins lymphoma. We evaluated the frequency of transformation in all patients diagnosed with NLPHL at the British Columbia Cancer Agency with long-term follow-up. PATIENTS AND METHODS The Lymphoid Cancer Database of the British Columbia Cancer Agency was searched to identify all patients diagnosed with NLPHL between 1965 and 2006. After pathologic review, 95 patients with NLPHL were confirmed. Results Patients with NLPHL had the following characteristics at diagnosis: median age of 37 years, 73% male, and 68% stage I or II disease. With a median follow-up time for living patients of 6.5 years (range, 2.5 to 33 years), 13 patients (14%) experienced transformation to aggressive lymphoma (median time to transformation, 8.1 years; range, 0.35 to 20.3 years). The actuarial risk of transformation to aggressive lymphoma was 7% and 30% at 10 and 20 years, respectively. Transformation was more likely in patients with initial splenic involvement (P = .006) at the time of diagnosis of NLPHL. The 10-year progression-free and overall survival rates in patients with transformed lymphoma were 52% and 62%, respectively. CONCLUSION The risk of transformation in patients with NLPHL to DLBCL is substantial and underappreciated. Because transformation can occur years after the primary diagnosis of NLPHL, long-term follow-up of these individuals is necessary to accurately estimate the risk of development of secondary DLBCL.

The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis

In a recent meta-analysis, we demonstrated that rich tumor-infiltrating lymphocytes (TILs) were significantly correlated to a favorable breast cancer (BC) outcome largely in estrogen receptor-negative tumors. It is known that TILs predominate in triple-negative (TN) BC, and to the best of our knowledge, there is no published meta-analysis that examined their prognostic value exclusively in that subtype. Therefore, we planned this meta-analysis to explore the clinical utility of rich TILs in TN-BC. According to predefined selection criteria, literature search identified eight eligible studies. The meta-analysis included data on 2,987 patients with early stage BC. The median percentage of lymph node positivity was 47xa0% (95xa0% confidence interval [CI] 23–82xa0%). Over a median follow-up of 113xa0months (95xa0% CI 80–144xa0months), it was found that rich TILs were associated with 30xa0% (hazard ratio [HR]xa0=xa00.70; 95xa0% CI 0.56–0.87; Pxa0=xa00.001), 22xa0% (HRxa0=xa00.78; 95xa0% CI 0.68–0.90; Pxa0=xa00.0008), and 34xa0% (HRxa0=xa00.66; 95xa0% CI 0.53–0.83; Pxa0=xa00.0003), reduction in the risk of recurrence, distant recurrence, and death, respectively. In addition, for every 10xa0% increments in rich TILs, there was an approximate 15–20xa0% reduction in any recurrence, distant recurrence, or mortality. Moreover, rich TILs predicted superior overall survival (OS) benefit irrespective of the disease phenotype (TN-BC or core-basal phenotype), TILs location (intratumoral or stromal), or TILs qualification as either TILs-non-specified, cytotoxic (CD8+) or regulatory (forkhead box protein 3, FOXP3+) T cells. Data on 5-negative phenotype population were limited, and rich TILs failed to demonstrate a prognostic significance in this phenotype. To investigate the heterogeneity that was shown in the analyses of disease-free survival and OS, a set of meta-analyses showed that the method used in TILs detection (hematoxylin and eosin stains vs. immunohistochemistry) could explain most of the variability in the pooled estimates. Rich TILs were significantly associated with better survival outcome in early TN-BC and should be considered as a strong prognostic factor in this subtype. The results from the current meta-analysis support integrating immunotherapy with conventional therapy in future BC research.

Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome.

The appropriate therapy for limited-stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL), chemotherapy is often omitted; however, it is unknown whether this impacts the risk of relapse. Herein, we compared the outcome of patients with limited-stage NLPHL treated in an era in which ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy was routinely incorporated into the primary therapy to an earlier era in which radiotherapy (RT) was used as a single modality. Using the British Columbia Cancer Agency Lymphoid Cancer Database, 88 patients with limited-stage NLPHL (stage 1A/1B or 2A, nonbulky disease < 10 cm) were identified. Treatment followed era-specific guidelines: before 1993, (n = 32) RT alone; and 1993 to present (n = 56), ABVD-like chemotherapy for 2 cycles followed by RT with the exception of 14 patients who received ABVD chemotherapy alone. Most patients were male (75%) with stage I disease (61%). In an era-to-era comparison, the 10-year time to progression (98% vs 76% P = .0074), progression-free survival (91% vs 65% P = .0024), and OS (93% vs 84%, P = .074) favored the ABVD treatment era compared with the RT alone era. Treating limited-stage NLPHL similarly to CHL may improve outcome compared with the use of radiation alone.

Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis

Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL.

Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis.

BackgroundPatients treated for Hodgkin’s lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. The aim of this meta-analysis was to quantify such risk and to analyze contributing risk factors in HL survivors.MethodsAccording to predefined selection criteria, a literature search identified 21 studies that were included in the analysis.ResultsAfter eliminating overlapping or duplicate data, 793 (76xa0% males) incidences of SLC were encountered in 74,831 patients (58xa0% males) with HL over a median follow-up of 11.5xa0years. The median age at HL diagnosis and the median age at SLC diagnosis were 33.0 and 45.9, respectively. The mean latency between treatment of HL and development of SLC was 11.5xa0years. The pooled relative risk (RR) of SLC was 4.62 (95xa0% confidence interval [CI], 3.18–6.70], I2xa0=xa098xa0%), with a median absolute excess rate of 10.4 per 10,000 person-years. RR was positively related to study size, male-to-female ratio, institutional versus population-based data sets, and the use of any radiotherapy (RT) or combined modality therapy (CMT), while age at diagnosis of HL was not significant. The highest risk was shown among patients aged 15–24xa0years (RRxa0=xa08.76 [95xa0% CI, 4.55–16.89]), while the lowest risk occurred in patients ≥55xa0years at primary treatment (RRxa0=xa02.88 [95xa0% CI, 2.33–3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10–14 years (RRxa0=xa04.17 [95xa0% CI, 3.62–8.81]), but did not increase after ≥15xa0years (RRxa0=xa04.01 [95xa0% CI, 2.68–5.98]). RT only, CMT, or chemotherapy only was associated with RR (95xa0% CI) of 4.88 (3.14–7.60), 5.15 (4.08–6.50), and 2.39 (1.60–3.55), respectively. Patients with SLC demonstrated poor prognosis.ConclusionsThe current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.

Breast cancer screening: review of benefits and harms, and recommendations for developing and low-income countries.

Breast cancer is the most common cancer in women worldwide. The disease remains a public health concern as recent evidence indicates that the breast cancer burden has increased mainly in developing and low-income countries (DLICs). Despite the demonstrated benefits, the debate about the real benefits and harms of breast cancer screening is ongoing. Many experts believe that the benefits of screening, in terms of reduced breast cancer mortality, outweigh the harms, whereas others think the opposite. In this review, we assess the clinical utility of available screening modalities, present evidence, overdiagnosis, cost-effectiveness, and other pertinent issues. We also examine relevant data from DLICs to underscore the barriers and challenges that impede implementation of screening strategies in those populations. We also provide recommendations concerning rational preventive strategies for breast cancer control for women in DLICs.

The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

Abstract The association between PIK3CA mutation and resistance to anti-HER2 therapy (AHT) is not precisely defined. This meta-analysis intended to explore the clinical utility of PIK3CA mutation in HER2-positive breast cancer treated with AHT. Literature search identified 19 eligible studies. There were 1720 patients with advanced, 828 with early and 1290 patients treated in the neoadjuvant setting. In metastatic breast cancer, AHT showed no differential objective response benefit between the wild type (WT) and the mutated type (MT) PIK3CA subgroups (odds ratio [OR]xa0=xa01.09; 95xa0% CI 0.60–2.00; Pxa0=xa00.78). AHT favorable affected progression-free survival (PFS) irrespective of PIK3CA mutation. There was no PFS difference between WT and MT regardless of the offered therapy. In early breast cancer, trastuzumab combined with the same chemotherapy conferred consistent relapse-free survival benefit in WT and MT subgroups (WT: HRxa0=xa00.59; 95xa0% CI 0.44–0.80; Pxa0<xa00.001 vs. MT: HRxa0=xa00.42; 95xa0% CI 0.24–0.74; Pxa0<xa00.001). In the neoadjuvant setting, AHT-based therapy produced a 72xa0% higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (ORxa0=xa01.72; 95xa0% CI 1.29–2.13; Pxa0<xa00.001). In that setting, there was no disease-free or overall survival difference based on PIK3CA mutational status. In this meta-analysis, AHT did not achieve differential benefit according to PIK3CA mutation in HER2-positive metastatic or early breast cancer; however, in the neoadjuvant setting, patients harboring WT PIK3CA tumors attained a higher pCR rate.

The Prognostic and Predicting Roles of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Meta-Analysis

Background: The relationship between lymphocyte infiltrates (LIs) and breast cancer outcome remains controversial. We performed this meta-analysis to elucidate the relationship. Methods: A literature search identified 21 eligible studies. Results: 16,097 patients were included. Multivariate analyses data for patients with unspecified receptors status showed that rich LIs expression was associated with 52% (hazard ratio (HR) = 0.48; 95% confidence interval (CI), 0.30-0.77), and 29% (HR = 0.71; 95% CI, 0.63-0.80) reduction in the risk of relapse and death, respectively. In the neoadjuvant setting, rich LIs predicted a 28% increase in complete pathological response rate. The prognostic and predictive utility of rich LIs was restricted to patients with estrogen receptor negative (ER-) or triple negative disease. Only rich CD8+ T cells tumors demonstrated clinical utility. Conclusion: LIs significantly correlated to outcome predominantly in ER- tumors. Integrating immunotherapy with conventional therapy may warrant future research in breast cancer.

Hodgkin Lymphoma Outcome: A Retrospective Study from 3 Tertiary Centers in Saudi Arabia

Background: Hodgkin lymphoma (HL) exhibits considerable clinicopathological variations in different parts of the world. This study was prompted by the limited availability of HL data in developing countries (particularly long-term outcomes). Methods: We performed a retrospective review of eligible adult HL patients treated at 3 tertiary centers in Saudi Arabia between January 1997 and December 2012. Results: The review included 340 patients with a median age of 26 years (range 15-82 years); 53% were male, 74% had an advanced stage, 22% had bulky disease, and 70% had low-to-intermediate risk according to the International Prognostic Score. Nodular sclerosis was the most common histological subtype (59%). Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) was offered to 92% and radiotherapy to 43%. Initial therapy outcomes were complete response, partial response, and progressive disease in 91%, 5%, and 2% of patients, respectively. At a median follow-up of 39 months, the actuarial freedom from treatment failure at 5 years was 74%, with a 5-year overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently predicted an adverse outcome. Conclusion: Our Saudi patient population exhibited outcomes that were comparable to those reported in developed countries.

Negative effect of hepatitis in overall and progression-free survival among patients with diffuse large B-cell lymphoma

BackgroundHepatitis B virus (HBV) is one of the most prevalent and serious infections worldwide. HBV reactivation is a serious complication for lymphoma patients who are being treated with rituximab-containing regimen. Since the impact of HBV has not been fully evaluated on the prognosis of diffuse large B cell lymphoma (DLBCL), this study examined the effect of the hepatitis infection on the progression-free survival (PFS) and overall survival (OS) in patients with DLBCL who received rituximab-containing chemotherapy.MethodsThis retrospective cohort study was conducted at Princess Noorah Oncology Center, Jeddah by reviewing all medical records of 172 DLBCL diagnosed patients and recieved Rituximab-containing chemotherapy dated from January 2009 to February 2016.ResultsOut of 172 patients, 53 were found positive in hepatitis serology. The 12 of those were HBsAg-positive and 41 were HBcAb-positive. Hepatitis reactivation was observed in 1% of the patients (i.e., 2 out of 172) and both of them were HBsAg-positive. Thus, the risk of hepatitis reactivation among the HBsAg-positive patients was 17% (i.e., 2 out of 12). The predicted 3-year PFS for HBsAg-positive and HBcAb-positive were 52% (± 8%), while 76% (± 4) for HBsAg-negative and HBcAb-negative patients. On the other hand, the predicted 3-year OS for HBsAg and HBcAb-negative group is 93% (±3) while for HBsAg-positive and HBcAb-positive is 77% (±7), respectively.ConclusionThe present study demonstrated a low HBV reactivation rate of 1% exclusively in 2 patients with HBsAg-positive status diagnosed with DLBCL and receiving R-CHOP chemotherapy.