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.

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.

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] = 1.09; 95 % CI 0.60-2.00; P = 0.78). 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: HR = 0.59; 95 % CI 0.44-0.80; P < 0.001 vs. MT: HR = 0.42; 95 % CI 0.24-0.74; P < 0.001). In the neoadjuvant setting, AHT-based therapy produced a 72 % higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (OR = 1.72; 95 % CI 1.29-2.13; P < 0.001). 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.

Bleomycin pulmonary toxicity in adult Saudi patients with Hodgkin's lymphoma.

BACKGROUND: Bleomycin pulmonary toxicity (BPT) has been described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. METHODOLOGY: We reviewed the records of 164 consecutive HL patients. RESULTS: BPT was observed in 24 of 164 patients (15%). Older age and history of concomitant lung disease were significantly associated with approximately threefold (odds ratio: 3.38; 95% CI: 1.25-9.13; p = 0.02) and sevenfold (odds ratio: 7.19; 95% CI: 2.64-19.54; p < 0.0001) increase in BPT risk, respectively. The actuarial 5-year progression-free and overall survival for BPT and non-BPT groups, were not significantly different. CONCLUSION: In Saudi Arabian HL patients, the risk of BPT and its effect on survival outcome were comparable to that reported from developed countries.

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 47% (95% confidence interval [CI] 23-82%). Over a median follow-up of 113 months (95% CI 80-144 months), it was found that rich TILs were associated with 30% (hazard ratio [HR] = 0.70; 95% CI 0.56-0.87; P = 0.001), 22% (HR = 0.78; 95% CI 0.68-0.90; P = 0.0008), and 34% (HR = 0.66; 95% CI 0.53-0.83; P = 0.0003), reduction in the risk of recurrence, distant recurrence, and death, respectively. In addition, for every 10% increments in rich TILs, there was an approximate 15-20% 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.

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

BACKGROUND: Patients 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. METHODS: According to predefined selection criteria, a literature search identified 21 studies that were included in the analysis. RESULTS: After eliminating overlapping or duplicate data, 793 (76 % males) incidences of SLC were encountered in 74,831 patients (58 % males) with HL over a median follow-up of 11.5 years. 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 11.5 years. The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), 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 15-24 years (RR = 8.76 [95 % CI, 4.55-16.89]), while the lowest risk occurred in patients ≥55 years at primary treatment (RR = 2.88 [95 % CI, 2.33-3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10-14 years (RR = 4.17 [95 % CI, 3.62-8.81]), but did not increase after ≥15 years (RR = 4.01 [95 % CI, 2.68-5.98]). RT only, CMT, or chemotherapy only was associated with RR (95 % 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. CONCLUSIONS: The 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.

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.

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.

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

BACKGROUND: Hepatitis 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. METHODS: This 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. RESULTS: Out 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. CONCLUSION: The 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.

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.

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.