Immunotherapy plus chemotherapy for patients with EGFR-mutated non-squamous cell lung cancer for disease progression after EGFR tyrosine-kinase inhibitor: A meta-analysis of randomized controlled trials.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain. METHODS: We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed. RESULTS: Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55 - 0.65; P < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49 - 0.76; P < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77 - 0.0.99; P value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32 - 2.76; P <0.0001). CONCLUSIONS: ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.

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.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis.

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39-0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

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.

Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab.

BACKGROUND: The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed might be able to predict patients' clinical outcome more accurately than RAS status alone. METHODS: K-RAS (exons 2, 3, 4) wild type colorectal cancer patients, candidates to second/third-line cetuximab with chemotherapy were prospectively allocated into 2 groups on the basis of their profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2) or unfavourable (any of the previous markers altered or mutated). After the introduction of N-RAS status (exons 2, 3, 4) only RAS wild type patients were considered eligible. Primary aim was response rate (RR). To detect a difference in terms of RR among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%), with a probability alpha of 0.05 and beta of 0.05, required sample size was 46 patients. Secondary endpoints were progression free survival (PFS) and overall survival (OS). RESULTS: Forty-six patients were enrolled. Seventeen patients (37%) were allocated to the favourable and 29 patients (63%) to the unfavourable profile. RR in the favourable and unfavourable group was 11/17 (65%) and 2/29 (7%) (p = 0.007) respectively. The favourable group also showed an improved PFS (8 months vs. 3 months, p < 0.0001) and OS (15 months vs. 6 months, p < 0.0001). CONCLUSIONS: Our results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcome.

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.

Correlation Between Oncotype Dx Recurrence Score and PREDICT Estimates in Early Breast Cancer: A Single Institution Experience.

PURPOSE: Oncotype Dx Recurrence Score (RS) is prognostic and predictive of chemotherapy benefit in women with node-negative and node-positive in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Nevertheless, its direct cost may be inhibitive. This study assesses the correlation between the RS and the free online PREDICT tools' estimations of adjuvant chemotherapy benefit. PATIENTS AND METHODS: A retrospective review of the electronic medical records of 112 patients with tumors tested for the RS and the PREDICT tool was used to estimate survival benefits. The correlation between RS and PREDICT estimations was analyzed using Spearman rank and McNemar tests. RESULTS: The median age of patients was 53 (95% CI, 50 to 55) years, with most patients having negative axillary lymph nodes (78%). While the absolute value for RS showed significant positive correlations with adjuvant chemotherapy's benefit as estimated by PREDICT, no significant correlations were found between the two methods in the percentage of chemotherapy gain. Notably, discordance rates between 48% and 67% between RS-based risk assignments and those based on PREDICT estimates were significant across the study population and subgroups. Only one disease recurrence and one breast cancer-related death were documented over a median follow-up of 23.5 (95% CI, 19.8 to 27.2) months. CONCLUSION: Our findings highlight a significant discordance between RS and PREDICT tools in predicting the benefits of adjuvant chemotherapy in patients with HR+, HER2- early breast cancer. While both tools aim to personalize cancer treatment, their discordance varies, suggesting that PREDICT could not substitute RS to predict adjuvant chemotherapy benefits regardless of patient risk classification. Further studies are needed to explore these relationships and optimize precision medicine approaches in breast cancer management.

Sunitinib adverse events in metastatic renal cell carcinoma: a meta-analysis.

BACKGROUND: Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated survival benefit in patients with metastatic renal cell carcinoma (mRCC); however, significant adverse events (AEs) have been associated with its use. The significant variation in the reported incidences of AEs has prompted this meta-analysis to quantify the risk and explore associated predictors. METHODS: According to predefined selection criteria, a literature search identified 12 studies that were included in the analyses. RESULTS: The meta-analysis included 5,658 patients; 66 % patients had prior systemic therapy whereas the remaining patients (34 %) received sunitinib in the first-line setting. For any grade toxicity, skin rash, fatigue, diarrhea, and mucositis were the most frequently encountered events (81, 52, 45, and 33 %, respectively). Anemia, neutropenia, or thrombocytopenia of any grade occurred in more than one-third of patients, although grades 3 or 4 were less common. Any grade raised by liver enzymes or serum creatinine occurred in 40 and 44 % of patients, respectively. Meta-regression analyses showed that study size was inversely related to the risk of experiencing fatigue, diarrhea, mucositis, anemia, and thrombocytopenia. In particular, the incidence of AEs was higher when sunitinib was used in pretreated versus naive patients; however, there was no significant difference between the two groups concerning the incidence of laboratory abnormalities. We addressed the limitations of reporting AEs in clinical studies. CONCLUSIONS: The present meta-analysis quantified sunitinib-associated AEs. The derived estimates would be similar to that to be expected from the use of sunitinib in community practice in unselected patients with metastatic renal cell carcinoma (mRCC).

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.

Risk of second breast cancer in female Hodgkin's lymphoma survivors: a meta-analysis.

BACKGROUND: Women treated for Hodgkin's lymphoma (HL) have an elevated risk of developing second breast cancer (SBC) compared with the general population. We planned this meta-analysis to quantify the long-term risk of SBC and analyze the contributing risk factors among HL survivors. METHODS: According to predefined selection criteria, literature search identified 34 studies that were included in the analyses. RESULTS: After eliminating overlapping or duplicate data, 957 incidences of SBC were encountered in 24,505 females with HL over a median follow-up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0, and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95% CI, 5.43-12.47, I² = 96%), with a median absolute excess rate of 22.9 per 10,000 person-years. The RR was found inversely related to age at diagnosis of HL with the highest rate (68.7; [95%CI, 28.08-168.11], I² = 79%), occurred in young patients (≤ 15 years old), where the RR in older women (≥ 40 years old) was not significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments since the treatment of HL showed that the risk was highest after 15-19 years of latency (13.87; [95% CI, 7.91-24.30], I² = 89%). Analysis of the effect of treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I² = 74%), (5.65; [95%CI, 2.94-10.88], I² = 91%), and (1.19; [95% CI, 0.50-2.82], I2 = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT only, respectively. To investigate the demonstrated heterogeneity, meta-regression analysis was performed when feasible. In most such analyses, the natural logarithm of RR was inversely associated with age at HL diagnosis. CONCLUSIONS: We conclude that, the current meta-analysis provided the most recent comprehensive estimate of the risk of SBC in a broad-range of HL survivors. Younger age at diagnosis proved to be a dominant risk factor. The obtained results would serve providing breast cancer screening recommendations for HL survivors.

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.

Cetuximab-based therapy is effective in chemotherapy-naïve patients with advanced and metastatic non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

Randomized controlled trails (RCTs) where cetuximab added to first-line platinum-based chemotherapy for patients with advanced/metastatic non-small-cell lung cancer (NSCLC) have yielded conflicting results. This meta-analysis intended to evaluate the efficacy and safety of cetuximab-based therapy (CBT) in that setting. We analyzed four eligible RCTs that included 1,003 and 1,015 patients randomized to CBT and control intervention, respectively. As compared with the noncetuximab group, CBT demonstrated an 9% reduction in the risk of disease progression [hazard ratio (HR) = 0.91; (CI = 0.83-1.00); p = 0.06], a 13% reduction in the risk of death [HR = 0.87; (CI = 0.78-0.96); p = 0.005], and an approximately 50% increase in objective response rate [odds ratio (OR) = 1.48; (CI = 1.22-1.80); p < 0.0001]. CBT-related adverse events were similar across comparisons except for toxicities known to be associated with anti-EGFR therapy. CBT produced significant clinical benefit with acceptable toxicity as a first-line strategy in patients with advanced/metastatic NSCLC. Further research is needed to identify markers predictive of cetuximab benefit in that disease.

Cetuximab-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of K-ras mutations.

BACKGROUND: Cetuximab has a favorable effect on patients with metastatic colorectal cancer harboring wild K-ras gene. This meta-analysis was planned to quantify the benefit. METHODS: A meta-analysis of clinical studies that have used cetuximab-based therapy (CBT) for patients with known K-ras status. RESULTS: There were four randomized studies (RS) that compared CBT versus non-cetuximab control (NCC) in 2,292 patients, and six non-randomized studies (NRS) included patients received cetuximab after failure of prior chemotherapy (411 patients). Patients in RS with wild K-ras tumor gained more benefit from CBT vs. NCC. For response rate (RR), the odds ratio was 2.10 (p = 0.0002), while the hazard ratio (HR) for progression-free survival (PFS) was 0.64 (p = 0.04). On the other hand, CBT was associated with an adverse effect on RR and no effect on PFS in mutated K-ras. In all patients who received CBT in RS and NRS, those with wild vs. mutated K-ras demonstrated higher RR (odds ratio 3.72; p < 0.0001). Compared with NCC in three RS, CBT showed significant overall survival (OS) advantage in patients with wild K-ras (HR = 0.68; p = 0.01). CONCLUSIONS: The significant clinical benefit of CBT concerning RR, PFS, and OS was restricted to patients with wild-type K-ras. There is a need to better define potential responders to CBT.

The present and the future of breast cancer burden in the Kingdom of Saudi Arabia.

BACKGROUND: Despite the low cancer incidence in the Kingdom of Saudi Arabia (KSA), the country must be ready to face the challenge of foreseeable increase in cancer burden attributed to growth and aging of population. This work was designed to study female breast cancer as a model to assess future cancer burden and the impact on healthcare resources. METHODS: Cancer statistics for the KSA were compared with that for the USA. The Joinpoint regression program was used to identify changes in secular trends, while the GLOBOCAN 2002 software projected future incidence and mortality. RESULTS: In the KSA, the age-standardized cancer rate (ASR) is 61 per 100,000 population, while the median age at diagnosis is 54 and 49 years for men and women, respectively. Fitting the ASR for breast cancer did not show any significant trend over a 10-year calendar period (16.2-18.2 per 100,000), a pattern that was similar to that for the USA in the prescreening mammography era. Considering the growth and aging of population and using conservative estimates for the annual percent change in incidence (increase) and mortality (decrease) by 2025, incidence and mortality cases are expected to increase by about 350% and 160%, respectively. CONCLUSION: In developing countries, future cancer rates could demonstrate a considerable increase and enormous demands on healthcare resources. The present work may provide an impetus to study other prevalent cancer types particularly in developing countries.

Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer.

BACKGROUND: Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC). This prospective phase-II study was designed to assess the efficacy and safety of CBCC as first-, second- or third-line among Saudi patients with mCRC. MATERIALS AND METHODS: Patients with mCRC were offered CBCC to assess time-to-disease progression (TTP), response rate and duration, overall survival (OS) and safety. RESULTS: Nineteen patients were eligible and their median age was 51 years. Seven patients received CBCC as first-line and 12 as second- or third-line. Responses: 11 (58%) partial responses, 5 (26%) stable disease and 3 (16%) disease progressions. The median response duration was 4.3 months [95% confidence interval (CI): 3.4-5.2 months]. The median TTP was 6.8 months (95% CI: 2-13.9 months) for all 19 patients compared to 9.3 months (95% CI: 3.9-14.6 months) for the seven patients who received CBCC as first-line. The median OS for the entire population was 12.3 months (95% CI could not be determined). On the other hand, while the median OS for those who received CBCC as first-line have not been reached, the median OS for those who received CBCC after failure of other salvage therapies was 12.3 months (95% CI: 3.2-21.4 months). CBCC was generally tolerable. One patient had a severe hypersensitivity reaction and another fatal cardiac arrest. CONCLUSION: CBCC is active with an acceptable safety profile. Until results from phase-III clinical trials are available, using CBCC as first-line is probably justified.

Extended adjuvant endocrine therapy in early breast cancer: a meta-analysis of published randomized trials.

Adjuvant endocrine therapy for 5 years is the standard adjuvant treatment for estrogen receptor-positive breast cancer while the benefits of extended adjuvant endocrine therapy (EAET) beyond 5 years are still controversial. That controversy prompted this meta-analysis to compare 5 years of adjuvant endocrine therapy only versus EAET. Eligible 11 randomized, controlled trials comprising 29,000 women were included. EAET showed no advantage in overall survival (OS) from all causes mortality (odds ratio [OR] = 0.98 (95% confidence interval [CI], 0.87-1.09); P = 0.67). On the other hand, compared with standard therapy, the pooled effects showed that EAET was associated with improvement in breast cancer-specific survival (OR = 0.87; 95% CI 0.79-0.96; P = 0.004), disease-free survival (DFS) (OR = 0.87; 95% CI 0.75-0.99; P = 0.002), disease recurrence (OR = 0.76; 95% CI 0.64-0.90; P = 0.001), and contralateral breast recurrence (OR = 0.74; 95% CI 0.59-0.93; P = 0.008). Improvement in DFS or disease recurrence was not shown in studies that compared 5 years of tamoxifen versus tamoxifen beyond 5 years. Subgroup analysis showed that EAET conferred more benefit for patients with positive lymph nodes. Rates of positive lymph nodes, the study size, and the median duration of follow-up were identified as variables that explained most of the demonstrated data heterogeneity. EAET should be considered as a preferred strategy for high-risk hormone-positive early breast cancer patients with positive lymph nodes; however, the benefit on OS could not be demonstrated.

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.

Adjuvant chemotherapy in 780 patients with early breast cancer: 10-year data from Saudi Arabia.

BACKGROUND: By and large, data about adjuvant chemotherapy for breast cancer in the Middle East are lacking. Retrospective analysis of prospectively captured data from a main referral center in the Kingdom of Saudi Arabia (KSA) may shed some light on the clinicopathological features and survival of patients offered adjuvant chemotherapy in a similar population in that part of the world. PATIENTS AND METHODS: Data on patients with invasive breast cancer (Stages I to IIIA) seen between 1992 and the end of 2001 and who received adjuvant chemotherapy were analyzed. A total of 780 patients were considered eligible and constitute the basis of this report. RESULTS: The median age +/- SD of the 780 patients was 42 +/- 9.6 yr. The majority of patients were younger than 50 yr (78%) and premenopausal (83%). Ten percent, 69%, and 21% of patients had Stage I, II, and IIIA, respectively. Patients expressed relatively high prevalence of adverse clinicopathological characteristics. Most patients (523 patients, 67%) received anthracyclines-containing adjuvant chemotherapy, 610 patients (78%) received adjuvant radiotherapy, and 296 (38%) received adjuvant tamoxifen. At a median follow-up of 42 mo (95% CI, 38.1-62.8 mo), the median overall (OS) and disease-free survival (DFS) were not reached; however, the 5-yr actuarial survival was estimated as 74% and 59%, respectively. Cox proportional regression hazard model identified positive axillary nodal status, and positive vascular invasion are the only variables that influenced OS adversely. The model also distinguished the same variables plus negative estrogen receptor status as covariates with negative effect on DFS. CONCLUSION: In conclusion, this series of 780 predominantly young patients with breast cancer receiving adjuvant chemotherapy highlighted the disease patterns and survival outcome in the KSA. The current series is significant being one of the few reports about adjuvant chemotherapy experience in a developing country and certainly the first from that part of the world.

HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer.

Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each HercepTest immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p = 0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p = 0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p = 0.26]) or overall survival (81% vs 84% [p = 0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer's approved guidelines failed to demonstrate a predictive or a prognostic role.