BackgroundWomen 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.MethodsAccording to predefined selection criteria, literature search identified 34 studies that were included in the analyses.ResultsAfter 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.ConclusionsWe 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.

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.

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).

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has a favorable effect on patients with metastatic colorectal cancer (mCRC) harboring wild-type (WT) KRAS gene. This meta-analysis was planned to quantify the benefit and assess safety. Selected for the analysis were randomized clinical studies that have used panitumumab-based therapy (PBT) for patients with mCRC and where the outcome of patients with WT KRAS was reported. Four eligible studies were analyzed including 1,010 and 1,105 patients who received PBT and the control intervention, respectively. Used in subsequent-line setting, PBT was associated with 42% improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.58; 95% CI, 0.36-0.93; P = 0.02), a non-significant overall survival (OS) benefit (HR = 0.90; [95% CI, 0.76-1.05]; P = 0.18), and a significant increase in objective response rate (ORR) (odds ratio (OR) = 0.67 [95% CI, 1.15-77.98]; P = 0.04). PBT showed no benefit in the first-line setting. Restricted analysis to two studies (first- and second-line setting), where the treatment effect of PBT was prospectively analyzed according to tumor KRAS status, showed significant PFS (HR = 0.77), OS (HR = 0.84), and ORR (OR = 2.06) advantage. Almost all patients' subgroups attained clinical benefit. PBT-related adverse events were similar across comparisons with the exception of toxicities known to be associated with anti-EGFR therapy. This meta-analysis showed significant clinical benefit for PBT for patients with WT KRAS mCRC predominantly when used following prior chemotherapy exposure. The benefit was demonstrated in most subgroup analyses. Further research to better define potential responders is needed.

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.