Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We ...performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies,
= 16; patients,
= 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24-1.91;
= 0.01 and HR = 1.34, 95% CI: 1.02-1.76;
= 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41-4.43;
< 0.01) or brain metastases (HR = 1.51, 95% CI 1.22-1.87;
< 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
We analyzed published studies on the efficacy and safety of the third dose of the COVID‐19 vaccine in various general population settings. We conducted systematic searches of PubMed and EMBASE for ...series published in the English language through November 15, 2021, using the search terms “third” or “booster” or “three” and “dose” and “COVID‐19” or “SARS‐CoV‐2.” All articles were selected according to the MOOSE guidelines. The seroconversion risk after third doses was descriptively expressed as a pooled rate ratio (seroconversion rate after the third dose/seroconversion rate after the second dose). The search returned 30 studies that included a total of 2 734 437 vaccinated subjects. In more than 2 700 000 Israeli patients extracted from the general population, the reduction in the risk of infection ranged from 88% to 92%. Conversion rates for IgG anti‐spike ranged from 95% to 100%. In cancer or immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses. A third dose seems necessary to protect against all COVID‐19 infection, severe disease, and death risk.
Highlights
We analyzed published studies on the efficacy and safety of the third dose of COVID‐19 vaccine in various settings.
A total of 30 studies that included a total of 2 734 437 vaccinated subjects.
The reduction in the risk of infection ranged from 88% to 92%.
In immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses.
A third dose seems necessary to protect against all COVID‐19 infection, severe disease, and death risk.
Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in ...addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patients with TNBC treated with NAC, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated platinum-based NAC in patients with TNBC. Random effect models were adopted to estimate the summary risk ratio (RR), and the publication bias was evaluated using a funnel plot and Egger’s regression asymmetry test. The primary endpoints were the pooled rate of the pathologic complete response (pCR) and the RR to obtain a pCR in patients treated versus not treated with NAC containing platinum agents. 28 studies were included (six randomized controlled trials and 22 retrospective or prospective studies) for a total of 1,598 TNBC patients. Overall, the pooled rate of pCR in patients treated with platinum-based NAC was 45 %. In randomized trials, NAC containing cisplatin or carboplatin significantly increased the rate of pCR compared with nonplatinum agents (RR = 1.45, 95 % CI 1.25–1.68;
P
< 0.0001). Compared with non-TN, TNBCs were associated with a threefold increase in the pCR rate when treated with platinum-based NAC (RR 3.32, 95 % CI 2.39–4.61;
P
< 0.0001). In conclusion, pCR rates increase significantly with the addition of cisplatin or carboplatin in TNBC compared with NAC containing no platinum drugs. TN status is a predictor of benefit from platinum-based NAC.
Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or metastatic pancreatic cancer ...(mPC). However, no randomized trials comparing the two schemes have been performed. This meta-analysis aims to compare GEM-NAB and FOLFIRINOX in terms of safety and effectiveness, taking into account data from real-life studies on mPC. We systematically searched PubMed, EMBASE and Cochrane library up to November 2018 to identify retrospective or cohort studies on mPC comparing GEM-NAB and FOLFIRINOX. We included 16 retrospective studies, including 3813 patients (2123 treated with GEM-NAB and 1690 treated with FOLFIRINOX). Despite a median weighted overall survival (OS) difference in favor of FOLFIRINOX (mean difference: 1.15, 95% confidence interval CI 0.08⁻2.22,
= 0.03), in whole population OS was similar (hazard ratio (HR = 0.99, 95% CI 0.84⁻1.16;
= 0.9). PFS was also not different between the two arms (HR = 0.88, 95% CI 0.71⁻1.1;
= 0.26). The overall response rate was similar (25 vs. 24% with GEM-NAB and FOLFIRINOX). Among grade 3⁻4 toxicities, neutropenia, febrile neutropenia, and nausea were lower with GEM-NAB, while neurotoxicity and anemia were lower with FOLFIRINOX. In conclusion, despite a numerically longer median OS with FOLFIRINOX as compared to GEM-NAB, the overall risk of death and progression were similar. Their toxicity was different with less nausea, neutropenia, and febrile neutropenia with GEM-NAB, as compared to less neurotoxicity and anemia with FOLFIRINOX. Therefore, analysis of non-randomized "real world" studies to date has not provided evidence of a major benefit of one regimen over the other.
Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK ...inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs.
A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR).
A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1-65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3-55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%.
Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy.
The association between antibiotic use and risk of cancer development is unclear, and clinical trials are lacking. We performed a systematic review and meta-analysis of observational studies to ...assess the association between antibiotic use and risk of cancer. PubMed, the Cochrane Library and EMBASE were searched from inception to 24 February 2019 for studies reporting antibiotic use and subsequent risk of cancer. We included observational studies of adult subjects with previous exposure to antibiotics and available information on incident cancer diagnoses. For each of the eligible studies, data were collected by three reviewers. Risk of cancer was pooled to provide an adjusted odds ratio (OR) with a 95% confidence interval (CI). The primary outcome was the risk of developing cancer in ever versus non-antibiotic users. Cancer risk's association with antibiotic intake was evaluated among 7,947,270 participants (
= 25 studies). Overall, antibiotic use was an independent risk factor for cancer occurrence (OR 1.18, 95%CI 1.12-1.24,
< 0.001). The risk was especially increased for lung cancer (OR 1.29, 95%CI 1.03-1.61,
= 0.02), lymphomas (OR 1.31, 95%CI 1.13-1.51,
< 0.001), pancreatic cancer (OR 1.28, 95%CI 1.04-1.57,
= 0.019), renal cell carcinoma (OR 1.28, 95%CI 1.1-1.5,
= 0.001), and multiple myeloma (OR 1.36, 95%CI 1.18-1.56,
< 0.001). There is moderate evidence that excessive or prolonged use of antibiotics during a person's life is associated with slight increased risk of various cancers. The message is potentially important for public health policies because minimizing improper antibiotic use within a program of antibiotic stewardship could also reduce cancer incidence.
Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer ...and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 95%CI 1.52, 2.63, p < 0.01) or with other malignancies (HR = 1.91 95%CI 1.53, 2.39, p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 95%CI 1.06, 2.03, p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio HR =2.73 95%CI 0.84, 8.94, p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.
The typical class side effect of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (panitumumab and cetuximab) is a cutaneous maculopapular rash, although hypomagnesemia is also ...described to be a frequent adverse event. The purpose of our meta-analysis is to evaluate the frequency and the relative risk of hypomagnesemia in patients treated with cetuximab or panitumumab in randomized trials.
Eligible studies included prospective randomized Phase III controlled trials in which cetuximab or panitumumab were compared with standard anti-neoplastic therapy or best supportive care. Summary incidence rates and relative risks with 95% confidence intervals were calculated.
The overall incidence of hypomagnesemia was 17% among the patients who received the treatment, whose risk of developing hypomagnesemia turned out to be significantly increased compared with the patients treated with control medication, with an overall relative risk of 5.83 (p < 0.00001), where 3.87 refers to cetuximab and 12.55 to panitumumab. The addition of anti-EGFR monoclonal antibodies to standard anticancer therapy showed a significantly increased risk of hypomagnesemia compared with controls. The risk seems to be even higher for panitumumab, probably correlated with the increased risk of other adverse events (e.g., diarrhea and dehydration). Hypomagnesemia does not seem to be linked with any serious complications.
Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review ...and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval hazard ratio (HR) (95% confidence interval {CI}). Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (
n
= 123 studies). Overall, RBC transfusions were associated with an increased risk of death HR = 1.50 (95% CI 1.42–1.57),
p
< 0.01 and relapse HR = 1.36 (95% CI 1.26–1.46),
p
< 0.01. The survival was reduced even in cancer at early stages HR = 1.45 (1.36–1.55),
p
< 0.01. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients’ blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued.
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