Hirsch Caroline, Zorger Ana-Mihaela, Baumann Mandy, Park Yun Soo, Bröckelmann Paul J, Mellinghoff Sibylle, Monsef Ina, Skoetz Nicole, Kreuzberger Nina
Cochrane Evidence Synthesis Unit Germany/UK, Cochrane Haematology, Institute of Public Health, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Cochrane Database Syst Rev. 2025 Apr 16;4(4):CD015551. doi: 10.1002/14651858.CD015551.pub2.
Infections are one of the most frequent complications seen in adults with cancer, often arising from the underlying condition or as a result of immunosuppressive treatments. Certain infections (e.g. influenza, pneumococcal disease, and meningococcal disease) may be prevented through vaccination. However, adults with solid tumours may elicit varying immune responses compared to healthy individuals.
To assess the benefits and risks of vaccines for the prevention of infectious diseases in adults with solid tumours.
We searched CENTRAL, MEDLINE, Embase, two further databases, and two study registries from inception to 2 December 2024 for randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs).
We included RCTs evaluating vaccines against the following infectious diseases in adults (≥ 18 years of age) with any diagnosis of solid tumour cancer compared to placebo or no vaccine: pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, diphtheria, influenza, herpes zoster, and COVID-19. In cases where RCTs were unavailable, we included prospective controlled NRSIs. We excluded live-attenuated vaccines.
We followed standard Cochrane methodology. Two review authors independently screened search results, extracted data, and assessed the risk of bias (RoB) in the included studies using the Cochrane RoB 2 tool for RCTs and ROBINS-I for NRSIs. We rated the certainty in the evidence using the GRADE approach for the following prioritised outcomes: incidence of infection concerned, all-cause mortality, quality of life, adverse events (AEs) of any grade, serious adverse events (SAEs), localised events at the injection site, and systemic events.
We included 10 studies (five RCTs and five NRSIs) involving 81,823 adults with solid tumours receiving vaccines to prevent infections with herpes zoster, influenza, or COVID-19. Six studies included participants with varied solid tumours, while two focused on neck and oesophageal cancer or lung cancer. We assessed the RCTs to be at low or moderate risk of bias, whereas most NRSIs were at critical risk of bias due to concerns about confounding. We identified two ongoing studies: one RCT evaluating an influenza vaccine, and one NRSI evaluating COVID-19 vaccines. Twelve studies are awaiting assessment. We did not identify RCTs or NRSIs of vaccines for preventing pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, or diphtheria compared to placebo or no vaccine. The results from the RCTs are presented below. The results from the NRSIs are detailed in the main text of the review. No study reported quality of life. Vaccines for preventing herpes zoster compared to placebo or no vaccine Three RCTs (3054 participants) evaluated vaccines to prevent herpes zoster. Herpes zoster vaccines decrease the incidence of herpes zoster up to 29.4 months after the final dose (RR 0.37, 95% CI 0.23 to 0.59; 1 RCT, 2678 participants; high-certainty evidence). Herpes zoster vaccines probably make little or no difference to all-cause mortality up to 28 days after the final dose (RR 1.17, 95% CI 0.91 to 1.50; 2 RCTs, 2744 participants; moderate-certainty evidence); make little or no difference to any-grade AEs up to 30 days after final dose (RR 1.02, 95% CI 0.98 to 1.05; 3 RCTs, 2976 participants; high-certainty evidence), and probably make little or no difference in SAEs up to 30 days (RR 1.08, 95% CI 0.93 to 1.24; I² = 0%; 3 RCTs, 2976 participants; moderate-certainty evidence). Vaccines to prevent herpes zoster increase the number of participants with localised events at the injection site compared to placebo or no vaccine (RR 6.81, 95% CI 2.52 to 18.40; 3 RCTs, 2966 participants; high-certainty evidence) and may make little or no difference to the number of participants with systemic events up to 30 days after final dose (RR 1.08, 95% CI 0.77 to 1.50; 3 RCTs, 2966 participants; low-certainty evidence). Vaccines for preventing influenza compared to placebo or no vaccine One RCT (75 participants) evaluated vaccines to prevent influenza. We are uncertain about the effects of influenza vaccines administered prior to surgery on all-cause mortality (RR 1.00, 95% CI 0.07 to 15.33; 1 RCT, 66 participants; very low-certainty evidence), any-grade AEs (RR 1.17, 95% CI 0.89 to 1.54; 1 RCT, 75 participants; very low-certainty evidence), and SAEs (RR 1.46, 95% CI 0.76 to 2.83; 1 RCT, 75 participants; very low-certainty evidence) up to 15 days post-surgery. The RCT did not report the incidence of influenza, localised events at the injection site, or systemic events. Vaccines for preventing COVID-19 compared to placebo or no vaccine One RCT (2256 participants) evaluated vaccines to prevent COVID-19. Participants may have been exposed to the SARS-CoV-2 variants alpha, beta, and gamma. Vaccines to prevent COVID-19 probably decrease the incidence of COVID-19 in participants without previous COVID-19 infection up to six months after the second dose (RR 0.08, 95% CI 0.02 to 0.25; 1 RCT, 2100 participants; moderate-certainty evidence). The COVID-19 vaccines probably increase any-grade AEs (RR 1.99, 95% CI 1.71 to 2.30; 1 RCT, 2328 participants; moderate-certainty evidence). They may have little or no effect on SAEs up to 6 months after the second dose (RR 1.43, 95% CI 0.80 to 2.54; 1 RCT, 2328 participants; low-certainty evidence). The RCT did not report localised events at the injection site or systemic events.
AUTHORS' CONCLUSIONS: In adults with solid tumours, herpes zoster vaccines reduced the incidence of herpes zoster (high-certainty evidence), although localised events at the injection site were more likely to occur (high-certainty evidence). The evidence is very uncertain about the effects of influenza vaccines on all-cause mortality, any-grade AEs, and SAEs (very low-certainty evidence); the incidence of influenza was not measured in the studies. COVID-19 vaccines probably decrease the incidence of COVID-19 in those without prior infection (moderate-certainty evidence) but probably increase any-grade AEs (moderate-certainty evidence). We found no RCTs or NRSIs investigating vaccines for preventing pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, diphtheria compared to placebo or no vaccine, in adults with solid tumours. Additional research, preferably of RCT design, is necessary to resolve uncertainties.
感染是成年癌症患者中最常见的并发症之一,通常源于基础疾病或免疫抑制治疗。某些感染(如流感、肺炎球菌病和脑膜炎球菌病)可通过接种疫苗预防。然而,与健康个体相比,实体瘤成年患者可能会产生不同的免疫反应。
评估疫苗对预防实体瘤成年患者感染性疾病的益处和风险。
我们检索了Cochrane系统评价数据库、医学期刊数据库、Embase数据库、另外两个数据库以及两个研究注册库,检索时间从建库至2024年12月2日,以查找随机对照试验(RCT)和干预性非随机对照研究(NRSI)。
我们纳入了评估疫苗预防以下感染性疾病的RCT,这些研究将成年(≥18岁)实体瘤癌症患者与安慰剂或未接种疫苗的情况进行比较:肺炎球菌病、B型流感嗜血杆菌病、脑膜炎球菌病、百日咳、乙型肝炎、破伤风、脊髓灰质炎、白喉、流感、带状疱疹和2019冠状病毒病。若没有RCT,则纳入前瞻性对照NRSI。我们排除了减毒活疫苗。
我们遵循标准的Cochrane方法。两位综述作者独立筛选检索结果、提取数据,并使用Cochrane偏倚风险2工具评估RCT中纳入研究的偏倚风险,使用ROBINS-I工具评估NRSI的偏倚风险。我们使用GRADE方法对以下优先结局的证据确定性进行评级:相关感染的发生率、全因死亡率、生活质量、任何等级的不良事件(AE)、严重不良事件(SAE)、注射部位的局部事件和全身事件。
我们纳入了10项研究(5项RCT和5项NRSI),涉及81,823名接受疫苗以预防带状疱疹、流感或2019冠状病毒病感染的实体瘤成年患者。6项研究纳入了患有多种实体瘤的参与者,而2项研究聚焦于头颈癌、食管癌或肺癌。我们评估RCT的偏倚风险为低或中度,而由于存在混杂因素的担忧,大多数NRSI的偏倚风险处于关键水平。我们确定了两项正在进行的研究:一项评估流感疫苗的RCT和一项评估2,019冠状病毒病疫苗的NRSI。12项研究正在等待评估。我们未找到与安慰剂或未接种疫苗相比,预防肺炎球菌病、B型流感嗜血杆菌病、脑膜炎球菌病、百日咳、乙型肝炎、破伤风、脊髓灰质炎或白喉疫苗的RCT或NRSI。RCT的结果如下。NRSI的结果在综述正文中有详细说明。没有研究报告生活质量。与安慰剂或未接种疫苗相比,预防带状疱疹的疫苗 三项RCT(3054名参与者)评估了预防带状疱疹的疫苗。带状疱疹疫苗可降低最后一剂后长达29.4个月的带状疱疹发病率(RR = 0.37,95%CI 0.23至0.59;1项RCT,2678名参与者;高确定性证据)。带状疱疹疫苗在最后一剂后长达28天对全因死亡率可能几乎没有影响(RR = 1.17,95%CI 0.91至1.50;2项RCT,2744名参与者;中度确定性证据);在最后一剂后长达30天对任何等级的AE可能几乎没有影响(RR = 1.02,95%CI 0.98至1.05;3项RCT,2976名参与者;高确定性证据),并且在长达30天内对SAE可能几乎没有影响(RR = 1.08,95%CI 0.93至1.24;I² = 0%;3项RCT,2976名参与者;中度确定性证据)。与安慰剂或未接种疫苗相比,预防带状疱疹的疫苗会增加注射部位局部事件的参与者数量(RR = 6.81,95%CI 2.52至18.40;3项RCT,2966名参与者;高确定性证据),并且在最后一剂后长达30天对全身事件的参与者数量可能几乎没有影响(RR = 1.08,95%CI 0.77至1.50;3项RCT,2966名参与者;低确定性证据)。与安慰剂或未接种疫苗相比,预防流感的疫苗 一项RCT(75名参与者)评估了预防流感的疫苗。我们不确定手术前接种流感疫苗对全因死亡率(RR = 1.00,95%CI 0.07至15.33;1项RCT,66名参与者;极低确定性证据)、任何等级的AE(RR = 1.17,95%CI 0.89至1.54;1项RCT,75名参与者;极低确定性证据)和SAE(RR = 1.46,95%CI 0.