Next Article in Journal
Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin
Previous Article in Journal
The Future of Precision Medicine in the Cure of Alzheimer’s Disease
Previous Article in Special Issue
High Incidence of Thyroid Cancer in Southern Tuscany (Grosseto Province, Italy): Potential Role of Environmental Heavy Metal Pollution
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE)

Division of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Via Ripamonti 435, 20141 Milan, Italy
Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Via Ripamonti 435, 20141 Milan, Italy
III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, 20157 Milan, Italy
Division of Laboratory Medicine, European Institute of Oncology (IEO), IRCCS, Via Ripamonti 435, 20141 Milan, Italy
Oncologic Department, ASST Lodi Hospital, Piazza Ospitale 10, 26900 Lodi, Italy
Authors to whom correspondence should be addressed.
Biomedicines 2023, 11(2), 336;
Received: 3 January 2023 / Revised: 20 January 2023 / Accepted: 23 January 2023 / Published: 25 January 2023
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)


The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients’ care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population.

1. Introduction

Since December 2019, reported in Wuhan (China) and then all over the world, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) dramatically distressed the balance of different health authorities, leading the World Health Organization (WHO) to declare it a pandemic in March 2020 [1]. Since then, over the last 2 years, coronavirus disease-19 (COVID-19) caused more than 500 million infections and over 6 million deaths worldwide [2].
The emergency caused by the pandemic led to crucial changes in healthcare management that dramatically impacted patients’ care: elective surgery, screening/follow-up diagnostic assessments [3], and access to non-urgent treatments were restricted or withheld to allocate resources and personnel to COVID-19 outbreak management [4,5,6].
Specifically, for oncologists and cancer patients, the COVID-19 outbreak led to delays in diagnosis and treatments [7], with a negative prognostic impact due to the detection of cases at a more advanced stage [8].
Moreover, despite the efforts made to maintain COVID-free oncological departments, the indications on the logistic management, and the planning of therapies for cancer patients [9], the pandemic heavily affected oncological patients. A higher risk of death and severe complications have indeed been evidenced in cancer patients compared to the general population, and treatment delay/interruption frequently occurred [10,11].
The introduction of COVID-19 vaccination at the end of 2020 deeply changed the clinical scenario of SARS-CoV-2 infection, with cutback of infections, reduction in viral load, and severe complications [12]. Owing to international efforts, several vaccines were developed, including mRNA-based, peptide, and inactivated vaccines. In Italy, two mRNA-based vaccines (Pfizer mRNA BNT162b2 and COVID-19 Vaccine Moderna mRNA-1273) have been approved, two non-replicating viral vector vaccines (Vaxzevria—ex COVID-19 AstraZeneca vaccine and Jcovden—ex COVID-19 Janssen vaccine), and one peptide vaccine (COVID-19 Nuvaxovid—Novavax) [13]. International guidelines immediately agreed on the benefit of SARS-CoV-2 vaccination for high-risk subjects, including the whole oncological population. However, despite the unconfutable benefit of vaccinations, indications relied on previous statements about other vaccinations in cancer patients [9,14]. In detail, evidence regarding the impact of anticancer treatment administration and the timing between vaccinations and treatment delivery were very limited, leaving physicians to choose according to the individual therapeutic scenarios.
In this evolving situation, we designed the VACCINATE trial, an observational study aimed to evaluate the timing of the SARS-CoV-2 vaccination in cancer patients receiving systemic treatments and potential factors influencing the efficacy and safety of COVID-19 vaccines.

2. Materials and Methods

2.1. Patients and Methods

The VACCINATE is a single-center, observational, prospective study performed between March 2021 and December 2021. We prospectively collected data of consecutive oncological patients with solid tumors, managed, and treated at the Gastrointestinal and Neuroendocrine Tumors Division of the European Institute of Oncology (IEO), Milan. We considered eligible for the study all patients ≥ 18 years (y) diagnosed with a gastrointestinal, (GI) hepato-biliary-pancreatic (HBP), or neuroendocrine neoplasm (NEN), receiving an ongoing anticancer treatment and a concomitant SARS-CoV-2 vaccine (first or second dose). All types of the vaccine were approved for cancer patients according to clinical practice; Moderna/SpikeVax [15] and Pfizer-BioNTech [16] were eligible for the purpose of the study.
For each patient, we collected demographic and clinical data, as well as the type and timing of the SARS-CoV-2 vaccination in addition to collecting tumor information including histology, pathological features, stage, grading, setting of treatment (adjuvant, neoadjuvant, first line for advanced disease, subsequent lines) and timing of therapy administration compared to timing of the vaccination. All data were collected in an electronic medical case report form (eCRF) and stored in a web-secured database (REDcap system). All patients underwent blood sampling to determine their lymphocyte count within 14 days before each dose of the vaccine; another blood sample for the assessment of SARS-CoV-2 IgG antibody response was collected after 15 ± 5 days from the vaccination, and then every 40 ± 10 days from the previous blood draw. For patients with a previous documented SARS-CoV-2 infection, a further IgG dosage was performed before vaccination. Blood samples for the immune response assessment were centrally analyzed at the laboratory of the Monzino Cardiologic Center, Milan, while complete blood cell counts were performed at the IEO laboratory. The SARS-CoV-2 antibodies titers were assessed by means of the DiaSorin LIAISON® SARS-CoV-2 trimeric test that detected anti-trimeric S spike protein IgG antibodies with sensitivity and specificity of 98.7% and 99.5%, respectively [17]. The IgG titers were expressed in AU/mL and the diagnostic cut-off of the test was 13 AU/mL. Additionally, patients received a questionnaire for reporting the most frequent adverse events. The patients indicated any health-related changes within 2 weeks of the vaccination, their duration, and their consequences (e.g., sequelae/resolution). Toxicity data from anticancer treatments after the vaccine dose were prospectively collected.
All patients provided written, informed consent. The study was approved by the IEO and Monzino’s internal medical ethics committee (IUD: IEO 1525) and performed in accordance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable government regulations.
The primary endpoint of the study was to collect data on the antibody response to SARS-CoV-2 vaccination in cancer patients. Secondly, we aimed to correlate the antibody response to the clinical, pathological, and biological features, in order to identify data relevant for the management of oncologic patients during the pandemic.

2.2. Statistical Methods

We calculated the median and interquartile range (IQR) for continuous variables and absolute and relative frequencies as summary measures of categorical variables. Based on the nature of variables, Fishers–Exact tests, Wilcoxon rank-sum tests, or the Kruskal–Wallis rank sum tests were performed. A multivariable logistic model was applied to identify independent factors associated with AEFI (Adverse Events Following Immunization). A multivariable mixed-effects model was adopted to analyze changes in IgG and associated factors over time. Normal distribution of residuals from fully adjusted models were graphically checked and log transformation was adopted when it was needed to achieve normality. All reported values were two sided and p < 0.05 was considered statistically significant. All analyses were carried out using the R studio (R version 4.0.2).

3. Results

In total, we enrolled 48 patients, but only 46 were considered in the final analysis due to consent withdrawal in one case and lack of immune-response data in another (Figure 1).
From 72 patients with gastro-entero-pancreatic and neuroendocrine neoplasms who were treated at our institute between March and December 2021 and underwent the COVID-19 vaccination, 24 were excluded due to COVID-19 logistic problems (e.g., the patients were unable to leave the hospital for the exams planned in the trial). Another 2 patients were excluded due to a withdrawal of consent and lack of data about the immune response. Therefore, forty-six patients were evaluated for the final analysis.
Altogether, 29 patients were male (63.1%) and the median age was 57 years (y) (range 47–64.75). The most represented tumor was colorectal cancer (28.3%) followed by GEP-NET (26.0%) and gastric cancer (15.2%). Table 1 reports the features of the population.
Around three-quarters of the population had a metastatic disease (n = 34, 73.9%) and 42 (91.3%) patients were receiving an active antitumoral therapy over the study. The overwhelming majority of patients (n = 40, 86.9%) received two-doses of the Pfizer-BioNTech vaccine, whereas five patients received the Moderna vaccine. Four patients (8.7%) did report a previous SARS-CoV-2 infection, and 37 (75%) had relevant comorbidities other than cancer (Table 1). After both vaccination doses, 12/46 (26%) reported any grade adverse event (all <Grade 3 according to the Common Terminology Criteria for Adverse Events v 5.0) and 7/46 (15.2%) reported any grade adverse after the second dose (all <Grade 3). Local effects including pain, oedema, and rash on injection site were the most common adverse event, followed by fever and asthenia.
The median baseline lymphocytes value was 1530 (range 1180–1940) and 1405 (1267–1870) one week after the vaccination. The median antibodies after 1 dose were 38.65, while after 2 vaccine doses, the median antibodies were 7344.8 AU/mL (3450.8–16,759).
The multivariate analysis, adjusted for age and lymphocytes values, showed a trend to a higher risk of adverse events in female patients compared to males (p = 0.059) (Figure 2).
No significant differences were reported between males and females in terms of adverse events.
All patients obtained an immune response to the SARS-CoV-2 vaccine (Figure 3), represented by an IgG titer greater than 13 AU/mL.
All the patients reported an immune response after the COVID-19 vaccination.
We observed significantly lower values of IgG for patients treated with chemotherapy compared with patients receiving other anti-cancer agents (p = 0.004) (Figure 4).
However, no significant effect on immune response was reported for vaccinations performed within 7 days vs. over 7 days from the last systemic treatment (p = 0.77). At the time of study entry, none of the patients developed a SARS-CoV-2 infection after the vaccination.
The analysis reported a significant decrease of the immune response during the observation (p = 0.01) (Figure 5), with higher anti-SARS-CoV-2 IgG values for patients ≤ 57 vs. >57 y of age (p = 0.002) (Figure 6).

4. Discussion

Compared to the first dramatic phase of the COVID-19 pandemic, when only symptomatic and supportive measures could be applied to reduce mortality, the introduction of efficient SARS-CoV-2 vaccines radically improved the outcomes of patients, including patients with cancer.
In this context of fast-emerging indications, our prospective study confirmed the efficacy and safety of vaccinations in cancer patients receiving systemic treatments, even though chemotherapy was significantly associated with lower levels of SARS-CoV-2 antibodies. However, we interestingly observed that the induction of an immune response was not affected by a close timing of systemic treatment administration and vaccination. Despite the low number of subjects, our study could provide meaningful clinical insights for oncologic patients management [18,19].
Several studies reported the efficacy and safety of COVID-19 vaccinations for oncologic patients. The VOICE trial was a multicenter study [20] that prospectively analyzed the efficacy and safety of the Moderna Spikevax vaccine in patients with solid tumors who were treated with chemotherapy, immunotherapy, or combinations. Almost the whole evaluable population showed an immune response to the vaccination (736/743, 99%) with a manageable toxicity profile. According to the Center of Disease Control and Prevention (data updated on 21 June 2022—, local reactions at the site of the injection are expected in almost 85% of adult subjects after the first dose of the COVID-19 vaccination, with a trend to a lower percentage after the second dose. The systemic events are instead expected in almost 77% of subjects after the COVID-19 vaccination, with a trend to lower manifestations after the first rather than the second dose. In both the situations, severe adverse events are expected in almost 0.6% of the vaccinated population, maintaining a good and well-manageable toxicity profile [13].
Even if we only used a small sample size, our real-life analysis prospectively showed a lower incidence of adverse events after the first and the second dose of vaccinations compared to the whole population and, similarly to other studies, local adverse events at the injection site were the most common [21]. One explanation of this phenomenon might be that oncological patients tend not to report effects that are negligible, compared to cancer and treatment-related consequences, unless they interfere with their quality of life. Another reason why our population showed less adverse events compared to the whole population may be related to a lower reactogenicity due to the immunosuppressive systemic treatments that they were receiving. Regarding the latter possibility, instead, our study prospectively confirmed the efficacy of Moderna and Pfizer-BioNTech vaccines in this specific gastrointestinal and neuroendocrine neoplasms population. Despite a moderately short follow-up, none of our patients developed a COVID-19 infection after vaccination at the time of the data analysis. Other studies reported comparable results, showing a significant antibody titer after the vaccine second dose in 83–86% of cancer patients [22,23].
Despite the encouraging data, the lack of indications on the optimal timing of the SARS-CoV-2 vaccination forced the oncological community to decide when to vaccinate the patients based on the individual patient’s therapeutic scenario, rather than with a shared and standardized approach. Indeed, the international guidelines recommended vaccinating patients with solid or hematologic malignancies at the earliest available opportunity [24]. For most solid tumors, the indicated timing should be drug-mechanism based; according to studies on flu, the optimal timing for patients treated with chemotherapy should be to administer the SARS-CoV-2 vaccine 1–2 weeks before or after the systemic therapy, to allow an adequate immune response. According to the results of our analysis, the age of patients and the type of systemic treatment seemed to be the only factors influencing the anti-COVID-19 IgG levels. A possible reason why aging may be associated with lower immune response after vaccination is that immunosenescence and inflamm-aging, given by a progressive change in proinflammatory factors and a remodulation of the immune system pattern, play the main role in reducing the immune response and worsening the viral infections’ outcome [25]. For chemotherapy, as reported in previous studies, a lymphocytes count reduction seemed to be the most impacting factor on immune response [26,27,28]. Anyway, most of these studies concerned hematologic malignancies and reported a higher vulnerability for those patients receiving CD20 B-cell depletion treatments. On the other hand, different methods of analysis and the lack of reference standards render the results of the few studies on solid tumors debatable and uncertain to apply in clinical practice.
The recent paper by Nelli F et al. analyzed the subset of peripheral lymphocyte counts and the SARS-CoV-2 immune response after vaccination and reported a significant impact of chemotherapy and corticosteroids on T helper and B lymphocyte counts [29].
However, although chemotherapy was associated with a lower immune-response to SARS-CoV-2 vaccination compared to the other treatments in our analysis, no significant correlation has been reported either between peripheral lymphocytes count and anti-COVID-19 IgG levels or between the timing of the therapies administration and antibody titers. A possible explanation is that the small sample size is a limitation of this study. Another explanation may be that not all of the regimens used to treat our population are associated with a real lymphocytes dysfunction. In fact, the sample consisted of NEN patients treated with temozolomide and others previously receiving peptide receptor radioligand therapy (PRRT), which often results in deep, long-lasting low lymphocyte levels [30,31,32,33,34].
On the other hand, our sample also included GI patients receiving platinum-based chemotherapy, which instead seems to induce active phenotypes and functions of CD8 tumor-infiltrating T lymphocytes, supporting a chemo-immunotherapy combination [35]. Therefore, according to these observations and our study results, a lower immune response in solid cancer patients might be associated with the impact of different therapeutic regimens on the phenotype of the lymphocytes subset, irrespective of the overall lymphocytes count. These findings are comparable to data on the timing of flu vaccinations during chemotherapeutic treatments which showed no significant differences on antibody responses between patients concurrently inoculated with chemotherapy and those inoculated during the lymphopenia period [36].
Our study presents several limitations. First of all, due to the urgency of the pandemic and the vaccination program, the sample of our analysis was small and heterogeneous in terms of treatments and disease biology, involving patients with only gastrointestinal carcinomas or neuroendocrine neoplasms. Second, we did not have the possibility to analyze the different lymphocytic subpopulations that may have allowed a better interpretation of our findings. Lastly, the short follow-up did not permit an evaluation of the protection induced by the vaccination against the new different SARS-CoV-2 viral strains. At the same time, the heterogeneity of the sample may be particularly representative of the real-life experience and provide insights and hypotheses for further analyses.

5. Conclusions

To our knowledge, this is the first prospective analysis focused on the SARS-CoV-2 vaccination timing in patients with solid cancers on systemic antitumor treatments. No significant impact on the count or timing of the systemic treatments administration of anti-COVID-19 IgG levels of the peripheral lymphocytes has emerged, while chemotherapy and age > 57 y seems to influence the immune response to the SARS-CoV-2 vaccination. These results suggest that the timing of the COVID-19 vaccination and lymphocytes count are not the issue, but rather that the functionality of the lymphocytic subsets before the vaccination can determine the efficacy level of the vaccines in solid cancers patients. Further prospective studies are needed to address this topic.

Author Contributions

Contribution according to the CRediT Criteria were the followings: A.L., L.G. and N.F. made a substantial contribution to the concept or design of the work; A.L. and L.G. cooperated to the acquisition of the data and drafted the article; A.L, L.G, O.D. and S.G. contributed to the formal analysis and the interpretation of data; O.D. and S.G cooperated to the methodology design; A.L., L.G., O.D., S.G, A.R., R.P., F.S., S.P., M.R., C.A.C., P.S.R., M.G.Z. and N.F. critically revised the manuscript and approved the version to be published. All authors have read and agreed to the published version of the manuscript.


This work was partially funded by private donations to the Division of Gastro-entero-pancreatic and Neuroendocrine Tumors of the European Institute of Oncology, IRCCS, Milan.

Institutional Review Board Statement

This prospective analysis complies with the Declaration of Helsinki, conform to the International Committee of Medical Journal Editors (ICMJE) recommendations, and has been approved according to the Ethical Committee of the European Institute of Oncology (IUD: IEO 1525).

Informed Consent Statement

Written informed consent was obtained according to the ICMJE Recommendations.

Data Availability Statement

IEO shall be classified as autonomous Data Controllers pursuant to Regulation (EU) 2016/679 of the European Parliament and Council of 27 April 2016 (GDPR).

Conflicts of Interest

The authors declare that there are no conflict of interest.


  1. Ochani, R.; Asad, A.; Yasmin, F.; Shaikh, S.; Khalid, H.; Batra, S.; Sohail, M.R.; Mahmood, S.F.; Ochani, R.; Hussham Arshad, M.; et al. COVID-19 pandemic: From origins to outcomes. A comprehensive review of viral pathogenesis, clinical manifestations, diagnostic evaluation, and management. Infez. Med. 2021, 29, 20–36. [Google Scholar]
  2. World Health Organization. COVID-19 Weekly Epidemiological Update. Available online: (accessed on 27 April 2022).
  3. Holland, J.; Cwintal, M.; Rigas, G.; Pang, A.J.; Vasilevsky, C.A.; Morin, N.; Ghitulescu, G.; Faria, J.; Boutros, M. The impact of delaying colonoscopies during the COVID-19 pandemic on colorectal cancer detection and prevention. Surg. Endosc. 2022, 36, 9364–9373. [Google Scholar] [CrossRef]
  4. Mallah, S.I.; Ghorab, O.K.; Al-Salmi, S.; Abdellatif, O.S.; Tharmaratnam, T.; Iskandar, M.A.; Sefen, J.A.N.; Sidhu, P.; Atallah, B.; El-Lababidi, R.; et al. COVID-19: Breaking down a global health crisis. Ann. Clin. Microbiol. Antimicrob. 2021, 20, 35. [Google Scholar]
  5. Spinelli, A.; Pellino, G. COVID-19 pandemic: Perspectives on an unfolding crisis. Br. J. Surg. 2020, 107, 785–787. [Google Scholar] [CrossRef]
  6. Santi, L.; Golinelli, D.; Tampieri, A.; Farina, G.; Greco, M.; Rosa, S.; Beleffi, M.; Biavati, B.; Campinoti, F.; Guerrini, S.; et al. Non-COVID-19 patients in times of pandemic: Emergency department visits, hospitalizations and cause-specific mortality in Northern Italy. PLoS ONE 2021, 16, e0248995. [Google Scholar] [CrossRef]
  7. Chang, A.Y.; Cullen, M.R.; Harrington, R.A.; Barry, M. The impact of novel coronavirus COVID-19 on noncommunicable disease patients and health systems: A review. J. Intern. Med. 2021, 289, 450–462. [Google Scholar] [CrossRef]
  8. Barcellini, A.; Massaro, M.; Dal Mas, F.; Langendijk, J.A.; Hoyer, M.; Calugaru, V.; Haustermans, K.; Timmermann, B.; Thariat, J.; Scartoni, D.; et al. A year of pandemic for European particle radiotherapy: A survey on behalf of EPTN working group. Clin. Transl. Radiat. Oncol. 2022, 34, 1–6. [Google Scholar] [CrossRef]
  9. Castelo-Branco, L.; Cervantes, A.; Curigliano, G.; Garassino, M.C.; Giesen, N.; Grivas, P.; Haanen, J.; Jordan, K.; Liebert, U.G.; Lordick, F.; et al. ESMO Statements on Vaccination against COVID-19 in People with Cancer. 2021. Available online: (accessed on 2 January 2023).
  10. Grivas, P.; Khaki, A.R.; Wise-Draper, T.M.; French, B.; Hennessy, C.; Hsu, C.Y.; Shyr, Y.; Li, X.; Choueiri, T.K.; Painter, C.A.; et al. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: A report from the COVID-19 and Cancer Consortium. Ann. Oncol. 2021, 32, 787–800. [Google Scholar]
  11. Curigliano, G.; Banerjee, S.; Cervantes, A.; Garassino, M.C.; Garrido, P.; Girard, N.; Haanen, J.; Jordan, K.; Lordick, F.; Machiels, J.P.; et al. Managing cancer patients during the COVID-19 pandemic: An ESMO Interdisciplinary Expert Consensus. Ann. Oncol. 2020, 31, 1320–1335. [Google Scholar]
  12. Lopez Bernal, J.; Andrews, N.; Gower, C.; Robertson, C.; Stowe, J.; Tessier, E.; Simmons, R.; Cottrell, S.; Roberts, R.; O’Doherty, M.; et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ 2021, 373, n1088. [Google Scholar] [CrossRef]
  13. Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events, Center of Disease Control and Prevention. Available online: (accessed on 2 January 2023).
  14. Cordonnier, C.; Einarsdottir, S.; Cesaro, S.; Di Blasi, R.; Mikulska, M.; Rieger, C.; de Lavallade, H.; Gallo, G.; Lehrnbecher, T.; Engelhard, D.; et al. Vaccination of haemopoietic stem cell transplant recipients: Guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect. Dis. 2019, 19, e200–e212. [Google Scholar] [PubMed]
  15. Food and Drug Administration. Moderna COVID-19 Vaccine. Available online: (accessed on 2 January 2023).
  16. Oliver, S.E.; Gargano, J.W.; Marin, M.; Wallace, M.; Curran, K.G.; Chamberland, M.; de Lavallade, H.; Gallo, G.; Lehrnbecher, T.; Engelhard, D.; et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine—United States, December 2020. MMWR Morb. Mortal. Wkly. Rep. 2020, 69, 1922–1924. [Google Scholar] [CrossRef]
  17. Bonelli, F.; Blocki, F.A.; Bunnell, T.; Chu, E.; De La, O.A.; Grenache, D.G.; Marzucchi, G.; Montomoli, E.; Okoyeet, L.; Pallavicini, L.; et al. Evaluation of the automated LIAISON((R)) SARS-CoV-2 TrimericS IgG assay for the detection of circulating antibodies. Clin. Chem. Lab. Med. 2021, 59, 1463–1467. [Google Scholar] [CrossRef]
  18. Cancer Care during the COVID-19 Pandemic: An ESMO Guide for Patients. Available online: (accessed on 8 April 2020).
  19. Hincapie, M.A.; Gallego, J.C.; Gempeler, A.; Pineros, J.A.; Nasner, D.; Escobar, M.F. Implementation and Usefulness of Telemedicine During the COVID-19 Pandemic: A Scoping Review. J. Prim. Care Community Health 2020, 11, 2150132720980612. [Google Scholar] [CrossRef]
  20. van der Veldt, A.A.M.; Oosting, S.F.; Dingemans, A.C.; Fehrmann, R.S.N.; GeurtsvanKessel, C.; Jalving, M.; Rimmelzwaan, G.F.; Kvistborg, P.; Blank, C.U.; Smit, E.F.; et al. COVID-19 vaccination: The VOICE for patients with cancer. Nat. Med. 2021, 27, 568–569. [Google Scholar] [CrossRef] [PubMed]
  21. Meo, S.A.; Bukhari, I.A.; Akram, J.; Meo, A.S.; Klonoff, D.C. COVID-19 vaccines: Comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Eur. Rev. Med. Pharmacol. Sci. 2021, 25, 1663–1669. [Google Scholar]
  22. Fendler, A.; Shepherd, S.T.C.; Au, L.; Wilkinson, K.A.; Wu, M.; Byrne, F.; Cerrone, M.; Schmitt, A.M.; Joharatnam-Hogan, N.; Shum, B.; et al. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study. Nat. Cancer 2021, 2, 1305–1320. [Google Scholar] [CrossRef] [PubMed]
  23. Ben-Aharon, I.; Waldhorn, I.; Holland, R.; Peer, A.; Halberthal, M.; Lago, T.G.G. 1559O Efficacy and toxicity of BNT162b2 vaccine in cancer patients. Ann. Oncol. 2021, 32, S1130. [Google Scholar] [CrossRef]
  24. Desai, A.; Gainor, J.F.; Hegde, A.; Schram, A.M.; Curigliano, G.; Pal, S.; Liu, S.V.; Halmos, B.; Groisberg, R.; Grande, E.; et al. COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Nat. Rev. Clin. Oncol. 2021, 18, 313–319. [Google Scholar] [CrossRef]
  25. Bajaj, V.; Gadi, N.; Spihlman, A.P.; Wu, S.C.; Choi, C.H.; Moulton, V.R. Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections? Front. Physiol. 2020, 11, 571416. [Google Scholar] [CrossRef]
  26. Redjoul, R.; Le Bouter, A.; Parinet, V.; Fourati, S.; Maury, S. Antibody response after third BNT162b2 dose in recipients of allogeneic HSCT. Lancet Haematol. 2021, 8, e681–e683. [Google Scholar] [CrossRef]
  27. Moor, M.B.; Suter-Riniker, F.; Horn, M.P.; Aeberli, D.; Amsler, J.; Moller, B.; Njue, L.M.; Medri, C.; Angelillo-Scherrer, A.; Borradori, L.; et al. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): An investigator-initiated, single-centre, open-label study. Lancet Rheumatol. 2021, 3, e789–e797. [Google Scholar] [CrossRef]
  28. Aleman, A.; Upadhyaya, B.; Tuballes, K.; Kappes, K.; Gleason, C.R.; Beach, K.; Agte, S.; Srivastava, K.; PVI/Seronet Study Group; Van Oekelen, O.; et al. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell. 2021, 39, 1442–1444. [Google Scholar] [CrossRef]
  29. Nelli, F.; Fabbri, A.; Panichi, V.; Giannarelli, D.; Topini, G.; Giron Berrios, J.R.; Virtuoso, A.; Marrucci, E.; Mazzotta, M.; Schirripaet, M.; et al. Peripheral lymphocyte subset counts predict antibody response after SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients: Results from the Vax-On-Profile study. Int. Immunopharmacol. 2022, 108, 108774. [Google Scholar] [CrossRef]
  30. Sierra, M.L.; Agazzi, A.; Bodei, L.; Pacifici, M.; Arico, D.; De Cicco, C.; Quarna, J.; Sansovini, M.; De Simone, M.; Paganelli, G. Lymphocytic toxicity in patients after peptide-receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC. Cancer Biother Radiopharm. 2009, 24, 659–665. [Google Scholar] [PubMed]
  31. Medaer, E.; Verslype, C.; Van Cutsem, E.; Dekervel, J.; Clement, P.M.; Nackaerts, K.; Laenenf, A.; Gheysensa, O.; Goffina, K.; Jentjensa, S.; et al. Influence of pretreatment with everolimus or sunitinib on the subacute hematotoxicity of (177)Lu-DOTATATE PRRT. Acta Oncol. 2020, 59, 644–651. [Google Scholar] [CrossRef]
  32. Kobayashi, N.; Takano, S.; Ito, K.; Sugiura, M.; Ogawa, M.; Takeda, Y.; Okubo, N.; Suzuki, A.; Tokuhisa, M.; Kaneta, T.; et al. Safety and efficacy of peptide receptor radionuclide therapy with (177)Lu-DOTA(0)-Tyr(3)-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors. Ann. Nucl. Med. 2021, 35, 1332–1341. [Google Scholar] [CrossRef]
  33. Zhang, Y.; Chen, S.; Chen, H.; Chen, S.; Li, Z.; Feng, E.; Li, W. Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis. Front. Neurol. 2021, 12, 726561. [Google Scholar] [CrossRef]
  34. Abdel-Rahman, O.; Fouad, M. Temozolomide-based combination for advanced neuroendocrine neoplasms: A systematic review of the literature. Future Oncol. 2015, 11, 1275–1290. [Google Scholar] [CrossRef]
  35. Guan, Y.; Kraus, S.G.; Quaney, M.J.; Daniels, M.A.; Mitchem, J.B.; Teixeiro, E. FOLFOX Chemotherapy Ameliorates CD8 T Lymphocyte Exhaustion and Enhances Checkpoint Blockade Efficacy in Colorectal Cancer. Front. Oncol. 2020, 10, 586. [Google Scholar] [CrossRef]
  36. Keam, B.; Kim, M.K.; Choi, Y.; Choi, S.J.; Choe, P.G.; Lee, K.H.; Kim, T.M.; Kim, T.Y.; Oh, D.Y.; Kim, D.W.; et al. Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles. Cancer 2017, 123, 841–848. [Google Scholar] [CrossRef]
Figure 1. Flowchart of enrollment of patients.
Figure 1. Flowchart of enrollment of patients.
Biomedicines 11 00336 g001
Figure 2. Lollipop chart of adverse events after SARS-CoV-2 vaccination between males (in blue) and females (in pink).
Figure 2. Lollipop chart of adverse events after SARS-CoV-2 vaccination between males (in blue) and females (in pink).
Biomedicines 11 00336 g002
Figure 3. Trend of the antibody response after 1 and 2 doses of the SARS-CoV-2 vaccine and at the following default times (40 ± 10 days from the last blood test).
Figure 3. Trend of the antibody response after 1 and 2 doses of the SARS-CoV-2 vaccine and at the following default times (40 ± 10 days from the last blood test).
Biomedicines 11 00336 g003
Figure 4. Boxplot of anti-ARS-CoV-2 IgG values of whole patients’ samples over time by therapy. Times on the Y-axis Y refer to 40 ± 10 days blood assessment after the previous. p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG (AU/mL) after first dose.
Figure 4. Boxplot of anti-ARS-CoV-2 IgG values of whole patients’ samples over time by therapy. Times on the Y-axis Y refer to 40 ± 10 days blood assessment after the previous. p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG (AU/mL) after first dose.
Biomedicines 11 00336 g004
Figure 5. Boxplot of anti-SARS-CoV-2 IgG values over time of the whole sample at the different times of observation. Times 1, 2, and 3 refer to the moment of further blood assessment (40 ± 10 days from the previous). p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG after first dose.
Figure 5. Boxplot of anti-SARS-CoV-2 IgG values over time of the whole sample at the different times of observation. Times 1, 2, and 3 refer to the moment of further blood assessment (40 ± 10 days from the previous). p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG after first dose.
Biomedicines 11 00336 g005
Figure 6. Boxplot of SARS-CoV-2 IgG values over time by age at diagnosis. p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG after first dose.
Figure 6. Boxplot of SARS-CoV-2 IgG values over time by age at diagnosis. p-value obtained from multivariable model for repeated measure analysis adjusted for age, therapy, time, and IgG after first dose.
Biomedicines 11 00336 g006
Table 1. Main subject and tumor characteristics (n = 46).
Table 1. Main subject and tumor characteristics (n = 46).
Age at Diagnosis, Median (IQR) 57 (47–64.75)
Sex, n (%)Female17 (36.9)
Male29 (63.1)
Comorbidities, n (%)No9 (25)
Yes37 (75)
Type of comorbidities:
PTE/DVT7 (18.9)
Other cancers8 (21.6)
Metabolic12 (32.4)
Cardiovascular13 (35.1)
Autoimmune disease1 (2.7)
Others28 (75.7)
Previous COVID-19, n (%)No42 (91.3)
Yes4 (8.7)
Esophagus2 (4.3)
Stomach7 (15.2)
Colorectal13 (28.3)
Tumor, n (%)Anus1 (2.2)
Pancreas (adenocarcinomas)3 (6.5)
Biliary tract1 (2.2)
NEN19 (41.3)
GEP-NET12 (63.1)
GEP-NEC2 (10.5)
Thoracic-NET2 (10.5)
Thoracic-NEC1 (5.3)
Other NEC2 (10.5)
Localized/locally advanced7 (15.2)
Current stage, n (%)Distant metastatic34 (73.9)
No evidence of disease5 (10.9)
Active antitumor therapy, n (%)No4 (8.7)
Yes42 (91.3)
SSA (somatostatin analogue)3 (3.8)
anti-mTOR2 (2.6)
Chemotherapy Platin 15 (19.2)
Etoposide 2 (2.6)
Fluoropyrimidines28 (35.9)
Irinotecan 8 (10.2)
Type of active antitumor therapy, n (%)Temozolomide 2 (2.6)
Immune checkpoint inhibitors 4 (5.1)
Anti-VEGFR 7 (9.0)
Gemcitabine 1 (1.3)
Taxane 5 (6.4)
Other 1 (1.3)
Hormonal therapy7 (15.2)
Chemotherapy21 (45.6)
Previous types of Systemic treatments, n (%)Targeted therapy12 (26.1)
PRRT7 (15.2)
Pfizer40 (86.9)
Vaccine type dose 1, n (%)Moderna5 (10.9)
Missing1 (2.2)
Vaccine type dose 2, n (%)Pfizer37 (80.4)
Moderna3 (6.6)
Missing6 (13.0)
Lymphocytes at baseline, median (IQR) 1530 (1180–1940)
Antibody response after 1 dose, median (IQR) 38.65 (21–3679.6)
Lymphocytes after 1 dose, after 2 dose median (IQR) 1405 (1267–1870)
Antibody response after 2 dose, median (IQR) 7344.8 (3450.8–16,759)
PTE/DVT: pulmonary thromboembolism/deep veins thrombosis; NEN: neuroendocrine neoplasm; GEP: gastro-entero-pancreatic; NET: neuroendocrine tumor; NEC: neuroendocrine carcinoma; SSA: somatostatin analogue; PRRT: Peptide Radionuclide Receptor Therapy.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Laffi, A.; Gervaso, L.; D’Ecclesiis, O.; Gandini, S.; Riva, A.; Passerini, R.; Spada, F.; Pellicori, S.; Rubino, M.; Cella, C.A.; Ravenda, P.S.; Zampino, M.G.; Fazio, N. Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE). Biomedicines 2023, 11, 336.

AMA Style

Laffi A, Gervaso L, D’Ecclesiis O, Gandini S, Riva A, Passerini R, Spada F, Pellicori S, Rubino M, Cella CA, Ravenda PS, Zampino MG, Fazio N. Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE). Biomedicines. 2023; 11(2):336.

Chicago/Turabian Style

Laffi, Alice, Lorenzo Gervaso, Oriana D’Ecclesiis, Sara Gandini, Agostino Riva, Rita Passerini, Francesca Spada, Stefania Pellicori, Manila Rubino, Chiara Alessandra Cella, Paola Simona Ravenda, Maria Giulia Zampino, and Nicola Fazio. 2023. "Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE)" Biomedicines 11, no. 2: 336.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop