Vol 73, No 3 (2023)
Research paper (original)
Published online: 2023-05-25

open access

Page views 1290
Article views/downloads 250
Get Citation

Connect on Social Media

Connect on Social Media

Efficacy of the mRNA SARS-CoV-2 vaccine in cancer patients during systemic therapy. A single-centre experience

Jakub S. Wnuk1, Agnieszka Bobola1, Łukasz Pietrzyński1, Iwona Gisterek1
Nowotwory. Journal of Oncology 2023;73(3):117-121.

Abstract

Introduction. A novel coronavirus, causing severe acute respiratory syndrome 2 (SARS-CoV-2) has spread globally since its emergence in December 2019. The mRNA SARS-CoV-2 vaccines have been proven to be an efficient and safe disease control means among adult patients without immunocompromising conditions. However, cancer patients were among the group of people that was initially excluded from the registration trials. 

Material and methods. 60 patients, enrolled to this study, had been voluntarily vaccinated either with the BNT162b2 or mRNA-1273 SARS-CoV-2 vaccine between March and June 2021 and have been undergoing systemic treatment in the Clinical Oncology Unit of the University Clinical Center of the Medical University of Silesia in Katowice, Poland. Patients received 2 injections of vaccine 21 days apart and were tested with ElecsysR Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, France) for the presence of anti-S-protein antibodies in the patients’ serum. The serum samples were collected 2 to 8 weeks after receiving the second dose of vaccine. 

Results. The BNT162b2 vaccine was administered to 57 patients, while the mRNA-1273 vaccine – to 3 patients. Seroconversion was achieved in 83.33% of patients. The median amount of anti-S-protein antibodies was 75,9 U/ml.There were no statistically significant differences in terms of age between the group with seroconversion and the group without seroconversion (Mann-Whitney U-test p = 0.762). There was no statistically significant correlation between neither the BMI (Spearman test, p = 0.079) norage (Spearman test, p = 0.762) and anti-S-protein antibody levels. Just as the diagnosis (primary tumor localization), clinical stage, type of modality (chemotherapy, chemoradiotherapy, immunotherapy) and the goal of treatment (radical, palliative) were not statistically significant in terms of anti-S-protein antibody levels. 

Conclusions. Due to the high number of unresponsive or poorly responsive results, patients undergoing systemic therapy should be advised to maintain other measures of disease control such as distancing, usage of masks. Nevertheless, implementing mRNA SARS-CoV-2 vaccinesinimmunocompromised patientsduring systemic therapyis reasoned, valuable and safe. 

Original article

NOWOTWORY Journal of Oncology

2023, volume 73, number 3, 117–121

DOI: 10.5603/NJO.2021.0022

© Polskie Towarzystwo Onkologiczne

ISSN: 0029–540X, e-ISSN: 2300-2115

www.nowotwory.edu.pl

Efficacy of the mRNA SARS-CoV-2 vaccine in cancer patients during systemic therapy. A single-centre experience

Jakub S. WnukAgnieszka BobolaŁukasz PietrzyńskiIwona Gisterek
Department of Oncology and Radiotherapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
Introduction. A novel coronavirus, causing severe acute respiratory syndrome 2 (SARS-CoV-2) has spread globally since its emergence in December 2019. The mRNA SARS-CoV-2 vaccines have been proven to be an efficient and safe disease control means among adult patients without immunocompromising conditions. However, cancer patients were among the group of people that was initially excluded from the registration trials.
Material and methods. 60 patients, enrolled to this study, had been voluntarily vaccinated either with the BNT162b2 or mRNA-1273 SARS-CoV-2 vaccine between March and June 2021 and have been undergoing systemic treatment in the Clinical Oncology Unit of the University Clinical Center of the Medical University of Silesia in Katowice, Poland. Patients received 2 injections of vaccine 21 days apart and were tested with Elecsys® Anti-SARS-CoV-٢ immunoassay (Roche Diagnostics, France) for the presence of anti-S-protein antibodies in the patients’ serum. The serum samples were collected 2 to 8 weeks after receiving the second dose of vaccine.
Results. The BNT162b2 vaccine was administered to 57 patients, while the mRNA-1273 vaccine to 3 patients. Seroconversion was achieved in 83.33% of patients. The median amount of anti-S-protein antibodies was 75,9 U/ml.There were no statistically significant differences in terms of age between the group with seroconversion and the group without seroconversion (Mann-Whitney U-test p = 0.762). There was no statistically significant correlation between neither the BMI (Spearman test, p = 0.079) norage (Spearman test, p = 0.762) and anti-S-protein antibody levels. Just as the diagnosis (primary tumor localization), clinical stage, type of modality (chemotherapy, chemoradiotherapy, immunotherapy) and the goal of treatment (radical, palliative) were not statistically significant in terms of anti-S-protein antibody levels.
Conclusions. Due to the high number of unresponsive or poorly responsive results, patients undergoing systemic therapy should be advised to maintain other measures of disease control such as distancing, usage of masks. Nevertheless, implementing mRNA SARS-CoV-2 vaccinesinimmunocompromised patientsduring systemic therapyis reasoned, valuable and safe.
Key words: cancer patients, systemic therapy, SARS-CoV-2, COVID-19, SARS-CoV-2 vaccine

How to cite:

Wnuk JS, Bobola A, Pietrzyński Ł, Gisterek I. Efficacy of the mRNA SARS-CoV-2 vaccine in cancer patients during systemic therapy. A single-centre experience.
NOWOTWORY J Oncol 2023; 73: 117–121.

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

Introduction

A novel coronavirus, causing severe acute respiratory syndrome 2 (SARS-CoV-2) has spread globally since its emergence in December 2019, affecting our lives dramatically [1]. Until now it has infected 650 million people worldwide [2]. Since then, governments have applied several control measures such as distancing, usage of masks, testing of exposed or symptomatic patients, isolation of symptomatic patients and vaccination programs.

The mRNA SARS-CoV-2 vaccines have been proven to be an efficient and safe disease control means among adult patients without immunocompromising conditions. Their effectiveness has been reported to oscillate around 95%. However, cancer patients were among the group of people that was initially excluded from the registration trials [3, 4]. Therefore, vaccine efficacy among patients in this group remains unclear.

What is more, cancer patients are also at greater risk of COVID-19 infection and worse outcomes of treatment [5, 6]. Therefore, it is implied that SARS-CoV-2 vaccination of patients treated with antineoplastic drugs should be prioritized [7, 8]. That is why the Ministry of Health in Poland in 05.03.2021 implemented guidelines encouraging cancer patients to be the first group of patients vaccinated in Poland, beside elderly citizens and health care workers [9].

Material and methods

There were 60 patients who were enrolled in this study. We have included the patients who were voluntarily vaccinated either with BNT162b2 or mRNA-1273 SARS-CoV-2 vaccine between March and June 2021, according to the Polish SARS-CoV-2 vaccination program conducted by the Polish Ministry of Health and were currently undergoing systemic treatment in the Clinical Oncology Unit of the University Clinical Center of the Medical University of Silesia in Katowice, Poland [9]. According to the vaccination program, patients undergoing chemotherapy were vaccinated between the third and seventh day from the last received chemotherapy infusion. Patients undergoing immunotherapy could be vaccinated at any time during their treatment.

Patients received 2 vaccine injections 21 days apart and were tested with Elecsys® Anti-SARS-CoV-٢ immunoassay (Roche Diagnostics, France) for the presence of anti-S-protein antibodies in their serum. The serum samples were collected 2 to 8 weeks after receiving the second dose of the vaccine. The test used to determine levels of anti-S-protein antibodies was an electrochemiluminescent immunoassay. Its positive cutoff value was set at 0.80 U/mL, according to procedures guidelines.

We have collected demographic data such as the patients’ sex, age, height, weight. Data concerning the oncologic treatment included the diagnosis, clinical stage, type of therapy carried out (chemotherapy, chemoradiotherapy, immunotherapy) and the goal of treatment (radical, palliative) were included in the analysis. We measured the time of receiving the second injection of the vaccine after the last dose of systemic treatment.

The Mann-Whitney U-test for comparing two groups or the Kruskal-Wallis ANOVA test for multi-group comparisons was used to compare quantitative variables. The relationships between quantitative variables were analyzed using the Spearman’s rank correlation coefficient. The Chi2 test and its variants were used to compare the qualitative data. The analysis was performed using STATISTICA 13.3 software (TIBCO software). The p < 0.05 values were considered significant.

Results

There were 60 patients included in the statistical analysis – 36 women and 24 men. Demographic details are presented in table I.

Table I. Demographic data

Parameter

Total

Females

Males

sex

60

36

24

age (years)

  • median: 63
  • min.–max.: 33–78
  • interquartile range:
    54.5–67.5
  • median: 62
  • min.–max.: 35–78
  • interquartile range:
    51–67
  • median: 63.5
  • min.–max.: 33–78
  • interquartile range:
    59–68

weight (kg)

  • median: 71
  • min.–max.: 47–137
  • interquartile range:
    59-81.5
  • median: 66
  • min.–max.: 47–121
  • interquartile range:
    58.5–76.5
  • median: 74
  • min.–max.: 50–137
  • interquartile range:
    68–86.5

BMI (kg/m2)

  • median: 25.36
  • min.–max.: 17.47–54.5
  • interquartile range:
    22.32–28.84
  • median: 25.39
  • min.–max.: 17.47–54.5
  • interquartile range:
    22.02–29.39
  • median: 25.04
  • min. –max.: 17.96–39.18
  • interquartile range:
    23.22–27.53

The BNT162b2 vaccine was administered to 57 patients, while the mRNA-1273 vaccine – to 3 patients. Seroconversion, defined as the amount of anti-S-protein antibodies above 0.80 U/ml was achieved in 83.33% of patients. The median amount of anti-S-protein antibodies was 75.9 U/ml, (min. –max. range: 0.4–2500 U/ml). There were no statistically significant differences in terms of age between the group with seroconversion and the group without seroconversion (Mann-Whitney U-test, p = 0.762). There was no statistically significant correlation between the body-mass index (BMI) and anti-S-protein antibody levels (Spearman test, p = 0.079) or age and anti-S-protein antibody levels (Spearman test, p = 0.762). Data concerning differences in anti-S-protein antibody levels among different diagnostic groups are presented in table II. The differences were not statistically significant (ANOVA Kruskal-Wallis, p = 0.125). The difference in vaccination efficacy between patients diagnosed with gastrointestinal cancers and other patients is not statistically significant (Fisher’s exact test, p = 0.144) (tab. II). There were no statistically significant differences between groups with different clinical stages of the disease in terms of antibody levels. Details of this analysis is presented in table III.

Table II. Antibody levels and vaccination efficacy according to patient diagnosis

Diagnostic group
(nr of patients)

Anti-S-protein antibody level [U/ml]

% of levels above 0.8 U/ml

breast cancer (14)

  • median: 64.86
  • min.–max.: 0.4–1,200

71.4%

lung cancer (9)

  • median: 76.08
  • min.–max.: 0.25–2,500

77.7%

gastrointestinal cancers (24)

  • median: 39.77
  • min.–max.: 0.4–2,500

91.67%

gynecologic cancers (7)

  • median: 39.77
  • min.–max.: 0.4–168.3

71.43%

Table III. Antibody levels and vaccination efficacy according to clinical stage of the diseases

Clinical stage (number of patients)

Anti-S-protein antibody level [U/ml]

% of levels
above 0.8 U/ml

I (6)

  • median: 75.9
  • min.–max.: 0.4–2,500

83.33%

II (9)

  • median: 47.6
  • min.–max.: 0.4–1,200

66.67%

III (18)

  • median: 55.3
  • min.–max.: 0.5–2,500

88.89%

IV (27)

  • median: 96.8
  • min.–max.: 0.2–2500

85.18%

The difference in vaccination efficacy between patients in II stage of the disease and other patients is not statistically significant (Fisher’s exact test, p = 0.166). There were no statistically significant differences in terms of anti-S-protein antibody levels between patients with palliative and radical intention of treatment (Mann-Whitney U-test, p = 0.326). Table IV presents data regarding different modalities of treatment. There were no statistically significant differences between those groups (ANOVA Kruskal-Wallis, p = 0.268).

Table IV. Antibody levels and vaccination efficacy according to treatment modality

Treatment modality (number of patients)

Anti-S-protein antibody level [U/ml]

% of levels above 0.8 U/ml

chemotherapy (42)

  • median: 71.1
  • min.–max.: 0.4–2,500

80.92%

chemoradiotherapy (2)

  • median: 16.3
  • min.–max.: 8.7–23.9

100%

immunotherapy (12)

  • median: 79.1
  • min.–max.: 0.25–2,500

83.33%

chemotherapy with concurrent immunotherapy (4)

  • median: 561.6
  • min.–max.: 39.7–2,500

100%

The median time between receiving a second injection of the vaccine and the last course of systemic therapy was 10 days (mean: 10.05, min.–max.: 0–46 days). This parameter was not correlated with any level of detected antibodies (Spearman test, p = 0.09). There were no severe adverse events connected with mRNA SARS-CoV-2 vaccinations reported by patients.

Discussion

According to registration trials, the mRNA SARS-CoV-2 vaccine is an effective and safe mean of disease control. Its efficacy was determined at to be 95% (BNT162b2 vaccine) and 94.1% (mRNA-1,273 vaccine).

Those studies as the primary end points had serologic or virologic evidence of SARS-CoV-2 infection or presence of COVID-19 symptoms [3, 4]. We have based our study on detecting seroconversion after at least 2 weeks of receiving the second dose of the vaccination. It was detected in 83.33% of tested patients and there were no statistically significant differences within secondary analyses performed in this study. This stands in accordance with other studies conducted on patients with immunocompromised conditions. In Barrière’s et al. study, 47.5% of patients had anti-S-seroconversion after 3 to 4 weeks, and 95.2% after 6 to 8 weeks after the second dose of the vaccination. What is more, antibody levels were significantly lower compared to the control group consisting of people with no known immunocompromising condition [10].

In Monin’s et al. study, seroconversion after the first dose of the vaccination was observed in 35% of cancer patients and in 95% after the booster – 21 days after the 1st injection [11]. According to Addeo et al., seroconversion was observed in 94% of patients after the receipt of two doses of vaccine [12].

Differences between our study and the cited examples may be caused by used methodology. We did not differentiate between patients tested after 2 or 8 weeks after the 2nd dose of the vaccine. Agbarya et al. provided data suggesting that up to 23.3% of patients were seronegative after the second dose of the vaccination [13]. Those results are also compliant with a systemic review by Tran et al. In their study, there were 21 works included providing data from a total of 2,309 patients with solid cancer. Seroconversion after the second dose of the vaccine was observed in 91–97% of patients [14]. The comparison of study results are presented in table V.

Table V. Comparison of study results

Author

Year

Seroconversion in cancer patients

Seroconversion in the control group

Malignancy

Addeo et al. [12]

2021

94%

solid tumor and hematologic malignancies

Ariamanesh et al. [15]

2021

86.9%

hematologic malignancies

Barrière et al. [10]

2021

95.2%

solid tumor

Cai et al. [16]

2022

83.3%

96.3%

solid tumor

Massarweh et al. [17]

2021

90%

100%

solid tumor

Monin et al. [11]

2021

95%

100%

solid tumor

Schmueli et al. [18]

2021

84.1%

98.9%

solid tumor

Waldhorn [19]

2021

79%

84%

solid tumor

Yasin et al. [20]

2022

85.2%

97.5%

solid tumor

this study

2023

83.33%

solid tumor

We did not observe any association between the seroconversion rate and age or chemotherapy in our study, which stands in contrast with a study by Yasim et al. [20]. This may be due to differences in the patient population size enrolled in the studies, which was larger in Yasim’s study. Similar effects were also detected in studies by Massarweh et al., Ariamanesh et al. and Buttiron Webber et al. [15, 17, 21]. The results of this study are also similar to studies on the influenza vaccination in patients undergoing chemotherapy [22, 23]. The goal of treatment (radical or palliative) or the patients’ age did also not affect the results of the vaccination [23]. In our study there was no correlation between BMI and the amount of anti-S antibodies detected. In the large prospective study by Nilles et al., after adjusted analysis there was no evidence of increased seroprevalence with increasing BMI among tested patients. There was also no statistically significant differences between seropositive obese and non-obese patients in terms of peak SARS-CoV-2 IgG titters [24].

Unfortunately, some patients did not follow the Ministry of Health recommendations and had themselves vaccinated within 2 days of finishing the last dose of systemic treatment. There were seven cases of such practice in our study, but only in one case was anti-S-protein antibodies undetectable (a 68-year-old male patient, treated with chemotherapy due to CS III lung cancer, sequential chemoradiation).

Conclusions

Due to the high number of unresponsive or poorly responsive results, patients undergoing systemic therapy should be advised to maintain other measures of disease control such as social distancing and the use of masks. Swab testing of asymptomatic patients should be considered before admission to the hospital.
The duration of immunity after receiving a 2-dose regimen remains unknown and requires further studies.

Conflict of interest: none declared. Elecsys® Anti-SARS-CoV-٢ immunoassay tests were provided by Roche.

Jakub S. Wnuk

Medical University of Silesia

Faculty of Medical Sciences in Zabrze

Department of Oncology and Radiotherapy

ul. Ceglana 35

40-515 Katowice, Poland

e-mail: jkb.wnuk@gmail.com

Received: 24 Jan 2023
Accepted: 24 May 2023

References

  1. Dykas P, Wisła R. The Socioeconomic Impact of COVID-19 on Eastern European Countries. 2021, doi: 10.4324/9781003211891.
  2. Coronavirus Resource Center John Hopkins University & Medicine. https://coronavirus.jhu.edu/map.html (13.12.2022).
  3. Absalon J, Koury K, Gruber WC, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2021; 384(16): 1576–1577, doi: 10.1056/NEJMc2036242, indexed in Pubmed: 33596348.
  4. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021; 384(5): 403–416, doi: 10.1056/NEJMoa2035389, indexed in Pubmed: 33378609.
  5. Wang QQ, Berger NA, Xu R. Analyses of Risk, Racial Disparity, and Outcomes among US Patients with Cancer and COVID-19 Infection. JAMA Oncol. 2021; 7(2): 220–227, doi: 10.1001/jamaoncol.2020.6178, indexed in Pubmed: 33300956.
  6. Sharafeldin N, Su J, Madhira V, et al. Outcomes of COVID-19 in cancer patients: Report from the National COVID Cohort Collaborative (N3C). J Clin Oncol. 2021; 39(15_suppl): 1500–1500, doi: 10.1200/jco.2021.39.15_suppl.1500.
  7. Desai A, Gainor J, Hegde A, et al. Author Correction: COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Nature Reviews Clinical Oncology. 2021; 18(5): 320–320, doi: 10.1038/s41571-021-00503-2.
  8. Hwang JK, Zhang T, Wang AZ, et al. COVID-19 vaccines for patients with cancer: benefits likely outweigh risks. J Hematol Oncol. 2021; 14(1): 38, doi: 10.1186/s13045-021-01046-w, indexed in Pubmed: 33640005.
  9. Wspólne wytyczne dla pacjentów z grupy 1B i personelu medycznego w zakresie szczepienia przeciwko COVID-19 - Ministerstwo Zdrowia. https://www.gov.pl/web/szczepimysie/wspolne-wytyczne-dla-pacjentow-z-grupy-1b-i-personelu-medycznego-w-zakresie-szczepienia-przeciwko-covid-19.
  10. Barrière J, Chamorey E, Adjtoutah Z, et al. Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors. Ann Oncol. 2021; 32(8): 1053–1055, doi: 10.1016/j.annonc.2021.04.019, indexed in Pubmed: 33932508.
  11. Monin L, Laing AG, Muñoz-Ruiz M, et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. Lancet Oncol. 2021; 22(6): 765–778, doi: 10.1016/S1470-2045(21)00213-8, indexed in Pubmed: 33930323.
  12. Addeo A, Shah PK, Bordry N, et al. Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer Cell. 2021; 39(8): 1091–1098.e2, doi: 10.1016/j.ccell.2021.06.009, indexed in Pubmed: 34214473.
  13. Agbarya A, Sarel I, Ziv-Baran T, et al. Efficacy of the mRNA-Based BNT162b2 COVID-19 Vaccine in Patients with Solid Malignancies Treated with Anti-Neoplastic Drugs. Cancers (Basel). 2021; 13(16), doi: 10.3390/cancers13164191, indexed in Pubmed: 34439346.
  14. Tran S, Truong TH, Narendran A. Evaluation of COVID-19 vaccine response in patients with cancer: An interim analysis. Eur J Cancer. 2021; 159: 259–274, doi: 10.1016/j.ejca.2021.10.013, indexed in Pubmed: 34798454.
  15. Ariamanesh M, Porouhan P, PeyroShabany B, et al. Immunogenicity and Safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with malignancy. Cancer Invest. 2022; 40(1): 26–34, doi: 10.1080/07357907.2021.1992420.
  16. Cai SW, Chen JY, Wan R, et al. Efficacy and safety profile of two-dose SARS-CoV-2 vaccines in cancer patients: An observational study in China. World J Clin Cases. 2022; 10(31): 11411–11418, doi: 10.12998/wjcc.v10.i31.11411, indexed in Pubmed: 36387801.
  17. Massarweh A, Eliakim-Raz N, Stemmer A, et al. Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer. JAMA Oncol. 2021; 7(8): 1133–1140, doi: 10.1001/jamaoncol.2021.2155, indexed in Pubmed: 34047765.
  18. Shmueli ES, Itay A, Margalit O, et al. Efficacy and safety of BNT162b2 vaccination in patients with solid cancer receiving anticancer therapy - a single centre prospective study. Eur J Cancer. 2021; 157: 124–131, doi: 10.1016/j.ejca.2021.08.007, indexed in Pubmed: 34508994.
  19. Waldhorn I, Holland R, Goshen-Lago T, et al. Six-Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors. Cancer Discov. 2021; 11(10): 2430–2435, doi: 10.1158/2159-8290.CD-21-1072, indexed in Pubmed: 34475136.
  20. Yasin AI, Aydin SG, Sümbül B, et al. Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study. Future Oncol. 2022; 18(10): 1235–1244, doi: 10.2217/fon-2021-1248, indexed in Pubmed: 35081732.
  21. Buttiron Webber T, Provinciali N, Musso M, et al. Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment. Eur J Cancer. 2021; 159: 105–112, doi: 10.1016/j.ejca.2021.09.030, indexed in Pubmed: 34742157.
  22. Lo W, Whimbey E, Elting L, et al. Antibody response to a two-dose influenza vaccine regimen in adult lymphoma patients on chemotherapy. Eur J Clin Microbiol Infect Dis. 1993; 12(10): 778–782, doi: 10.1007/BF02098469, indexed in Pubmed: 8307050.
  23. Nordøy T, Aaberge IS, Husebekk A, et al. Cancer patients undergoing chemotherapy show adequate serological response to vaccinations against influenza virus and Streptococcus pneumoniae. Med Oncol. 2002; 19(2): 71–78, doi: 10.1385/MO:19:2:71, indexed in Pubmed: 12180483.
  24. Nilles EJ, Siddiqui SM, Fischinger S, et al. Epidemiological and Immunological Features of Obesity and SARS-CoV-2. Viruses. 2021; 13(11), doi: 10.3390/v13112235, indexed in Pubmed: 34835041.



Nowotwory. Journal of Oncology