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12 augustus 2017: Bron: PLOS one, online september 2014.

Dat immuuntherapie met dendritische celtherapie bij hersentumoren van het type Glioblastoma multiforme (GBM) wel degelijk zin kan hebben blijkt uit een reviewstudie.

De overall overlevingspercentages per jaar geanalyseerd staan hieronder maar op 3 jaar is het verschil 20 % (24% vs 4%) tussen wel of geen immuuntherapie met dendritische celtherapie en op 5 jaar 14% versus 0 procent. Echt een wezenljik en statistisch hoog significant verschil. 1 op de 7 patiënten overleeft een hooggradige  hersentumor. Een resultaat dat met geen enkele andere behandeling is te halen bij hooggradige hersentumoren. Nog duidelijker uit deze studies blijkt dat 0 procent een glioblastoma de 5 jaar overleeft. Alle reden dus om ons project Utopie of uitdaging door te zetten.

Hieornder het schema dat de onderzoekers hanteerden in hun studiekeuze. Uiteindelijk bleven er 31 studies over voor de meta-analyse (Tekst loopt verder onder grafiek).

immuuntherapie bij glioblastomen, studie overzicht

Ik heb niet alle teksten vertaald in het Nederlands maar wel de belangrijkste cijfers vertaald en vet gemaakt in onderstaande teksten:

1 jaar overall overleving (OS):

Information on the 1-year survival was available for seven trials , . These seven trials contained 354 patients in total (98 patients received DC therapy, and 256 control patients did not receive DC therapy). De 1 jaar overall overleving (OS) was 82% (80/98) voor glioma patiënten die de DC behandeling hadden gekregen, waar de OS 63% (160/256) bleek voor de patiënten uit de controlegroep. The meta-analysis showed a significantly improved 1-year OS for the patients who received DC therapy compared with those who did not (OR 2.89, 95% CI 1.58–5.27, P = 0.0006). Cochran's Q test yielded a P value of 0.09, and the corresponding I2 quantity was 45% (Figure 2A).

1.5 jaar overall overleving (OS):

Information on the 1.5-year survival was available for six trials , , . These six trials contained 320 patients in total (80 patients received DC therapy, and 240 patients who did not receive DC therapy served as a control).De 1,5 jaar overall overleving was 59% (47/80) voor glioma patiënten die de DC behandeling hadden gekregen, waar deze 28% (66/240) was voor de controlegroep. The meta-analysis showed a significant benefit for the 1.5-year OS in the HGG patients who received DC therapy compared with non-DC therapy (OR 5.13, 95% CI 2.80–9.41, P<0.00001). Cochran's Q test yielded a P value of 0.35, and the corresponding I2 quantity was 10% (<50%), indicating that the degree of variability between the trials was consistent with what would be expected to occur by chance alone (Figure 2A).

2 jaar overall overleving (OS):

Information on the 2-year survival was available for seven trials , . These seven trials contained 354 patients in total (98 patients received DC therapy, and 256 patients who did not receive DC therapy served as a control). De 2 jaar overall overleving was 34% (33/98) voor glioma patiënten die de DC behandeling hadden gekregen en 14% (35/256) voor de controlegroep. The estimated pooled OR for these seven trials showed a significantly increased 2-year OS for the patients who received DC therapy compared with those who did not (OR 4.69, 95% CI 2.48–8.85, P<0.00001). Cochran's Q test had a P value of 0.50, and the corresponding I2 quantity was 0% (Figure 2A).

3 jaar overall overleving (OS):

Information on the 3-year survival was available for six trials , , . These six trials included 354 patients in total (98 patients received DC therapy, and 256 patients who did not receive DC therapy were used as controls). De 3 jaar OS  was 24% (24/98) voor glioma patiënten die de DC behandeling hadden gekregen, versus 4% (10/256) voor de controlegroep. The meta-analysis showed a significantly longer 3-year OS for the patients who received DC therapy compared with those who did not (OR 11.52, 95% CI 4.66–28.45, P<0.00001). Cochran's Q test had a P value of 0.82, and the corresponding I2 quantity was 0% (Figure 2B).

4 jaar overall overleving (OS):

Information on the 4-year survival was available for five trials , . These five trials contained 320 patients in total (80 patients received DC therapy, and 240 patients who did not receive DC therapy were used as a control). The 4-year OS rates were 20% (16/80) for glioma patients receiving DC treatment and 1% (3/240) for the controls. The meta-analysis showed a significant improvement of the 4-year OS in the HGG patients who received DC therapy compared with those who did not (OR 16.61, 95% CI 5.06–54.52, P<0.00001). Cochran's Q test had a P value of 0.97, and the corresponding I2 quantity was 0% (Figure 2B).

5 jaar overall overleving (OS):

Information on the 5-year survival was available for two trials , . These two trials contained 216 patients in total (42 patients received DC therapy, and 174 control patients did not). De 5 jaar OS  was 14% (6/42) voor glioma patiënten die een DC behandeling kregen, versus 0% (0/174) voor de controlegroep. The meta-analysis showed a significantly greater 5-year OS for the patients who received DC therapy compared with those who did not (OR 44.40, 95% CI 5.00–394.16, P = 0.0007). Cochran's Q test had a P value of 0.69, and the corresponding I2 quantity was 0% (Figure 2B), indicating that the degree of variability between the trials was consistent with what would be expected to occur by chance alone.

In onderstaande grafieken zijn bovenstaande resultaten terug te vinden:

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Figure 2. Comparison of 0.5-, 1-, 1.5- and 2-year overall survival (OS) between the non-DC and DC groups (A); Forest plot for 3-, 4-, and 5-year OS between the non-DC and DC groups in HGG patients (B).

The fixed-effects meta-analysis model (Mantel-Haenszel method) was used. OR, odds ratio. DC, DC-containing therapy; non-DC, non-DC-containing therapy. Each trial is represented by a square, the center of which gives the odds ratio for that trial. The size of the square is proportional to the information in that trial. The ends of the horizontal bars denote a 95% CI. The black diamond gives the overall odds ratio for the combined results of all trials.

Het volledige studierapport: Clinical Efficacy of Tumor Antigen-Pulsed DC Treatment for High-Grade Glioma Patients: Evidence from a Meta-Analysis is gratis in te zien.

Hier het abstract van de studie met de referentielijst:

A meta-analysis shows: DC immunotherapy markedly prolongs survival rates and progression-free time, enhances immune function, and improves the efficacy of the treatment of High Grade Glioma patients (GBM)

Clinical Efficacy of Tumor Antigen-Pulsed DC Treatment for High-Grade Glioma Patients: Evidence from a Meta-Analysis

PLOS

Abstract

Background

The effectiveness of immunotherapy for high-grade glioma (HGG) patients remains controversial. To evaluate the therapeutic efficacy of dendritic cells (DCs) alone in the treatment of HGG, we performed a systematic review and meta-analysis in terms of patient survival with relevant published clinical studies.

Materials and methods

A total of 409 patients, including historical cohorts, nonrandomized and randomized controls with HGG, were selected for the meta-analysis.

Results

The treatment of HGG with DCs was associated with a significantly improved one-year survival (OS) (p<0.001) and 1.5-, 2-, 3-, 4-, and 5-year OS (p<0.001) compared with the non-DC group. A meta-analysis of the patient outcome data revealed that DC immunotherapy has a significant influence on progression-free survival (PFS) in HGG patients, who showed significantly improved 1-,1.5-, 2-, 3- and 4-year PFS (p<0.001). The analysis of Karnofsky performance status (KPS) demonstrated no favorable results for DC cell therapy arm (p = 0.23).The percentages of CD3+CD8+ and CD3+CD4+ T cells and CD16+ lymphocyte subset were not significantly increased in the DC group compared with the baseline levels observed before treatment (p>0.05), whereas CD56+ lymphocyte subset were significantly increased after DC treatment (p = 0.0001). Furthermore, the levels of IFN-γ in the peripheral blood of HGG patients, which reflect the immune function of the patients, were significantly increased after DC immunotherapy (p<0.001).

Conclusions

Thus, our meta-analysis showed that DC immunotherapy markedly prolongs survival rates and progression-free time, enhances immune function, and improves the efficacy of the treatment of HGG patients.

Author Contributions

Conceived and designed the experiments: ZXW JXC. Performed the experiments: ZXW JXC XYZ JL-Liu YSL MW DL JL-Li BLX HBW. Analyzed the data: JXC XYZ JL-Liu YSL DL MW JL-Li BLX HBW. Contributed reagents/materials/analysis tools: JXC DL MW. Contributed to the writing of the manuscript: ZXW JXC XYZ JL-Liu.

References

  1. 1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, et al.. (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114(2):97–109. Epub 2007 Jul 6.
  2. 2. Ruzevick J, Jackson C, Phallen J, Lim M (2012) Clinical trials with immunotherapy for high-grade glioma. Neurosurg Clin N Am. 23(3): 459–470
  3. 3. Badhiwala J, Decker WK, Berens ME, Bhardwaj RD (2013) Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 13(4): 405–424
  4. 4. Wilson EH, Weninger W, Hunter CA (2010) Trafficking of immune cells in the central nervous system. J Clin Invest. 120(5): 1368–1379
  5. 5. Sagar D, Foss C, Baz ER, Pomper MG, Khan ZK, et al. (2012) Mechanisms of dendritic cell trafficking across the blood-brain barrier. J Neuroimmune Pharmacol. 7(1): 74–94
  6. 6. Xu X, Stockhammer F, Schmitt M (2012) Cellular-based immunotherapies for patients with glioblastoma multiforme. Clin Dev Immunol. 2012: 764213
  7. 7. Fabry Z, Raine CS, Hart MN (1994) Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Today. 15(5): 218–224.
  8. 8. Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 22 12(4): 265–277
  9. 9. Ardon H, De Vleeschouwer S, Van Calenbergh F, Claes L, Kramm CM, et al. (2010) Adjuvant dendritic cell-based tumour vaccination for children with malignant brain tumours. Pediatr Blood Cancer. 54(4): 519–525
  10. 10. Ardon H, Van Gool SW, Verschuere T, Maes W, Fieuws S, et al. (2012) Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother. 61(11): 2033–2044
  11. 11. De Vleeschouwer S, Ardon H, Van Calenbergh F, Sciot R, Wilms G, et al. (2012) Stratification according to HGG-IMMUNO RPA model predicts outcome in a large group of patients with relapsed malignant glioma treated by adjuvant postoperative dendritic cell vaccination. Cancer Immunol Immunother. 61(11): 2105–2112
  12. 12. Van Gool S, De Vleeschouwer S (2012) Should dendritic cell-based tumor vaccination be incorporated into standard therapy for newly diagnosed glioblastoma patients? Expert Rev Neurother. 12(10): 1173–1176
  13. 13. Bregy A, Wong TM, Shah AH, Goldberg JM, Komotar RJ (2013) Active immunotherapy using dendritic cells in the treatment of glioblastoma multiforme. Cancer Treat Rev. 39(8): 891–907
  14. 14. Van Gool S, Maes W, Ardon H, Verschuere T, Van Cauter S, et al. (2009) Dendritic cell therapy of high-grade gliomas. Brain Pathol. 19(4): 694–712
  15. 15. Mineharu Y, Castro MG, Lowenstein PR, Sakai N, Miyamoto S. (2013) Dendritic Cell-Based Immunotherapy for Glioma: Multiple Regimens and Implications in Clinical Trials. Neurol Med Chir (Tokyo). 53(11):741–754. Epub 2013 Oct 21.
  16. 16. Wang ZX, Cao JX, Liu ZP, Cui YX, Li CY, et al. (2014) Combination of chemotherapy and immunotherapy for colon cancer in China: a meta-analysis. World J Gastroenterol. 28 20(4): 1095–1106
  17. 17. Chang CN, Huang YC, Yang DM, Kikuta K, Wei KJ, et al. (2011) A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci. 18(8): 1048–1054
  18. 18. Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, et al. (2005) Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin Cancer Res. 11(11): 4160–4167.
  19. 19. Wheeler CJ, Das A, Liu G, Yu JS, Black KL (2004) Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res. 10(16): 5316–5326.
  20. 20. Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, et al. (2005) Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 11(15): 5515–5525.
  21. 21. Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, et al. (2001) Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother. 50(7): 337–344.
  22. 22. Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, et al. (2003) Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial. Br J Cancer. 89(7): 1172–1179.
  23. 23. Yu JS, Liu G, Ying H, Yong WH, Black KL, et al. (2004) Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 64(14): 4973–4979.
  24. 24. Jie X, Hua L, Jiang W, Feng F, Feng G, et al. (2012) Clinical application of a dendritic cell vaccine raised against heat-shocked glioblastoma. Cell Biochem Biophys. 62(1): 91–99
  25. 25. Cho DY, Yang WK, Lee HC, Hsu DM, Lin HL, et al. (2012) Adjuvant immunotherapy with whole-cell lysate dendritic cells vaccine for glioblastoma multiforme: a phase II clinical trial. World Neurosurg. 77(5-6): 736–744
  26. 26. Van Gool S (2013) Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials. Immunotherapy. 5(10): 1043–1046
  27. 27. Shah AH, Bregy A, Heros DO, Komotar RJ, Goldberg J (2013) Dendritic cell vaccine for recurrent high-grade gliomas in pediatric and adult subjects: clinical trial protocol. Neurosurgery. 73(5): 863–867
  28. 28. Izumoto S, Tsuboi A, Oka Y, Suzuki T, Hashiba T, et al. (2008) Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme. J Neurosurg. 108(5): 963–971
  29. 29. Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, et al. (2010) Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 28(31): 4722–4729
  30. 30. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 331(6024): 1565–1570
  31. 31. Wheeler CJ, Black KL, Liu G, Mazer M, Zhang XX, et al. (2008) Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res. 68(14): 5955–5964
  32. 32. Hussain SF, Heimberger AB (2005) Immunotherapy for human glioma: innovative approaches and recent results. Expert Rev Anticancer Ther. 5(5): 777–790.
  33. 33. Ogbomo H, Cinatl J Jr, Mody CH, Forsyth PA (2011) Immunotherapy in gliomas: limitations and potential of natural killer (NK) cell therapy. Trends Mol Med. 17(8): 433–441
  34. 34. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell. 140(6): 883–899
  35. 35. Jackson C, Ruzevick J, Brem H, Lim M (2013) Vaccine strategies for glioblastoma: progress and future directions. Immunotherapy. 5(2): 155–167
  36. 36. Reardon DA, Wucherpfennig KW, Freeman G, Wu CJ, Chiocca EA, et al. (2013) An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma. Expert Rev Vaccines. 12(6): 597–615
  37. 37. Li Z, Lee JW, Mukherjee D, Ji J, Jeswani SP, et al. (2012) Immunotherapy targeting glioma stem cells-insights and perspectives. Expert Opin Biol Ther. 12(2): 165–178
  38. 38. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, et al. (2011) Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 17(6): 1603–1615
  39. 39. Jackson C, Ruzevick J, Phallen J, Belcaid Z, Lim M (2011) Challenges in immunotherapy presented by the glioblastoma multiforme microenvironment. Clin Dev Immunol. 2011: 732413

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