Update artikel 1 februari 2024.

Abstract en link naar volledige studieverslag van de PANDA fase II studie toegevoegd, zie verderop in artikel. Het studieverslag is zeer uitgebreid en gedetailleerd. En ook daarbij adresgegevens hoe u zich voor de fase III studie op kunt geven bij studieleidster drs. M. Chalabi, internist-oncoloog.

15 januari 2024:

zie ook dit artikel: https://kanker-actueel.nl/maagkanker-onderhoudstherapie-met-immuuntherapie-met-avelumab-na-chemotherapie-geeft-verbeterde-2-jaars-overleving-van-6-maanden-in-vergelijking-met-voortzetting-van-chemotherapie.html

Zie ook in gerelateerde artikelen

9 januari 2024: Bron: Anthony van Leeuwenhoek ziekenhuis

Uitstekende hoopvolle resultaten komen uit de PANDA studie met immuuntherapie uitgevoerd in het Anthony van Leeuwenhoek ziekenhuis onder leiding van drs. M. Chalabi, internist-oncoloog.

Van de 20 deelnemende patiënten met maagkanker en kwaadaardige tumoren in de overgang van slokdarm naar de maag blijken er 14 patiënten die zeer goed op de behandeling reageerden. Bij negen patiënten was de tumor zelfs volledig verdwenen op moment van opereren. Na bijna vier jaar waren de meeste patiënten bij wie de tumor geslonken was nog steeds kankervrij.

De kankerpatiënten met maagkanker en kwaadaardige tumoren in de overgang van slokdarm naar de maag kregen als eerste 1 kuur immuuntherapie met het anti-PD medicijn atezolizumab gevolgd door 4 kuren atezolizumab samen met chemotherapie (Docetaxel/ Oxaliplatine/ Capecitabine) gevolgd door een operatieve ingreep. En zoals gezegd deze aanpak sloeg bijzonder goed aan. Er is nu een fase II/III studie opgezet met meer patiënten begrijp ik uit het verslag van het AvL.

Internist-oncoloog en onderzoeksleider Myriam Chalabi zegt ook: "het unieke aspect van deze studie is dat patiënten de eerste kuur immuuntherapie kregen zonder chemotherapie, wat de resultaten gunstiger lijkt te maken dan vergelijkbare studies waar chemotherapie en immuuntherapie worden gecombineerd.¨

Wat naar mijn mening echt een open deur is want waar immuuntherapie wordt gegeven bij verschillende vormen van kanker met solide tumoren vooraf aan welke andere behandeling dan ook, zijn de resultaten bijna altijd beter dan in combinatie. 

Op de website van het AvL staat een nieuwsbericht over deze studieresultaten:

Doorbraak in behandeling van maag- en slokdarmkanker

Patiënten met maag- of slokdarm-maag overgang kanker blijken goed te reageren op een nieuwe vorm van behandeling. Dit blijkt uit de veelbelovende resultaten van een kleinschalige studie van het Antoni van Leeuwenhoek. De onderzoekers ontdekten ook nog een mogelijk mechanisme achter dit succes.

Doorgaans worden patiënten met maag- of slokdarm-maag overgang kanker zonder uitzaaiingen behandeld met een combinatie van bestraling met chemotherapie voorafgaand aan de operatie, ofwel chemotherapie zowel voor als na de operatie. Ondanks vooruitgang in de behandeling, blijft de prognose somber. Om dit te verbeteren, hebben onderzoekers zich met de fase-2 PANDA studie gericht op een nieuwe vorm van behandelen. Zij onderzochten de effecten van het combineren van immuuntherapie en chemotherapie voorafgaand aan de operatie. Met succes; de behandeling leidde tot aanzienlijke afname van de tumor bij een groot deel van de patiënten.>>>>>>>>>lees verder

Ook in het Algemeen dagblad wordt melding gemaakt van deze resultaten: 

Prognose bij maag- en slokdarmkanker is slecht, maar er gloort nieuwe hoop

Voorzichtig goed nieuws voor patiënten met maag- en slokdarmkanker. Ze lijken vaker te genezen als ze ook immuuntherapie krijgen. Het Antoni van Leeuwenhoek (AVL) ziet hoopvolle resultaten in een nieuw onderzoek.

Een kleine vierduizend patiënten kregen in 2022 de diagnose maag- of slokdarmkanker. Zelfs als patiënten geen uitzaaiingen hebben, is de prognose slecht. Na vijf jaar is meer dan de helft van deze mensen aan de ziekte overleden.

Maar uit een nieuwe studie van het Amsterdamse AVL blijkt dat de kans op overleving met immuuntherapie aanzienlijk groter wordt. Het gaat om mensen met maagkanker of een tumor in het onderste deel van de slokdarm.

Patiënten kregen eerst immuuntherapie, daarna een combinatie van immuun- en chemotherapie en als laatste een operatie. Bij veertien van de twintig patiënten sloeg de behandeling goed aan. Bij 70 procent was de tumor na de immuun- en chemotherapie bijna helemaal geslonken, bij 45 procent waren de samengeklonterde kankercellen zelfs verdwenen.>>>>>>>>>lees verder  

Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial

Nature Medicine (2024)Cite this article

Abstract

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46–88%) patients, including 9 (45%, 95% confidence interval 23–68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835.

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Article Open access06 July 2021

Data availability

The RNA and DNA sequencing data will be deposited in the European Genome-Phenome Archive under EGAS00001007676, and these data will be shared on reasonable request for academic use and within the limitations of the provided informed consent and under General Data Protection Regulation law. All data requests supported by the principal investigator/corresponding author of the study will be reviewed by the institutional review board of the NKI. The researcher will need to sign a data access agreement with the NKI after approval. The form to request access can be found at https://ega.nki.nl/ and will be centrally reviewed through repository@nki.nl, which will contact the corresponding author (M.C.). Estimated time to response is 2–4 weeks.

References

  1. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    Article PubMed Google Scholar 

  2. Shapiro, J. et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 16, 1090–1098 (2015).

    Article PubMed Google Scholar 

  3. Al-Batran, S. E. et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 393, 1948–1957 (2019).

    Article PubMed Google Scholar 

  4. Al-Batran, S. E. et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 17, 1697–1708 (2016).

    Article CAS PubMed Google Scholar 

  5. Thompson, E.D. et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut 66, 794–801 (2017).

  6. Kawazoe, A. et al. Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein–Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer 20, 407–415 (2017).

    Article CAS PubMed Google Scholar 

  7. Geng, Y. et al. Expression of costimulatory molecules B7-H1, B7-H4 and Foxp3+ Tregs in gastric cancer and its clinical significance. Int. J. Clin. Oncol. 20, 273–281 (2015).

    Article CAS PubMed Google Scholar 

  8. Gu, L. et al. PD-L1 and gastric cancer prognosis: a systematic review and meta-analysis. PLoS ONE12, e0182692 (2017).

    Article PubMed PubMed Central Google Scholar 

  9. Bang, Y.-J. et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 22, 828–837 (2019).

    Article CAS PubMed PubMed Central Google Scholar 

  10. Janjigian, Y. Y. et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 398, 27–40 (2021).

    Article CAS PubMed PubMed Central Google Scholar 

  11. Kelly, R. J. et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N. Engl. J. Med. 384, 1191–1203 (2021).

    Article CAS PubMed Google Scholar 

  12. Amaria, R. N. et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat. Med. 24, 1649–1654 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  13. Blank, C. U. et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat. Med. 24, 1655–1661 (2018).

    Article CAS PubMed Google Scholar 

  14. Huang, A. C. et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat. Med. 25, 454–461 (2019).

    Article CAS PubMed PubMed Central Google Scholar 

  15. Forde, P. M. et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N. Engl. J. Med. 378, 1976–1986 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  16. Powles, T. et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat. Med. 25, 1706–1714 (2019).

  17. Chalabi, M. et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat. Med. 26, 566–576 (2020).

    Article CAS PubMed Google Scholar 

  18. Cercek, A. et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N. Engl. J. Med. 386, 2363–2376 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  19. Versluis, J. M., Long, G. V. & Blank, C. U. Learning from clinical trials of neoadjuvant checkpoint blockade. Nat. Med. 26, 475–484 (2020).

    Article CAS PubMed Google Scholar 

  20. Reijers, I. L. M. et al. The interferon-gamma (IFN-y) signature from baseline tumor material predicts pathologic response after neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) in stage III melanoma. J. Clin. Oncol. 40, 9539–9539 (2022).

    Article Google Scholar 

  21. Bailly, C., Thuru, X. & Quesnel, B. Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times. NAR Cancer 2, zcaa002 (2020).

    Article PubMed PubMed Central Google Scholar 

  22. Xue, Y. et al. Platinum-based chemotherapy in combination with PD-1/PD-L1 inhibitors: preclinical and clinical studies and mechanism of action. Expert Opin. Drug Deliv. 18, 187–203 (2021).

    Article CAS PubMed Google Scholar 

  23. Golchin, S., Alimohammadi, R., Rostami Nejad, M. & Jalali, S. A. Synergistic antitumor effect of anti-PD-L1 combined with oxaliplatin on a mouse tumor model. J. Cell Physiol. 234, 19866–19874 (2019).

    Article CAS PubMed Google Scholar 

  24. Loibl, S. et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann. Oncol. 30, 1279–1288 (2019).

    Article CAS PubMed Google Scholar 

  25. Loibl, S. et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann. Oncol. 33, 1149–1158 (2022).

    Article CAS PubMed Google Scholar 

  26. Tetzlaff, M. T. et al. Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma. Ann. Oncol. 29, 1861–1868 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  27. Cottrell, T. R. et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann. Oncol. 29, 1853–1860 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  28. Vos, J. L. et al. FDG-PET accurately identifies pathological response early upon neoadjuvant immune checkpoint blockade in head and neck squamous cell carcinoma. Eur. J. Nucl. Med. Mol. Imaging 49, 2010–2022 (2022).

    Article CAS PubMed Google Scholar 

  29. Reijers, I. L. M. et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial. Nat. Med. 28, 1178–1188 (2022).

    Article CAS PubMed Google Scholar 

  30. Rozeman, E. A. et al. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma. Nat. Med. 27, 256–263 (2021).

    Article CAS PubMed Google Scholar 

  31. Cascone, T. et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat. Med. 27, 504–514 (2021).

    Article CAS PubMed PubMed Central Google Scholar 

  32. Gros, A. et al. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J. Clin. Invest. 124, 2246–2259 (2014).

    Article CAS PubMed PubMed Central Google Scholar 

  33. Hummelink, K. et al. PD-1T TILs as a predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC. Clin. Cancer Res. 28, 4893–4906 (2022).

  34. Thommen, D. S. et al. A transcriptionally and functionally distinct PD-1(+) CD8(+) T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat. Med. 24, 994–1004 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  35. Duhen, T. et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat. Commun. 9, 2724 (2018).

    Article PubMed PubMed Central Google Scholar 

  36. Ayers, M. et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Invest. 127, 2930–2940 (2017).

    Article PubMed PubMed Central Google Scholar 

  37. Schumacher, T. N. & Thommen, D. S. Tertiary lymphoid structures in cancer. Science 375, eabf9419 (2022).

    Article CAS PubMed Google Scholar 

  38. Siddiqui, I. et al. Intratumoral Tcf1(+)PD-1(+)CD8(+) T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy. Immunity 50, 195–211.e110 (2019).

    Article CAS PubMed Google Scholar 

  39. Zhao, X., Shan, Q. & Xue, H. H. TCF1 in T cell immunity: a broadened frontier. Nat. Rev. Immunol. 22, 147–157 (2022).

    Article CAS PubMed Google Scholar 

  40. Krystel-Whittemore, M., Dileepan, K. N. & Wood, J. G. Mast cell: a multi-functional master cell. Front Immunol. 6, 620 (2015).

    PubMed Google Scholar 

  41. Network, C.G.A.R. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202–209 (2014).

    Article Google Scholar 

  42. Chen, Y. et al. Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nat. Commun. 13, 4851 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  43. Basham, T. Y. & Merigan, T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J. Immunol. 130, 1492–1494 (1983).

    Article CAS PubMed Google Scholar 

  44. Blomberg, O. S. et al. IL-5-producing CD4(+) T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell 41, 106–123.e110 (2023).

    Article CAS PubMed Google Scholar 

  45. Cunningham, D. et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol. 18, 357–370 (2017).

    Article CAS PubMed PubMed Central Google Scholar 

  46. Lombardi, P. M. et al. Prognostic value of pathological tumor regression grade in locally advanced gastric cancer: new perspectives from a single‐center experience. J. Surg. Oncol. 123, 923–931 (2021).

    Article PubMed Google Scholar 

  47. Huffman, B. M. et al. Analysis of circulating tumor DNA to predict risk of recurrence in patients with esophageal and gastric cancers. JCO Precis. Oncol. 6, e2200420 (2022).

    Article PubMed PubMed Central Google Scholar 

  48. Kotani, D. et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat. Med. 29, 127–134 (2023).

    Article CAS PubMed PubMed Central Google Scholar 

  49. Janjigian, Y. et al. LBA73 Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): interim results of the global, phase III MATTERHORN study. Ann. Oncol. 34, S1315–S1316 (2023).

    Article Google Scholar 

  50. Gordon, A. et al. Primary results of the ICONIC phase 2 trial of perioperative FLOT plus avelumab (FLOT-A) in operable oesophagogastric adenocarcinoma (OGA). J. Clin. Oncol. 41, 446–446 (2023).

    Article Google Scholar 

  51. van Hagen, P. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N. Engl. J. Med. 366, 2074–2084 (2012).

    Article PubMed Google Scholar 

  52. Lorenzen, S. et al. Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial. J. Clin. Oncol. https://doi.org/10.1200/JCO.23.00975 (2023).

  53. Guo, H. et al. Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: a single-arm, open-label, phase II trial. Front. Oncol. 12, 927781 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  54. Yin, Y. et al. Neoadjuvant tislelizumab and tegafur/gimeracil/octeracil (S-1) plus oxaliplatin in patients with locally advanced gastric or gastroesophageal junction cancer: early results of a phase 2, single-arm trial. Front. Oncol. 12, 959295 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  55. Jiang, H. et al. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J. Immunother. Cancer 10, e003635 (2022).

    Article PubMed PubMed Central Google Scholar 

  56. Tang, X. et al. Neoadjuvant PD-1 blockade plus chemotherapy induces a high pathological complete response rate and anti-tumor immune subsets in clinical stage III gastric cancer. Oncoimmunology 11, 2135819 (2022).

    Article PubMed PubMed Central Google Scholar 

  57. Shitara, K., et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastrooesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. https://doi.org/10.1016/S1470-2045(23)00541-7 (2023).

  58. Klempner, S. et al. Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor immune microenvironment in advanced gastric cancer: a phase II chemoimmunotherapy trial. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-2793348/v1 (2023).

  59. Li, S. et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nat. Commun. 14, 8 (2023).

    Article CAS PubMed PubMed Central Google Scholar 

  60. Al-Batran, S.-E. et al. Surgical and pathological outcome, and pathological regression, in patients receiving perioperative atezolizumab in combination with FLOT chemotherapy versus FLOT alone for resectable esophagogastric adenocarcinoma: interim results from DANTE, a randomized, multicenter, phase IIb trial of the FLOT-AIO German Gastric Cancer Group and Swiss SAKK. J. Clin. Oncol. 40, 4003–4003 (2022).

    Article Google Scholar 

  61. van der Werf, L. R., Busweiler, L. A. D., van Sandick, J. W., van Berge Henegouwen, M. I. & Wijnhoven, B. P. L. Reporting national outcomes after esophagectomy and gastrectomy according to the esophageal complications consensus Group (ECCG). Ann. Surg. 271, 1095–1101 (2020).

    Article PubMed Google Scholar 

  62. Voeten, D. M. et al. Outcomes of esophagogastric cancer surgery during eight years of surgical auditing by the dutch upper gastrointestinal cancer audit (DUCA). Ann. Surg. 274, 866–873 (2021).

    Article PubMed Google Scholar 

  63. Blomberg, O. S. et al. Neoadjuvant immune checkpoint blockade triggers persistent and systemic T(reg) activation which blunts therapeutic efficacy against metastatic spread of breast tumors. Oncoimmunology 12, 2201147 (2023).

    Article PubMed PubMed Central Google Scholar 

  64. Arce Vargas, F. et al. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies. Cancer Cell 33, 649–663.e644 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  65. Waight, J. D. et al. Selective FcγR co-engagement on APCs modulates the activity of therapeutic antibodies targeting T cell antigens. Cancer Cell 33, 1033–1047.e1035 (2018).

    Article CAS PubMed PubMed Central Google Scholar 

  66. Haruna, M. et al. The impact of CCR8+ regulatory T cells on cytotoxic T cell function in human lung cancer. Sci. Rep. 12, 5377 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  67. Kidani, Y. et al. CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory. Proc. Natl Acad. Sci. USA 119, e2114282119 (2022).

    Article CAS PubMed PubMed Central Google Scholar 

  68. Amin, M. B. et al. The eighth edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more ‘personalized’ approach to cancer staging. CA Cancer J. Clin. 67, 93–99 (2017).

    Article PubMed Google Scholar 

  69. Revised common terminology criteria for adverse events (CTCAE) version 4.0. National Cancer Institute https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40 (2009).

  70. R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2009).

  71. Bartley, A. N. et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J. Clin. Oncol. 35, 446–464 (2017).

    Article CAS PubMed Google Scholar 

  72. Mandard, A. M. et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73, 2680–2686 (1994).

    Article CAS PubMed Google Scholar 

  73. Travis, W. D. et al. IASLC Multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy. J. Thorac. Oncol. 15, 709–740 (2020).

    Article CAS PubMed PubMed Central Google Scholar 

  74. Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021).

    Article CAS PubMed Google Scholar 

  75. Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).

    Article PubMed PubMed Central Google Scholar 

  76. Ijsselsteijn, M. E., van der Breggen, R., Farina Sarasqueta, A., Koning, F. & de Miranda, N. A 40-marker panel for high dimensional characterization of cancer immune microenvironments by imaging mass cytometry. Front. Immunol. 10, 2534 (2019).

    Article CAS PubMed PubMed Central Google Scholar 

  77. Somarakis, A., Van Unen, V., Koning, F., Lelieveldt, B. & Hollt, T. ImaCytE: visual exploration of cellular micro-environments for imaging mass cytometry data. IEEE Trans. Vis. Comput. Graph. 27, 98–110 (2021).

    Article PubMed Google Scholar 

  78. Höllt, T. et al. Cytosplore: interactive immune cell phenotyping for large single‐cell datasets. Comput. Graph. Forum 35, 171–180 (2016).

    Article Google Scholar 

  79. Priestley, P. et al. Pan-cancer whole-genome analyses of metastatic solid tumours. Nature 575, 210–216 (2019).

    Article CAS PubMed PubMed Central Google Scholar 

  80. Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020).

    Article CAS PubMed PubMed Central Google Scholar 

  81. Danaher, P. et al. Gene expression markers of tumor infiltrating leukocytes. J. Immunother. Cancer 5, 18 (2017).

    Article PubMed PubMed Central Google Scholar 

  82. de Vries, N. L. et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. Nature 613, 743–750 (2023).

    Article PubMed PubMed Central Google Scholar 

  83. Reinert, T. et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 5, 1124–1131 (2019).

    Article PubMed PubMed Central Google Scholar 

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Acknowledgements

We thank Hoffman-La Roche for funding this study. We thank all the patients and their families for participating in the present study. We thank the Core Facility of Molecular Pathology and Biobanking, in particular A. Broeks, S. Cornelissen and M. Alkemade, for their support in processing samples and performing immunohistochemistry; M. Nieuwland, R. Kluin, A. Velds and the Genomics Core Facility for their support with sequencing; I. Seignette for her support in digital imaging analysis using HALO; R. Harkes and Y. Ge for their support in quantification of CD8+ cells using QuPath; L. Al-van Wijck and M. van de Belt from the scientific administration department for data management and for support in trial conduct and management; N. Brandhorst for facilitating sample acquisition and processing; T. Korse, M. Lucas and E. Platte for PBMC acquisition and processing; Y. Hilhorst and M. Warmerdam for patient care; and St Jansdal Hospital, Rode Kruis Hospital, Tergooi Medical Center, Haga Hospital, Noordwest Hospital Group, Gelre Hospitals, Amsterdam UMC, Franciscus Hospital, PoliDirect IJburg, Slotervaart Hospital, Laurentius Hospital and St Antonius Hospital for patient referral. We would also like to acknowledge M.C. Liu and G. Laliotis from Natera for their supervision and critical review of the ctDNA analysis. The present study was funded by Hoffman-La Roche and sponsored by the NKI. The funding source had no role in design and execution of the study, data analysis or writing of the manuscript.

Author information

Author notes

  1. These authors contributed equally: Joris van de Haar, José G. van den Berg.

Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Yara L. Verschoor, Jolanda M. van Dieren, Cecile Grootscholten, Marieke A. Vollebergh, Peggy den Hartog, Monique E. van Leerdam, Emile E. Voest & Myriam Chalabi

  2. Department of Molecular Oncology and Immunology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Joris van de Haar, Ton N. Schumacher & Emile E. Voest

  3. Oncode Institute, Amsterdam, the Netherlands

    Joris van de Haar, Ton N. Schumacher & Emile E. Voest

  4. Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    José G. van den Berg & Liudmila L. Kodach

  5. Department of Surgery, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Johanna W. van Sandick, Alexander A. F. A. Veenhof & Koen J. Hartemink

  6. Biometrics department, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Sara Balduzzi

  7. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

    Marieke E. IJsselsteijn & Noel F. C. C. de Miranda

  8. Department of Medical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Marieke A. Vollebergh, John B. A. G. Haanen & Myriam Chalabi

  9. Natera, Inc, Austin, TX, USA

    Adham Jurdi, Shruti Sharma & Erik Spickard

  10. Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Emilia C. Owers

  11. Department of Radiology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands

    Annemarieke Bartels-Rutten

  12. Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands

    Monique E. van Leerdam

  13. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands

    John B. A. G. Haanen

  14. Oncology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    John B. A. G. Haanen

  15. Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands

    Ton N. Schumacher

Contributions

Y.L.V. analyzed and interpreted clinical and translational data and wrote the manuscript under supervision of M.C. J.v.d.H performed the genomic/transcriptomic biomarker analyses. S.B. performed statistical analyses. J.G.v.d.B. and L.L.K. performed the histo- and immunopathologic scoring. J.G.v.d.B. annotated tumor areas for IHC quantification analysis. M.E.I. and N.F.C.C.d.M. performed IMC and interpreted the data. A.J., S.S., E.S. performed ctDNA analysis and interpreted the data together with Y.L.V. and M.C. C.G., M.A.V. and P.d.H. were responsible for patient care. J.W.v.S., A.A.F.A.V. and K.J.H. informed patients and performed surgery. J.M.v.D. and M.E.v.L. performed endoscopies. J.M.v.D. revised all endoscopic reports and images. A.B.-R. revised CT scans, and E.C.O. revised FDG-PET scans. M.C., T.N.S. and J.B.A.G.H. made the experimental plan of investigation. M.C. designed the trial and coordinated trial procedures. All authors reviewed, edited and approved the manuscript and vouch for the accuracy of the data reported and adherence to the protocol.

Corresponding author

Correspondence to Myriam Chalabi.




maagkanker, tumoren op de overgang van slokdarm naar de maag, immuuntherapie, atezolizumab, betere ziektevrije overleving, AvL, Nederlandse studie, Panda studie


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