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Chemotherapy-associated foam cell aggregates as a prognostic factor in patients with pelvic high-grade serous carcinoma receiving neo-adjuvant chemotherapy

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Abstract

High-grade serous carcinoma (HGSC) tends to recur after treatment; therefore, the Chemotherapy Response Score (CRS) has been proposed as a histopathological prognostic scoring system for measuring the response to neo-adjuvant chemotherapy and the risk of recurrence. This study aimed to evaluate the CRS in only those with an R0 debulking status and to investigate new prognostic factors for progression-free survival (PFS). We reviewed the CRS of HGSC patients with R0 using surgical specimens of the omental sections. Patients were categorized according to foam cell change (FCC), defined as foam cells occupying more than half of the area of the chemotherapy-associated scar. In total, 100 HGSC patients were evaluated. PFS was significantly different according to the CRS. For CRSs of 1/2 and 3, the median PFS were 18 and 27 months, respectively (HR, 1.84; 95% CI 1.01–3.33, p = 0.045). Moreover, the FCC group showed significantly longer PFS than did the non-FCC group (20 vs 59 months; HR 2.43; 95% CI 1.15–5.14; p = 0.020). The present study validated the CRS of those in the R0 cohort. Furthermore, an increase in foam cells in the regression scar reflects the chemotherapy response and the FCC may be a useful novel prognostic factor for patients undergoing R0 resection. This finding must be further validated independently.

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References

  1. Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg M, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS, European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group, NCIC Clinical Trials Group (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953

    Article  CAS  Google Scholar 

  2. Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM (2015) Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 386:249–257

    Article  Google Scholar 

  3. Vergote I, Coens C, Nankivell M et al (2018) Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol 0:1–8

  4. Böhm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, Fitzpatrick A, Ennis D, Dowe T, Santos JL, Cook LS, Tinker AV, le ND, Gilks CB, Singh N (2015) Chemotherapy response score: development and validation of a system to quantify histopathologic response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. J Clin Oncol 33:2457–2463

    Article  Google Scholar 

  5. Glenn Mccluggage W, Judge MJ, Clarke BA et al (2015) Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Mod Pathol 28:1101–1122

    Article  Google Scholar 

  6. College of American Pathologists (2018) Protocol for the examination of specimens from patients with primary tumours of the ovary, fallopian tube, or peritoneum. https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates.

  7. Coghlan E, Meniawy TM, Munro A, Bulsara M, Stewart CJ, Tan A, Koay MHE, MaGee D, Codde J, Tan J, Salfinger SG, Mohan GR, Leung Y, Nichols CB, Cohen PA (2017) Prognostic role of histological tumour regression in patients receiving neoadjuvant chemotherapy for high-grade serous tubo-ovarian carcinoma. Int J Gynecol Cancer 27:708–713

    Article  Google Scholar 

  8. Lee JY, Chung YS, Na K et al (2017) External validation of chemotherapy response score system for histopathological assessment of tumour regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. J Gynecol Oncol 28:1–9

    Article  Google Scholar 

  9. Singh P, Kaushal V, Rai B, Rajwanshi A, Gupta N, Dey P, Garg R, Rohilla M, Suri V, Ghoshal S, Srinivasan R (2018) The chemotherapy response score is a useful histological predictor of prognosis in high-grade serous carcinoma. Histopathology 72:619–625

    Article  Google Scholar 

  10. Rajkumar S, Polson A, Nath R, Lane G, Sayasneh A, Jakes A, Begum S, Mehra G (2018) Prognostic implications of histological tumour regression (Böhm’s score) in patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian carcinoma. Gynecol Oncol 151:264–268

    Article  Google Scholar 

  11. Ditzel HM, Strickland KC, Meserve EE, Stover E, Konstantinopoulos PA, Matulonis UA, Muto MG, Liu JF, Feltmate C, Horowitz N, Berkowitz RS, Gupta M, Hecht JL, Lin DI, Jochumsen KM, Welch WR, Hirsch MS, Quade BJ, Lee KR, Crum CP, Mutter GL, Nucci MR, Howitt BE (2019) Assessment of a Chemotherapy Response Score (CRS) system for tubo-ovarian high-grade serous carcinoma (HGSC). Int J Gynecol Pathol 38:230–240

    Article  Google Scholar 

  12. Cohen PA, Powell A, Böhm S et al (2019) Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: a systematic review and meta-analysis of individual patient data. Gynecol Oncol 154:441–448

    Article  Google Scholar 

  13. Sassen S, Schmalfeldt B, Avril N et al (2007) Histopathologic assessment of tumour regression after neoadjuvant chemotherapy in advanced-stage ovarian cancer. Hum Pathol 38:926–934

    Article  CAS  Google Scholar 

  14. Genetic Pathology Evaluation Centre (2019) Chemotherapy Response Score (CRS): training web site for CRS system. http://www.gpecimage.ubc.ca/aperio/images/crs/.

  15. Petrillo M, Zannoni GF, Tortorella L et al (2014) Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer. Am J Obstet Gynecol 211:632.e1–632.e8

    Article  Google Scholar 

  16. Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48:452–458

    Article  CAS  Google Scholar 

  17. Said I, Böhm S, Beasley J, Ellery P, Faruqi AZ, Ganesan R, Hirschowitz L, Jeetle S, Leen SL, McCluggage W, McDermott J, Merard R, Millner TO, Trevisan G, Vella J, Gilks CB, Singh N (2017) The chemotherapy response score (CRS): Interobserver reproducibility in a simple and prognostically relevant system for reporting the histologic response to neoadjuvant chemotherapy in tuboovarian high-grade serous carcinoma. Int J Gynecol Pathol 36:172–179

    Article  CAS  Google Scholar 

  18. Ravichandran KS (2010) Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 207:1807–1817

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank Editage (www.editage.jp) for the English language editing.

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Authors and Affiliations

  1. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Naoki Kojima, Takeshi Ushigusa & Hiroshi Yoshida

  2. Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan

    Ikumi Kuno & Tomoyasu Kato

Authors
  1. Naoki Kojima
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  2. Ikumi Kuno
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  3. Takeshi Ushigusa
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  4. Tomoyasu Kato
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  5. Hiroshi Yoshida
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Contributions

NK and HY designed and conducted the analysis and drafted the manuscript. IK and TU collected the data and performed the analysis. TK analyzed the data and supervised the study. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Hiroshi Yoshida.

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The present study has been approved by the institutional review board of the National Cancer Center Japan and was conducted in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Kojima, N., Kuno, I., Ushigusa, T. et al. Chemotherapy-associated foam cell aggregates as a prognostic factor in patients with pelvic high-grade serous carcinoma receiving neo-adjuvant chemotherapy. Virchows Arch 477, 429–436 (2020). https://doi.org/10.1007/s00428-020-02778-9

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  • DOI: https://doi.org/10.1007/s00428-020-02778-9

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