Neoadjuvant Chemotherapy-induced Severe Neutropenia is Associated with Histopathological Response and Survival in Locally Advanced Gastric Cancer

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2022 Feb 4

PMID 35117182

Authors

Chaorui Wu

Tongbo Wang

Hong Zhou

Xiaojie Zhang

Chunguang Guo

Yingtai Chen

Dongbing Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Neoadjuvant chemotherapy (NAC) has been shown to improve the prognosis for patients with locally advanced gastric cancer (LAGC). Neutropenia, a predominant chemotherapy-related adverse event, affects the therapeutic course for NAC.

Methods: Data for 233 patients with LAGC treated with NAC and curative gastrectomy at our center were retrospectively analysed in terms of the relationship between neutropenia and clinicopathological features or outcomes.

Results: NAC-induced neutropenia, NAC-induced severe (grade 3/4) neutropenia (NISN), and a favorable histopathological response (HPR) were observed in 102 (43.8%), 35 (15.0%), and 103 (44.2%) patients, respectively. Together with tumor differentiation, clinical response, and lymphovascular invasion (LVI), and NISN independently predicted a favorable HPR [odds ratio (OR) =4.158, 95% confidence interval (CI): 1.762-9.812, P=0.001). Among patients treated with postoperative chemotherapy, NISN independently predicted poor compliance with postoperative chemotherapy (OR 0.364, 95% CI: 0.148-0.894, P=0.028) and thus poor overall survival (OS) and disease-free survival (DFS). Among patients treated with preoperative chemotherapy alone, NISN was associated with a tendency towards a better DFS (P=0.116) and independently predicted superior OS (hazard ratio =0.253, 95% CI: 0.077-0.830, P=0.023).

Conclusions: In conclusion, our study revealed a link between NISN, HPR, treatment compliance, and survival. NISN is useful for guiding treatment strategies and predicting prognosis for LAGC patients.

References

Kadota T, Hatogai K, Yano T, Fujita T, Kojima T, Daiko H . Pathological tumor regression grade of metastatic tumors in lymph node predicts prognosis in esophageal cancer patients. Cancer Sci. 2018; 109(6):2046-2055. PMC: 5989742. DOI: 10.1111/cas.13596. View

Taplitz R, Kennedy E, Bow E, Crews J, Gleason C, Hawley D . Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018; 36(14):1443-1453. DOI: 10.1200/JCO.2017.77.6211. View

Tomasello G, Petrelli F, Ghidini M, Pezzica E, Passalacqua R, Steccanella F . Tumor regression grade and survival after neoadjuvant treatment in gastro-esophageal cancer: A meta-analysis of 17 published studies. Eur J Surg Oncol. 2017; 43(9):1607-1616. DOI: 10.1016/j.ejso.2017.03.001. View

Bozzetti F . Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol. 2017; 28(9):2107-2118. DOI: 10.1093/annonc/mdx271. View

Schwartz L, Litiere S, de Vries E, Ford R, Gwyther S, Mandrekar S . RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016; 62:132-7. PMC: 5737828. DOI: 10.1016/j.ejca.2016.03.081. View

Sunaga T, Suzuki S, Kogo M, Kurihara T, Kaji S, Koike N . The association between neutropenia and prognosis in stage III colorectal cancer patients receiving adjuvant chemotherapy. Eur J Cancer Care (Engl). 2013; 23(3):394-400. DOI: 10.1111/ecc.12120. View

Zhou S, Zhou Z, Hu Z, Huang X, Wang Z, Chen E . Tumor-Associated Neutrophils Recruit Macrophages and T-Regulatory Cells to Promote Progression of Hepatocellular Carcinoma and Resistance to Sorafenib. Gastroenterology. 2016; 150(7):1646-1658.e17. DOI: 10.1053/j.gastro.2016.02.040. View

Cunningham D, Allum W, Stenning S, Thompson J, van de Velde C, Nicolson M . Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006; 355(1):11-20. DOI: 10.1056/NEJMoa055531. View

Erpenbeck L, Schon M . Neutrophil extracellular traps: protagonists of cancer progression?. Oncogene. 2016; 36(18):2483-2490. DOI: 10.1038/onc.2016.406. View

10.

Saunders J, Bowman C, Reece-Smith A, Pang V, Dorrington M, Mumtaz E . The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery. J Surg Oncol. 2017; 115(7):821-829. DOI: 10.1002/jso.24601. View

11.

Smith T, Bohlke K, Lyman G, Carson K, Crawford J, Cross S . Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015; 33(28):3199-212. DOI: 10.1200/JCO.2015.62.3488. View

12.

Nieuweboer A, Smid M, de Graan A, Elbouazzaoui S, de Bruijn P, Martens J . Predicting paclitaxel-induced neutropenia using the DMET platform. Pharmacogenomics. 2015; 16(11):1231-41. DOI: 10.2217/pgs.15.68. View

13.

Hamauchi S, Yamazaki K, Masuishi T, Kito Y, Komori A, Tsushima T . Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102. Clin Colorectal Cancer. 2016; 16(1):51-57. DOI: 10.1016/j.clcc.2016.07.005. View

14.

Hatogai K, Fujii S, Kojima T, Daiko H, Kadota T, Fujita T . Prognostic significance of tumor regression grade for patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery. J Surg Oncol. 2016; 113(4):390-6. DOI: 10.1002/jso.24151. View

15.

Wu C, Wang N, Zhou H, Wang T, Mao Q, Zhang X . Effects of Neoadjuvant Chemotherapy Toxicity and Postoperative Complications on Short-term and Long-term Outcomes After Curative Resection of Gastric Cancer. J Gastrointest Surg. 2019; 24(6):1278-1289. DOI: 10.1007/s11605-019-04257-2. View

16.

Diefenhardt M, Hofheinz R, Martin D, Beissbarth T, Arnold D, Hartmann A . Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial. Int J Cancer. 2019; 145(8):2282-2291. DOI: 10.1002/ijc.32274. View

17.

Schraa S, Frerichs K, Agterof M, Hunting J, Los M, de Jong P . Relative dose intensity as a proxy measure of quality and prognosis in adjuvant chemotherapy for breast cancer in daily clinical practice. Eur J Cancer. 2017; 79:152-157. DOI: 10.1016/j.ejca.2017.04.001. View

18.

Lalami Y, Klastersky J . Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical data. Crit Rev Oncol Hematol. 2017; 120:163-179. DOI: 10.1016/j.critrevonc.2017.11.005. View

19.

Cortejoso L, Garcia-Gonzalez X, Garcia M, Garcia-Alfonso P, Sanjurjo M, Lopez-Fernandez L . Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines. Pharmacogenomics. 2016; 17(9):979-84. DOI: 10.2217/pgs-2016-0006. View

20.

Langer R, Becker K . Tumor regression grading of gastrointestinal cancers after neoadjuvant therapy. Virchows Arch. 2017; 472(2):175-186. DOI: 10.1007/s00428-017-2232-x. View