title: Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer.
abstract: OBJECTIVE
  To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT).
  
  
  METHODS
  Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models.
  
  
  RESULTS
  Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001).
  
  
  CONCLUSIONS
  Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression.
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. Electronic address: giorgiobogani@yahoo.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bogani
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sabatucci
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Maltese
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lecce
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Signorelli
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Martinelli
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiappa
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Indini
authors.affiliation: Academic Unit of Obstetrics and Gynecology, IRCCS AOU San-Martino-IST, Genoa, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Leone Roberti Maggiore
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Ferrara, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Borghi
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fucà
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Ditto
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raspagliesi
authors.affiliation: Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002173:Cancer Care Facilities; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007044:Hysterectomy; D007558:Italy; D007970:Leukopenia / Q000139:chemically induced* / Q000503:physiopathology; D008197:Lymph Node Excision; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010052:Ovariectomy; D017671:Platinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D058994:Salpingectomy; D012720:Severity of Illness Index; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017671:Platinum Compounds
keywords: Cervical cancer; Leukopenia; Neoadjuvant chemotherapy; Survival