Background:
The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates.
Methods:
A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates.
Results:
PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group (
p
=0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients (
p
=0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates.
Conclusion:
Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival.
Keywords:
uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival
The paclitaxel-cisplatin is a non-infusional alternative for induction chemotherapy (IC) for LASCCHN based on phase-II trials. Here, we describe our institutional experience with this combination in Southern Brazil. Methods: Thirty-three consecutive patients with unresectable LASCCHN were selected between April/2012 and June/2014. They received weekly paclitaxel 80mg/m 2 on days 1, 8, 15 and cisplatin 75mg/m 2 on day 1 for three cycles followed by chemoradiotherapy (CRT) with cisplatin at standard dose. Overall response, toxicity, progression free survival (PFS) and overall survival (OS) were evaluated. Results: The median follow-up was 25.5 months. Median age was 58.6 years and 96% had PS 1. Most patients presented with bulky disease at stages IVA and IVB (60.6% and 21.2%, respectively). Concerning primary site of tumor, 33.3% were oropharingeal tumors, 27.3% larynx tumors and 33.3% oral cavity tumors. The majority of patients had both smoking and alcohol abuse records. Twenty-eight patients (84.8%) at the time of diagnosis had a BMI <25. Twenty-seven patients (81.8%) completed the planned treatment and three patients (9%) underwent exclusive radiotherapy after IC. All patients were evaluated for response; 75.7% presented complete response and 21.2% presented partial response. Severe toxicity (grades 3-5) for asthenia, neutropenia, anemia and thrombocytopenia were observed in 6.1%, 9.1%, 6.1% and 3% of patients, respectively. One treatment-related death was associated with febrile neutropenia. The 2-and 3-year PFS rates were 63.3% and 68.4%, respectively; 2-and 3-year OS rates were 62.3.5% and 50.6%. Conclusions: Our results corroborate previous observations that IC (paclitaxel-cisplatin) is a well-tolerated and highly active regimen for the treatment of patients with LASSHNC, being associated with acceptable toxicity, good locoregional control and survival rates. This may be a good treatment option for patients in developing countries.
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