Page 57 - JCTR-9-4

Li et al. | Journal of Clinical and Translational Research 2023; 9(4): 272-281 273
1. Introduction 2.2. Immunohistochemistry

Neuroendocrine carcinoma of the cervix (NECC) is a rare Immunohistochemistry was performed on 3-5-µm-thick
histologic type of cervical cancer, accounting for 0.9 – 1.5% of sections. The sections were incubated with antibodies against
cervical cancer cases [1-3]. Unlike squamous cell carcinoma and CgA, Syn, CD56, Ki-67, and PD-L1. PD-L1 immunostaining
adenocarcinoma, NECC is more prone to lymphatic infiltration, lymph was performed using clone 28-8 as an anti-PD-L1 antibody
node involvement, local recurrence, and distant metastasis (DM) [4]. (Dako, Carpentaria, CA, USA). PD-L1 expression was scored
Small-cell NECC (SCNEC) is the most common type of by counting the total number of PD-L1-positive cells, including
NECC, accounting for approximately 80% of NECC cases. tumor cells, lymphocytes, and macrophages, and dividing by the
Large-cell NECC (LCNEC) and other histological types represent total number of living tumor cells ×100 [14]. PD-L1 expression
approximately 12% and 8% of NECC cases, respectively. Common in tissues (or assays) with a score of ≥1 was considered positive.
markers of NECC include chromogranin A (CgA), synaptophysin
(Syn), and CD56. 2.3. Treatment
Adjuvant chemoradiotherapy after radical hysterectomy 2.3.1. RT
is feasible for early-stage cervical cancer, and concurrent
chemoradiotherapy (CCRT) or chemotherapy alone is feasible The standard protocol included external beam RT (EBRT) and
for locally advanced and metastatic disease [5-7]. The first-line high-dose-rate brachytherapy (HDR-BT). From January 2009 to
chemotherapy for NECC is etoposide or paclitaxel combined December 2014, EFI was performed in the pelvis and para-aortic
with a platinum agent (cisplatin or carboplatin). The National lymph nodes (PALNs) if PALN metastasis was detected at the
Comprehensive Cancer Network (2022) recommends using CCRT initial diagnosis. From January 2015 to December 2020, patients
with or without adjuvant chemotherapy as the standard treatment received EFI routinely. The patients were planned using 3D
for stage IB3-IVA NECC and CCRT for patients with early lesions conformal RT or intensity-modulated RT. EBRT was performed
confined to the cervix. Prognostic factors for cervical cancer using either 40.0 – 46.0 Gy in 20 – 23 fractions or 45.0 – 50.4 Gy
include race, age, tumor stage and grade, histological type, tumor in 1.8 Gy fractions. HDR-BT was performed during or after EBRT
volume, lymph node involvement and location, performance at a dose of 6.0 – 7.0 Gy for each fraction once or twice a week,
status, and type of treatment [8]. However, the prognosis of NECC with a median total dose of 28.0 Gy (range, 21.0 – 35.0 Gy).
patients treated with radical radiotherapy (RT) is unknown. Palliative RT included EBRT with or without brachytherapy.
Immune checkpoint inhibitors are a promising therapeutic
strategy for locally advanced cervical cancer (LACC) [9]. 2.3.2. Chemotherapy
A clinical trial found that ipilimumab combined with nivolumab Patients with no contraindications to platinum received
achieved satisfactory results in three patients with recurrent chemotherapy. Therapies included CCRT with etoposide-
NECC, including two with positive PD-L1 expression [10]. PD- platinum (EP) or paclitaxel-platinum (TP), followed by adjuvant
L1 expression in solid tumors correlates with prognosis. For chemotherapy with EP or TP. In addition, a few patients were
instance, PD-L1 expression is a good prognostic biomarker in treated with chemoradiotherapy involving a single platinum
human papillomavirus (HPV)-associated head and neck cancer. agent concurrent radiotherapy (CRT) followed by adjuvant
Conversely, PD-L1 expression is associated with poor prognosis chemotherapy with EP or TP.
in patients with renal cancer [11-13].
This study assessed the efficacy of radiation therapy for NECC, 2.3.3. Observation and follow-up
prognostic factors for NECC, and the relationship between PD-L1 The patients were followed up every 3 months for the first
expression and patient survival.
2 years, every 6 months for the next 3 years, and every 12 months
th
2. Methods after the 5 year. A physical examination, Papanicolaou smear,
and routine blood tests were performed during the follow-up.
2.1. Patients Radiographic examinations were performed if disease recurrence
The study included patients with histologically confirmed was suspected. Patient survival with or without recurrence or
NECC who received RT with or without chemotherapy at our metastasis was measured.
cancer center between January 2009 and December 2020. Patients 2.4. Statistical analysis
gave written informed consent before therapy. The diagnosis
was based on the morphological and immunohistochemical Statistical analysis was performed using the Statistical Package
characteristics of tumors. The inclusion criteria were patients with for the Social Sciences (SPSS) version 20.0 (SPSS Inc., Chicago,
no history of previous treatment or malignancies, patients who IL). Median overall survival (OS) and median progression-free
completed a treatment course, patients with a follow-up of at least survival (PFS) were estimated using the Kaplan–Meier method
3 months, and patients whose imaging data allowed tumor staging and compared between groups using the log-rank test. Prognostic
based on the 2018 International Federation of Gynecology and factors were analyzed by Cox regression analysis. P < 0.05 were
Obstetrics (FIGO) cervical cancer staging system. considered statistically significant.
DOI: http://dx.doi.org/10.18053/jctres.09.202304.23-00067