We conducted a retrospective analysis of data from 60 patients with cervical cancer who underwent definitive concurrent chemoradiotherapy at the researchers’ hospital from October 2021 to October 2024. Inclusion criteria: (1) Patients with cervical cancer staged as IB3, IIA2, and IIB-IVA according to FIGO 2018, who were jointly examined by two attending Gynecologist physicians; (2) All pathologically confirmed to have squamous cell carcinoma, with differentiation grades of G2, G3, or G2 - 3; (3) Treatment plan consists of concurrent chemoradiotherapy plus brachytherapy with or without adjuvant chemotherapy; (4) Prior to radiotherapy, white blood cell count (WBC) > 4.0 × 10⁹/L, and absolute neutrophil count (ANC) > 2.0 × 10⁹/L; (5) Age between 18 and 70 years old, ECOG performance status ≤ 2; (6) Patients who have not received prior chemotherapy/surgery/targeted therapy, with no history of previous malignant tumors, and no severe hematological, immune system, or other systemic diseases; (7) Complete and traceable imaging data.

A total of 60 patients were enrolled based on the inclusion criteria and divided into two groups according to whether they received regular subcutaneous injections of PEG-rhG-CSF during treatment: the PEG-rhG-CSF group (30 patients) received 6 mg of PEG-rhG-CSF via subcutaneous injection every 21 days, while the non-PEG-rhG-CSF group (30 patients) received subcutaneous injections of rhG-CSF only when a decrease in WBC or ANC was observed during treatment.

During radical radiotherapy, external-beam irradiation is delivered using intensity-modulated radiation therapy (IMRT) at a total dose of 45 Gy in 25 fractions of 1.8 Gy each. Positive nodal regions receive an additional boost to 50 Gy. Patients with parametrial involvement or pelvic sidewall invasion receive a parametrial boost of 10 – 12 Gy administered in 5 – 6 fractions of 2.0 Gy each. Intracavitary brachytherapy is generally initiated after approximately 20 fractions of external-beam radiotherapy (weeks 4 – 5), when substantial tumor regression and restoration of pelvic anatomy facilitate applicator insertion and reduce bleeding risk. During external-beam therapy, one 6-Gy fraction is delivered weekly (with EBRT omitted on that day). After completion of EBRT, the frequency of brachytherapy is increased to twice weekly. A total of five 6-Gy fractions are administered using an intrauterine tandem applicator, with interstitial techniques utilized when necessary. Pelvic MRI and gynecological examinations are subsequently performed to assess residual lesions. If active disease persists, an extra application of brachytherapy dose of 3 – 6 Gy may be administered within the tolerance of critical organs, ensuring the entire treatment course is completed within 8 weeks. The therapeutic goal is to achieve an equivalent dose in 2-Gy fractions (EQD₂) of 85 – 92 Gy to 90% of the high-risk clinical target volume (HRCTV D90).

Target volumes and organs at risk (OARs) were precisely delineated using CT-based multi-modal image fusion: the HR-CTV encompassed primary lesions and positive lymph nodes, while the IR-CTV covered potential areas of microscopic spread. OARs included the bladder, rectum, small bowel, and bone marrow cavity, all with predefined dose constraints. Dose-volume histograms (DVH) of the bone marrow cavity were utilized to assess the risks of myelosuppression, aiming to achieve an optimal balance between tumor control and bone marrow protection.

During radiation therapy, cisplatin at a dose of 40 mg/m² is administered as single-agent concurrent chemotherapy for 4 to 6 cycles (13, 16). Four weeks after the completion of radiotherapy, a re-evaluation is conducted with imaging studies, either an enhanced abdominal CT or an enhanced pelvic MRI, to determine whether to administer adjuvant chemotherapy. If there is still active disease present, a chemotherapy regimen combining cisplatin with paclitaxel will be given for 3 to 4 cycles every 21 days.

The 60 patients were divided into two groups based on whether they received regular subcutaneous injections of PEG-rhG-CSF during treatment. Among them, 30 patients were administered a single 6 mg subcutaneous dose of PEG-rhG-CSF within 24 to 48 hours before the first radiotherapy session, with subsequent doses repeated every 21 days thereafter (36). For patients who experienced bone pain or muscle pain, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen sustained-release capsules or loxoprofen sodium tablets, were administered for 3 to 5 days during treatment (10). A complete blood count was performed every Friday, and all treatment-emergent adverse events were recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) (37). The threshold for supplemental rhG-CSF administration in this study was determined based on our institutional laboratory reference ranges and clinical experience, taking into full consideration patients’ underlying conditions, the risk of myelosuppression during radiotherapy, and the high requirement for uninterrupted treatment. Compared with some guideline recommendations, this threshold is more stringent and was adopted to maximize patient safety and to ensure the smooth progression of radiotherapy. If the WBC count was below 3.5 × 10⁹/L or the ANC was below 1.8 × 10⁹/L, rhG-CSF was supplemented at a dose of 5 μg/kg/day until the WBC count exceeded 3.5 × 10⁹/L and the ANC exceeded 1.8 × 10⁹/L. In the non-PEG-rhG-CSF group, 30 patients also underwent weekly complete blood count checks every Friday. If either the WBC or ANC fell below these thresholds during treatment, subcutaneous rhG-CSF was administered immediately as an intervention.

The primary endpoints include the radiotherapy completion rate within 8 weeks, the incidence of grade 3/4 neutropenia, and the incidence of FN. The secondary endpoints include the time of onset of neutropenia and treatment safety. Additionally, routine blood tests are conducted weekly during radiotherapy to evaluate WBC count, ANC, hemoglobin (HB) levels, and platelet (PLT) counts, with comparative analysis performed. Failure to complete radiotherapy within 8 weeks is defined as a delay, and treatment will be paused in the event of grade 3/4 toxicity.

Data analysis was conducted using GraphPad Prism version 10 software. If the data follows a normal distribution, a t-test was used to analyze the measured data, which is expressed as the mean ± standard deviation. For categorical data, Chi-square or Fisher’s exact test was used, and the data is presented as percentages. A p-value of < 0.05 indicates that the difference is statistically significant.

The baseline characteristics of 60 patients were analyzed, and a summary of their background is presented in Table 1 . Based on whether they received PEG-rhG-CSF during treatment, the patients were divided into two groups: the PEG-rhG-CSF group and the non-PEG-rhG-CSF group. The average ages of the PEG-rhG-CSF and non-PEG-rhG-CSF groups were 54.67 ± 1.39 years and 54.30 ± 1.57 years, respectively, with BMI values distributed as 24.36 ± 3.78 and 24.15 ± 3.06. There were no statistically significant differences between the two groups. The pathological types were all squamous cell carcinoma, with differentiation grades of G2, G3, or G2 - 3, and the differences between the two groups were not statistically significant (P = 0.865). According to the FIGO staging, the PEG-rhG-CSF group included 2 cases of stage IB3 and IIA2, 10 cases of stage IIB, 9 cases of stage IIIA+IIIB, and 9 cases of stage IIIC. The non-PEG-rhG-CSF group comprised 3 cases of stage IB3 and IIA2, 7 cases of stage IIB, 8 cases of stage IIIA+IIIB, and 12 cases of stage IIIC. There was no statistically significant difference in staging between the two groups (P = 0.809). In summary, there were no significant differences in baseline characteristics between the two groups. Furthermore, before treatment, there were no statistically significant differences in the baseline levels of WBC and ANC between the two groups, as shown in Figure 1 .

The equivalent biological dose (EQD2) delivered to the treatment targets was 89.25 ± 2.56 Gy in the PEG-rhG-CSF group and 88.88 ± 2.39 Gy in the non-PEG-rhG-CSF group, with no statistically significant difference between the two groups (P = 0.062) ( Table 2 ). However, in terms of overall radiotherapy duration, the PEG-rhG-CSF group completed treatment in an average of 7.85 ± 0.604 weeks, which was significantly shorter than the 8.86 ± 0.972 weeks observed in the non-PEG-rhG-CSF group ( Table 2 ). Furthermore, 83.33% of patients in the PEG-rhG-CSF group were able to complete radiotherapy within 8 weeks, compared to only 51.72% in the non-PEG-rhG-CSF group—a statistically significant difference (P < 0.001) ( Figure 2A ). These findings indicate that the use of PEG-rhG-CSF facilitates timely completion of radiotherapy and reduces the risk of treatment delays. Regarding hematological toxicity, we performed a detailed analysis of hematologic recovery following supportive care. For patients with grade 1 – 2 myelosuppression, leukocyte-elevating therapies generally resulted in blood count recovery within 3 – 5 days. For grade 3 – 4 myelosuppression, radiotherapy was typically suspended and supportive measures were intensified, with most patients experiencing hematologic recovery sufficient to resume radiotherapy within 3 – 5 days. However, in the non-PEG-rhG-CSF group, one patient developed grade 4 myelosuppression that did not resolve to the required threshold for radiotherapy, even after active intervention, ultimately leading to discontinuation of treatment. In addition, the proportion of patients requiring supplementary rhG-CSF during treatment was 26.67% in the PEG-rhG-CSF group, whereas 83.33% in the non-PEG-rhG-CSF group required additional rhG-CSF administration ( Table 2 ). There was no significant difference in the number of patients who completed the extra application of brachytherapy between the PEG-rhG-CSF (n=26) and non-PEG-rhG-CSF (n=23) groups (P > 0.05) ( Table 2 ). Collectively, these results demonstrate that PEG-rhG-CSF not only reduces the incidence of severe myelosuppression but also decreases the need for remedial leukocyte-elevating therapy, thereby helping to maintain the continuity and completion rate of radiotherapy.

The incidence of grade 3/4 ANC reductions in the PEG-rhG-CSF group was 5 cases (16.67%), compared to 17 cases (56.67%) in the non-PEG-rhG-CSF group, which was significantly lower than that of the non-PEG-rhG-CSF group (P = 0.0028) ( Figure 3A ). Similarly, there were no cases of FN in the PEG-rhG-CSF group (0%), while in the non-PEG-rhG-CSF group, six cases of FN were observed—five in week 5 and one in week 8—yielding an incidence of 20%, which was significantly higher than that in the PEG-rhG-CSF group (P = 0.0237) ( Figure 3B ).

According to the World Health Organization (WHO) standards, chemotherapy-induced bone marrow suppression is classified into grades 0 to IV to assess acute and subacute toxic reactions (38). The analysis of hematological toxicity is shown in Figures 2B and 4 . During the treatment period, in terms of hematological toxicity, the time to the initial decrease in WBC was 4.93 ± 0.22 weeks in the PEG-rhG-CSF group, while it was 4.07 ± 0.22 weeks in the non-PEG-rhG-CSF group ( Figure 2B ). The difference was statistically significant (P < 0.05). Figure 4 . Analyzing from the lowest values of WBC and ANC, the mean ± SD WBC count in the PEG-rhG-CSF group was 2.46 ± 0.13 × 10⁹/L, while in the non-PEG-rhG-CSF group it was 2.04 ± 0.13 × 10⁹/L. The difference between the two groups was statistically significant (P = 0.025). Similarly, the mean ± SD ANC in the PEG-rhG-CSF group was 1.44 ± 0.11 × 10⁹/L, while in the non-PEG-rhG-CSF group it was 1.04 ± 0.08 × 10⁹/L. The difference between the two groups was statistically significant (P = 0.004). And also, the mean ± SD HB and PLT was no statistically significant.

During the treatment period, non-hematologic adverse events primarily consisted of gastrointestinal reactions. Nausea was most commonly observed during the first week of radiotherapy; for most patients, the severity was mild and did not interfere with the continuation of radiotherapy. Prophylactic antiemetic medications were administered during chemotherapy. Diarrhea and increased bowel movements occurred more frequently during weeks 2 to 3. All patients received oral probiotics starting from the initiation of radiotherapy. When gastrointestinal symptoms occurred, symptomatic antidiarrheal medications and adjunctive traditional Chinese medicine therapies were administered promptly, effectively controlling symptoms without any cases leading to treatment interruption or delay. No significant urogenital adverse events affecting the treatment were observed during radiotherapy. Bone pain related to PEG-rhG-CSF could be effectively managed with nonsteroidal anti-inflammatory drugs (NSAIDs). There was no statistically significant difference in the incidence of non-hematologic adverse events between the two groups.