Radiation-induced lymphopenia and the survival of women with cervical cancer: a meta-analysis

Figures & data

Figure 1. A summary of the literature search and study identification process.

Table 1. Study characteristics.

Study	Country	Design	Number of patients	Mean age (years)	FIGO stage	Histology type	Treatment modality	Definition of lymphopenia (ALC)/ Data collection time	No. of patients with lymphopenia	Median follow-up durations (months)	Outcomes reported	Variables adjusted/matched
Cho et al. (2016)	Korea	RC	124	57	I-III	SCC 96%, adeno subtype 4%	Cisplatin-based CCRT and HDR BT	Grade 4 (min ALC < 200/ul), during treatment	20	63	PFS	Age, histology type, FIGO stage, Hb, baseline ALC, overall radiation treatment time and dose
Wu et al. (2016)	USA	RC	71	49	I-IV	SCC 83%, other 17%	Cisplatin-based CCRT with/without HDR BT	Grade 3-4 (min ALC < 500/ul), post treatment	25	25	PFS, OS	Age, smoking, FIGO stage, and baseline ALC
Onal et al. (2018)	Turkey	RC	95	56	I-IV	SCC 100%	CCRT and HDR BT	Grade 3-4 (min ALC < 500/ul), post treatment	58	68	PFS, OS	Age, tumour size, FIGO stage, baseline ALC, and treatment response
Holub et al. (2020)	France	RC	139	51	I-IV	SCC 76.3%, ADC 15.1%, other 5.7%	CCRT or RT with/ without HDR BT	Any lymphopenia (<1000/ul), post treatment	84	44	OS	Age, histology type, and FIGO stage
Taguchi et al. (2020)	Japan	RC	168	64	I-IV	SCC 90%, other 10%	CCRT or RT with HDR-BT	Severe lymphopenia (<600/ul), post treatment	42	44	PFS, OS	Age, histology type, BMI, FIGO stage, and baseline ALC
Yang et al. (2022)	China	RC	104	53	I-IV	SCC 97%, other 3%	Definitive RT	Grade 3-4 (min ALC < 500/ul), during treatment	62	26	PFS, OS	Age, PS, FIGO stage, chemotherapy, total radiation dose, and baseline ALC
Xu et al. (2022)	China	RC	130	53	I-IV	SCC 100%	CCRT or RT with/ without HDR BT	Grade 4 (min ALC < 200/ul), during treatment	43	26	PFS, OS	Age, ECOG, FIGO stage, BMI, RT technology, chemotherapy, and ALC at baseline
Shi et al. (2022)	USA	RC	121	45	I-III	SCC 83.5%, ADC 11.6 %, other 4.9%	CCRT and HDR BT	Grade 4 (min ALC < 200/ul), during treatment	44	34	PFS, OS	Age, FIGO stage, chemotherapy, Hb, length of radiation treatment, and baseline ALC

FIGO: International Federation of Gynaecology and Obstetrics; ALC: absolute lymphocyte count; RC: retrospective cohort; SCC: squamous cell carcinoma; ACC: adenocarcinoma; CCRT: concurrent chemoradiotherapy; RT: radiotherapy; HDR BT: high-dose intracavitary brachytherapy; PFS: progression-free survival; OS: overall survival; Hb, haemoglobin; BMI: body mass index; PS: performance status; ECOG; Eastern Cooperative Oncology Group.

Table 2. Study quality evaluation via the Newcastle-Ottawa Scale.

Study	Representativeness of the exposed cohort	Selection of the non- exposed cohort	Ascertainment of exposure	Outcome not present at baseline	Control for age	Control for other confounding factors	Assessment of outcome	Enough long follow-up duration	Adequacy of follow-up of cohorts	Total
Cho et al. (2016)	0	1	1	1	1	1	1	1	1	8
Wu et al. (2016)	0	1	1	1	1	0	1	1	1	7
Onal et al. (2018)	0	1	1	1	1	0	1	1	1	7
Holub et al. (2020)	1	1	1	1	1	0	1	1	1	8
Taguchi et al. (2020)	0	1	1	1	1	0	1	1	1	7
Yang et al. (2022)	0	1	1	1	1	1	1	1	1	8
Xu et al. (2022)	0	1	1	1	1	0	1	1	1	7
Shi et al. (2022)	0	1	1	1	1	1	1	1	1	8

Figure 2. Forest plots for the meta-analyses regarding the association between RIL and OS in women with CC. A, overall meta-analysis; and B, subgroup analysis according to grade of RIL.

Figure 3. Forest plots for the subgroup-analyses regarding the association between RIL and OS in women with CC. A, subgroup analysis according to the timing of RIL diagnosis; and B, subgroup analysis according to the study quality scores.

Figure 4. Forest plots for the meta-analyses regarding the association between RIL and PFS in women with CC. A, overall meta-analysis; and B, subgroup analysis according to grade of RIL.

Figure 5. Forest plots for the subgroup-analyses regarding the association between RIL and PFS in women with CC. A, subgroup analysis according to the timing of RIL diagnosis; and B, subgroup analysis according to the study quality scores.

Figure 6. Funnel plots for the publication bias underlying the meta-analyses; A, funnel plots for the meta-analysis of OS; and B, funnel plots for the meta-analysis of PFS.

Cho, O., et al., 2016. Prognostic value of severe lymphopenia during pelvic concurrent chemoradiotherapy in cervical cancer. Anticancer Research, 36 (7), 3541–3547.

 PubMed Web of Science ®Google Scholar

Wu, E.S., et al., 2016. Lymphopenia and its association with survival in patients with locally advanced cervical cancer. Gynecologic Oncology, 140 (1), 76–82.

 PubMed Web of Science ®Google Scholar

Onal, C., et al., 2018. The utility of pretreatment and posttreatment lymphopenia in cervical squamous cell carcinoma patients treated with definitive chemoradiotherapy. International Journal of Gynecological Cancer, 28 (8), 1553–1559.

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Holub, K., Vargas, A. and Biete, A., 2020. Radiation-induced lymphopenia: the main aspects to consider in immunotherapy trials for endometrial and cervical cancer patients. Clinical & Translational Oncology, 22 (11), 2040–2048.

 PubMed Web of Science ®Google Scholar

Taguchi, A., et al., 2020. Postradiotherapy persistent lymphopenia as a poor prognostic factor in patients with cervical cancer receiving radiotherapy: a single-center, retrospective study. International Journal of Clinical Oncology, 25 (5), 955–962.

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Yang, L., et al., 2022. Early onset of severe lymphopenia during definitive radiotherapy correlates with mean body dose and predicts poor survival in cervical cancer. Cancer Biomarkers: Section A of Disease Markers, 34 (1), 149–159.

 PubMed Web of Science ®Google Scholar

Xu, Z., et al., 2022. A machine learning model for grade 4 lymphopenia prediction during pelvic radiotherapy in patients with cervical cancer. Frontiers in Oncology., 12, 905222.

 PubMedGoogle Scholar

Shi, F., et al., 2022. Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer. Obstetrics & Gynecology Science, 65 (2), 176–187.

 PubMedGoogle Scholar

Data availability statement

All data used in this paper are from published articles.