放化疗联合区域热疗治疗老年宫颈癌患者有效性及安全性分析

Efficacy and safety of chemoradiotherapy combined with regional hyperthermia for elderly patients with cervical cancer

摘要

目的：探讨老年宫颈癌患者使用放化疗联合区域热疗治疗的效果和安全性。方法：选取2018年2月至2021年2月在西安交通大学第一附属医院就诊治疗的154例老年宫颈癌患者，根据患者选择治疗方法分为联合治疗组（n=77，放化疗联合区域热疗）和放化疗治疗组（n=77，放化疗治疗）。比较两组患者的近期治疗情况（肿瘤缓解率）、血清肿瘤标志物水平［癌胚抗原（CEA)、恶性肿瘤特异生长因子（SCC）、糖抗原125（CA125）］、疼痛缓解率、不良反应发生情况和远期治疗效果。结果：联合治疗组近期肿瘤缓解率高于放化疗治疗组（P<0.05）；治疗后联合治疗组CEA、SCC和CA125水平均低于放化疗治疗组（P<0.05）；联合治疗组疼痛缓解率高于放化疗治疗组［86.54%（45/52）vs 60.00%（30/50）,χ²=9.224,P=0.002）；联合治疗组与放化疗治疗组不良反应发生无显著差异（P>0.05）；联合治疗组无进展生存期（PFS）为6~36月，无进展生存率为23.38%，放化疗治疗组PFS为7~36月，无进展生存率为10.39%，Kaplan-Meier生存分析，两组患者的无进展生存分布差异有统计学意义（Log-rank 检验χ²=13.512,P<0.001）；联合治疗组总生存期（OS）为6~36 月，总生存率为49.35%，放化疗治疗组OS为7~36月，总生存率为25.97%。Kaplan-Meier生存分析显示两组患者的生存期分布差异有统计学意义（Log-rank检验χ²=21.541,P<0.001）。结论：老年宫颈癌患者使用放化疗联合区域热疗可有效提升肿瘤治疗效果，降低CEA、SCC、CA125等血清肿瘤标志物水平，缓解患者疼痛情况，提升患者PFS和OS。

Abstract

Objective To investigate the efficacy and safety of chemoradiotherapy combined with regional hyperthermia in the treatment of elderly patients with cervical cancer. Methods A total of 154 elderly patients with cervical cancer treated at the First Affiliated Hospital of Xi'an Jiaotong University between February 2018 and February 2021 were enrolled and divided into a combination group (n=77, chemoradiotherapy combined with regional hyperthermia) and a chemoradiotherapy group (n=77, chemoradiotherapy). Short-term therapeutic efficacy (tumor remission rate), serum tumor markers (CEA, SCC, CA125), pain relief rate, incidence of adverse events, and long-term therapeutic outcomes were compared between the two groups. Results Compared with the chemoradiotherapy group, the combination group had a higher tumor remission rate (P<0.05), lower post-treatment serum CEA, SCC, and CA125 levels (P<0.05), and a higher pain relief rate [86.54% (45/52)vs 60.00% (30/50),χ ²=9.224,P=0.002]. No significant differences were observed in the adverse events between the two groups (P>0.05). The progression-free survival (PFS) of the combination group ranged from 6 to 36 months, with a PFS rate of 23.38%, whereas the PFS of the chemoradiotherapy group was 7 to 36 months, with a PFS rate of 10.39%. Kaplan-Meier survival analysis revealed a statistically significant difference in PFS between the two groups (Log-rank testχ ²=13.512,P<0.001). The overall survival (OS) of the combination group was 6 to 36 months, with an OS rate of 49.35%, whereas the OS of the chemoradiotherapy group was 7 to 36 months, with an OS rate of 25.97%. Kaplan-Meier survival analysis demonstrated a statistically significant difference in OS between the two groups (Log-rank testχ ²=21.541,P<0.001). Conclusion The application of chemoradiotherapy combined with regional hyperthermia in elderly patients with cervical cancer can effectively enhance anti-tumor efficacy, reduce serum levels of tumor markers such as CEA, SCC and CA125, relieve the pain, and prolong PFS and OS.

关键词

宫颈癌 / 老年患者 / 放化疗 / 区域热疗 / 安全性

Key words

cervical cancer / elderly patient / chemoradiotherapy / regional hyperthermia / safety

参考文献

[1] Minciuna CE, Bitere O, Lacatus M, et al. Is there a role for minimally invasive surgery in cervical cancer treatment: carry on, discard, or modify? A literature review and case series presentation[J]. Chirurgia (Bucur), 2022, 117(3): 258-265.

[2] Schaafsma M, Plante M, Mom CH, et al. Is less more in the surgical treatment of early—stage cervical cancer?[J]. Curr Opin Oncol, 2022, 34(5): 473-489.

[3] Chargari C, Peignaux K, Escande A, et al. Radiotherapy of cervical cancer[J]. Cancer Radiother, 2022, 26(1/2): 298-308.

[4] Monk BJ, Toita T, Wu XH, et al. Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double—blind, phase 3 trial[J]. Lancet Oncol, 2023, 24(12): 1334-1348.

[5] VilasBoas—Ribeiro I, Franckena M, van Rhoon GC, et al. Using MRI to measure position and anatomy changes and assess their impact on the accuracy of hyperthermia treatment planning for cervical cancer[J]. Int J Hyperthermia, 2023, 40(1): 2151648.

[6] Bala VM, Lampropoulou DI, Grammatikaki S, et al. Nanoparticle—Mediated hyperthermia and cytotoxicity mechanisms in cancer[J]. Int J Mol Sci, 2023, 25(1): 296.

[7] Le Guevelou J, Chirila ME, Achard V, et al. Combined hyperthermia and radiotherapy for prostate cancer: a systematic review[J]. Int J Hyperthermia, 2022, 39(1): 547-556.

[8] Valizadeh A, Asghari S, Abbaspoor S, et al. Implantable smart hyperthermia nanofibers for cancer therapy: challenges and opportunities[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2023, 15(6): e1909.

[9] Grimaldi S, Terroir M, Caramella C . Advances in oncological treatment: limitations of RECIST 1.1 criteria[J]. Q J Nucl Med Mol Imaging, 2018, 62(2): 129-139.

[10] Cox JD, Fu KK, Pajak TF, et al. Radiation Therapy Oncology Group (RTOG) trials for head and neck cancer[J]. Rays, 2000, 25(3): 321-323.

[11] Toita T, Wada K, Sutani S, et al. Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image—guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose—response analyses for local control in the low—dose range[J]. Jpn J Clin Oncol, 2023, 53(6): 480-488.

[12] Revathidevi S, Murugan AK, Nakaoka H, et al. APOBEC: a molecular driver in cervical cancer pathogenesis[J]. Cancer Lett, 2021, 496: 104-116.

[13] Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high—risk, locally advanced cervical cancer (ENGOT—cx11/GOG—3047/KEYNOTE—A18): a randomised, double—blind, phase 3 clinical trial[J]. Lancet, 2024, 403(10434): 1341-1350.

[14] Yoshikawa N, Itoh Y, Matsukawa T, et al. Local hyperthermia with built—in endoscopy for radioresistant cervical cancer: a case series[J]. Nagoya J Med Sci, 2023, 85(3): 639-647.

[15] Yea JW, Park JW, Oh SA, et al. Chemoradiotherapy with hyperthermia versus chemoradiotherapy alone in locally advanced cervical cancer: a systematic review and meta—analysis [J]. Int J Hyperthermia, 2021, 38(1): 1333-1340.

[16] Wang Y, Hong W, Che SM, et al. Outcomes for hyperthermia combined with concurrent radiochemotherapy for patients with cervical cancer[J]. Int J Radiat Oncol Biol Phys, 2020, 107(3): 499-511.

[17] Jiang P, Wei SH, Bai Y, et al. The efficacy of volumetric modulated arc therapy combined with chemotherapy, brachytherapy, and local hyperthermia on patients with locally advanced cervical cancer: a retrospective study[J]. Technol Cancer Res Treat, 2023, 22: 15330338231185013.

[18] Ijff M, Crezee J, Oei AL, et al. The role of hyperthermia in the treatment of locally advanced cervical cancer: a comprehensive review[J]. Int J Gynecol Cancer, 2022, 32(3): 288-296.

[19] Herrera TD, Ödén J, Lorenzo Polo A, et al. Thermoradiotherapy optimization strategies accounting for hyperthermia delivery uncertainties[J]. Int J Radiat Oncol Biol Phys, 2024, 120(5): 1435-1447.

[20] Servayge J, Olthof EP, Mom CH, et al. Survival of women with advanced stage cervical cancer: neo—adjuvant chemotherapy followed by radiotherapy and hyperthermia versus chemoradiotherapy [J]. Cancers (Basel), 2024, 16(3): 635.

[21] IJff M, Mei XE, Scutigliani EM, et al. Addition of PARP1—inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model [J]. Int J Hyperthermia, 2025, 42(1): 2450514.

[22] De Tommasi F, Massaroni C, Grasso RF, et al. Temperature monitoring in hyperthermia treatments of bone tumors: state—of—the—art and future challenges[J]. Sensors (Basel), 2021, 21(16): 5470.

[23] Xie X, Gao W, Hao JN, et al. Self—synergistic effect of Prussian blue nanoparticles for cancer therapy: driving photothermal therapy and reducing hyperthermia—induced side effects[J]. J Nanobiotechnology, 2021, 19(1): 126.

[24] Kok HP, Herrera TD, Crezee J . The relevance of high temperatures and short time intervals between radiation therapy and hyperthermia: insights in terms of predicted equivalent enhanced radiation dose[J]. Int J Radiat Oncol Biol Phys, 2023, 115(4): 994-1003.

[25] Ribeiro TP, Moreira JA, Monteiro FJ, et al. Nanomaterials in cancer: reviewing the combination of hyperthermia and triggered chemotherapy[J]. J Control Release, 2022, 347: 89-103.

基金资助

陕西省科技计划项目(2025JC-YBMS-1065)