Efficacy and Safety of Hyperthermia as Adjunctive Treatment for Cervical Cancer: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 HUANGBi-fen ¹ ,  ZHENGJian-qing ² , LIWen-yuan ² , LVRan ² , CHENJian-wu ²

1. Department of Obstetrics and Gynecology, Affiliated People's Hospital of Quanzhou Medical College, Quanzhou 362000, China;
2. Department of Radiation Oncology, Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China;

Corresponding author：

ZHENGJian-qing, Email: 408933537@qq.com

Keywords：

Cervical cancer; Chemotherapy; Radiotherapy; Hyperthermia; Combined treatment; Survival; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20150035

Video：

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Objective To systematically review the efficacy and safety of hyperthermia in combination with radiation, chemotherapy or both for middle/advanced cervical cancer patients (LACC). Methods The databases such as PubMed, The Cochrane Library (Issue 6, 2013), CNKI, WanFang Data and VIP were searched from inception to July 1^st, 2013 for randomized controlled trials (RCTs) that investigated hyperthermia in combination with radiation, chemotherapy or both for LACC for cervical cancer at middle/advanced stage. Two reviewers screened literature according to the inclusion and exclusion criteria, extracted data, and evaluated methodological quality of included studies. Meta-analysis was then performed using RevMan 5.2.6 software. Results Six RCTs were included. A descriptive analysis was conducted due to significant heterogeneities among the results of studies. Out of 6 studies, the results of 4 studies showed that hyperthermia increased complete remission rate; the results of 3 studies reported objective effectiveness; while only one study showed statistical significance. Overall survival was reported in all studies, while only one study showed that hyperthermia significantly improved overall survival. Only one study reported 3-year progression-free survival with statistical significance. Two studies reported disease-free survival but only one showed statistical significance. Only two studies reported adverse events, and the data in one study showed acute toxicities of Grade 2-3 were higher for hyperthermia with unclear long-term reaction. Conclusion Current evidence is insufficient to confirm the efficacy and safety of hyperthermia for cervical cancer, and large-scale well-designed RCTs are further needed to verify the efficacy and safety of hyperthermia in the combined treatment of cervical cancer.

Citation： HUANGBi-fen, ZHENGJian-qing, LIWen-yuan, LVRan, CHENJian-wu. Efficacy and Safety of Hyperthermia as Adjunctive Treatment for Cervical Cancer: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2015, 15(2): 201-205. doi: 10.7507/1672-2531.20150035 Copy

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2.	Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage ⅡB-IVA carcinoma of the cervix with negative para-aortic lymph nodes:a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol, 1999, 17(5):1339-1348.
3.	Franckena M, vander Zee J. Use of combined radiation and hyperthermia for gynecological cancer. Curr Opin Obstet Gynecol, 2010, 22(1):9-14.
4.	Hehr T, Wust P, Bamberg M, et al. Current and potential role of thermoradiotherapy for solid tumours. Onkologie, 2003, 26(3):295-302.
5.	Sharma S, Singhal S, Sandhu AP, et al. Local thermo-radiotherapy in carcinoma cervix:improved local control versus increased incidence of distant metastasis. Asia Oceania J Obstet Gynaecol, 1991, 17(1):5-12.
6.	vander Zee J, Gonzalez GD. The Dutch Deep Hyperthermia Trial:results in cervical cancer. Int J Hyperthermia, 2002, 18(1):1-12.
7.	Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage ⅢB cervical carcinoma. Int J Hyperthermia, 2009, 25(5):338-343.
8.	Vasanthan A, Mitsumori M, Park JH, et al. Regional hyperthermia combined with radiotherapy for uterine cervical cancers:a multiinstitutional prospective randomized trial of the international atomic energy agency. Int J Radiat Oncol Biol Phys, 2005, 61(1):145-153.
9.	陈宏伟, 范俊杰, 李明众, 等. 宫颈癌热放化随机分组治疗疗效. 中国肿瘤临床, 2001, 28(9):35-37.
10.	方绳权, 张洁清, 高琨, 等. 深部热疗加同步放化疗治疗Ⅲb期宫颈癌临床价值. 中国实用妇科与产科杂志, 2008, 24(11):827-829.
11.	Franckena M, Stalpers LJ, Koper PC, et al. Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer:an update of the Dutch Deep Hyperthermia Trial. Int J Radiat Oncol Biol Phys, 2008, 70(4):1176-1182.
12.	Sharma S, Pate lF, Sandhu A, et al. A prospective randomized study of local hyperthermia as a supplement and radiosensitizer in the treatment of carcinoma of the cervix with radiotherapy. Endocurietherapy/Hyperth Oncol, 1989, 5:151-159.
13.	Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage ⅢB cervical carcinoma. Int J Hyperthermia, 2001, 17(2):97-105.
14.	陈宏伟, 范俊杰, 罗伟, 等. 宫颈癌热放化随机分组治疗. 中国肿瘤临床, 1997, 24(4):249-251.
15.	Trimble E, Gius D, Harlan LC. Impact of NCI announcement upon use of chemoradiation for women with cervical cancer. J Clin Oncol, 2007, 25:S283.
16.	Rojas-Espaillat LA, Rose PG. Management of locally advanced cervical cancer. Curr Opin Oncol, 2005, 17(5):485-492.
17.	Sagowski C, Jaehne M, Kehrl W, et al. Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in a case of recurrent carcinoma of the oral cavity. Eur Arch Otorhinolaryngol, 2002, 259(1):27-31.
18.	Hilger I, Rapp A, Greulich KO, et al. Assessment of DNA damage in target tumor cells after thermoablation in mice. Radiology, 2005, 237(2):500-506.
19.	Wust P, Hildebrandt B, Sreenivasa G, et al. Hyperthermia in combined treatment of cancer. Lancet Oncology, 2002, 3(8):487-497.
20.	Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol, 2002, 43(1):33-56.
21.	vander Zee J, González D, van Rhoon GC, et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours:a prospective, randomised, multicentre trial. Lancet, 2000, 355(9210):1119-1125.

1. Trimble T. Global strategies for cervical cancer control in the 21^st century. Gynecol Oncol, 2005, 99(3 Suppl 1):S245.
2. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage ⅡB-IVA carcinoma of the cervix with negative para-aortic lymph nodes:a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol, 1999, 17(5):1339-1348.
3. Franckena M, vander Zee J. Use of combined radiation and hyperthermia for gynecological cancer. Curr Opin Obstet Gynecol, 2010, 22(1):9-14.
4. Hehr T, Wust P, Bamberg M, et al. Current and potential role of thermoradiotherapy for solid tumours. Onkologie, 2003, 26(3):295-302.
5. Sharma S, Singhal S, Sandhu AP, et al. Local thermo-radiotherapy in carcinoma cervix:improved local control versus increased incidence of distant metastasis. Asia Oceania J Obstet Gynaecol, 1991, 17(1):5-12.
6. vander Zee J, Gonzalez GD. The Dutch Deep Hyperthermia Trial:results in cervical cancer. Int J Hyperthermia, 2002, 18(1):1-12.
7. Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage ⅢB cervical carcinoma. Int J Hyperthermia, 2009, 25(5):338-343.
8. Vasanthan A, Mitsumori M, Park JH, et al. Regional hyperthermia combined with radiotherapy for uterine cervical cancers:a multiinstitutional prospective randomized trial of the international atomic energy agency. Int J Radiat Oncol Biol Phys, 2005, 61(1):145-153.
9. 陈宏伟, 范俊杰, 李明众, 等. 宫颈癌热放化随机分组治疗疗效. 中国肿瘤临床, 2001, 28(9):35-37.
10. 方绳权, 张洁清, 高琨, 等. 深部热疗加同步放化疗治疗Ⅲb期宫颈癌临床价值. 中国实用妇科与产科杂志, 2008, 24(11):827-829.
11. Franckena M, Stalpers LJ, Koper PC, et al. Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer:an update of the Dutch Deep Hyperthermia Trial. Int J Radiat Oncol Biol Phys, 2008, 70(4):1176-1182.
12. Sharma S, Pate lF, Sandhu A, et al. A prospective randomized study of local hyperthermia as a supplement and radiosensitizer in the treatment of carcinoma of the cervix with radiotherapy. Endocurietherapy/Hyperth Oncol, 1989, 5:151-159.
13. Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage ⅢB cervical carcinoma. Int J Hyperthermia, 2001, 17(2):97-105.
14. 陈宏伟, 范俊杰, 罗伟, 等. 宫颈癌热放化随机分组治疗. 中国肿瘤临床, 1997, 24(4):249-251.
15. Trimble E, Gius D, Harlan LC. Impact of NCI announcement upon use of chemoradiation for women with cervical cancer. J Clin Oncol, 2007, 25:S283.
16. Rojas-Espaillat LA, Rose PG. Management of locally advanced cervical cancer. Curr Opin Oncol, 2005, 17(5):485-492.
17. Sagowski C, Jaehne M, Kehrl W, et al. Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in a case of recurrent carcinoma of the oral cavity. Eur Arch Otorhinolaryngol, 2002, 259(1):27-31.
18. Hilger I, Rapp A, Greulich KO, et al. Assessment of DNA damage in target tumor cells after thermoablation in mice. Radiology, 2005, 237(2):500-506.
19. Wust P, Hildebrandt B, Sreenivasa G, et al. Hyperthermia in combined treatment of cancer. Lancet Oncology, 2002, 3(8):487-497.
20. Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol, 2002, 43(1):33-56.
21. vander Zee J, González D, van Rhoon GC, et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours:a prospective, randomised, multicentre trial. Lancet, 2000, 355(9210):1119-1125.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Hyperthermia as Adjunctive Treatment for Cervical Cancer: A Systematic Review

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