Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy: A randomized non-inferiority study

Miriam Cremer, Karla Alfaro, Jillian Garai, Manuel Salinas, Mauricio Maza, Alberto Zevallos, Luis Taxa, Ana C. Diaz, Philip E. Castle, Todd A. Alonzo, Rachel Masch, Montserrat Soler, Gabriel Conzuelo-Rodriguez, Julia C. Gage, Juan C. Felix

Research output: Contribution to journalArticle

Abstract

Introduction Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. Methods We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO 2) cryotherapy (referent), single-freeze CO 2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90% confidence interval (90% CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). Results A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO 2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO 2 = 0.4 mm (90% CI-0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90% CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90% CI-0.2 to 1.2 mm), and thermoablation = 2.6 mm (90% CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO 2 cryotherapy), 1.8±0.8 (single-freeze CO 2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). Discussion Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.

Original languageEnglish (US)
Pages (from-to)851-856
Number of pages6
JournalInternational Journal of Gynecological Cancer
Volume29
Issue number5
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

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Cryotherapy
Uterine Cervical Neoplasms
Carbon Monoxide
Gases
Necrosis
Confidence Intervals
Pain
Hysterectomy
Therapeutics
Carbon Dioxide
Randomized Controlled Trials
Pathology

Keywords

  • cervix uteri
  • genitalia, female
  • gynecology

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy : A randomized non-inferiority study. / Cremer, Miriam; Alfaro, Karla; Garai, Jillian; Salinas, Manuel; Maza, Mauricio; Zevallos, Alberto; Taxa, Luis; Diaz, Ana C.; Castle, Philip E.; Alonzo, Todd A.; Masch, Rachel; Soler, Montserrat; Conzuelo-Rodriguez, Gabriel; Gage, Julia C.; Felix, Juan C.

In: International Journal of Gynecological Cancer, Vol. 29, No. 5, 01.06.2019, p. 851-856.

Research output: Contribution to journalArticle

Cremer, M, Alfaro, K, Garai, J, Salinas, M, Maza, M, Zevallos, A, Taxa, L, Diaz, AC, Castle, PE, Alonzo, TA, Masch, R, Soler, M, Conzuelo-Rodriguez, G, Gage, JC & Felix, JC 2019, 'Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy: A randomized non-inferiority study', International Journal of Gynecological Cancer, vol. 29, no. 5, pp. 851-856. https://doi.org/10.1136/ijgc-2018-000148
Cremer, Miriam ; Alfaro, Karla ; Garai, Jillian ; Salinas, Manuel ; Maza, Mauricio ; Zevallos, Alberto ; Taxa, Luis ; Diaz, Ana C. ; Castle, Philip E. ; Alonzo, Todd A. ; Masch, Rachel ; Soler, Montserrat ; Conzuelo-Rodriguez, Gabriel ; Gage, Julia C. ; Felix, Juan C. / Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy : A randomized non-inferiority study. In: International Journal of Gynecological Cancer. 2019 ; Vol. 29, No. 5. pp. 851-856.
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abstract = "Introduction Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. Methods We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO 2) cryotherapy (referent), single-freeze CO 2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90{\%} confidence interval (90{\%} CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). Results A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO 2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO 2 = 0.4 mm (90{\%} CI-0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90{\%} CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90{\%} CI-0.2 to 1.2 mm), and thermoablation = 2.6 mm (90{\%} CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO 2 cryotherapy), 1.8±0.8 (single-freeze CO 2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). Discussion Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.",
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T1 - Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy

T2 - A randomized non-inferiority study

AU - Cremer, Miriam

AU - Alfaro, Karla

AU - Garai, Jillian

AU - Salinas, Manuel

AU - Maza, Mauricio

AU - Zevallos, Alberto

AU - Taxa, Luis

AU - Diaz, Ana C.

AU - Castle, Philip E.

AU - Alonzo, Todd A.

AU - Masch, Rachel

AU - Soler, Montserrat

AU - Conzuelo-Rodriguez, Gabriel

AU - Gage, Julia C.

AU - Felix, Juan C.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Introduction Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. Methods We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO 2) cryotherapy (referent), single-freeze CO 2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90% confidence interval (90% CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). Results A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO 2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO 2 = 0.4 mm (90% CI-0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90% CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90% CI-0.2 to 1.2 mm), and thermoablation = 2.6 mm (90% CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO 2 cryotherapy), 1.8±0.8 (single-freeze CO 2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). Discussion Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.

AB - Introduction Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. Methods We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO 2) cryotherapy (referent), single-freeze CO 2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90% confidence interval (90% CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). Results A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO 2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO 2 = 0.4 mm (90% CI-0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90% CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90% CI-0.2 to 1.2 mm), and thermoablation = 2.6 mm (90% CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO 2 cryotherapy), 1.8±0.8 (single-freeze CO 2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). Discussion Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.

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KW - genitalia, female

KW - gynecology

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