Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: Clinical experience with and without chemotherapy

Brij M. Sood, Giridhar Gorla, Sajel Gupta, Madhur K. Garg, Shivaji Deore, Carolyn D. Runowicz, Abbie L. Fields, Gary L. Goldberg, Patrick S. Anderson, Bhadrasain Vikram

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. Methods: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m2/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. Results: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. Conclusions: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.

Original languageEnglish (US)
Pages (from-to)702-706
Number of pages5
JournalInternational Journal of Radiation Oncology Biology Physics
Volume53
Issue number3
DOIs
StatePublished - Jul 1 2002

Fingerprint

Brachytherapy
chemotherapy
Uterine Cervical Neoplasms
cancer
Drug Therapy
dosage
toxicity
grade
bladder
radiation therapy
Radiotherapy
fear
Urinary Bladder
metastasis
Cervix Uteri
Cisplatin
Fear
Dose Fractionation
Neoplasm Metastasis
Carcinoma

Keywords

  • Brachytherapy
  • Cervix cancer
  • Chemoradiotherapy
  • Fractionation
  • High dose rate

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Two fractions of high-dose-rate brachytherapy in the management of cervix cancer : Clinical experience with and without chemotherapy. / Sood, Brij M.; Gorla, Giridhar; Gupta, Sajel; Garg, Madhur K.; Deore, Shivaji; Runowicz, Carolyn D.; Fields, Abbie L.; Goldberg, Gary L.; Anderson, Patrick S.; Vikram, Bhadrasain.

In: International Journal of Radiation Oncology Biology Physics, Vol. 53, No. 3, 01.07.2002, p. 702-706.

Research output: Contribution to journalArticle

Sood, Brij M. ; Gorla, Giridhar ; Gupta, Sajel ; Garg, Madhur K. ; Deore, Shivaji ; Runowicz, Carolyn D. ; Fields, Abbie L. ; Goldberg, Gary L. ; Anderson, Patrick S. ; Vikram, Bhadrasain. / Two fractions of high-dose-rate brachytherapy in the management of cervix cancer : Clinical experience with and without chemotherapy. In: International Journal of Radiation Oncology Biology Physics. 2002 ; Vol. 53, No. 3. pp. 702-706.
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abstract = "Purpose: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. Methods: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88{\%}) and nonsquamous in 6 (12{\%}). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61{\%}) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50{\%}) and 9.4 Gy for 43 applications (44{\%}), and it varied from 7 to 11 Gy for the rest (6{\%}). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51{\%}) received concomitant chemotherapy (cisplatin 20 mg/m2/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. Results: The observed survival rates after 2, 3, and 5 years were 83{\%}, 78{\%}, and 78{\%}, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77{\%}; it was 88{\%} among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91{\%} of the patients in each group were free of distant metastases. Ten of the 49 patients (20{\%}) suffered Grade 3 acute toxicity; 11 (22{\%}) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4{\%}) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32{\%}) suffered Grade 3 and 12 (48{\%}) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5{\%}, with or without chemotherapy. Conclusions: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.",
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T1 - Two fractions of high-dose-rate brachytherapy in the management of cervix cancer

T2 - Clinical experience with and without chemotherapy

AU - Sood, Brij M.

AU - Gorla, Giridhar

AU - Gupta, Sajel

AU - Garg, Madhur K.

AU - Deore, Shivaji

AU - Runowicz, Carolyn D.

AU - Fields, Abbie L.

AU - Goldberg, Gary L.

AU - Anderson, Patrick S.

AU - Vikram, Bhadrasain

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N2 - Purpose: In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective. Methods: We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m2/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear. Results: The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy. Conclusions: Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.

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KW - Brachytherapy

KW - Cervix cancer

KW - Chemoradiotherapy

KW - Fractionation

KW - High dose rate

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