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Efficacy of high-dose brachytherapy for cervical cancer differs by dose

May Abdel-Wahab

High-dose brachytherapy delivered in four fractions of 7 Gy conferred a higher rate of 5-year tumor control than two fractions of 9 Gy among patients with cervical cancer undergoing external beam radiotherapy, according to results of a prospective, multicenter study conducted in resource-constrained settings and presented at the American Society for Radiation Oncology Annual Meeting.

However, the two dosing schedules did not demonstrate different rates of OS or adverse events.

“Eight out of 10 patients with locally advanced cervical cancer live in low- or middle-income countries,” May Abdel-Wahab, MD, PhD, FASTRO, director of division of human health at International Atomic Energy Agency in Vienna, Austria, said during a press conference. “It is a big problem. We shouldn’t be seeing death from this in this day in age; we should be able to prevent and treat it. But, we don’t have as many studies as we’d like to be able to determine the best way to treat these patients in different settings.”

Abdel-Wahab and colleagues evaluated data from 601 women (median age, 48.7 years) with stage IIB (n = 440) and stage IIIB (n = 161) cervical cancer treated with curative intent from Mumbai (n = 257), Peru (n = 147), South Africa (n = 76), Brazil (n = 53), Pakistan (n = 31), Morocco (n = 19) and Macedonia (n = 18).

All women received 46 Gy external beam radiotherapy in 23 fractions to the pelvis.

Researchers randomly assigned women to high-dose brachytherapy with or without chemotherapy in one of four arms:

  • arm A: four fractions of 7 Gy;
  • arm B: two fractions of 9 Gy;
  • arm C: four fractions of 7 Gy plus 40 mg/m2 cisplatin in weeks 1 through 5; or
  • arm D: two fractions of 9 Gy plus 40 mg/m2 cisplatin in weeks 1 through 5.

Researchers compared locoregional tumor control, OS, and acute and late adverse events among the arms.

Seventy-one percent of patients with stage IIB disease and 58% of patients with stage IIIB disease achieved 5-year OS (P = .03).

Researchers reported rates of 5-year OS of 67.2% (95% CI, 62.7-71.2) for the whole cohort, 62.2% for arm A, 68.3% for arm B, 73.1% for arm C and 65.1% for arm D. These rates did not appear significantly different by log-rank test.

However, significantly more patients achieved 5-year tumor control in arms A (88%; 95% CI, 81-92) and C (89%; 95% CI, 82-94) — or the arms assigned four fractions of 7 Gy radiation — than arms B (78%; 95% CI, 71-84) and D (75%; 95% CI, 67-82; P = .0007).

When researchers conducted a subgroup analysis that combined the two-fraction arms and the four-fraction arms, the locoregional control benefit with the four-fraction schedule became even more significant (88% vs. 77%; P = .0008).

“The findings that chemotherapy did not significantly affect survival or tumor control in this setting seem to be different than the results of the meta-analysis from the Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration, which found 6% differences in local control due to the effect of chemotherapy,” Abdel-Wahab said in a press release. “However, it is important to note that our study was not powered to detect difference in local control that are less than 10%. In other words, the results of the two studies are not mutually exclusive.”

Rates of grade 3 to grade 5 genitourinary toxicity ranges from 5.3% to 7.3% among the arms, and grade 3 to grade 5 gastrointestinal toxicity ranged from 4% to 6%.

Researchers observed a trend toward increased adverse events in arm B, but reported no other significant differences.

“Basically, we saw a dose-effect relationship,” Abdel-Wahab said during the press conference. “There was an 11% reduction in local failure with the four-fraction schedule. But, it did not affect OS, and there was no difference in the grade 3 or greater toxicity.

“In situations where the resources are limited, and you’re considering doing two fractions of 9 Gy, you have to be aware of the fact that there could be an 11% or 10% decrease in locoregional control,” Abdel-Wahab added. – by Alexandra Todak

Disclosures: Abdel-Wahab reports member roles on the United Nations interagency task force on the prevention and control of noncommunicable disease, as well as American College of Radiology and Florida Radiological Society. The other authors report no relevant financial disclosures.

May Abdel-Wahab

High-dose brachytherapy delivered in four fractions of 7 Gy conferred a higher rate of 5-year tumor control than two fractions of 9 Gy among patients with cervical cancer undergoing external beam radiotherapy, according to results of a prospective, multicenter study conducted in resource-constrained settings and presented at the American Society for Radiation Oncology Annual Meeting.

However, the two dosing schedules did not demonstrate different rates of OS or adverse events.

“Eight out of 10 patients with locally advanced cervical cancer live in low- or middle-income countries,” May Abdel-Wahab, MD, PhD, FASTRO, director of division of human health at International Atomic Energy Agency in Vienna, Austria, said during a press conference. “It is a big problem. We shouldn’t be seeing death from this in this day in age; we should be able to prevent and treat it. But, we don’t have as many studies as we’d like to be able to determine the best way to treat these patients in different settings.”

Abdel-Wahab and colleagues evaluated data from 601 women (median age, 48.7 years) with stage IIB (n = 440) and stage IIIB (n = 161) cervical cancer treated with curative intent from Mumbai (n = 257), Peru (n = 147), South Africa (n = 76), Brazil (n = 53), Pakistan (n = 31), Morocco (n = 19) and Macedonia (n = 18).

All women received 46 Gy external beam radiotherapy in 23 fractions to the pelvis.

Researchers randomly assigned women to high-dose brachytherapy with or without chemotherapy in one of four arms:

  • arm A: four fractions of 7 Gy;
  • arm B: two fractions of 9 Gy;
  • arm C: four fractions of 7 Gy plus 40 mg/m2 cisplatin in weeks 1 through 5; or
  • arm D: two fractions of 9 Gy plus 40 mg/m2 cisplatin in weeks 1 through 5.

Researchers compared locoregional tumor control, OS, and acute and late adverse events among the arms.

Seventy-one percent of patients with stage IIB disease and 58% of patients with stage IIIB disease achieved 5-year OS (P = .03).

Researchers reported rates of 5-year OS of 67.2% (95% CI, 62.7-71.2) for the whole cohort, 62.2% for arm A, 68.3% for arm B, 73.1% for arm C and 65.1% for arm D. These rates did not appear significantly different by log-rank test.

However, significantly more patients achieved 5-year tumor control in arms A (88%; 95% CI, 81-92) and C (89%; 95% CI, 82-94) — or the arms assigned four fractions of 7 Gy radiation — than arms B (78%; 95% CI, 71-84) and D (75%; 95% CI, 67-82; P = .0007).

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When researchers conducted a subgroup analysis that combined the two-fraction arms and the four-fraction arms, the locoregional control benefit with the four-fraction schedule became even more significant (88% vs. 77%; P = .0008).

“The findings that chemotherapy did not significantly affect survival or tumor control in this setting seem to be different than the results of the meta-analysis from the Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration, which found 6% differences in local control due to the effect of chemotherapy,” Abdel-Wahab said in a press release. “However, it is important to note that our study was not powered to detect difference in local control that are less than 10%. In other words, the results of the two studies are not mutually exclusive.”

Rates of grade 3 to grade 5 genitourinary toxicity ranges from 5.3% to 7.3% among the arms, and grade 3 to grade 5 gastrointestinal toxicity ranged from 4% to 6%.

Researchers observed a trend toward increased adverse events in arm B, but reported no other significant differences.

“Basically, we saw a dose-effect relationship,” Abdel-Wahab said during the press conference. “There was an 11% reduction in local failure with the four-fraction schedule. But, it did not affect OS, and there was no difference in the grade 3 or greater toxicity.

“In situations where the resources are limited, and you’re considering doing two fractions of 9 Gy, you have to be aware of the fact that there could be an 11% or 10% decrease in locoregional control,” Abdel-Wahab added. – by Alexandra Todak

Disclosures: Abdel-Wahab reports member roles on the United Nations interagency task force on the prevention and control of noncommunicable disease, as well as American College of Radiology and Florida Radiological Society. The other authors report no relevant financial disclosures.

    Perspective
    Brian Czito

    Brian Czito

    In women with locally advanced cervical cancer which is a very common malignancy worldwide, especially in low- and middle-income countries using a high-dose rate brachytherapy regimen of 7 Gy times four fractions is effective. The study provides high-level evidence supporting this regimen as compared with a shorter, potentially more convenient regimen of 9 Gy times two fractions. This indicates that a higher biologic dose of radiation therapy directly influences tumor control in this disease.

    • Brian Czito, MD, FASTRO
    • Duke University

    Disclosures: Czito reports no relevant financial disclosures.

    Perspective

    This trial is an international trial that addresses the schedule of brachytherapy. The International community is especially interested in the possibility of decreasing the amount of brachytherapy administration as resources are limited in many countries. However, the abstract results support the greater number of treatments to increase local control.

    • Krisha J. Howell , MD
    • Fox Chase Cancer Center

    Disclosures: Howell reports no relevant financial disclosures.

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