title: The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.
abstract: OBJECTIVE
  The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB.
  
  
  METHODS
  From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years.
  
  
  RESULTS
  Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients.
  
  
  CONCLUSIONS
  Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.
authors.affiliation: Department of Radiation Therapy and Oncology, Shin Kong Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Shang Wen
authors.initials: SW
authors.lastname: Chen
authors.forename: Ji An
authors.initials: JA
authors.lastname: Liang
authors.forename: Shih Neng
authors.initials: SN
authors.lastname: Yang
authors.forename: Hui Ling
authors.initials: HL
authors.lastname: Ko
authors.forename: Fang Jen
authors.initials: FJ
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D003196:Computer Graphics; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011829:Radiation Dosage; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013624:Taiwan; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*