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Title: Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer

Abstract

Purpose: To evaluate the long-term results of computed tomography (CT)–planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. Methods and Materials: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. Results: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph nodemore » enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. Conclusions: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography–CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.« less

Authors:
 [1]; ;  [2];  [3];  [1];  [3];  [4]; ;  [2]
  1. Department of Brachytherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)
  2. Department of Medical Physics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)
  3. Department of Teleradiotherapy, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)
  4. Department of Clinical Trials and Biostatistics, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)
Publication Date:
OSTI Identifier:
22648784
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRACHYTHERAPY; CHEMOTHERAPY; EXTERNAL BEAM RADIATION THERAPY; LYMPH NODES; NEOPLASMS; PATIENTS; RADIATION HAZARDS; SIDE EFFECTS

Citation Formats

Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl, Gruszczynska, Ewelina, Bijok, Michal, Jonska-Gmyrek, Joanna, Dabkowski, Mateusz, Staniaszek, Jagna, Michalski, Wojciech, Kowalczyk, Adam, and Milanowska, Katarzyna. Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.04.025.
Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl, Gruszczynska, Ewelina, Bijok, Michal, Jonska-Gmyrek, Joanna, Dabkowski, Mateusz, Staniaszek, Jagna, Michalski, Wojciech, Kowalczyk, Adam, & Milanowska, Katarzyna. Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer. United States. doi:10.1016/J.IJROBP.2016.04.025.
Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl, Gruszczynska, Ewelina, Bijok, Michal, Jonska-Gmyrek, Joanna, Dabkowski, Mateusz, Staniaszek, Jagna, Michalski, Wojciech, Kowalczyk, Adam, and Milanowska, Katarzyna. 2016. "Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer". United States. doi:10.1016/J.IJROBP.2016.04.025.
@article{osti_22648784,
title = {Computed Tomography–Planned High-Dose-Rate Brachytherapy for Treating Uterine Cervical Cancer},
author = {Zolciak-Siwinska, Agnieszka, E-mail: agnieszka.zolciak@wp.pl and Gruszczynska, Ewelina and Bijok, Michal and Jonska-Gmyrek, Joanna and Dabkowski, Mateusz and Staniaszek, Jagna and Michalski, Wojciech and Kowalczyk, Adam and Milanowska, Katarzyna},
abstractNote = {Purpose: To evaluate the long-term results of computed tomography (CT)–planned high-dose-rate (HDR) brachytherapy (BT) for treating cervical cancer patients. Methods and Materials: CT-planned HDR BT was performed according to the adapted Group European de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations in 216 consecutive patients with locally advanced cervical cancer, International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA, who were treated with conformal external beam radiation therapy and concomitant chemotherapy. We analyzed outcomes and late side effects evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Subjective, Objective, Management, Analysis evaluation scoring system and compared them with the results from a historical group. Results: The median age was 56 years (range, 32-83 years). The median follow-up time for living patients was 52 months (range 37-63 months). The 5-year cumulative incidence function for the local recurrence rate for patients with FIGO II and III was 5.5% and 20%, respectively (P=.001). The 5-year rates of overall survival (OS) and disease-free survival (DFS) were 66.4% and 58.5%, respectively. The relative risk of failure for OS and DFS for FIGO III in relation to FIGO II was 2.24 (P=.003) and 2.6 (P=.000) and for lymph node enlargement was 2.3 (P=.002) and 2 (P=.006), respectively. In 2 patients, rectovaginal fistula occurred, and in 1 patient, vesicovaginal fistula occurred without local progression. Comparison of late adverse effects in patients treated according to the GEC-ESTRO recommendations and in the historical group revealed a reduction in fistula formation of 59% and also a reduction in rectal grade 3 to 4 late toxicity of >59%. Conclusions: This is the largest report with mature data of CT-planned BT HDR for the treatment of cervical cancer with good local control and acceptable toxicity. In comparison with the historical series, there is a substantial benefit in terms of severe late effects. FIGO III and enlarged lymph nodes in positron emission tomography–CT/CT are negative prognostic factors, both with a relative risk of failure of approximately 2.},
doi = {10.1016/J.IJROBP.2016.04.025},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 96,
place = {United States},
year = 2016,
month = 9
}
  • Purpose: To compare the dose-volume histogram (DVH) parameters obtained by three-dimensional gynecologic brachytherapy planning with the rectosigmoid mucosal changes observed by flexible sigmoidoscopy. Methods and Materials: Between January 2004 and July 2005, 71 patients with International Federation of Gynecology and Obstetrics Stage IB-IIIB uterine cervical cancer underwent computed tomography-based high-dose-rate intracavitary brachytherapy. The total dose (external beam radiotherapy [RT] plus intracavitary brachytherapy) to the International Commission of Radiation Units and Measurements rectal point (ICRU{sub RP}) and DVH parameters for rectosigmoid colon were calculated using the equivalent dose in 2-Gy fractions ({alpha}/{beta} = 3 Gy). Sigmoidoscopy was performed every 6 monthsmore » after RT, with the 6-scale scoring system used to determine mucosal changes. Results: The mean values of the DVH parameters and ICRU{sub RP} were significantly greater in patients with a score of {>=}2 than in those with a score <2 at 12 months after RT (ICRU{sub RP}, 71 Gy{sub {alpha}}{sub /{beta}}{sub 3} vs. 66 Gy{sub {alpha}}{sub /{beta}}{sub 3}, p = 0.02; D{sub 0.1cc}, 93 Gy{sub {alpha}}{sub /{beta}}{sub 3} vs. 85 Gy{sub {alpha}}{sub /{beta}}{sub 3}, p = 0.04; D{sub 1cc}, 80 Gy{sub {alpha}}{sub /{beta}}{sub 3} vs. 73 Gy{sub {alpha}}{sub /{beta}}{sub 3}, p = 0.02; D{sub 2cc}, 75 Gy{sub {alpha}}{sub /{beta}}{sub 3} vs. 69 Gy{sub {alpha}}{sub /{beta}}{sub 3}, p = 0.02). The probability of a score of {>=}2 showed a significant relationship with the DVH parameters and ICRU{sub RP} (ICRU{sub RP}, p = 0.03; D{sub 0.1cc}, p = 0.05; D{sub 1cc}, p = 0.02; D{sub 2cc}, p = 0.02). Conclusion: Our preliminary data have shown that DVH values of the rectosigmoid colon obtained by computed tomography-based three-dimensional brachytherapy planning are reliable and predictive of score {>=}2 rectosigmoid mucosal changes.« less
  • Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional-planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB-IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose-volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gymore » +- 0.14 (CF: 7 Gy), L 1.43 +- 0.15 (CF: 7.15 Gy), and Bil 1.41 +- 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement.« less
  • Purpose: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Methods and Materials: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs ofmore » the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD{sub 2}). Results: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D{sub 2cc} of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Conclusions: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.« less
  • Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgicalmore » staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall survival continues to be limited by the high rates of distant metastasis.« less
  • Purpose: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. Methods and Materials: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBTmore » of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy{sub 10} ({alpha}/{beta} = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. Results: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade {>=}1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade {>=}3 cases were observed for genitourinary/gastrointestinal late complications. Conclusions: These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy{sub 10} at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer.« less