Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer

Authors: Nikola Cihoric, Alexandros Tsikkinis, Coya Tapia, Daniel M. Aebersold, Inti Zlobec, Kristina Lössl

Published in: Radiation Oncology | Issue 1/2015

Login to get access

Abstract

Purpose

Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy.

Material and methods

Thirty-nine patients with cervical carcinoma FIGO stage IB2 – IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with 18FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15–18 Gy in three fractions (single fraction: 4–6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).

Results

Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness.

Conclusion

Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low.
Literature
1.
Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340(15):1144–53.CrossRefPubMed
2.
Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340(15):1137–43.CrossRefPubMed
3.
Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs 3rd CL, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340(15):1154–61.CrossRefPubMed
4.
Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001;358(9284):781–6.CrossRefPubMed
5.
Beadle BM, Jhingran A, Yom SS, Ramirez PT, Eifel PJ. Patterns of regional recurrence after definitive radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys. 2010;76(5):1396–403.CrossRefPubMed
6.
Kidd EA, Siegel BA, Dehdashti F, Rader JS, Mutic S, Mutch DG, et al. Clinical outcomes of definitive intensity-modulated radiation therapy with fluorodeoxyglucose-positron emission tomography simulation in patients with locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2010;77(4):1085–91.CrossRefPubMed
7.
Veldeman L, Madani I, Hulstaert F, De Meerleer G, Mareel M, De Neve W. Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies. Lancet Oncol. 2008;9(4):367–75.CrossRefPubMed
8.
Gandhi AK, Sharma DN, Rath GK, Julka PK, Subramani V, Sharma S, et al. Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3):542–8.CrossRefPubMed
9.
10.
Beadle BM, Jhingran A, Salehpour M, Sam M, Iyer RB, Eifel PJ. Cervix regression and motion during the course of external beam chemoradiation for cervical cancer. Int J Radiat Oncol Biol Phys. 2009;73(1):235–41.CrossRefPubMed
11.
Cihoric N, Tapia C, Kruger K, Aebersold DM, Klaeser B, Lossl K. IMRT with (1)(8)FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer. Radiat Oncol. 2014;9:83.PubMedCentralCrossRefPubMed
12.
Potter R, Dimopoulos J, Kirisits C, Lang S, Haie-Meder C, Briot E, et al. Recommendations for image-based intracavitary brachytherapy of cervix cancer: the GYN GEC ESTRO Working Group point of view: in regard to Nag et al. (Int J Radiat Oncol Biol Phys 2004;60:1160–1172). Int J Radiat Oncol Biol Phys. 2005;62(1):293–5. author reply 295–296.CrossRefPubMed
13.
Nag S, Erickson B, Thomadsen B, Orton C, Demanes JD, Petereit D. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2000;48(1):201–11.CrossRefPubMed
14.
Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC). Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis. Cochrane Database of Systematic Reviews. 2010;(1):CD008285. doi:10.​1002/​14651858.
15.
Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ. Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2000;48(5):1613–21.CrossRefPubMed
16.
Chan P, Yeo I, Perkins G, Fyles A, Milosevic M. Dosimetric comparison of intensity-modulated, conformal, and four-field pelvic radiotherapy boost plans for gynecologic cancer: a retrospective planning study. Radiat Oncol. 2006;1:13.PubMedCentralCrossRefPubMed
17.
Portelance L, Chao KS, Grigsby PW, Bennet H, Low D. Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer receiving pelvic and para-aortic irradiation. Int J Radiat Oncol Biol Phys. 2001;51(1):261–6.CrossRefPubMed
18.
Kavanagh BD, Schefter TE, Wu Q, Tong S, Newman F, Arnfield M, et al. Clinical application of intensity-modulated radiotherapy for locally advanced cervical cancer. Semin Radiat Oncol. 2002;12(3):260–71.CrossRefPubMed
19.
Esthappan J, Chaudhari S, Santanam L, Mutic S, Olsen J, Macdonald DM, et al. Prospective clinical trial of positron emission tomography/computed tomography image-guided intensity-modulated radiation therapy for cervical carcinoma with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys. 2008;72(4):1134–9.CrossRefPubMed
20.
Ahmed RS, Kim RY, Duan J, Meleth S, De Los Santos JF, Fiveash JB. IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. Int J Radiat Oncol Biol Phys. 2004;60(2):505–12.CrossRefPubMed
21.
Salama JK, Mundt AJ, Roeske J, Mehta N. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2006;65(4):1170–6.CrossRefPubMed
22.
Beriwal S, Gan GN, Heron DE, Selvaraj RN, Kim H, Lalonde R, et al. Early clinical outcome with concurrent chemotherapy and extended-field, intensity-modulated radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys. 2007;68(1):166–71.CrossRefPubMed
23.
Gerszten K, Colonello K, Heron DE, Lalonde RJ, Fitian ID, Comerci JT, et al. Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity-modulated radiotherapy (IMRT) for carcinoma of the cervix. Gynecol Oncol. 2006;102(2):182–8.CrossRefPubMed
24.
Peters 3rd WA, Liu PY, Barrett 2nd RJ, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18(8):1606–13.PubMed
25.
Hasselle MD, Rose BS, Kochanski JD, Nath SK, Bafana R, Yashar CM, et al. Clinical outcomes of intensity-modulated pelvic radiation therapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2011;80(5):1436–45.CrossRefPubMed
26.
Chen CC, Lin JC, Jan JS, Ho SC, Wang L. Definitive intensity-modulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer. Gynecol Oncol. 2011;122(1):9–13.CrossRefPubMed
27.
Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;52(5):1330–7.CrossRefPubMed
28.
Mundt AJ, Mell LK, Roeske JC. Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy. Int J Radiat Oncol Biol Phys. 2003;56(5):1354–60.CrossRefPubMed
29.
Du XL, Tao J, Sheng XG, Lu CH, Yu H, Wang C, et al. Intensity-modulated radiation therapy for advanced cervical cancer: a comparison of dosimetric and clinical outcomes with conventional radiotherapy. Gynecol Oncol. 2012;125(1):151–7.CrossRefPubMed
30.
Zhang G, He F, Fu C, Zhang Y, Yang Q, Wang J, et al. Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer. J Gynecol Oncol. 2014;25(1):14–21.PubMedCentralCrossRefPubMed
31.
Jensen LG, Hasselle MD, Rose BS, Nath SK, Hasan Y, Scanderbeg DJ, et al. Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin. Int J Gynecol Cancer. 2013;23(1):119–25.CrossRefPubMed
32.
Stehman FB, Bundy BN, DiSaia PJ, Keys HM, Larson JE, Fowler WC. Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer. 1991;67(11):2776–85.CrossRefPubMed
33.
Choi HJ, Roh JW, Seo SS, Lee S, Kim JY, Kim SK, et al. Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma: a prospective study. Cancer. 2006;106(4):914–22.CrossRefPubMed
34.
Loft A, Berthelsen AK, Roed H, Ottosen C, Lundvall L, Knudsen J, et al. The diagnostic value of PET/CT scanning in patients with cervical cancer: a prospective study. Gynecol Oncol. 2007;106(1):29–34.CrossRefPubMed
35.
Scheidler J, Hricak H, Yu KK, Subak L, Segal MR. Radiological evaluation of lymph node metastases in patients with cervical cancer. A meta-analysis. Jama. 1997;278(13):1096–101.PubMed
36.
Li X, Yin Y, Sheng X, Han X, Sun L, Lu C, et al. Distribution pattern of lymph node metastases and its implication in individualized radiotherapeutic clinical target volume delineation of regional lymph nodes in patients with stage IA to IIA cervical cancer. Radiat Oncol. 2015;10(1):352.
37.
Duenas-Gonzalez A, Zarba JJ, Patel F, Alcedo JC, Beslija S, Casanova L, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29(13):1678–85.CrossRefPubMed
38.
Maduro JH, Pras E, Willemse PH, de Vries EG. Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer. Cancer Treat Rev. 2003;29(6):471–88.CrossRefPubMed
Metadata
Title
Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer
Authors
Nikola Cihoric
Alexandros Tsikkinis
Coya Tapia
Daniel M. Aebersold
Inti Zlobec
Kristina Lössl
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0551-0

Other articles of this Issue 1/2015

Radiation Oncology 1/2015 Go to the issue

Research

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54–56 Gy given in 9–7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size

Research

Long-term results of a study using individualized planning target volumes for hypofractionated intensity-modulated radiotherapy boost for prostate cancer

Research

Hypofractionated irradiation in elderly patients with breast cancer after breast conserving surgery and mastectomy : Analysis of 205 cases

Research

Palliative radiotherapy with or without additional care by a multidisciplinary palliative care team in patients with newly diagnosed cancer: a retrospective matched pairs comparison

Research

Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells

Research

The effectiveness and side effects of conformal external beam radiotherapy combined with high-dose-rate brachytherapy boost compared to conformal external beam radiotherapy alone in patients with prostate cancer