DOI QR코드

DOI QR Code

Management for locally advanced cervical cancer: new trends and controversial issues

  • Cho, Oyeon (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Chun, Mison (Department of Radiation Oncology, Ajou University School of Medicine)
  • Received : 2018.11.07
  • Accepted : 2018.12.17
  • Published : 2018.12.31

Abstract

This article reviewed new trends and controversial issues, including the intensification of chemotherapy and recent brachytherapy (BT) advances, and also reviewed recent consensuses from different societies on the management of locally advanced cervical cancer (LACC). Intensive chemotherapy during and after radiation therapy (RT) was not recommended as a standard treatment due to severe toxicities reported by several studies. The use of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for pelvic RT planning has increased the clinical utilization of intensity-modulated radiation therapy (IMRT) for the evaluation of pelvic lymph node metastasis and pelvic bone marrow. Recent RT techniques for LACC patients mainly aim to minimize toxicities by sparing the normal bladder and rectum tissues and shortening the overall treatment time by administering a simultaneous integrated boost for metastatic pelvic lymph node in pelvic IMRT followed by MRI-based image guided adaptive BT.

Keywords

References

  1. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 1999;17:1339-48.
  2. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137-43.
  3. Peters WA 3rd, Liu PY, Barrett RJ 2nd, 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;18:1606-13.
  4. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154-61.
  5. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144-53.
  6. Bae HS, Kim YJ, Lim MC, et al. Predictors of radiation field failure after definitive chemoradiation in patients with locally advanced cervical cancer. Int J Gynecol Cancer 2016;26:737-42.
  7. Han CH, Cho HJ, Lee SJ, et al. The increasing frequency of cervical cancer in Korean women under 35. Cancer Res Treat 2008;40:1-5.
  8. Ramlov A, Kroon PS, Jurgenliemk-Schulz IM, et al. Impact of radiation dose and standardized uptake value of (18)FDG PET on nodal control in locally advanced cervical cancer. Acta Oncol 2015;54:1567-73.
  9. Hang D, Jia M, Ma H, et al. Independent prognostic role of human papillomavirus genotype in cervical cancer. BMC Infect Dis 2017;17:391.
  10. Joo J, Shin HJ, Park B, et al. Integration pattern of human papillomavirus is a strong prognostic factor for disease-free survival after radiation therapy in cervical cancer patients. Int J Radiat Oncol Biol Phys 2017;98:654-61.
  11. Wang CC, Lai CH, Huang YT, Chao A, Chou HH, Hong JH. HPV genotypes predict survival benefits from concurrent chemotherapy and radiation therapy in advanced squamous cell carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2012;84:e499-506.
  12. Li P, Tan Y, Zhu LX, et al. Prognostic value of HPV DNA status in cervical cancer before treatment: a systematic review and meta-analysis. Oncotarget 2017;8:66352-9.
  13. Koulis TA, Kornaga EN, Banerjee R, et al. Anemia, leukocytosis and thrombocytosis as prognostic factors in patients with cervical cancer treated with radical chemoradiotherapy: a retrospective cohort study. Clin Transl Radiat Oncol 2017;4:51-6.
  14. Cho Y, Kim KH, Yoon HI, Kim GE, Kim YB. Tumor-related leukocytosis is associated with poor radiation response and clinical outcome in uterine cervical cancer patients. Ann Oncol 2016;27:2067-74.
  15. Wu ES, Oduyebo T, Cobb LP, et al. Lymphopenia and its association with survival in patients with locally advanced cervical cancer. Gynecol Oncol 2016;140:76-82.
  16. Serkies K, Badzio A, Jassem J. Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy. Acta Oncol 2006;45:695-701.
  17. Cho O, Chun M, Oh YT, et al. Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma. Tumour Biol 2017;39:1010428317733144.
  18. Cho O, Chun M, Chang SJ, Oh YT, Noh OK. Prognostic value of severe lymphopenia during pelvic concurrent chemoradiotherapy in cervical cancer. Anticancer Res 2016;36:3541-7.
  19. Klopp AH, Eifel PJ. Biological predictors of cervical cancer response to radiation therapy. Semin Radiat Oncol 2012;22:143-50.
  20. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol 2004;22:872-80.
  21. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 2008;26:5802-12.
  22. Datta NR, Stutz E, Liu M, et al. Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: a systematic review and meta-analysis. Gynecol Oncol 2017;145:374-85.
  23. Schmid MP, Franckena M, Kirchheiner K, et al. Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy. Gynecol Oncol 2014;133:256-62.
  24. Potter R, Tanderup K, Kirisits C, et al. The EMBRACE II study: the outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies. Clin Transl Radiat Oncol 2018;9:48-60.
  25. Petrelli F, De Stefani A, Raspagliesi F, Lorusso D, Barni S. Radiotherapy with concurrent cisplatin-based doublet or weekly cisplatin for cervical cancer: a systematic review and meta-analysis. Gynecol Oncol 2014;134:166-71.
  26. Wang CC, Chou HH, Yang LY, et al. A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: an Asian Gynecologic Oncology Group study. Gynecol Oncol 2015;137:462-7.
  27. Choi CH, Lee YY, Kim MK, et al. A matched-case comparison to explore the role of consolidation chemotherapy after concurrent chemoradiation in cervical cancer. Int J Radiat Oncol Biol Phys 2011;81:1252-7.
  28. Tang J, Tang Y, Yang J, Huang S. Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma. Gynecol Oncol 2012;125:297-302.
  29. Jelavic TB, Mise BP, Strikic A, Ban M, Vrdoljak E. Adjuvant chemotherapy in locally advanced cervical cancer after treatment with concomitant chemoradiotherapy: room for improvement? Anticancer Res 2015;35:4161-5.
  30. Lorvidhaya V, Chitapanarux I, Sangruchi S, et al. Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. Int J Radiat Oncol Biol Phys 2003;55:1226-32.
  31. Tangjitgamol S, Katanyoo K, Laopaiboon M, Lumbiganon P, Manusirivithaya S, Supawattanabodee B. Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer. Cochrane Database Syst Rev 2014;(12):CD010401.
  32. Duenas-Gonzalez A, Zarba JJ, Patel F, et al. Phase III, openlabel, 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;29:1678-85.
  33. Duenas-Gonzalez A, Orlando M, Zhou Y, Quinlivan M, Barraclough H. Efficacy in high burden locally advanced cervical cancer with concurrent gemcitabine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial. Gynecol Oncol 2012;126:334-40.
  34. Gupta S, Maheshwari A, Parab P, et al. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: a randomized controlled trial. J Clin Oncol 2018;36:1548-55.
  35. de Azevedo CRAS, Thuler LCS, de Mello MJG, et al. Phase II trial of neoadjuvant chemotherapy followed by chemoradiation in locally advanced cervical cancer. Gynecol Oncol 2017;146:560-5.
  36. Verma J, Monk BJ, Wolfson AH. New strategies for multimodality therapy in treating locally advanced cervix cancer. Semin Radiat Oncol 2016;26:344-8.
  37. Schefter T, Winter K, Kwon JS, et al. RTOG 0417: efficacy of bevacizumab in combination with definitive radiation therapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma. Int J Radiat Oncol Biol Phys 2014;88:101-5.
  38. Gandhi AK, Sharma DN, Rath GK, 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;87:542-8.
  39. Chen CC, Lin JC, Jan JS, Ho SC, Wang L. Definitive intensitymodulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer. Gynecol Oncol 2011;122:9-13.
  40. Hasselle MD, Rose BS, Kochanski JD, et al. Clinical outcomes of intensity-modulated pelvic radiation therapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2011;80:1436-45.
  41. Naik A, Gurjar OP, Gupta KL, Singh K, Nag P, Bhandari V. Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: a randomized prospective study. Cancer Radiother 2016;20:370-6.
  42. Mell LK, Sirak I, Wei L, et al. Bone marrow-sparing intensity modulated radiation therapy with concurrent cisplatin for stage IB-IVA cervical cancer: an International Multicenter Phase II Clinical Trial (INTERTECC-2). Int J Radiat Oncol Biol Phys 2017;97:536-45.
  43. Noticewala SS, Li N, Williamson CW, et al. Longitudinal changes in active bone marrow for cervical cancer patients treated with concurrent chemoradiation therapy. Int J Radiat Oncol Biol Phys 2017;97:797-805.
  44. Jadon R, Pembroke CA, Hanna CL, et al. A systematic review of organ motion and image-guided strategies in external beam radiotherapy for cervical cancer. Clin Oncol (R Coll Radiol) 2014;26:185-96.
  45. Lim K, Small W Jr, Portelance L, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer. Int J Radiat Oncol Biol Phys 2011;79:348-55.
  46. Castelnau-Marchand P, Chargari C, Maroun P, et al. Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer. Gynecol Oncol 2015;139:288-94.
  47. Potter R, Georg P, Dimopoulos JC, et al. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol 2011;100:116-23.
  48. Kang HC, Shin KH, Park SY, Kim JY. 3D CT-based high-doserate brachytherapy for cervical cancer: clinical impact on late rectal bleeding and local control. Radiother Oncol 2010;97:507-13.
  49. Tan LT, Coles CE, Hart C, Tait E. Clinical impact of computed tomography-based image-guided brachytherapy for cervix cancer using the tandem-ring applicator - the Addenbrooke's experience. Clin Oncol (R Coll Radiol) 2009;21:175-82.
  50. Charra-Brunaud C, Harter V, Delannes M, et al. Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: results of the French STIC prospective study. Radiother Oncol 2012;103:305-13.
  51. Simpson DR, Scanderbeg DJ, Carmona R, et al. Clinical outcomes of computed tomography-based volumetric brachytherapy planning for cervical cancer. Int J Radiat Oncol Biol Phys 2015;93:150-7.
  52. Han K, Milosevic M, Fyles A, Pintilie M, Viswanathan AN. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;87:111-9.
  53. Gill BS, Lin JF, Krivak TC, et al. National Cancer Data Base analysis of radiation therapy consolidation modality for cervical cancer: the impact of new technological advancements. Int J Radiat Oncol Biol Phys 2014;90:1083-90.
  54. Grover S, Harkenrider MM, Cho LP, et al. Image guided cervical brachytherapy: 2014 Survey of the American Brachytherapy Society. Int J Radiat Oncol Biol Phys 2016;94:598-604.
  55. Potter R, Haie-Meder C, Van Limbergen E, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:67-77.
  56. Potter R, Dimopoulos J, Georg P, et al. Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol 2007;83:148-55.
  57. Mayadev J , Viswanathan A, Liu Y, et a l . American Brachytherapy Task Group Report: a pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer. Brachytherapy 2017;16:22-43.
  58. Sturdza A, Potter R, Fokdal LU, et al. Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol 2016;120:428-33.
  59. Tanderup K, Fokdal LU, Sturdza A, et al. Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer. Radiother Oncol 2016;120:441-6.
  60. Kim H, Houser CJ, Kalash R, et al. Workflow and efficiency in MRI-based high-dose-rate brachytherapy for cervical cancer in a high-volume brachytherapy center. Brachytherapy 2018;17:753-60.
  61. Mendez LC, Leung E, Cheung P, Barbera L. The role of stereotactic ablative body radiotherapy in gynaecological cancers: a systematic review. Clin Oncol (R Coll Radiol) 2017;29:378-84.
  62. Marnitz S, Kohler C, Budach V, et al. Brachytherapy-emulating robotic radiosurgery in patients with cervical carcinoma. Radiat Oncol 2013;8:109.
  63. Hsieh CH, Tien HJ, Hsiao SM, et al. Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients: a preliminary result. Onco Targets Ther 2013;6:59-66.
  64. Haas JA, Witten MR, Clancey O, Episcopia K, Accordino D, Chalas E. CyberKnife boost for patients with cervical cancer unable to undergo brachytherapy. Front Oncol 2012;2:25.
  65. Kubicek GJ, Xue J, Xu Q, et al. Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer. Biomed Res Int 2013;2013:898953.
  66. Molla M, Escude L, Nouet P, et al. Fractionated stereotactic radiotherapy boost for gynecologic tumors: an alternative to brachytherapy? Int J Radiat Oncol Biol Phys 2005;62:118-24.
  67. Wulf J, Hadinger U, Oppitz U, Thiele W, Flentje M. Stereotactic boost irradiation for targets in the abdomen and pelvis. Radiother Oncol 2004;70:31-6.
  68. Mazzola R, Ricchetti F, Fiorentino A, et al. Weekly cisplatin and volumetric-modulated arc therapy with simultaneous integrated boost for radical treatment of advanced cervical cancer in elderly patients: feasibility and clinical preliminary results. Technol Cancer Res Treat 2017;16:310-5.
  69. Kim H, Kim JY, Kim J, et al. Current status of brachytherapy in Korea: a national survey of radiation oncologists. J Gynecol Oncol 2016;27:e33.
  70. Viswanathan AN, Thomadsen B; American Brachytherapy Society Cervical Cancer Recommendations Committee; American Brachytherapy Society. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part I: general principles. Brachytherapy 2012;11:33-46.
  71. Cibula D, Potter R, Planchamp F, et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the management of patients with cervical cancer. Int J Gynecol Cancer 2018;28:641-55.
  72. Gouy S, Morice P, Narducci F, et al. Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic paraaortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging. J Clin Oncol 2013;31:3026-33.
  73. Dabi Y, Simon V, Carcopino X, et al. Therapeutic value of surgical paraaortic staging in locally advanced cervical cancer: a multicenter cohort analysis from the FRANCOGYN study group. J Transl Med 2018;16:326.
  74. Moore KN, Java JJ, Slaughter KN, et al. Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis. Gynecol Oncol 2016;143:294-301.
  75. Sharma C, Deutsch I, Horowitz DP, et al. Patterns of care and treatment outcomes for elderly women with cervical cancer. Cancer 2012;118:3618-26.

Cited by

  1. Dosimetric comparison of two different applicators and rectal retraction methods used in inverse optimization-based intracavitary brachytherapy for cervical cancer vol.12, pp.1, 2020, https://doi.org/10.5114/jcb.2020.92699
  2. Increased High-Risk Human Papillomavirus Viral Load Is Associated With Immunosuppressed Microenvironment and Predicts a Worse Long-Term Survival in Cervical Cancer Patients vol.153, pp.4, 2020, https://doi.org/10.1093/ajcp/aqz186
  3. Significance of the number of high-risk factors in patients with cervical cancer treated with radical hysterectomy and concurrent chemoradiotherapy vol.157, pp.2, 2018, https://doi.org/10.1016/j.ygyno.2020.02.031
  4. Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer vol.50, pp.10, 2018, https://doi.org/10.1093/jjco/hyaa091
  5. Prognostic Significance of Tumor Regression Rate during Concurrent Chemoradiotherapy in Locally Advanced Cervix Cancer: Analysis by Radiation Phase and Histologic Type vol.9, pp.11, 2018, https://doi.org/10.3390/jcm9113471
  6. A dummy-run evaluation of postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trials for cervical cancer vol.62, pp.1, 2018, https://doi.org/10.1093/jrr/rraa085
  7. GAGE mediates radio resistance in cervical cancers via the regulation of chromatin accessibility vol.36, pp.9, 2021, https://doi.org/10.1016/j.celrep.2021.109621