Feasibility and Safety of High Dose Chemoradiation in Locally Advanced Cervical Cancer: A Preliminary Experience of Gynecologic Oncology Management Italian Team 

Authors

  • Donatella Russo Radiotherapy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Graziana Ronzino Oncology Unit - “Vito Fazzi” Hospital - Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Antonella Papaleo Radiotherapy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Elisa Cavalera Radiotherapy Unit - “Vito Fazzi” Hospital – Lecce, Italy
  • Angela Leone Radiotherapy Unit - “Vito Fazzi” Hospital – Lecce, Italy
  • Marianna Giampaglia Oncology Unit - “Vito Fazzi” Hospital - Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Simona Caretto Gynecology and Obstetricy Unit - “I. Veris Delli Ponti” Hospital – Scorrano, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Fabrizio Totaro Aprile Gynecology and Obstetricy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Alex Cristiano De Marzi Gynecology and Obstetricy Unit - “San Giuseppe da Copertino” Hospital – Copertino, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Mario Santantonio Radiotherapy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Antonio Perrone Gynecology and Obstetricy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy
  • Andrea Tinelli Gynecology and Obstetricy Unit - “Vito Fazzi” Hospital – Lecce, Italy and Disease Management Team of Gynecologic Oncology – Lecce, Italy

DOI:

https://doi.org/10.12974/2309-6160.2013.01.01.2

Keywords:

Advanced cervical cancer, chemoradiation, chemotherapy, brachytherapy, external radiotherapy, Intensity Modulated Radiation Therapy, Programmed Temperature Vaporization, Biological Effective Dose, Radiation Therapy Oncology Group, colposcopy, cytology, gynecological cancer, lomboaortic nodes, CT-scan, RM, and PET/CT.

Abstract

Locally advanced cervical cancer has a poor prognosis and is difficult to treat by surgery; authors’ evaluated feasibility and safety of the simultaneous integrated boost (SIB) technique for dose escalation in patients with cervical cancer using a rotational dynamic Intensity Modulated Radiation Therapy Technique (VMAT®).

Authors evaluated 10 patients affected by loco-regionally advanced, node negative, inoperable cervical cancer. All women received primary chemoradiation (CRT). Six pts received three cycles of platinum-based chemotherapy (CT) plus CRT. Three Programmed Temperature Vaporization (PTV) were delineated: PTV1 (primary, cervix and parametria with a 1cm-margin); PTV2 (body of uterus with a 1cm-margin); PTV3 (pelvic nodes). PTV1 was defined using image fusion between CT-scan and RM or PET/CT. Treatment plans, calculated using a rotational dynamic Intensity Modulated Radiation Therapy (IMRT) system on Oncentra Masterplan® (VMAT®), and consisted in a simultaneous integrated boost. Total treatment time was 45 days. Concomitant CT consisted of weekly cisplatin 40 mg/m2. Dose–volume histograms and acute gastrointestinal, genitourinary, and hematological toxicity were evaluated. Secondary endpoint was evaluation of short term disease free survival. Three months after CTRT, patients were revaluated with colposcopy and cytology and Pelvic imaging. After six and twelve months from CTRT, reevaluation included PET-CT or Chest CT scan and Abdominal and Pelvic RM. All patients concluded radiation without suspension. Cytology demonstrated complete response (CR) in 4 pts in the ERT fraction of brachytherapy (BRT) group and in 1 pts in ERT alone group. All other patients showed a partial response (PR) > 75%. After a median follow up of 20 month (range 16-22), 5 patients are free from disease (NED), 4 patients are alive with disease (AWD) and 1 patient died after three months (DOD). In 2 AWD patients, re-staging PET showed a RC of pelvic disease with evidence of disease in lomboaortic nodes. One of them received salvage radiation therapy on recurrence. After this preliminary experience, in patients with inaccessible cervical canal, authors could propose the dose escalation on PTV1, with the aim of delivering BED as near as possible to 85Gy. 

References

Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of diseasefree interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1990; 38: 352-57. http://dx.doi.org/10.1016/0090-8258(90)90072-S

Burghardt E, Baltzer J, Tulusan AH, Haas J. Results of surgical treatment of 1028 cervical cancers studied with volumetry. Cancer 1992; 70: 648-55. http://dx.doi.org/10.1002/1097- 0142(19910601)67:11<2776::AIDCNCR2820671111> 3.0.CO;2-L

Stehman FB, Bundy BN, DiSaia PJ, Keys HM, Larson JE, Fowler WC. Carcinoma of the cervix treated with radiation therapy. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 1991; 67: 2776- 85.

NCCN Practice Guidelines in Oncology Version 1-2013.

Ahamad A, D’Souza W, Salehpour M, Iyer R, Tucker SL, Jhingran A, Eifel PJ. Intensity-modulated radiation therapy after hysterectomy: Comparison with conventional treatment and sensitivity of the normal-tissue- sparing effect to margin size. Int J Radiat Oncol Biol Phys 2005; 62: 1117-24. http://dx.doi.org/10.1016/j.ijrobp.2004.12.029

Lukka H, Hirte H, Fyles A, Thomas G, Johnston M, Fung MF, Browman G. Concurrent cisplatin based chemotherapy plus radiotherapy for cervical cancer - a meta-analysis. Clin Oncol 2002; 14: 203-12. http://dx.doi.org/10.1053/clon.2002.0076

Tharavichitkul E, Pinitpatcharalerd A, Lorvidhaya V, Kamnerdsupaphon P, Pukanhaphan N, Sukthomya V, et al. Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer. J Radiat Res 2011; 52: 9-14. http://dx.doi.org/10.1269/jrr.10021

Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 1988; 27: 131-46. http://dx.doi.org/10.3109/02841868809090333

Lanciano RM, Pajak TF, Martz K, Hanks GE. The influence of treatment time on outcome of the uterine cervix treated with radiation: a patterns-of-care study. Int J Radiat Oncol Biol Phys 1993; 25(3): 391-97. http://dx.doi.org/10.1016/0360-3016(93)90058-4

Petereit DG, Sarkaria JN, Chappell R, Fowler JF, Hartmann TJ, Kinsella TJ, et al. The advers effect of treatment prolongation in cervical carcinoma. Int J Radiat Oncol Biol Phys 1995; 32(5): 1301-307. http://dx.doi.org/10.1016/0360-3016(94)00635-X

Perez C, Grigsby PW, Castro-Vita H, Lockett MA. Carcinoma of uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1995; 32(5): 1275-88. http://dx.doi.org/10.1016/0360-3016(95)00220-S

Guerrero M, Li XA, Ma L, Linder J, Deyoung C, Erickson B. Simultaneous integrated intensity-modulated radiotherapy boost for locally advanced gynecological cancer: Radiobiological and dosimetric considerations. Int J Radiat Oncol Biol Phys 2005; 62: 933-9. http://dx.doi.org/10.1016/j.ijrobp.2004.11.040

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: 505-12. http://dx.doi.org/10.1016/j.ijrobp.2004.03.035

Zhai D-Y, Yin Y, Gong G-Z, Liu TH, Chen JH, Ma CS, Lu J. RapidArc radiotherapy for whole pelvic lymph node in cervical cancer with 6 and 15 MV: a treatment planning comparison with fixed field IMRT. J Radiat Res 2013; 54: 166-73. http://dx.doi.org/10.1093/jrr/rrs066

Steve Webb. VMAT its role in Radiotherapy. Medicalphysicsweb-Review; Winter 2009 (http:// medicalphysicsweb.org/blog/MPWRwinter09_digitalPDF.pdf)

Guckenberger M, Richter A, Krieger T, Wilbert J, Baier K, Flentje M. Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes? Radiot Oncol 2009; 93: 259-65. http://dx.doi.org/10.1016/j.radonc.2009.08.015

Viswanathan AN, Yorke LD, Marks LB, Eifel PJ, Shipley WU. Radiation dose-volume effects of the urinary bladder. Int J Radiat Oncol Biol Phys 2010; 76 (3): S116-S122. http://dx.doi.org/10.1016/j.ijrobp.2009.02.090

Michalsky JM, Gay H, Jackson A, Tucker SL, Deasy JO. Radiation dose-volume effects in Radiation-induced rectal injury. Int J Radiat Oncol Biol Phys 2010; 76 (3): S123-S129. http://dx.doi.org/10.1016/j.ijrobp.2009.03.078

Gay HA, Barthold HJ, O’Meara E, Bosch WR, El Naqa I, Al- Lozi R, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group Consensus Panel Atlas. Int J Radiat Oncol Biol Phys 2012; 83(3): 353-62. http://dx.doi.org/10.1016/j.ijrobp.2012.01.023

Cozzi L, Dinshaw KA, Shrivastava SK, Mahantshetty U, Engineer R, Deshpande DD, et al. A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy. Radiot Oncol 2008; 89(2): 180-91. http://dx.doi.org/10.1016/j.radonc.2008.06.013

Gandhi AK, Rath GK, Sharma DN. Early clinical outcomes of Intensity Modulated versus Conventional Pelvic radiation therapy for locally advanced carcinoma cervix: a prospective randomized study. Int J Radiat Oncol Biol Phys 2012; 84(35): S17-S18. http://dx.doi.org/10.1016/j.ijrobp.2012.07.050

Burghardt E, Baltzer J, Tulusan AH, Haas J. Results of surgical treatment of 1028 cervical cancers studied with volumetry. Cancer 1992 70: 648-55. http://dx.doi.org/10.1002/1097- 0142(19920801)70:3<648::AIDCNCR2820700318> 3.0.CO;2-R

Liu S-P, Huang X, Ke G-H, Huang X-W. 3D Radiation Therapy or Intensity-Modulated Radiotherapy for Recurrent and Metastatic Cervical Cancer: The Shanghai Cancer Hospital Experience. PLoS ONE 2012; 7(6): e40299.doi: 10.1371/journal.pone.00402

Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 2004; 22: 3113-19. http://dx.doi.org/10.1200/JCO.2004.04.170

Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardmen CH, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2009; 27: 4649-55. http://dx.doi.org/10.1200/JCO.2009.21.8909

Van Nagell JR, Rayburn W Jr, Donaldson ES, Hanson M, Gay EC, Yoneda J, et al. Therapeutic implications of patterns of recurrence in cancer of the uterine cervix. Cancer 1979; 44: 2354-61. http://dx.doi.org/10.1002/1097-0142(197912)44:6<2354::AIDCNCR2820440653> 3.0.CO;2-J

Piver MS, Barlow JJ, Krishnamsetty R. Five-year survival (with no evidence of disease) in patients with biopsyconfirmed aortic node metastasis from cervical carcinoma. Am J Obstet Gynecol 1981; 139: 575-78.

Grigsby PW, Lu JD, Mutch DG, Kim RY, Eifel PJ. Twice-daily fractionation of external irradiation with brachytherapy and chemotherapy in carcinoma of the cervix with positive paraaortic lymph nodes: Phase II study of the Radiation Therapy Oncology Group 92-10. Int J Radiat Oncol Biol Phys 1998; 41: 817-22. http://dx.doi.org/10.1016/S0360-3016(98)00132-1

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: 261-66. http://dx.doi.org/10.1016/S0360-3016(01)01664-9

Du XL, Sheng XG, Jiang T, Yu H, Yan YF, Gao R, et al. Intensity-modulated radiation therapy versus para-aortic field radiotherapy to treat para-aortic lymph node metastasis in cervical cancer: prospective study. Croat Med J 2010; 51: 229-36. http://dx.doi.org/10.3325/cmj.2010.51.229

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: 505-12. http://dx.doi.org/10.1016/j.ijrobp.2004.03.035

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: 1354-60. http://dx.doi.org/10.1016/S0360-3016(03)00325-0

Roeske JC, Bonta D, Mell LK, Lujan AE, Mundt AJ. A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity-modulated whole-pelvic radiation therapy. Radiother Oncol 2003; 69: 201-207. http://dx.doi.org/10.1016/j.radonc.2003.05.001

Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ. Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002; 54: 1388- 96. http://dx.doi.org/10.1016/S0360-3016(02)03801-4

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Published

2013-04-04

How to Cite

Russo, D., Ronzino, G., Papaleo, A., Cavalera, E., Leone, A., Giampaglia, M., Caretto, S., Aprile, F. T., De Marzi, A. C. ., Santantonio, M., Perrone, A., & Tinelli, A. (2013). Feasibility and Safety of High Dose Chemoradiation in Locally Advanced Cervical Cancer: A Preliminary Experience of Gynecologic Oncology Management Italian Team . Global Journal of Oncologists, 1(1), 6–12. https://doi.org/10.12974/2309-6160.2013.01.01.2

Issue

Vol. 1 No. 1 (2013)

Section

Articles