Evaluation of an Apoptotic Test for Predicting Late Toxicities After Radiotherapy in Breast and Prostate Cancer Patients
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the prediction of late toxicity by the radiation induced CD8 T-lymphocyte apoptosis
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
The two cancer sites concerned by this trial are intermediate risk prostate cancer treated with conformational radiotherapy with or without intensity modulation, and breast cancer patients treated with adjuvant radiotherapy after breast conservative surgery for patients aged under 60 years of age. The identification of 5% of patients at risk of severe toxicity should allow to deliver high dose radiotherapy among 95% of patients with a lower risk of severe late complications.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Intermediate prognosis prostate cancer Intermediate prognosis prostate cancer |
|
| Breast cancer conservative treatment and age<60 Boost irradiation and age>60 |
Outcome Measures
Primary Outcome Measures
- Late complications [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria for prostate cancer patients:
-
localised prostate cancer, histologically proven
-
Absence of metastases (M0) : normal bone scintigraphy
-
Absence of radiological lymph node invasion (N0).
-
Clinical Stage : T ≥ T1c-T2a and < T3b Or T1b or c with PSA ≤ 10 ng/ml . Or T1b or c with Gleason ≥ 6
-
PSA < 30 ng/ml.
-
Signs and symptoms according to NCI/CTC v3.0 < grade 2
-
ECOG Performance status ≤ 1
-
Absence of hip prothesis
-
Absence de endopenian stent
-
Patient aged > 18 and < 80
-
Patient affiliated with social security
-
Written informed consent, dated and signed
Exclusion Criteria for prostate cancer patients:
-
Antecedents of invasive cancer (unless if treated more than 5 years ago without evolution) except basocellular carcinoma
-
positive biopsy of seminal vesicle
-
PSA ≥ 30 ng/ml for two successive dosages
-
Previous pelvic irradiation
-
Previous radical prostatectomy for cancer
-
Patients with another systemic disease (cardiovascular, renal, hepatic, pulmonary embolism, etc.) non stabilised or generalised sclerodermitis.
-
Patients known to be HIV seropositive (no specific test is necessary for defining eligibility)
-
Known homozygote ATM (Ataxy telangiectasy) mutation
-
Impossibility for a correct follow up (for social family or geographical reasons)
-
Patients incapable of providing consent, protected majors, vulnerable persons
-
Patients participating in other clinical trials
Inclusion Criteria for breast cancer patients:
-
Breast Conservative surgery
-
Non metastatic, M0
-
negative surgical margins
-
T1, T2; negative sentinel lymph node N0, N1 or N2.
-
Signs and symptoms according to NCI/CTC v3.0 < grade 2
-
Patient aged over 18 years and less than 60 or more than 60 with an indication for boost irradiation.
-
Patient affiliated with social security
-
Written informed consent, dated and signed
Exclusion Criteria for breast cancer patients:
-
Metastatic patients
-
Bilateral breast cancer (concomitant or previous) except in situ
-
T4 or N3 or treated by mastectomy
-
Patients with chemotherapy or neoadjuvant hormonotherapy
-
Patients with a previous other cancer within the last 5 years EXCEPT basocellular carcinoma of the skin or in situ cancer of the uterus.
-
Patients with another systemic disease (cardiovascular, renal, hepatic, pulmonary embolism, etc.) non stabilised or generalised sclerodermia.
-
Pregnant or breast feeding women
-
Patients known to be HIV seropositive (no specific test is necessary for defining eligibility)
-
Known homozygote ATM (Ataxy telangiectasy) mutation
-
Impossibility for a correct follow up (for social family or geographical reasons)
-
Patients incapable of providing consent, protected majors, vulnerable persons
-
Patients participating in other clinical trials
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CRLC Val d'Aurelle | Montpellier | France | 34000 |
Sponsors and Collaborators
- Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
- Principal Investigator: David Azria, CRLC Val d'Aurelle
Study Documents (Full-Text)
None provided.More Information
Publications
- Arriagada R, Mouriesse H, Sarrazin D, Clark RM, Deboer G. Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital. Int J Radiat Oncol Biol Phys. 1985 Oct;11(10):1751-7.
- Azria D, Gourgou S, Sozzi WJ, Zouhair A, Mirimanoff RO, Kramar A, Lemanski C, Dubois JB, Romieu G, Pelegrin A, Ozsahin M. Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients. Br J Cancer. 2004 Oct 4;91(7):1251-60.
- Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I, Fourquet A, Borger J, Jager J, Hoogenraad W, Collette L, Pierart M; European Organization for Research and Treatment of Cancer Radiotherapy and Breast Cancer Groups. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001 Nov 8;345(19):1378-87.
- Buchholz TA. Finding our sensitive patients. Int J Radiat Oncol Biol Phys. 1999 Oct 1;45(3):547-8.
- Cesaretti JA, Stock RG, Lehrer S, Atencio DA, Bernstein JL, Stone NN, Wallenstein S, Green S, Loeb K, Kollmeier M, Smith M, Rosenstein BS. ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):196-202.
- Crompton NE, Ozsahin M. A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity. Radiat Res. 1997 Jan;147(1):55-60.
- Crompton NE, Shi YQ, Emery GC, Wisser L, Blattmann H, Maier A, Li L, Schindler D, Ozsahin H, Ozsahin M. Sources of variation in patient response to radiation treatment. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):547-54.
- Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. 1999 Oct;17(10):3283-90.
- Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003 Jul 1;21(13):2545-50.
- Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Calais G. Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA, RTOG/EORTC, and NCI-CTC scoring systems. Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):93-8.
- Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995 Nov 1;33(4):781-96. Review.
- Dubray B. [Late complications of radiotherapy. Role of the time factor]. Bull Cancer Radiother. 1995;82(2):98-100. French.
- Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. Review.
- Fine JP. Regression modeling of competing crude failure probabilities. Biostatistics. 2001 Mar;2(1):85-97.
- Floyd DN, Cassoni AM. Intrinsic radiosensitivity of adult and cord blood lymphocytes as determined by the micronucleus assay. Eur J Cancer. 1994;30A(5):615-20.
- Hoeller U, Borgmann K, Bonacker M, Kuhlmey A, Bajrovic A, Jung H, Alberti W, Dikomey E. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol. 2003 Nov;69(2):137-44.
- Hsieh FY, Lavori PW. Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates. Control Clin Trials. 2000 Dec;21(6):552-60.
- Iannuzzi CM, Atencio DP, Green S, Stock RG, Rosenstein BS. ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects. Int J Radiat Oncol Biol Phys. 2002 Mar 1;52(3):606-13.
- Jacob R, Hanlon AL, Horwitz EM, Movsas B, Uzzo RG, Pollack A. Role of prostate dose escalation in patients with greater than 15% risk of pelvic lymph node involvement. Int J Radiat Oncol Biol Phys. 2005 Mar 1;61(3):695-701.
- Johansen J, Bentzen SM, Overgaard J, Overgaard M. Relationship between the in vitro radiosensitivity of skin fibroblasts and the expression of subcutaneous fibrosis, telangiectasia, and skin erythema after radiotherapy. Radiother Oncol. 1996 Aug;40(2):101-9.
- Kiltie AE, Ryan AJ, Swindell R, Barber JB, West CM, Magee B, Hendry JH. A correlation between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiotherapy reactions in breast cancer patients. Radiother Oncol. 1999 Apr;51(1):55-65.
- Lartigau E, Dubray B, Mornex F. [Biological mechanisms of late effects of ionizing radiations]. Cancer Radiother. 1997;1(6):669-76. Review. French.
- Latouche A, Porcher R, Chevret S. Sample size formula for proportional hazards modelling of competing risks. Stat Med. 2004 Nov 15;23(21):3263-74.
- Ozsahin M, Ozsahin H, Shi Y, Larsson B, Würgler FE, Crompton NE. Rapid assay of intrinsic radiosensitivity based on apoptosis in human CD4 and CD8 T-lymphocytes. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):429-40.
- Pepe MS, Mori M. Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data? Stat Med. 1993 Apr 30;12(8):737-51.
- Pollack A, Smith LG, von Eschenbach AC. External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era. Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):507-12.
- Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak JA, Starkschall G, Rosen I. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol. 2000 Dec 1;18(23):3904-11.
- Radford IR, Murphy TK. Radiation response of mouse lymphoid and myeloid cell lines. Part III. Different signals can lead to apoptosis and may influence sensitivity to killing by DNA double-strand breakage. Int J Radiat Biol. 1994 Feb;65(2):229-39.
- Romestaing P, Lehingue Y, Carrie C, Coquard R, Montbarbon X, Ardiet JM, Mamelle N, Gérard JP. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol. 1997 Mar;15(3):963-8.
- Słonina D, Gasińska A. Intrinsic radiosensitivity of healthy donors and cancer patients as determined by the lymphocyte micronucleus assay. Int J Radiat Biol. 1997 Dec;72(6):693-701.
- Stone HB, Coleman CN, Anscher MS, McBride WH. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003 Sep;4(9):529-36. Review.
- Thames HD, Hendry JH, Moore JV, Ang KK, Travis EL. The high steepness of dose-response curves for late-responding normal tissues. Radiother Oncol. 1989 May;15(1):49-53.
- Trotti A, Byhardt R, Stetz J, Gwede C, Corn B, Fu K, Gunderson L, McCormick B, Morrisintegral M, Rich T, Shipley W, Curran W. Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):13-47. Review.
- Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003 Jul;13(3):176-81. Review.
- TROWELL OA. The sensitivity of lymphocytes to ionising radiation. J Pathol Bacteriol. 1952 Oct;64(4):687-704.
- Withers HR, Taylor JM, Maciejewski B. Treatment volume and tissue tolerance. Int J Radiat Oncol Biol Phys. 1988 Apr;14(4):751-9.
- Zelefsky MJ, Fuks Z, Hunt M, Yamada Y, Marion C, Ling CC, Amols H, Venkatraman ES, Leibel SA. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1111-6.
- PHRC 2005 DA