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3D Conformal Radiotherapy and Cisplatin for Recurrent Malignant Glioma

Published online by Cambridge University Press:  02 December 2014

Lauren VanderSpek ,
Barbara Fisher ,
Glenn Bauman  and
David Macdonald
Lauren VanderSpek
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Barbara Fisher
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Glenn Bauman
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
David Macdonald
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
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Abstract

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Purpose:

To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas.

Methods:

From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy.

Results:

Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin.

Conclusion:

The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.

Résumé:

RÉSUMÉ: <span class='italic'> <span class='bold'>But</span></span>:

Il s'agit d'une étude visant à déterminer la dose maximale tolérée de radiothérapie conformationnelle 3D en combinaison avec l'administration de cisplatine chez les patients qui présentent une récidive de gliome malin.

<span class='italic'> <span class='bold'>Méthodes</span></span>:

Neuf patients présentant une récidive d'un gliome malin ont reçu de la radiothérapie fractionnée et du cisplatine (20 mg/m2/j IV les jours 1 - 5) au cours d'une étude clinique de phase I à dose croissante. Trois niveaux séquentiels de doses ont été évalués : 25 Gy, 30 Gy et 35 Gy, en fractions de 5 Gy. Tous les patients avaient reçu préalablement de la radiothérapie externe (dose médiane 59,4 Gy ; écart de 20 à 60 Gy) et cinq patients avaient reçu de la chimiothérapie.

<span class='italic'> <span class='bold'>Résultats</span></span>:

Six hommes et trois femmes, dont l'âge médian était de 52 ans et le score médian à l'échelle de Karnofsky était de 70, ont été inclus dans l'étude. Le volume médian de la tumeur réirradiée était de 18,9 cm (0,1 à 78,5 cm) et la durée médiane du suivi était de 8,8 mois (3,2 à 31,2 mois). Un patient, qui avait reçu 30 Gy/6 fractions, a présenté une toxicité aiguë de grade 3 réversible avec le traitement médical. Un second patient, qui avait reçu 35 Gy/7 fractions, a présenté une toxicité aiguë de grade 2 et à l'examen anatomopathologique on a constaté des phénomènes reliés à la tumeur et à l'irradiation. Un troisième patient, qui avait reçu 25 Gy/5 fractions, a présenté une toxicité tardive de grade 3 causée par la nécrose due à l'irradiation. Les réponses radiologiques étaient les suivantes : réponse complète (1 patient), réponse partielle (1 patient) et maladie stable (2 patients). La survie globale médiane était de 8,8 mois (IC de 95% : 8,0 à 9,9), et la survie médiane sans récidive était de 2,0 mois (IC de 95% : 1,4 à 4,4). Sept patients ont reçu de la chimiothérapie après la réirradiation et du cisplatine.

<span class='italic'> <span class='bold'>Conclusion</span></span>:

La dose maximale tolérée de radiothérapie conformationnelle 3D était de 30 Gy en 6 fractions associée à du cisplatine à faible dose. Ce traitement a été bien toléré en ce qui concerne la toxicité aiguë chez nos patients. Ce régime de traitement s'est avéré modestement efficace dans le traitement de la récidive du gliome malin. La combinaison de réirradiation conformationnelle à d'autres agents systémiques mérite d'être étudiée. Nous recommandons actuellement la dose de 30 Gy en 6 fractions chez des patients sélectionnés.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 35 , Issue 1 , March 2008 , pp. 57 - 64
Copyright
Copyright © The Canadian Journal of Neurological 2008

References

1. Grosu, AL, Weber, WA, Franz, M, Stark, S, Piert, M, Thamm, R, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2005; 63: 511–9.Google Scholar
2. Nieder, C, Grosu, AL, Mehta, MP, Andratschke, N, Molls, M. Treatment of malignant gliomas: radiotherapy, chemotherapy and integration of new targeted agents. Expert Rev Neurother. 2004; 4: 691–703.Google Scholar
3. Gaspar, LE, Fisher, BJ, Macdonald, DR, LeBer, DV, Halperin, EC, Schold, SC Jr., et al. Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment. Int J Radiat Oncol Biol Phys. 1992; 24: 55–7.Google Scholar
4. Hochberg, FH, Pruitt, A. Assumptions in the radiotherapy of glioblastoma. Neurology. 1980; 30: 907–11.Google Scholar
5. Lee, SW, Fraass, BA, Marsh, LH, Herbort, K, Gebarski, SS, Martel, MK, et al. Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999; 43: 79–88.Google Scholar
6. Guyotat, J, Signorelli, F, Frappaz, D, Madarassy, G, Ricci, AC, Bret, P. Is reoperation for recurrence of glioblastoma justified? Oncol Rep. 2000; 7: 899–904.Google Scholar
7. Bauman, GS, Sneed, PK, Wara, WM, Stalpers, LJ, Chang, SM, McDermott, MW, et al. Reirradiation of primary CNS tumors. Int J Radiat Oncol Biol Phys. 1996; 36: 433–41.Google Scholar
8. Brandes, A, Vastola, F, Monfardini, S. Reoperation in recurrent high-grade gliomas: literature review of prognostic factors and outcome. Am J Clin Oncol. 1999; 22: 387–90.Google Scholar
9. Stupp, R, Hegi, M, van den Bent, M, Mason, W, Weller, M, Mirimanoff, R, et al. Changing paradigms - an update on the multidisciplinary management of malignant glioma. Oncologist. 2006; 11: 165–80.Google Scholar
10. Butowski, N, Sneed, P, Chang, S. Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol. 2006; 24: 1273–80.Google Scholar
11. Voynov, G, Kaufman, S, Hong, T, Pinkerton, A, Simon, R, Dowsett, R. Treatment of recurrent malignant gliomas with stereotactic intensity modulated radiation therapy. Am J Clin Oncol. 2002; 25: 606–11.Google Scholar
12. Ernst-Stecken, A, Ganslandt, O, Lambrecht, U, Sauer, R, Grabenbauer, G. Survival and quality of life after hypofractionated stereotactic radiotherapy for recurrent malignant glioma. J Neurooncol. 2007; 81(3):287–94.Google Scholar
13. Gutin, P, Leibel, S, Wara, W, Choucair, A, Levin, V, Philips, T, et al. Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources. J Neurosurg. 1987; 67: 864–73.Google Scholar
14. Huncharek, M, Muscat, J. Treatment of recurrent high grade astrocytoma; results of a systematic review of 1,415 patients. Anticancer Res. 1998; 18: 1303–11.Google Scholar
15. Glass, J, Silverman, C, Axelrod, R, Corn, B, Andrews, D. Fractionated stereotactic radiotherapy with cis-platinum radiosensitization in the treatment of recurrent, progressive, or persistent malignant astrocytoma. Am J Clin Oncol. 1997; 20: 226–9.Google Scholar
16. Arcicasa, M, Roncadin, M, Bidoli, E, Dedkov, A, Gigante, M, Trovo, M. Reirradiation and lomustine in patients with relapsed highgrade gliomas. Int J Radiat Oncol Biol Phys. 1999; 43: 789–93.CrossRefGoogle ScholarPubMed
17. Peiffert, D. Rationale and progress of the phase III trial: intensification of the treatment of locally advanced squamous cell carcinoma of the anal canal. Cancer Radiother. 2003; 7 Suppl 1: 100–7.Google Scholar
18. Flam, M, John, M, Pajak, TF, Petrelli, N, Myerson, R, Doggett, S, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996; 14: 2527–39.CrossRefGoogle ScholarPubMed
19. Keys, HM, Bundy, BN, Stehman, FB, Muderspach, LI, Chafe, WE, Suggs, CL III, 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.CrossRefGoogle ScholarPubMed
20. Peters, WA III, Liu, PY, Barrett, 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: 1606–13.Google Scholar
21. 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: 1144–53.Google Scholar
22. Eifel, PJ, Winter, K, Morris, M, Levenback, C, Grigsby, PW, Cooper, J, 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.Google Scholar
23. Whitney, CW, Sause, W, Bundy, BN, Malfetano, JH, Hannigan, EV, Fowler, WC Jr., 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.Google Scholar
24. Sharma, VM, Wilson, WR. Radiosensitization of advanced squamous cell carcinoma of the head and neck with cisplatin during concomitant radiation therapy. Eur Arch Otorhinolaryngol. 1999; 256: 462–5.Google Scholar
25. Sauer, R, Dunst, J, Altendorf-Hofmann, A, Fischer, H, Bornhof, C, Schrott, KM. Radiotherapy with and without cisplatin in bladder cancer. Int J Radiat Oncol Biol Phys. 1990; 19: 687–91.CrossRefGoogle ScholarPubMed
26. Stewart, D, Leavens, M, Maor, M, Feun, L, Luna, M, Bonura, J, et al. Human central nervous system distribution of cisdiamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Res. 1982; 42: 2474–9.Google Scholar
27. Chamberlain, M, Barba, D, Komanik, P, Benson, A, Saunders, W, Shea, M. Toxicity and safety study of concurrent cisplatin and I125 brachytherapy. Arch Neurol. 1995; 52: 162–7.Google Scholar
28. Shepherd, S, Laing, R, Cosgrove, V, Warrington, A, Hines, F, Ashley, S, et al. Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. Int J Radiat Oncol Biol Phys. 1997; 37: 393–8.Google Scholar
29. Shaw, E, Scott, C, Souhami, L, Dinapoli, R, Kline, R, Loeffler, J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000; 47: 291–8.Google Scholar
30. Macdonald, D, Cascino, T, Schold, SJ, Cairncross, J. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990; 8: 1277–80.Google Scholar
31. Kaplan, E, Meier, P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958; 53: 457–81.Google Scholar
32. International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon beam therapy. ICRU Report 50. 50. Bethesda, MD; 1993.Google Scholar
33. Lichter, A, Sandler, H, Robertson, J, Lawrence, T, Ten Haken, R, McShan, D, et al. Clinical experience with three-dimensional treatment planning. Semin Radiat Oncol. 1992; 2: 257–66.Google Scholar
34. Dhermain, F, Ducreux, D, Bidault, F, Bruna, A, Parker, F, Roujeau, T, et al. Use of the functional imaging modalities in radiation therapy treatment planning in patients with glioblastoma. Bull Cancer. 2005; 92: 333–42.Google Scholar
35. Larson, D, Prados, M, Lamborn, K, Smith, V, Sneed, P, Chang, S, et al. Phase II study of high central dose gamma knife radiosurgery and marimastat in patients with recurrent malignant glioma. Int J Radiat Oncol Biol Phys. 2002; 54: 1397–404.Google Scholar
36. Lederman, G, Arbit, E, Odaimi, M, Lombardi, E, Wrzolek, M, Wronski, M. Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report. Int J Radiat Oncol Biol Phys. 1998; 40: 661–6.Google Scholar
37. Schafer, U, Micke, O, Schuller, P, Schuck, A, Willich, N. The effect of sequential radiochemotherapy in preirradiated malignant gliomas in a phase II study. J Neurooncol. 2004; 67: 233–9.Google Scholar
38. Schonekaes, K, Mucke, R, Panke, J, Rama, B, Wagner, W. Combined radiotherapy and temozolomide in patients with recurrent high grade glioma. Tumori. 2002; 88: 28–31.Google Scholar
39. Laing, W, Warrington, A. Efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent gliomas (phase I/II study). Radiother Oncol. 1993; 27: 22–9.Google Scholar
40. Hudes, R, Corn, B, Werner-Wasik, M, Andrews, D, Rosenstock, J, Thoron, L, et al. A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Int J Radiat Oncol Biol Phys. 1999; 43: 293–9.Google Scholar
41. Vordermark, D, Kolbl, O, Ruprecht, K, Vince, G, Bratengeier, K, Flentje, M. Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer. 2005; 5: 55.Google Scholar
42. Dhermain, F, de Crevoisier, R, Parker, F, Cioloca, C, Kaliski, A, Beaudre, A, et al. Role of radiotherapy in recurrent gliomas. Bull Cancer. 2004; 91: 883–9.Google Scholar
43. Flickinger, J, Kondziolka, D, Pollock, B, Maitz, A, Lunsford, L. Complications from arteriovenous malformation radiosurgery: multivariate analysis and risk modeling. Int J Radiat Oncol Biol Phys. 1997; 38: 485–90.Google Scholar
44. Cho, K, Hall, W, Gerbi, B, Higgins, P, McGuire, W, Clark, H. Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas. Int J Radiat Oncol Biol Phys. 1999; 45: 1133–41.Google Scholar
45. Schultheiss, T, Kun, L, Ang, K, Stephens, L. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys. 1995; 31: 1093–112.Google Scholar
46. Shapiro, W, Green, S, Burger, P, Mahaley, MJ, Selker, R, VanGilder, J, et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg. 1989; 71: 1–9.Google Scholar
47. Enami, B, Lyman, J, Brown, A, Coia, L, Goitein, M, Munzenrider, JE. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991; 21: 109–22.Google Scholar
48. Sheline, G, Wara, W, Smith, V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980; 6: 1215–28.Google Scholar
49. Flickinger, J, Deutsch, M, Lunsford, L. Repeat megavoltage irradiation of pituitary and suprasellar tumors. Int J Radiat Oncol Biol Phys. 1989; 17: 171–5.Google Scholar
50. Flickinger, J, Lunsford, L, Kondziolka, D. Dose prescription and dose-volume effects in radiosurgery. Neurosurg Clin N Am. 1992; 3: 51–9.Google Scholar
51. Coughlin, C, Scott, C, Langer, C, Coia, L, Curran, W, Rubin, P. Phase II, two-arm RTOG trial (94-11) of bischloroethylnitrosurea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 Gy) based on tumor volume (>20 or < or = 20 cm(2), respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients. Int J Radiat Oncol Biol Phys. 2000; 48: 1351–8.Google Scholar
52. Wood, J, Green, S, Shapiro, W. The prognostic importance of tumor size in malignant gliomas: a computed tomographic scan study by the Brain Tumor Cooperative Group. J Clin Oncol. 1988; 6: 338–43.Google Scholar
53. Curran, W, Scott, C, Weinstein, A, Martin, L, Nelson, J, Phillips, T, et al. Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02. J Clin Oncol. 1993; 11: 857–62.Google Scholar
54. Stupp, R, van den Bent, M, Hegi, M. Optimal role of temozolomide in the treatment of malignant gliomas. Curr Neurol Neurosci Rep. 2005; 5: 198–206.CrossRefGoogle ScholarPubMed
55. Stupp, R, Mason, WP, van den Bent, MJ, Weller, M, Fisher, B, Taphoorn, MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352: 987–96.Google Scholar
56. Stupp, R, Pavlidis, N, Jelic, S. ESMO minimum clinical recommendations for diagnosis, treatment and follow-up in malignant glioma. Ann Oncol. 2005; 16: i64–i65.Google Scholar
57. Douple, E, Richmond, R. Enhancement of the potentiation of radiotherapy by platinum drugs in a mouse tumor. Int J Radiat Oncol Biol Phys. 1982; 8: 501–3.Google Scholar
58. Fu, K. Biological basis for the interaction of chemotherapeutic agents and radiation therapy. Cancer. 1985; 55: 2123–30.Google Scholar
59. Phillips, T, Fu, K. The interaction of drug and radiation effects on normal tissues. Int J Radiat Oncol Biol Phys. 1978; 4: 59–64.Google Scholar
60. Douple, E, Eaton, W, Tulloh, M. Skin radiosensitization studies using combined cis-dichlorodiaminneplatinum (II) and radiation. Int J Radiat Oncol Biol Phys. 1979; 5: 1383–5.Google Scholar
61. Wilkins, D, Ng, C, Raaphorst, G. Cisplatin and low dose rate irradiation in cisplatin resistant and sensitive human glioma cells. Int J Radiat Oncol Biol Phys. 1996; 36: 105–11.Google Scholar
62. Sheleg, S, Korotkevich, E, Zhavrid, E, Muravskaya, G, Smeyanovich, A, Shanko, Y, et al. Local chemotherapy with cisplatin-depot for glioblastoma multiforme. J Neurooncol. 2002; 60: 53–9.Google Scholar
63. Thompson, S, Davis, L, Kornfeld, M, Hilgers, R, Standefer, J. Cisplatin neuropathy, clinical, electrophysiology, morphologic, and toxicologic studies. Cancer. 1984; 54: 1269–75.Google Scholar
64. Stewart, D, Leavens, M, Maor, M, Feun, L, Luna, M, Bonura, J, et al. Human central nervous system distribution of cis-Diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Res. 1982; 42: 247–9.Google Scholar
65. Rich, J, Reardon, D, Peery, T, Dowell, JM, Quinn, JA, Penne, KL, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol. 2004; 22: 133–42.Google Scholar
66. Fine, HA, Figg, WD, Jaeckle, K, Wen, PY, Kyritsis, AP, Loeffler, JS, et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol. 2000; 18: 708–15.Google Scholar
67. Brem, H, Piantadosi, S, Burger, PC, Walker, M, Selker, R, Vick, NA, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas: the polymer-brain tumor treatment group. Lancet. 1995; 345: 1008–12.Google Scholar