Advertisement

Strahlentherapie und Onkologie

, Volume 187, Issue 11, pp 736–743 | Cite as

PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

  • Andrei Fodor
  • Claudio Fiorino
  • Italo Dell’Oca
  • Sara Broggi
  • Marcella Pasetti
  • Giovanni Mauro Cattaneo
  • Luigi Gianolli
  • Riccardo Calandrino
  • Nadia Gisella Di Muzio
Original Article

Abstract

Purpose

To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM).

Patients and Methods

A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV).

Results

Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2–10 weeks. Median overall survival was 8 months (1.2–50.5 months) and 20 months (4.3–33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003).

Conclusions

The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.

Key Words

Helical tomotherapy Malignant pleural mesothelioma IGRT PET imaging 

PET-geführte Dosiseskalationsstudie mit Tomotherapie bei malignen Pleuramesotheliomen

Zusammenfassung

Zweck

Prüfung der Machbarkeit von Salvage-Strahlentherapie mit der Hilfe PET-geführter helikaler Tomotherapie bei Patienten mit progredientem malignem Pleuramesotheliom (MPM).

Patienten und Methoden

Die erste Gruppe von 12 aufeinanderfolgenden MPM-Patienten wurde mit 56 Gy/25 Fraktionen im Planungszielvolumen behandelt. Eine FDG-PET/CT-Simulation wurde stets durchgeführt, um alle positiven Lymphknoten und MPM-Infiltrationen einzuschließen. Danach wurde eine zweite Gruppe von 12 aufeinanderfolgenden Patienten mit der gleichen Dosis auf der gesamten Pleura behandelt mit gleichzeitigem integriertem Boost von 62,5 Gy auf die FDG–PET/CT-positiven Bereiche (BTV).

Ergebnisse

Gute dosimetrische Ergebnisse wurden in beiden Gruppen erzielt. In der ersten Gruppe wurde keine akute oder späte Grad-3-Toxizität (RTOG / EORTC) berichtet, während drei Fälle von später Grad-3-Pneumonitis in der zweiten Gruppe auftraten. Die Symptome hielten 2 bis 10 Wochen an. Das mediane Gesamtüberleben betrug 8 Monate (1,2–50,5 Monate) und 20 Monate (4,3–33,8 Monate) ab Therapiebeginn in Gruppe I und II (p = 0,19). Es wurde signifikanter Einfluss der Strahlentherapie auf Lokalrezidive beobachtet (mediane Zeit bis zum Lokalrezidiv: 8 vs 17 Monate; Rate 1-jähriger Lokalrezidivfreiheit: 16% vs 81%, p = 0,003).

Schlussfolgerungen

Die Ergebnisse dieser Pilotstudie sprechen für die Planung einer Phase-III-Studie der kombinierten sequentiellen Radiochemotherapie mit Dosiseskalation auf BTV bei inoperablen Patienten.

Schlüsselwörter

Helikale Tomotherapie Maligne Pleuramesotheliome IGRT PET-Bildgebung 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ahamad A, Stevens CW, Smithe WR et al. Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2003;55:768–75.PubMedCrossRefGoogle Scholar
  2. 2.
    Allen AM, Czerminska M, Janne PA et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys 2006;65:640–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Allen AM, Den R, Wong JS et al. Influence of radiotherapy technique and dose on patterns of failure for mesothelioma patients after extrapleural pneumonectomy. Int J Radiat Oncol Biol Phys 2007;68:1366–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Benard F, Sterman D, Smith RJ et al. Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest 1998;114(3):713–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Benard F, Sterman D, Smith RJ et al. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 1999;40:1241–5.PubMedGoogle Scholar
  6. 6.
    Boutin, Rey F, Viallat J-R. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma: a randomized trial of local radiotherapy. Chest 1995;108:754–98.PubMedCrossRefGoogle Scholar
  7. 7.
    Cattaneo GM, Dell’Oca I, Broggi S et al. Treatment planning comparison between conformal radiotherapy and helical tomotherapy in case of locally advanced stage NSCLC. Radiother Oncol 2008;88:310–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Chapman E, Berenstein EG, Dieguez M et al. Radiotherapy for malignant pleural mesothelioma (Review). Cochrane Database of Systematic Reviews 2006. Art. No.: CD003880.Google Scholar
  9. 9.
    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Della Volpe A, Ferreri A, Annaloro C et al. Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total-body irradiation. Int J Radiat Oncol Biol Phys 2002;52:483–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Di Muzio N, Fiorino C, Cozzarini C et al. Phase I-II study of hypofractionated simultaneous integrated boost with tomotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2009;74:392–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Fiorino C, Alongi F, Broggi S et al. Physics aspects of prostate tomotherapy: planning optimization and image-guidance issues. Acta Oncol 2008;47: 1309–16.PubMedCrossRefGoogle Scholar
  13. 13.
    Fodor A, Di Muzio N, Cattaneo M et al. Hemithoracic helical tomotherapy for malignant pleural mesothelioma. Radiother Oncol 2008;88:S281.Google Scholar
  14. 14.
    Flores RM. The role of PET in the surgical management of malignant pleural mesothelioma. Lung Cancer 2005;49(Suppl1):S27–S32.PubMedCrossRefGoogle Scholar
  15. 15.
    Francis RJ, Byrne MJ, van der Schaaf AA et al. Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans. J Nucl Med 2007;48(9):1449–58.PubMedCrossRefGoogle Scholar
  16. 16.
    Gerbaudo VH, Sugarbaker DJ, Britz-Cunningham S et al. Assessment of malignant pleural mesothelioma with 18F-FDG dual-head gamma camera coincidence imaging: comparison with histopathology. J Nucl Med 2002;43(9):1144–9.PubMedGoogle Scholar
  17. 17.
    Giaccone G. Pleural mesothelioma: combined modality treatments. Ann Oncol 2002;13(suppl 4):217–25.PubMedGoogle Scholar
  18. 18.
    Gupta V, Mychalczak B, Krug L et al. Hemithoracic radiation therapy after pleurectomy/decortications for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2005;63:1045–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Hakkinen AM, Laasonen A, Linnainmaa K et al. Radiosensitivity of mesothelioma cell lines. Acta Oncol 1996;35:451–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Herm H, Kaiser D, Grohé C et al. Helical intensity modulated radiation therapy (tomotherapy) in the primary treatment of pleural cancers. Strahlenther Onkol 2009;185:77Google Scholar
  21. 21.
    Kristensen CA, Nottrup TJ, Berthelsen AK et al. Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignat pleural mesothelioma. Radiother Oncol 2009;92:96–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Lammering G, De Ruysscher D, van Baardwijk A et al. The use of FDG-PET to target tumors by radiotherapy. Strahlenther Onkol 2010;9:471.CrossRefGoogle Scholar
  23. 23.
    Lisenmeier C, Thoennessen D, Negretti L et al. Total body irradiation (TBI) in patients: a single-center experience after 30 years of low-dose rate irradiation. Strahlenther Onkol 2010;11:614.CrossRefGoogle Scholar
  24. 24.
    Lee YC, Light RW, Musk AW. Management of malignant pleural mesothelioma: a critical review. Curr Opin Pulm Med 2000;6:267–74.PubMedCrossRefGoogle Scholar
  25. 25.
    McAleer M, Tsao AS, Liao Z. Radiotherapy in malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2009;75:326–37.PubMedCrossRefGoogle Scholar
  26. 26.
    Munter MW, Nill S, Thilmann C et al. Stereotactic intensity modulated radiation therapy (IMRT) and inverse treatment planning for advanced pleural mesothelioma. Feasibility and initial results, Strahelenther Onkol 2003;179:535–41.CrossRefGoogle Scholar
  27. 27.
    Nakas A, Trousse DS, Martin-Ucar AE et al. Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodality therapy. Eur J Card Thorac Surg 2008;34:886–91.CrossRefGoogle Scholar
  28. 28.
    Pagan V, Ceron L, Paccagnella A et al. 5-year prospective results of trimodality treatment for malignant pleural mesothelioma. J Cardiovasc Surg 2006;47:595–601.Google Scholar
  29. 29.
    Parker C, Neville E. Lung cancer. 8: Management of malignant mesothelioma. Thorax 2003;58:809–813.PubMedCrossRefGoogle Scholar
  30. 30.
    Rice TW, Adelstein DJ, Kirby TJ et al. Aggressive multimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1994;58:24–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Rice DR, Smythe WR, Liao Z et al. Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2007;69:350–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Rusch VW. Pleurectomy/decortication in the setting of multimodality treatment for diffuse malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg 1997;9:367–372.PubMedGoogle Scholar
  33. 33.
    Schneider DB, Clary-Macy C, Challa S et al. Positron emission tomography with F18- fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2000;120:128–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Sterzing F, chubert K, Sroka-Perez G, Kalz J, Debus J, Herfarth K. Helical tomotherapy. Experiences of the first 150 patients in Heidelberg. Strahelenther Onkol 2008, 184:8–14.CrossRefGoogle Scholar
  35. 35.
    Sterzing F, Sroka-Perez G, Schubert K et al. Evaluating target coverage and normal tissue sparing in the adjuvant radiotherapy of malignant pleural mesothelioma: helical tomotherapy compared with step-and-shoot IMRT. Radiother Oncol 2008;86:251–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Sugarbaker DJ, Flores RM, Jaklitsch MT et al. Resection margins, extrapleural nodal status, and cell type to determine postoperative long-term survival in trimodal therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999;117:54–65.PubMedCrossRefGoogle Scholar
  37. 37.
    Truong MT, Marom EM, Erasmus JJ. Preoperative evaluation of patients with malignant pleural mesothelioma: role of integrated CT-PET imaging. J Thorac Imaging 2006;21(2):146–53.PubMedCrossRefGoogle Scholar
  38. 38.
    Ung YC, Yu E, Falkson C et al. The role of radiation therapy in malignant pleural mesothelioma: a systematic review. Radiother Oncol 2006;80:13–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Vogelzang NJ, Rusthoven J, Symanowski J et al. A phase III study of permetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636–44.PubMedCrossRefGoogle Scholar
  40. 40.
    Wurstbauer K, Weise H, Deutschmann H et al. Non-small cell lung cancer in stages I–III B, long-term results of definitive radiotherapy with doses ≥ 80 Gy in standard fractionation. Strahlenther Onkol 2010;10:551.CrossRefGoogle Scholar
  41. 41.
    Yajnik S, Rosenzweig KE, Mychalczak B et al. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2003;56:1319–26.PubMedCrossRefGoogle Scholar

Copyright information

© Urban & Vogel 2011

Authors and Affiliations

  • Andrei Fodor
    • 1
    • 4
  • Claudio Fiorino
    • 2
  • Italo Dell’Oca
    • 1
  • Sara Broggi
    • 2
  • Marcella Pasetti
    • 1
  • Giovanni Mauro Cattaneo
    • 2
  • Luigi Gianolli
    • 3
  • Riccardo Calandrino
    • 2
  • Nadia Gisella Di Muzio
    • 1
  1. 1.Department of RadiotherapySan Raffaele Scientific InstituteMilanItaly
  2. 2.Medical PhysicsSan Raffaele Scientific InstituteMilanItaly
  3. 3.Department of Nuclear MedicineSan Raffaele Scientific InstituteMilanItaly
  4. 4.Department of RadiotherapySan Raffaele Scientific InstituteMilanItaly

Personalised recommendations