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Neoadjuvante radiochemotherapie von weichteilsarkomen

Optimierung der lokalen funktionserhaltenden tumorkontrolle

Preoperative radiochemotherapy in soft tissue sarcomas for improving local tumor control and postoperative functional outcome

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Abstract

Hintergrund

Das Erreichen einer R0-Resektion bei gutem funktionellen Ergebnis und eine lokale Tumorkontrollrate von > 90% gelten bei der Therapie von Weichteilsarkomen als oberstes Ziel.

Patienten und Methode

Wegen fraglich kurativer Resektionsmoglichkeit wurden 23 Patienten mit Weichteilsarkomen (Stadium rIA: 2, rIIA: 5, IIA: 4, IIB: 2, III: 7, IV: 3), davon 16 Primär- und sieben Rezidivtumoren, einer neoadjuvanten Radiochemotherapie bis fünf Wochen vor der Operation unterzogen. Radiotherapie: akzelerierte Hyperfraktionierung, 2mal 1,5 bis 1,6 Gy/d, fünfmal wöchentlich, Pause in der dritten Woche, bis 60 bis 64 Gy/fünf Wochen (n = 18) oder bei einigen Becken-oder retroperitonealen Tumoren Normalfraktionierung mit 5mal 1,8 Gy/Woche bis 50,4 bis 69 Gy. Chemotherapie: simultan an den Tagen 1 bis 5 und 29 bis 33 1,5 g Ifosfamid/m2 Körperoberfläche (KO) pro Tag unter Mesna-Prophylaxe plus 50 mg Doxorubicin/m2 KO an Tag 2 und 30. Die mediane Nachbeobachtungszeit beträgt median 26 (zwei bis 94) Monate.

Ergebnisse

1. Die Resektion von 20/22 Patienten erfolgte R0 und je einmal RX und R2. Bei 4/21 (19%) Tumoren gab es ein Downstaging, davon einmal von T2 nach ypT1 und in drei Fallen nach ypT0. 2. Die lokale Tumorkontrolle nach RO/RX-Resektion beträgt 100%. 3. Ohne prognostischen Einfluß auf Tumoransprechen und lokale Kontrolle waren die Variablen Primärtumor vs. Rezidiv, Grading, Stadium und Geschlecht. 4. Vier zusätzliche Patienten entwickelten Fernmetastasen. Nach drei Jahren beträgt die Gesamtüberlebensrate 83%, das fernmetastasenfreie Überleben 68% und das krankheitsfreie Überleben 64%. 5. l/22mal trat bei ungünstigem Tumorsitz eine Wundheilungsstörung auf. Therapielimitierend waren eine Leukopenie Grad 3 und 4 nach WHO bei 21/46 Chemotherapiezyklen. Eine Patientin starb daran therapiebedingt vor der geplanten Operation. 6. Das funktionelle Resultat war bei 18/22 operierten Patienten ausgezeichnet.

Schlußfolgerung

Ab Stadium IIA nach AJCC/UICC (1997) und bei allen Rezidiven wird präoperativ eine simultane Radiochemotherapie mit Ifosfamid und Doxorubicin empfohlen. Eine akzeleriert hyperfraktionierte Radiotherapie mit 60 bis 64 Gy wird dabei ohne gravierende Wundheilungsstorungen oder chronische Toxizität toleriert.

Abstract

Background

Adequate local control rates > 90% and acceptable functional results are the paramount goals in the treatment of soft-tissue sarcoma. Purpose of this paper is to evaluate response, long-term control, functional outcome arid toxicity following neoadjuvant radiochemotherapy (RCT) in advanced and recurrent soft tissue sarcoma.

Patients and Methods

Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible entered the study. Sixteen patients had primary and 7 patients recurrent sarcoma. The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-course radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of 1 week after 30 Gy) with concomitant chemotherapy using adriamycin (50 mg/m2/d on days 2 and 30) and ifosfamide (1.5 g/m2/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 months).

Results

Twenty-two patients underwent surgery with a curative (R0) resection being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-downstaging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 patient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED-and distant-metastases-free survival rates were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dying of septicemia. The functional results were good to excellent in 18/22 (82%) patients.

Conclusion

Accelerated split-course radiation with 60 to 64 Gy and concurrent chemotherapy using adriamycin/ifosfamide is a safe and effective treatment for soft tissue sarcoma. This regimen may be considered in all cases with recurrent and advanced disease not amenable to primary curative or limb sparing surgery.

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Literatur

  1. Antman K, Crowley J, Balcerzak P, et al. An intergroup phase III randomized study of Doxorubicin and Dacarbazine with or without Ifosfamide and Mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 1993;11:1276–85.

    CAS  PubMed  Google Scholar 

  2. Barkley HT, Martin RG, Romsdahl MM, et al. Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection. Int J Rad Oncol Biol Phys 1988;14:693–9.

    Google Scholar 

  3. Bramwell V, Rouesse J, Steward W, et al. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma-reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1994;12:1137–49.

    CAS  PubMed  Google Scholar 

  4. Brant TA, Parsons JT, Marcus RB, et al. Preoperative irradiation for soft tissue sarcomas of the trunk and extremities in adults. Int J Radiat Oncol Biol Phys 1990;19:899–906.

    CAS  PubMed  Google Scholar 

  5. Cancer Statistics 1997. Ca-A Cancer Journal for Clinicians. Am Cancer Soc Jan/Febr 1997:Vol 1.

  6. Cheng EY, Dusenbery KE, Winters MR, et al. Soft tissue sarcoma: Preoperative versus postoperative radiotherapy. J Surg Oncol 1996;61:90–9.

    Article  CAS  PubMed  Google Scholar 

  7. Coindre JM, Terrier P, Bul NB, et al. Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Feration of Cancer Centers Sarcoma Group. J Clin Oncol 1996;14:869–77.

    CAS  PubMed  Google Scholar 

  8. Cordon-Cardo C, Latres E, Drobnjak M, et al. Molecular abnormalitites of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res 1994;54:794–9.

    CAS  PubMed  Google Scholar 

  9. Dinges S, Budach V, Budach W, et al. Lokalrezidive im Erwachsenenalter: Eine retrospektive Analyse prognostischer Faktoren in 102 Fallen nach Chirurgie und Strahlentherapie. Strahlenther Onkol 1996;172:106–7.

    CAS  PubMed  Google Scholar 

  10. Dreinhofer KE, Akerman M, Willen H, et al. Proliferating cell nuclear antigen (PCNA) in high-grade prognostic value in 48 patients. Int J Cancer 1994;59:379–82.

    Article  CAS  PubMed  Google Scholar 

  11. Dunst J, Sauer R. Therapie des Ewing-Sarkoms. Strahlenther Onkol 1993;169:695–703.

    CAS  PubMed  Google Scholar 

  12. Edmonson JH, Ryan LM, Blum RH, et al. Randomized comparison of Doxorubicin alone versus Ifosfamide plus Doxorubicin or Mttomycin, Doxorubicin, and Cisplatin against advanced soft tissue sarcomas. J Clin Oncol 1993;11:1269–75.

    CAS  PubMed  Google Scholar 

  13. Enzinger FM, Weiss SW. Soft tissue tumors. St. Louis-Toronto-London: CV Mosby, 1983.

    Google Scholar 

  14. Fagundes HM, Lai PP, Dehner LP, et al. Postoperative radiotherapy for malignant fibrous histiocytoma. Int J Radiat Oncol Biol Phys 1992;23: 615–9.

    CAS  PubMed  Google Scholar 

  15. Herbert SH, Corn BW, Solin LJ, et al. Limb-preserving treatment for soft tissue sarcomas of the extremities. Cancer 1993;72:1230–8.

    Article  CAS  PubMed  Google Scholar 

  16. Kawai A, Noguchi M, Beppu Y, et al. Nuclear immunoreaction of p53 protein in soft tissue sarcomas. Cancer 1994;73:2499–505.

    Article  CAS  PubMed  Google Scholar 

  17. Lawrence W {jrJr}, Donegan WL, Natarajan N, et al. Adult soft tissue sarcomas. Ann Surg 1987;205:349–59.

    Article  PubMed  Google Scholar 

  18. LeVay J, O’Sullivan B, Catton C, et al. Outcome and prognostic factors in soft tissue sarcoma in the adult. Int J Radiat Oncol Biol Phys 1993;27: 1091–9.

    CAS  PubMed  Google Scholar 

  19. Mazeron JJ, Suit HD. Lymph nodes as sites of metastases from sarcomas of soft tissue. Cancer 1987;60:1800–8.

    Article  CAS  PubMed  Google Scholar 

  20. Pezzi CM, Pollock RE, Evans HL, et al. Preoperative chemotherapy for soft-tissue sarcomas of the extremities. Ann Surg 1990:211:476–80.

    Article  CAS  PubMed  Google Scholar 

  21. Pisters PW, Patel SR, Varma DG, et al. Preoperative chemotherapy for stage IIIB extremity soft tissue sarcoma:long-term results from a single institution. J Clin Oncol 1997;15:3481–7.

    CAS  PubMed  Google Scholar 

  22. Rydholm A, Berg NO. Prognosis for soft tissue sarcoma in the locomotor system. Acta Pathol Microbiol Immunol Scand 1984;92:375–86.

    CAS  Google Scholar 

  23. Rydholm A, Berg NO, Gullberg B, et al. Epidemiology of soft-tissue sarcoma in the locomotor system. Acta Pathol Microbiol Immunol Scand 1984;92:363–74.

    CAS  Google Scholar 

  24. Sadoski C, Suit H, Rosenberg A, et al. Preoperative radiation, surgical margins and local control of extremity sarcomas of soft tissues. J Surg Oncol 1993;52:223–30.

    Article  CAS  PubMed  Google Scholar 

  25. Sarcoma Meta-Analysis Collaboration. Adjuvant chemotherapy for localized resectabel soft-tissue sarcoma of adults:meta-analysis of indivudual data. Lancet 1997;350:1647–54.

    Google Scholar 

  26. Sauer H. Adjuvante Chemotherapie bei Weichteilsarkomen? Strahlenther Onkol 1995;171:185–94.

    CAS  PubMed  Google Scholar 

  27. Stuschke M. Stellenwert der neoadjuvanten Radiochemotherapie bei undifferenzierten Weichteilsarkomen. Strahlenther Onkol 1994;170:480–3.

    CAS  PubMed  Google Scholar 

  28. Suit HD. Tumors of the connective and supportive tissues. Radiother Oncol 1995;34:93–104.

    Article  CAS  PubMed  Google Scholar 

  29. Tanabe KK, Pollock RE, Ellis LM, et al. Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer 1994;73:1652–9.

    Article  CAS  PubMed  Google Scholar 

  30. Todoroki T, Suit HD. Therapeutic advantage in pre-operative single dose radiation combined with conservative and radical surgery in different size murine fibrosarcomas. J Surg Oncol 1985;29:207–15.

    Article  CAS  PubMed  Google Scholar 

  31. Wagner W, Willich N, Rübe C et al. Behandlungsergebnisse bei Weichteilsarkomen im Erwachsenenalter. Strahlenther Onkol 1994;170:91–9.

    CAS  PubMed  Google Scholar 

  32. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197–203.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Strahlenklinik der Universität Erlangen-Nürnberg, Deutschland

    Rolf Sauer, Ulrike Schuchardt & Gerhard G. Grabenbauer

  2. Chirurgische Klinik der Universität Erlangen-Nürnberg, Deutschland

    Werner Hohenberger

  3. Institut für Pathologie der Universität Leipzig, Deutschland

    Christian Wittekind

  4. Pathologisches Institut der Universität Erlangen-Nürnberg, Deutschland

    Thomas Papadopoulos

  5. Klinik für Strahlentherapie der Universität Rostock, Deutschland

    Rainer Fietkau

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Sauer, R., Schuchardt, U., Hohenberger, W. et al. Neoadjuvante radiochemotherapie von weichteilsarkomen. Strahlentherapie und Onkologie 175, 259–266 (1999). https://doi.org/10.1007/BF02743576

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