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Korrelation histologischer und nuklearmedizinischer Befunde der Tumorregression in behandelten bösartigen Lungentumoren

Correlation of histologic results with PET findings for tumor regression and survival in locally advanced non-small cell lung cancer after neoadjuvant treatment

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Zusammenfassung

Die CT ist nach neoadjuvanter Radio-Chemo-Therapie zur Charakterisierung der Tumorregression nur begrenzt einsetzbar. Daher sollte die Wertigkeit der 18F-FDG-PET als molekulares, nichtinvasives bildgebendes Verfahren analysiert werden.

Bislang 32/100 Patienten mit NSCLC Stadium IIIA/IIIB wurden in einer multizentrischen, randomisierten Therapiestudie (LUCAS-MD) untersucht. Prätherapeutisch erfolgten eine 18F-FDG-PET und eine Spiral-CT. Der neoadjuvante Therapieblock bestand aus 2–3 Zyklen Paclitaxel und Carboplatin sowie einer simultanen Radio-Chemo-Therapie. Es folgte eine zweite PET direkt vor der Operation mit Bestimmung des Glukosemetabolismus für Primärtumor und Lymphknotenmetastasen sowie eine PET-CT-Bildfusion. Der am OP-Präparat bestimmte Regressionsgrad wurde mit den PET-Befunden und dem Überleben der Patienten korreliert.

In Lymphknoten von 10 Patienten mit kompletter Remission in der FDG-PET zeigte sich ein Regressionsgrad/RG III im OP-Präparat (Sensitivität 100%). Zu 94% wiesen die 16/32 Patienten mit kompletter Remission im Primärtumor RG IIb oder III auf, ein Patient RG IIa (falsch-negativ). Die Zweijahresüberlebenswahrscheinlichkeit bei kompletter Remission war nach 24 Monaten signifikant erhöht (76 vs. 20%, p=0,0079). Patienten mit RG III bzw. IIb lebten signikant länger als Patienten mit RG IIa bzw. I (63 vs. 36%, p=0,0123).

Der RG korreliert mit der in der FDG-PET bestimmten metabolischen Remission. Die PET eilt metabolisch dem durch die CT bestimmten Tumoransprechen nach neoadjuvanter Behandlung deutlich voraus und ermöglicht wahrscheinlich eine prospektive Aussage über den Langzeittherapieerfolg von Patienten mit NSCLC im Stadium III.

Abstract

CT cannot provide useful information in a timely manner after neoadjuvant treatment. To evaluate the role of 18F FDG PET after neoadjuvant chemoradiation for early therapy response and its effect on survival as compared to histopathologic tumor response, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD).

Inclusion criteria: histologically confirmed NSCLC stage IIIA/IIIB. Neoadjuvant treatment: 2–3 cycles with paclitaxel/carboplatin and a block of chemoradiation followed by surgery. Pretherapeutic staging: PET scan in addition to a spiral CT and/or MRI. Second PET scan after completion of neoadjuvant therapy prior to surgery. Documentation of lymph node involvement. Assessment of SUV and the metabolic tumor index for primary tumor and metastatic lymph nodes. Image fusion of PET with CT data followed by molecular radiation treatment planning. Evaluation of histologic regression grade and correlation with PET for primary tumor and each lymph node location.

All patients (10/32) with complete response in lymph node metastases detected by PET prior to surgery, had no vital tumor cells (i.e. histologic regression grade/RG III, sensitivity 100%). In primary tumors showing complete response, the RG was IIb or III, in one patient IIa (false negative in PET). False positive findings in PET are due to inflammation (5 patients, histologically confirmed). Univariate analyses: actuarial tumor-specific survival for complete metabolic remission vs. incomplete remission after 24 months: 76 vs. 20% (p=0,0079); for RG III/IIb vs. RG IIa/I after 24 months: 63 vs. 36% (p=0,0123).

18F FDG PET precedes CT in measuring the tumor response and may predict (long term) therapeutic outcome in stage III NSCLC. Histologic regression grade correlates well with metabolic remission as detected by PET.

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Danksagung

Für die exakte Dokumentation der Daten aus der LUCAS-MD-Studie sind wir Frau Frenkel zu großem Dank verpflichtet.

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Schmücking, M., Baum, R.P., Bonnet, R. et al. Korrelation histologischer und nuklearmedizinischer Befunde der Tumorregression in behandelten bösartigen Lungentumoren. Pathologe 26, 178–190 (2005). https://doi.org/10.1007/s00292-005-0758-1

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