Response of locally advanced rectal cancer (LARC) to radiochemotherapy: DW-MRI and multiparametric PET/CT in correlation with histopathology

Abstract

Aim To prospectively evaluate histological significance and predictive value of changes in apparent diffusion coefficient (ADC) and ¹⁸F-FDG PET/CT parameters in locally advanced rectal cancer (LARC) after neoadjuvant radiochemotherapy (RCT).

Methods Twenty-one patients with untreated LARC underwent pre-RCT and post-RCT ¹⁸F-FDG PET/CT and diffusion-weighted magnetic resonance imaging (DW-MRI), followed by surgery. For both datasets, two readers measured the tumor SUVmax, SUVmean, MTV, TLG, ADCmin, ADCmean, and respective differences (∆SUVmax, ∆SUVmean, ∆MTV, ∆TLG, ∆ADCmin, ∆ADCmean) for the whole tumor. Tumor regression grade according to Mandard (TRGm), percentage of residual tumor cells and fibrosis were estimated by two pathologists in consensus. Relationship between parameters was assessed on stepwise multivariate regression analysis and ROC curve analysis to evaluate their performance and predict the treatment response.

Results Eighteen LARCs were analyzed. SUVmax and SUVmean decreased from 21.3 ± 8.9 to 9.3 ± 5.5 g/mL, (p = 0.0002) and 12.3 ± 5.1 to 5.4 ± 3.1 g/mL, (p = 0.0002), respectively, after RCT, whereas ADCmin and ADCmean increased from 396 ± 269 to 573 ± 313×10^–6mm²/s (p = 0.014) and 1159 ± 212 to 1355 ± 194×10^–6mm²/s (p = 0.0008), respectively. TRGm and percentage of residual tumor cells independently correlated with post-RCT SUVmean (β = 0.73 and β = 0.76, p < 0.001) and post-RCT SUVmax (β = 0.72 and β = 0.78, p < 0.001), whereas percentage of fibrosis independently correlated with ∆ADCmean (β = 0.38, p = 0.008). Post-RCT, SUVmax and SUVmean performed well in predicting TRGm < 3 and residual tumor cells ≤ 20 %. ΔADCmean predicted fibrosis > 70 % well.

Conclusion Post-RCT SUVmean, SUVmax and ∆ADCmean are complementary parameters for respectively evaluating residual tumor burden and amount of fibrosis in LARC. However, only SUV independently correlated with TRGm.

Zusammenfassung

Ziel Prospektive Untersuchung des Änderungseinflusses von apparenten Diffusionskoeffizienten (ADC) und ¹⁸F-FDG PET/CT Parameter auf Histologie und Prognose bei lokal fortgeschrittenem und mit neoadjuvanter Radiochemotherapie (NRC) behandelten Rektumkarzinom (LFRK)

Methoden Einundzwanzig Patienten mit unbehandeltem LFRK wurden vor und nach NRC mit ¹⁸F-FDG PET/CT und diffusionsgewichteter Magnetresonanztomographie (DW-MRI) untersucht. Anschliessend wurden sie operiert. Für beide Datensätze wurden von zwei Beobachtern nach Einschluss des gesamten Tumors SUVmax, SUVmean, MTV, TLG, ADCmin, ADCmean sowie die jeweiligen Unterschiede (∆SUVmax, ∆SUVmean, ∆MTV, ∆TLG, ∆ADCmin, ∆ADCmean) gemessen.

Zwei Pathologen ermittelten gemeinsam das Tumorregressionsausmass gemäss Mandard (TRGm), sowie den residuellen Tumorzellen- und Fibroseprozentsatz. Mit multivariater Regression und ROC-Kurvenanalyse wurde das Parameterverhältnis untereinander, und ihre Fähigkeit, den Behandlungserfolg vorherzusagen, errechnet.

Ergebnisse Achtzehn LFRK wurden analysiert. Nach NRC verringerten sich SUVmax und SUVmean von 21.3 ± 8.9 auf 9.3 ± 5.5 g/mL (p = 0.0002), beziehungsweise von 12.3 ± 5.1 auf 5.4 ± 3.1 g/mL (p = 0.0002), während ADCmin und ADCmean von 396 ± 269 auf 573 ± 313×10^–6mm²/s (p = 0.014), beziehungsweise von 1159 ± 212 auf 1355 ± 194×10^–6mm²/s (p = 0.0008) anstiegen. TRGm und der residuelle Tumorzellenprozentsatz korrelierten unabhängig mit post-NRC SUVmean (β = 0.73 und β = 0.76, p < 0.001) und post-NRC SUVmax (β = 0.72 und β = 0.78, p < 0.001), während der Fibroseprozentsatz unabhängig mit ∆ADCmean (β = 0.38, p = 0.008) korrelierte.

Post-NRC SUVmax und SUVmeanerlaubten die Vorhersage von TRGm < 3 und von residuellen Tumorzellen ≤ 20 %, sowie ΔADCmean eine Fibrose > 70 %.

Schlussfolgerung Post-NRC SUVmean, SUVmax und ∆ADCmean sind komplementäre Parameter, um die residuelle Tumorlast, beziehungsweise den Fibroseanteil von LFRK zu beurteilen. Jedoch korreliert nur der SUV unabhängig mit TRGm.

Key words

Rectal neoplasms - neoadjuvant therapy - chemoradiotherapy - diffusion magnetic resonance imaging - positron emission tomography computed tomography

Schlüsselwörter

Rektumtumoren - neoadjuvante Therapie - Radiochemotherapie - diffusionsgewichtete Magnetresonanztomographie - Positronen-Emissions-Computertomographie

^* contributed equally to this work

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