Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

Abstract Aim: The concept of personalized medicine has brought increased awareness to the importance of inter- and intra-tumor heterogeneity for cancer treatment. The aim of this study was to explore simultaneous multi-parametric PET/MRI prior to chemoradiotherapy for cervical cancer for characterization of tumors and tumor heterogeneity. Methods: Ten patients with histologically proven primary cervical cancer were examined with multi-parametric 68Ga-NODAGA-E[c(RGDyK)]2-PET/MRI for radiation treatment planning after diagnostic 18F-FDG-PET/CT. Standardized uptake values (SUV) of RGD and FDG, diffusion weighted MRI and the derived apparent diffusion coefficient (ADC), and pharmacokinetic maps obtained from dynamic contrast-enhanced MRI with the Tofts model (iAUC60, Ktrans, ve, and kep) were included in the analysis. The spatial relation between functional imaging parameters in tumors was examined by a correlation analysis and joint histograms at the voxel level. The ability of multi-parametric imaging to identify tumor tissue classes was explored using an unsupervised 3D Gaussian mixture model-based cluster analysis.Results: Functional MRI and PET of cervical cancers appeared heterogeneous both between patients and spatially within the tumors, and the relations between parameters varied strongly within the patient cohort. The strongest spatial correlation was observed between FDG uptake and ADC (median r=-0.7). There was moderate voxel-wise correlation between RGD and FDG uptake, and weak correlations between all other modalities. Distinct relations between the ADC and RGD uptake as well as the ADC and FDG uptake were apparent in joint histograms. A cluster analysis using the combination of ADC, FDG and RGD uptake suggested tissue classes which could potentially relate to tumor sub-volumes. Conclusion: A multi-parametric PET/MRI examination of patients with cervical cancer integrated with treatment planning and including estimation of angiogenesis and glucose metabolism as well as MRI diffusion and perfusion parameters is feasible. A combined analysis of functional imaging parameters indicates a potential of multi-parametric PET/MRI to contribute to a better characterization of tumor heterogeneity than the modalities alone. However, the study is based on small patient numbers and further studies are needed prior to the future design of individually adapted treatment approaches based on multi-parametric functional imaging.

Download Full-text

Early Prediction of Treatment Outcome: Functional MR Imaging and Standard Clinical Prognostic Factors in Advanced Cervical Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2005.07.167 ◽

2005 ◽

Vol 63 ◽

pp. S97 ◽

Cited By ~ 1

Author(s):

N.A. Mayr ◽

W.T. Yuh ◽

J.Z. Wang ◽

J.F. Montebello ◽

S. Nag ◽

...

Keyword(s):

Cervical Cancer ◽

Treatment Outcome ◽

Prognostic Factors ◽

Mr Imaging ◽

Early Prediction ◽

Advanced Cervical Cancer ◽

Functional Mr Imaging

Download Full-text

Tumor Volume Predicts High-Risk Patients and Guides Initial Chemoradiotherapy for Early Cervical Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.640846 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jingjing Zhang ◽

Dongyan Cao ◽

Jiaxin Yang ◽

Keng Shen ◽

Yonglan He ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Tumor Volume ◽

Free Margin ◽

High Risk Patients ◽

Node Metastasis ◽

Vascular Space ◽

Risk Patients ◽

Early Cervical Cancer ◽

Vascular Space Invasion

We evaluated the relationship between the minimum tumor-free margin, tumor volume, and adverse pathological risk factors in early cervical cancer and explored the predictive value of these parameters for different types of risk patients to guide individualized therapeutic strategies. Patients who received the initial treatment of radical operation of cervical cancer and their postoperative pathological reports in our hospital from July 1, 2017, to June 30, 2019, were reviewed. Their minimum tumor-free margin and tumor volume were measured on preoperative magnetic resonance imaging. Student’s t-test and the receiver operating characteristic curve analysis were used for data analysis. A total of 240 patients were included. Adverse pathological risk factors were as follows: deep cervical infiltration, 95 (39.6%) cases; lymph vascular space invasion, 91 (37.9%); lymph node metastasis, 20 (8.3%); parametrial infiltration, 8 (3.3%); tumor diameter ≥4 cm, 7 (2.9%); and positive surgical margin, 1 (0.4%). According to the adverse pathological factors, there were 20 (8.3%) high-risk patients, 50 (20.8%) medium-risk patients, and 170 (70.8%) low-risk patients. The ranges of the minimum tumor-free margin and tumor volume were 0.01–13.5 mm and 105–27,990 mm3, respectively. The minimum tumor-free margin with lymph node metastasis was significantly smaller than that without (P <0.05). The tumor volume with parametrial infiltration, deep cervical infiltration, or lymph vascular space invasion was significantly greater than that without (P < 0.05). The tumor volume was significantly different among low-, medium-, and high-risk patients (P <0.05). Tumor volume was of predictive value for high-risk patients (P < 0.05). With 3,505 mm3 as the cutoff value, the sensitivity and specificity for the prediction of high-risk patients were 88.9% and 84.8%, respectively. Tumor volume can be used as a great predictor of high-risk patients (cutoff value, 3,505 mm3), which could be an indication of initial chemoradiotherapy for early cervical cancer.

Download Full-text

Therapy Outcome Prediction of Cervical Cancer with the Regression Rate of Physiologic High-risk Tumor Subvolume Assessed by DCE MRI

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2011.06.095 ◽

2011 ◽

Vol 81 (2) ◽

pp. S47

Author(s):

N.A. Mayr ◽

Z. Huang ◽

S.S. Lo ◽

G. Jia ◽

J.C. Grecula ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Outcome Prediction ◽

Therapy Outcome ◽

Regression Rate ◽

Dce Mri ◽

High Risk Tumor

Download Full-text

The value of tumor paramaters and dosimetry on prognostic nomograms for cervical cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17026 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17026-e17026

Author(s):

Shun Lu

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Cancer Patients ◽

Clinical Features ◽

Clinical Target Volume ◽

Tumor Volume ◽

External Beam Radiotherapy ◽

Figo Stage ◽

Target Volume ◽

External Beam

e17026 Background: A range of prognostic factors had been reported to be associated with clinical outcome of cervical cancer patients. However, most of these parameters were measured before the start of treatment but without consideration of tumor response to RT. We believed that it might be possible to provide locally advanced cervical cancer patients an opportunity to modify and guide the treatment strategies in the midway of treatment based on the early response evaluation during RT. To establish effective prognostic nomograms using clinical features including tumor volume and size mesured by MRI before treatment and after the completion of external beam radiotherapy (EBRT), and detailed dosimetry of brachytherapy dose for high-risk clinical target volume (HRCTV)D90 and Low-risk Clinical Target Volume(LR-CTV)D90. Methods: The nomogram for local control (LC) was based on a retrospective study of 316 patients who underwent IMRT at our hospital from 2010 to 2015. The predictive accuracy and discriminative ability of our nomogram models were determined by concordance index and calibration curve, and were compared with the nomogram models combining clinical features with FIGO stage. The results were validated using bootstrap resampling and a cohort study of 141 patients. The same data cohort was used to predict the progress-free survival (PFS) of cervical cancer with 3:1 training cohort (N = 310) and validation cohort (N = 155). Results: The following factors were assembled into our prognostic survival nomogram models: Age, tumor volume and size (TV & TS) before treatment, TV and TS after the completion of external beam radiotherapy (EBRT), brachytherapy dose of high-risk clinical target volume (HRCTV)D90 and Low-risk Clinical Target Volume(LR-CTV)D90. The calibration curves showed good agreement between nomogram-predicted and actual survival. Our nomogram models for LC and PFS, provided better results than the nomogram models combining clinical features with FIGO stage. Results were further confirmed in the validation set. Conclusions: Clinical features including tumor size and volume mesured before treatment and after EBRT, as well as detailed dosimetry of brachytherapy dose are able to improve the performance of prognostic nomograms for patients with cervical cancer.

Download Full-text