The influence of tumor volume on the risk of distant metastases in head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: Distant metastases (DM) in head and neck squamous cell carcinomas (HNSCC) are in most circumstances non-curable. The TNM staging system is insufficient to predict the risk of DM. This study investigates if the DM risk can be predicted using a multivariate model including pre-treatment total tumor volume for both p16-positive oropharyngeal squamous cell carcinoma (OPSCC) and all other sites (other HNSCC). MATERIALS AND METHODS: The study includes patients with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017 from three head and neck cancer centers. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database. Total (nodal and primary) tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems. The GTV was grouped by volume (cm3) in four intervals and included in a multivariate Cox proportional hazard regression controlled for pre-selected clinical values incl. stage. RESULTS: The study includes 2,865 patients, of which 321 (11 %) had DM post-treatment. The risk of DM was assessed in a multivariate model based on 2,751 patients (p16-positive OPSCC: 1,032; and other HNSCC: 1,719). There was a significant association between GTV and the risk of DM, and in tumor volumes ≥ 50 cm3 hazard ratios of 7.6 (2.5-23.4) for p16-positive OPSCC and 4.1 (2.3-7.2) in other HNSCC were observed. CONCLUSION: Tumor volume is an independent risk factor for DM. The addition of total tumor volume to a predictive model is important to identify subgroups of HNSCC patients at high risk of DM.

Multi-parametric PET/MRI for enhanced tumor characterization of patients with cervical cancer.

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.

Plasma total cell-free DNA is a prognostic biomarker of overall survival in metastatic solid tumour patients.

BACKGROUND: Selecting patients for early clinical trials is a challenging process and clinicians lack sufficient tools to predict overall survival (OS). Circulating cell-free DNA (cfDNA) has recently been shown to be a promising prognostic biomarker. The aim of this study was to investigate whether baseline cfDNA measurement could improve the prognostic information of the Royal Marsden Hospital (RMH) score. METHODS: Solid tumour patients referred for phase I trials were included in the Copenhagen Personalized Oncology (CoPPO) programme. Baseline characteristics were collected prospectively, including the RMH prognostic score, Eastern Cooperative Oncology Group (ECOG) performance status and concentration of cfDNA per millilitre plasma. Cox proportional hazards model was used to assess the prognostic value of baseline variables. RESULTS: Plasma cfDNA concentration was quantifiable in 302 patients out of a total of 419 included in the study period of 2 years and 5 months. The RMH score was confirmed to be associated with OS. Cell-free DNA was shown to be an independent prognostic marker of OS and improved the risk model, including RMH, performance status and age. Furthermore, both plasma cfDNA concentration and RMH score were associated with treatment allocation (p < 0.00001). CONCLUSION: Our model based on RMH score, age, ECOG performance status and cfDNA improved prediction of OS and constitutes a clinically valuable tool when selecting patients for early clinical trials. An interactive version of the prognostic model is published on http://bit.ly/phase1survival .

Artifacts in conventional computed tomography (CT) and free breathing four-dimensional CT induce uncertainty in gross tumor volume determination.

PURPOSE: Artifacts impacting the imaged tumor volume can be seen in conventional three-dimensional CT (3DCT) scans for planning of lung cancer radiotherapy but can be reduced with the use of respiration-correlated imaging, i.e., 4DCT or breathhold CT (BHCT) scans. The aim of this study was to compare delineated gross tumor volume (GTV) sizes in 3DCT, 4DCT, and BHCT scans of patients with lung tumors. METHODS AND MATERIALS: A total of 36 patients with 46 tumors referred for stereotactic radiotherapy of lung tumors were included. All patients underwent positron emission tomography (PET)/CT, 4DCT, and BHCT scans. GTVs in all CT scans of individual patients were delineated during one session by a single physician to minimize systematic delineation uncertainty. The GTV size from the BHCT was considered the closest to true tumor volume and was chosen as the reference. The reference GTV size was compared to GTV sizes in 3DCT, at midventilation (MidV), at end-inspiration (Insp), and at end-expiration (Exp) bins from the 4DCT scan. RESULTS: The median BHCT GTV size was 4.9 cm(3) (0.1-53.3 cm(3)). Median deviation between 3DCT and BHCT GTV size was 0.3 cm(3) (-3.3 to 30.0 cm(3)), between MidV and BHCT size was 0.2 cm(3) (-5.7 to 19.7 cm(3)), between Insp and BHCT size was 0.3 cm(3) (-4.7 to 24.8 cm(3)), and between Exp and BHCT size was 0.3 cm(3) (-4.8 to 25.5 cm(3)). The 3DCT, MidV, Insp, and Exp median GTV sizes were all significantly larger than the BHCT median GTV size. CONCLUSIONS: In the present study, the choice of CT method significantly influenced the delineated GTV size, on average, leading to an increase in GTV size compared to the reference BHCT. The uncertainty caused by artifacts is estimated to be in the same magnitude as delineation uncertainty and should be considered in the design of margins for radiotherapy.