Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.

BACKGROUND: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma. MATERIAL AND METHODS: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively. RESULTS: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34). CONCLUSIONS: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

Can positron emission tomography be more than a diagnostic tool? A survey on clinical practice among radiation oncologists in India.

AIM: The purpose of the survey was to understand the role of positron emission tomography (PET) in clinical radiotherapy practice among the radiation oncologists' in India. SETTINGS AND DESIGN: An online questionnaire was developed to survey the oncologists on their use of PET, viewing protocols, contouring techniques practiced, the barriers on the use of PET and the need for training in use of PET in radiotherapy. The questionnaire was sent to about 500 oncologists and 76 completed responses were received. RESULTS: The survey shows that radiation oncologists use PET largely to assess treatment response and staging but limitedly use it for radiotherapy treatment planning. Only manual contouring and fixed threshold based delineation techniques (e.g. 40% maximum standard uptake value [SUV max ] or SUV 2.5) are used. Cost is the major barrier in the wider use of PET, followed by limited availability of FDG radionuclide tracer. Limited or no training was available for the use of PET. CONCLUSIONS: Our survey revealed the vast difference between literature suggestions and actual clinical practice on the use of PET in radiotherapy. Additional training and standardization of protocols for use of PET in radiotherapy is essential for fully utilizing the capability of PET.

Validation of image registration and fusion of MV CBCT and planning CT for radiotherapy treatment planning.

In areas like adaptive therapy, multi-phase radiotherapy, and single fraction palliative treatment or in the treatment of patients with metal implants where megavoltage(MV) CT could be considered as a treatment planning modality, the reduced contrast in the MV CT images could lead to limited accuracy in localization of the structures. This would affect the precision of the treatment. In this study, as an extension our previous work on bespoke MV cone beam CT (MV CBCT), we propose to register the MV CBCT with kilovoltage (kV) CT for treatment planning. The MV CBCT images registered with kV CT would be effective for treatment planning as it would account for the inadequate soft tissue information in the MV CBCT and would allow comparison of changes in patient dimensions and assist in localization of the structures. The intensity based registration algorithm of the BrainSCAN therapy planning software was used for image registration of the MV CBCT and kV CT images. The accuracy of the registration was validated using qualitative and quantitative measures. The effect of image quality on the level of agreement between the contouring done on both the MV CBCT and kV CT was assessed by comparing the volumes of six structures delineated. To assess the level of agreement between the plans after the registration, two independent plans were generated on the MV CBCT and the planning CT using the posterior fossa of the skull as the target. The dose volume histograms and conformity indices of the plans were compared. The results of this study show that treatment planning with MV CBCT images would be effective, using additional anatomical structure information derived from registering the MV CBCT image with a standard kVCT.