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Damage to DNA has emerged as a major culprit in cancer. Mammalian cells are continuously exposed to DNA damage, caused by exogenous toxins as well as endogenous activities such as DNA replication and cellular free radical generation. It is therefore essential that cells have DNA repair mechanisms in place to preserve its genomic integrity. Interestingly, cancer cells frequently harbour defects in DNA repair pathways, leading to genomic instability. This can foster tumorigenesis, but also provides a weakness in the tumour that can be exploited therapeutically. In this context, it has been shown that homologous recombination (HR)-deficient tumour cells--including those with defects in BRCA1/2--are highly sensitive to blockade of the base excision repair (BER) pathway via inhibition of the poly (ADP-ribose) polymerase (PARP) enzyme. This provides the basis for a novel 'synthetic lethal' approach to cancer therapy. Recent clinical trials have shown an enhancement of the cytotoxic effect of chemotherapy by adding a PARP inhibitor to the standard treatment. Still, clinical outcome may be even further improved if these drugs would be used as first-line therapy. In conclusion, it can be stated that an exciting new class of drugs has entered the arena of cancer therapy. However, additional clinical studies are needed before PARP inhibitors can definitely enter daily clinical practice.

The aim of this study was to report on the reproducibility of F-18-fluorodeoxyglucose (FDG) PET MTV (metabolic tumor volume) 40% and MTV2.5, as well as on the intratumor reproducibility in patients, predominantly suffering from lung cancer and squamous cell carcinoma of the head and neck (SCCHN).Nineteen patients (14 men) who underwent a baseline staging FDG PET-CT examination and a second radiotherapy treatment planning FDG PET-CT examination prior to treatment initiation within 17 days (range: 7-37 days) from each other were included. Bland-Altman analysis was performed on MTV40% and MTVSUV2.5 values obtained of the primary tumor. For voxelwise comparison of the FDG distribution within tumors the transformation matrices, defined on the CT images, were applied to the corresponding FDG images. Accordingly, the MTV40% of the primary tumor volume was defined and copied on the second FDG image. The coordinates and SUV values of each pixel in the corresponding volumes in both FDG images were used for paired comparison.The standard deviation of the percentage spread around the means of both measurements was respectively 32.5% for MTVSUV2.5 versus 18.8% for MTV40%. Using a cut-off value of 1.96 SD, differences exceeding 64% in MTVSUV2.5 and 37% in MTV40% may be considered to be clinically relevant. Correlation coefficients derived from the voxelwise paired comparison of SUV values within MTV40% volumes delineated on scan 1 and scan 2 ranged from 0.67 to 0.96 (mean: 0.83). Bland-Altman plots demonstrated a low reproducibility for low SUV values and a high(er) reproducibility for high SUV values (inverted triangular shape) in all tumor volumes under study.The reproducibility of MTV40% proved better than that of MTVSUV2.5 with a cut-off of 37% (increase or decrease) in MTV allowing to define clinically significant changes. Furthermore, intratumoral voxelwise FDG distribution did not change significantly in most of the patients during the time interval studied.

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