The role of neoadjuvant chemotherapy in the management of advanced ovarian cancer in geriatric patients

It is increasingly common for ovarian cancer to affect older women, with over half of all cases involving patients aged 65 years and older. Unfortunately, elderly patients with ovarian malignancy tend to be treated less aggressively than younger patients, with less extensive surgery and less intensive chemotherapy regimens. This is due to a variety of factors, such as overall medical fitness and the function of specific organs. Moreover, multiple morbidities are typical for geriatric patients and affect their eligibility for certain forms of cancer therapy as well as their treatment outcomes, which are commonly less satisfactory than in younger patients. Additionally, for fear of complications, treating physicians sometimes limit the extent of the necessary surgery, or adjust chemotherapy doses, even though such a course of management tends to be largely misguided. One available management option is neoadjuvant chemotherapy followed by a surgical treatment known as interval debulking surgery. This type of combination therapy is associated with fewer postoperative complications, thus increasing the patient's chances of receiving a full course of adjuvant treatment. The decision to begin treatment with neoadjuvant chemotherapy tends to restrict later surgical therapy; however, under certain circumstances, this therapy can be a valid therapeutic option and, in fact, facilitate surgery. Prior to initiating therapy in elderly patients, their eligibility for combination therapy must be evaluated and the geriatric assessment of their performance and condition must be considered during the course of interdisciplinary preoperative management

Introducing novel type of human DNA markers for forensic tissue identification: DNA copy number variation allows the detection of blood and semen

Establishing the cellular or tissue-type origin of human biological traces found at crimes scenes is forensically relevant, as it allows evaluating the crime relevance of such traces and enables reconstructing the sequence of crime events. Messenger RNA and micro RNA markers are useful for forensic tissue identification, but provide challenges for linking RNA-identified cell/tissue types with DNA-identified trace donors, especially in mixed traces. DNA methylation markers overcome this problem, but provide technical challenges due to the DNA treatment required by most analysis methods. Here we introduce a novel type of DNA markers for forensic tissue identification analysed without prior DNA treatment, namely copy number variation (CNV). Using genome-wide CNV screening followed-up by targeted qPCR confirmation, and using qPCR analysis of additional CNV-like candidate DNA markers, in samples of several individuals from all commonly encountered forensically-relevant tissue types, we identified DNA markers specific for blood and semen, respectively. Preliminary forensic validation testing demonstrates that the developed qPCR assays are highly sensitive – delivering positive results down to picogram level of input DNA, specific, and can cope well with degraded DNA, providing suitable prerequisites for forensic applications. Moreover, we exemplified that using the CNV qPCR products as input material for subsequent forensic STR analysis delivered full STR profiles, opening-up new avenues of using the same DNA aliquot for both forensic purposes, tissue and individual identification. Provided additional forensic validation studies, we envision the application of these novel DNA markers for forensic tissue identification in future forensic casework. Such CNV markers are particularly useful for tissue identification in old/cold cases, where aged/old DNA extracts are available that contain no RNA and are not suitable for DNA methylation analysis due to limited DNA quantity and quality