Gene expression profiling impacts treatment decision making in newly diagnosed multiple myeloma patients in the prospective PROMMIS trial

Abstract Multiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard‐ or high‐risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard‐risk. After unblinding SKY92, 16 patients were re‐assigned as high‐risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high‐risk patients, SKY92 indicated 46 patients to be standard‐risk; for 31 of these patients the treatment strategy was impacted consistent with a de‐escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (p < 0.001). For clinical decision‐making, physicians incorporated SKY92, and the final assigned clinical risk was in line with SKY92 for 89% of patients. Furthermore, SKY92 significantly increased the confidence of the physicians’ treatment decisions (p < 0.001). This study shows potential added value of SKY92 in MM for treatment decision making

Urinary and sexual dysfunction after rectal cancer treatment

In light of the improving prognosis for patients with rectal cancer, the quality of functional outcome has become increasingly important. Despite the good functional results achieved by expert surgeons, large multicenter studies show that urogenital dysfunction remains a common problem after rectal cancer treatment. More than half of patients experience a deterioration in sexual function, consisting of ejaculatory problems and impotence in men and vaginal dryness and dyspareunia in women. Urinary dysfunction occurs in one-third of patients treated for rectal cancer. Surgical nerve damage is the main cause of urinary dysfunction. Radiotherapy seems to have a role in the development of sexual dysfunction, without affecting urinary function. Pelvic autonomic nerves are especially at risk in cases of low rectal cancer and during abdominoperineal resection. Data concerning nerve damage during laparoscopic surgery for resection of rectal cancer are awaited. Structured education of surgeons with regard to pelvic neuroanatomy, and systematic registration of identified nerves, could well be the key to improving functional outcome for these patients. Meanwhile, patients should be informed of all associated risks before their operation, and their functional status should be evaluated before and after surgery.Surgical oncolog

Stable plastid transformation in lettuce (Lactuca sativa L.)

Although plastid transformation in higher plants was first demonstrated in the early 1990s it is only recently that the technology is being extended to a broader range of species. To date, the production of fertile transplastomic plants has been reported for tobacco, tomato, petunia, soybean, cotton and Lesquerella fendleri (Brassicaceae). In this study we demonstrate a polyethylene glycol-mediated plastid transformation system for lettuce that generates fertile, homoplasmic, plastid-transformed lines. Transformation was achieved using a vector that targets genes to the trnA/trnI intergenic region of the lettuce plastid genome employing the aadA gene as a selectable marker against spectinomycin. Spectinomycin resistance and heterologous gene transcription were shown in T(1) plants derived from self-pollinated primary regenerants demonstrating transmission of the plastid-encoded transgene to the first seed generation. Crossing with male sterile wild-type lettuce showed that spectinomycin resistance was not transmitted via pollen. Constructs containing the gfp gene showed plastid-based expression of green fluorescent protein. The lettuce plastid could have potential both as a production and a delivery system for edible human therapeutic proteins