Gemcitabine combination therapies induce apoptosis in uterine carcinosarcoma patient-derived organoids.

Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor with lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark of carcinosarcoma is the presence of both sarcomatous and carcinomatous elements. The survival rates for UCS have not improved for over 40 years; therefore, there is a profound need to identify new treatments. To investigate novel chemotherapy treatment combinations for UCS, we generated a UCS patient-derived organoid (PDO) cell line from a patient that received neoadjuvant treatment with paclitaxel and carboplatin. The PDO cell line (UCS1) was grown in three-dimensional domes. The PDO domes were treated with six individual chemotherapies or nine combinations of those six drugs. Cell death in response to chemotherapy was assessed. We found that the six monotherapies had minimal effectiveness at inducing cell death after 48 h of treatment. The combination of paclitaxel and carboplatin (which is the standard-of-care chemotherapy treatment for UCS) led to a small increase in apoptosis compared with the monotherapies. Importantly, when either carboplatin or paclitaxel was combined with gemcitabine, there was an appreciable increase in cell death. In conclusion, for the UCS1 patient-derived tumor cells, gemcitabine combinations were more effective than carboplatin/paclitaxel. Our data support the use of PDOs to predict responses to second-line chemotherapy.

Recent advances in non-surgical management of cancer in the elderly.

This article summarizes the seminal publications from mid-2016 through 2017 in the area of medical care for older adults with cancer. Areas addressed include chemotherapy tolerance and efficacy in the aged, geriatric fitness assessments, and advancements in palliative and supportive care. The practice-changing finding from this past year's publications is that antipsychotics should not be used in the management of terminal delirium in older adults receiving palliative care. The other trials demonstrated an improved understanding of the utility of geriatric assessments in patients with cancer, developed the body of information about which chemotherapy agents are safe and effective in older adults (and which are not), and expanded our understanding of good palliative and supportive care.

Lifestyle Modifications and Policy Implications for Primary and Secondary Cancer Prevention: Diet, Exercise, Sun Safety, and Alcohol Reduction.

Improved cancer treatments and cancer detection methods are not likely to completely eradicate the burden of cancer. Primary prevention of cancer is a logical strategy to use to control cancer while also seeking novel treatments and earlier detection. Lifestyle modification strategies to improve primary prevention and risk reduction for the development of cancer include choosing a healthy diet with an emphasis on plant sources, maintaining a healthy weight throughout life, being physically active, regularly using sunscreen and wearing protective clothing, limiting sun exposure during the hours of 10 AM to 2 PM, avoiding indoor tanning, and reducing or eliminating alcohol use. In addition to continued use of ongoing education of the public, health care providers, and cancer support communities, other policy and public health efforts should be pursued as well. Examples of supported and successful policy approaches are included in this article, including efforts to limit indoor tanning and improve community-wide interventions to reduce ultraviolet radiation exposure as well as to formally support various alcohol policy strategies including increasing alcohol taxes, reducing alcohol outlet density, improving clinical screening for alcohol use disorders, and limiting youth exposure to alcohol marketing and advertising. These prevention strategies are expected to have the largest impact on the development of melanoma as well as breast, colorectal, head and neck, liver, and esophageal cancers. The impact of these strategies as secondary prevention is less well understood. Areas of additional needed research and implementation are also highlighted. Future areas of needed research are the effects of these modifications after the diagnosis of cancer (as secondary prevention).

Imaging Pandora's Box: incidental findings in elderly patients evaluated for transcatheter aortic valve replacement.

OBJECTIVE: To determine the frequency and clinical impact of noncardiovascular incidental findings (IFs) detected on preoperative computed tomographic angiography (CTA) of the chest/abdomen/pelvis performed in elderly patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR). PATIENTS AND METHODS: The CTA studies for 424 consecutive patients being evaluated for TAVR between January 1, 2009, through January 24, 2012, were reviewed for noncardiovascular IFs (62.0% male; median ± SD age, 82 ± 8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival. RESULTS: Potentially pathologic IFs (PPIFs) were present in 285 patients (67.2%). The mean ± SD number of PPIFs per patient was 1.1 ± 1.0 (range, 0-4). Factors associated with higher numbers of PPIFs were reduced ejection fraction (P=.02) and history of smoking (P=.06). Potentially pathologic incidental findings prompted clinical work-up in 39 patients (9.2%) and delayed or canceled treatment plans for aortic stenosis in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of PPIFs was predictive of poor overall survival before (hazard ratio, 1.58; 95% CI, 1.31-1.88) and after (hazard ratio, 1.45; 95% CI, 1.19-1.76) adjustment for baseline clinical variables (P<.001 for both). CONCLUSION: This investigation found that PPIFs are common in elderly patients undergoing TAVR-CTA scans and, once discovered, commonly generate further clinical evaluation. Higher numbers of PPIFs may be predictive of poorer survival, but further study is required to guide the appropriateness of pursuing diagnostic evaluations for asymptomatic PPIFs in this elderly population.