Advance Care Planning as a Shared Endeavor: Completion of ACP Documents in a Multidisciplinary Cancer Program

Objective—We examined the roles of oncology providers in advance care planning (ACP) delivery in the context of a multidisciplinary cancer program. Methods—Semi-structured interviews were conducted with 200 women with recurrent and/or metastatic breast or gynecologic cancer. Participants were asked to name providers they deemed important in their cancer care and whether they had discussed and/or completed ACP documentation. Evidence of ACP documentation was obtained from chart reviews. Results—Fifty percent of participants self-reported completing an advance directive (AD) and 48.5% had named a healthcare power of attorney (HPA), 38.5% had completed both, and 39.0% had completed neither document. Among women who self-reported completion of the documents, only 24.0% and 14.4% of women respectively had documentation of an AD and HPA in their chart. Completion of an AD was associated with number (adjusted odds ratio [AOR] = 1.49) and percentage (AOR = 6.58) of providers with whom the participant had a conversation about end-of-life decisions. Participants who named a social worker or nurse practitioner were more likely to report having completed an AD. Participants who named at least one provider in common (e.g., named the same oncologist) were more likely to have comparable behaviors related to naming a HPA (AOR = 1.13, p = 0.011) and completion of an AD (AOR = 1.06, p = 0.114). Conclusions—Despite the important role of physicians in facilitating ACP discussions, involvement of other staff was associated with a greater likelihood of completion of ACP documentation. Patients may benefit from opportunities to discuss ACP with multiple members of their cancer care team

Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study

PURPOSE: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC). PATIENTS AND METHODS: Eligible OC patients had measurable (RECIST1.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. RESULTS: 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. CONCLUSION: The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone

COVID-19 Vaccine Uptake Among Residents and Staff Members of Assisted Living and Residential Care Communities-Pharmacy Partnership for Long-Term Care Program, December 2020-April 2021

OBJECTIVES: In December 2020, CDC launched the Pharmacy Partnership for Long-Term Care Program to facilitate COVID-19 vaccination of residents and staff in long-term care facilities (LTCFs), including assisted living (AL) and other residential care (RC) communities. We aimed to assess vaccine uptake in these communities and identify characteristics that might impact uptake. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: AL/RC communities in the Pharmacy Partnership for Long-Term Care Program that had ≥1 on-site vaccination clinic during December 18, 2020-April 21, 2021. METHODS: We estimated uptake using the cumulative number of doses of COVID-19 vaccine administered and normalizing by the number of AL/RC community beds. We estimated the percentage of residents vaccinated in 3 states using AL census counts. We linked community vaccine administration data with county-level social vulnerability index (SVI) measures to calculate median vaccine uptake by SVI tertile. RESULTS: In AL communities, a median of 67 residents [interquartile range (IQR): 48-90] and 32 staff members (IQR: 15-60) per 100 beds received a first dose of COVID-19 vaccine at the first on-site clinic; in RC, a median of 8 residents (IQR: 5-10) and 5 staff members (IQR: 2-12) per 10 beds received a first dose. Among 3 states with available AL resident census data, median resident first-dose uptake at the first clinic was 93% (IQR: 85-108) in Connecticut, 85% in Georgia (IQR: 70-102), and 78% (IQR: 56-91) in Tennessee. Among both residents and staff, cumulative first-dose vaccine uptake increased with increasing social vulnerability related to housing type and transportation. CONCLUSIONS AND IMPLICATIONS: COVID-19 vaccination of residents and staff in LTCFs is a public health priority. On-site clinics may help to increase vaccine uptake, particularly when transportation may be a barrier. Ensuring steady access to COVID-19 vaccine in LTCFs following the conclusion of the Pharmacy Partnership is critical to maintaining high vaccination coverage among residents and staff

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p

Preliminary analysis of ophthalmic prednisolone acetate and diclofenac on diabetes mellitus regulation in 12 of 40 dogs

Master of ScienceDepartment of Clinical SciencesAmy RankinObjective- To evaluate the use of a topical ophthalmic steroid (1% prednisolone acetate) and non-steroidal anti-inflammatory drug (0.1% diclofenac) on blood glucose concentrations, serum fructosamine concentrations, and clinical scores in diabetic dogs with cataracts using descriptive analysis. Animals- Twelve client-owned dogs with naturally-occurring, controlled (per history and physical examination), insulin-treated diabetes mellitus and cataract. A total of 40 dogs will be enrolled in the study, as determined by power analysis. Procedures- This was a prospective, randomized, double-masked, experimental study with 2 phases of data collection. Dogs were enrolled from October 2011 to March 2014 and were assigned to 1 of 2 treatments (Drug Red or Drug Blue) using blocked randomization; dogs received either 1% prednisolone acetate suspension or 0.1% diclofenac solution. Patient history, physical, and ophthalmic examinations were performed and a clinical score assigned at enrollment (Phase 1 [day 0]) and upon return (Phase 2 [day 32]). At these times, a complete blood count, serum chemistry, urinalysis, and serum fructosamine concentration were performed prior to hospitalization for up to 72 hours for continuous glucose monitoring. For 4 weeks (day 3 to 31), dogs returned home, and owners administered the dispensed ophthalmic medication 4 times daily to both eyes. Descriptive analysis of data was performed; statistical analysis will follow enrollment of 40 dogs. Results- Twelve dogs have completed the study, with 6 dogs assigned to each treatment group. Dogs received 4.44 or 0.44 mg/day of prednisolone acetate or diclofenac, respectively. Dogs assigned to Drug Red more commonly exhibited elevations in serum liver enzyme activity. Drug Red group showed a greater percent increase in fructosamine concentrations over time. Based on glucose curves alone (22 curves analyzed), an insulin dose increase was recommended for 12 curves. An insulin dose decrease and no dose change were recommended for 5 curves each. During treatment, 1 dog reportedly developed polyuria and polydipsia. Conclusions- Descriptive analysis revealed differences in some outcomes of interest among dogs treated with 2 different ophthalmic anti-inflammatory medications. Data collection is ongoing to determine if statistically significant differences exists for outcomes per group

Breast Cancer Epidemiology and Risk Factors

Between the years 2010 and 2012, the lifetime probability of developing female breast cancer was 12.3%, or approximately 1 in 8. Worldwide, breast cancer is the most common cancer in women. Survival is increasing. Between 2005 and 2011, the 5-year relative survival was found to be 89%. This is thought to be due to both the increase in utilization of population-wide screening, as well as advances in treatment. Less than 10% of breast cancers can be attributed to an inherited genetic mutation. Breast cancer is more commonly associated with environmental, reproductive, and lifestyle factors, some of which are potentially modifiable

Breast-Specific Sensuality and Sexual Function in Cancer Survivorship: Does Surgical Modality Matter?

More early-staged breast cancer patients are choosing mastectomy. No studies have addressed breast-specific sensuality (BSS), defined as the breast's role during intimacy. We explored BSS among women undergoing lumpectomy (L), mastectomy alone (M), or with reconstruction (MR) and analyzed the association of surgical modality with sexual function. Women undergoing breast cancer surgery between 2000 and 2013 were eligible for survey using investigator-generated questions and the Female Sexual Function Index (FSFI). Demographic and surgical data were collected by chart review. The Kruskal-Wallis test was used to analyze FSFI scores, and chi (2) or Fisher's exact tests were used for categorical data. Of 453 invited participants, 268 (59%) completed the survey. Of these, 69.4, 22.4, and 8.2% underwent L, MR, or M, respectively. The importance of the breast/chest wall during intimacy declined significantly regardless of surgical modality (L 83-74%, p = 0.0006; M 95-47%, p = 0.003; MR 93-77%, p = 0.002). No difference in sexual function was found between L, MR, and M (median FSFI score 28.2, 27.5, 25.9, respectively; p = 1.0). Comparing L versus MR, higher FSFI scores resulted with appearance satisfaction (29.0 vs. 22.6 p = 0.002) and preserved BSS as pleasurable breast caress (28.8 vs. 26.5, p = 0.04) and the breast as part of intimacy (28.8 vs. 24.8, p = 0.1). Breast cancer surgery is associated with lowered BSS. However, BSS and appearance satisfaction scores are better for L and appear to correlate with improved sexual function postoperatively. These data may guide surgical counseling and contribute to survivorship outcomes

Influential Forces in Breast Cancer Surgical Decision Making and the Impact on Body Image and Sexual Function

BACKGROUND: Shared decision making with one\u27s partner and body image satisfaction may affect surgical choices of breast cancer patients. This study analyzed whether partner opinion was associated with choice of operation and whether comfort level with one\u27s partner was altered postoperatively. METHODS: A prospective anonymous survey was administered to breast cancer patients who underwent breast surgery between 2000 and 2014. Categorical variables were compared by chi (2) or Fisher\u27s exact test. RESULTS: Women who elected to undergo mastectomy with reconstruction (MR) placed greater emphasis on their own decision making than on input from their partner, surgeon, or others (56.5 vs. 8.3 vs. 23.2 vs. 12, respectively), whereas those who chose lumpectomy (L) placed similar weight on surgeon input and self-input (44.2 vs. 42.7 %). Only 7.5 % of all patients identified their partner as the greatest influence on their surgical choice. Preoperatively, the L group was the most comfortable with their partner seeing their chest (91.9 % L vs. 83.9 % MR vs. 75.9 % mastectomy alone (M); p = 0.01), and postoperatively, the comfort levels for all were remarkably decreased. Furthermore, if a patient was a candidate for L but chose MR, the role her chest played in intimacy dropped more compared with those who chose L (83.8 % L vs. 91.7 % MR; p = 0.3 preoperatively to 65.1 % L vs. 42.9 % MR; p = 0.01 postoperatively). CONCLUSIONS: When making surgical decisions, most patients indicate that they value their own opinion over that of others. Mastectomy, regardless of reconstruction, leads to a significant reduction in comfort with one\u27s partner postoperatively compared with lumpectomy. This information may be helpful in counseling couples at the time of consultation for breast cancer treatment