Comorbid Dementia and Cancer Therapy Decision-Making: A Scoping Review.

Comorbid dementia complicates cancer therapy decision-making in older adults. We aimed to synthesize the recent literature (<5 years) on the challenges associated with cancer therapy decision-making among older people living with dementia (PLWD) and their caregivers. Of the 20,763 references, 8767 had their title and abstract screened, and eight met the inclusion criteria. Six studies were qualitative, one study employed mixed methods, and one study was quasi-experimental. Most studies were conducted in the UK (89%) and reported homogeneity in race and geography. Breast (56%) and prostate (45%) were the most frequent reported cancers. Five studies (56%) reported multiple types of dementia, with two (22%) indicating stages. The studies indicated that communication between patients, caregivers, and clinical teams might alleviate stress caused by worsening health prospects and potential ethical concerns. Information from this review can lead to better-informed, patient-centered treatment decision processes among older PLWD and cancer, their caregivers, and clinicians.

Current cannabis use and pain management among US cancer patients.

BACKGROUND: National studies reporting the prevalence of cannabis use have focused on individuals with a history of cancer without distinction by their treatment status, which can impact symptom burden. While pain is a primary motivation to use cannabis in cancer, the magnitude of its association with cannabis use remains understudied. METHODS: We examined cannabis use and pain management among 5523 respondents of the Behavioral Risk Factor Surveillance System with a cancer history. Survey-weighted prevalence proportions of respondents' cannabis use are reported, stratified on cancer treatment status. Regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer-related pain and cannabis use. RESULTS: Cannabis use was slightly more prevalent in those undergoing active treatment relative to those who were not undergoing active treatment (9.3% vs. 6.2%; P=0.05). Those under active treatment were more likely to use cannabis medicinally (71.6% vs. 50.0%; P=0.03). Relative to those without cancer-related pain, persons with pain under medical control (OR 2.1, 95% CI, 1.4-3.2) or uncontrolled pain were twice as likely to use cannabis (OR 2.0, 95% CI, 1.1-3.5). CONCLUSIONS: Use of cannabis among cancer patients may be related to their treatment and is positively associated with cancer-related pain. Future research should investigate the associations of cannabis use, symptom burden, and treatment regimens across the treatment spectrum to facilitate interventions.

Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer.

Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFß expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCAwt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCAwt patients.

Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-ß1 and TGF-ß2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance. METHODS: This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA. Women aged 18 years and older with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer in clinical complete response after a combination of surgery and five to eight cycles of chemotherapy involving carboplatin and paclitaxel, and an Eastern Cooperative Oncology Group status of 0 or 1 were eligible for inclusion in the study. Patients were randomly assigned (1:1) to gemogenovatucel-T or placebo by an independent third party interactive response system after successful screening using randomly permuted block sizes of two and four and stratified by extent of surgical cytoreduction and neoadjuvant versus adjuvant chemotherapy. Gemogenovatucel-T (1 × 107 cells per injection) or placebo was administered intradermally (one per month) for a minimum of four and up to 12 doses. Patients, investigators, and clinical staff were masked to patient allocation until after statistical analysis. The primary endpoint was recurrence-free survival, analysed in the per-protocol population. All patients who received at least one dose of gemogenovatucel-T were included in the safety analysis. The study is registered with ClinicalTrials.gov, NCT02346747. FINDINGS: Between Feb 11, 2015, and March 2, 2017, 310 patients consented to the study at 22 sites. 217 were excluded. 91 patients received gemogenovatucel-T (n=47) or placebo (n=44) and were analysed for safety and efficacy. The median follow-up from first dose of gemogenovatucel-T was 40·0 months (IQR 35·0-44·8) and from first dose of placebo was 39·8 months (35·5-44·6). Recurrence-free survival was 11·5 months (95% CI 7·5-not reached) for patients assigned to gemogenovatucel-T versus 8·4 months (7·9-15·5) for patients assigned to placebo (HR 0·69, 90% CI 0·44-1·07; one-sided p=0·078). Gemogenovatucel-T resulted in no grade 3 or 4 toxic effects. Two patients in the placebo group had five grade 3 toxic events, including arthralgia, bone pain, generalised muscle weakness, syncope, and dyspnea. Seven patients (four in the placebo group and three in the gemogenovatucel-T group) had 11 serious adverse events. No treatment-related deaths were reported in either of the groups. INTERPRETATION: Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted. FUNDING: Gradalis.

Exploring and Managing the Impostor Phenomenon in Palliative Care: A Case Series.

The impostor phenomenon (IP) describes the experience of questioning one's abilities and fearing exposure as an intellectual fraud, despite objective evidence of success. The IP has been identified in high-achieving professionals across a variety of disciplines, including clinical medicine, and can be associated with significant anxiety and psychological distress. In this series, we present three authentic cases that demonstrate how the IP may manifest in palliative care practice. Acknowledging the current emphasis on clinician wellness and burnout, we suggest that the IP may be one important source of distress for many early-career clinicians in palliative care. With the physician as the focus of each case, we explore the difficult emotions faced and highlight how palliative care clinicians may be uniquely vulnerable to the IP. We then identify concrete strategies to help clinicians manage feelings of IP and enhance their professional well-being.

Adding Silver to the Rainbow: Palliative and End-of-Life Care for the Geriatric LGBTQ Patient.

Lesbian, gay bisexual, transgender, and queer or questioning (LGBTQ) older adults have unique health care needs, especially in the palliative care and hospice setting. In this article, we present a male patient with metastatic ovarian cancer, admitted with worsening dyspnea, now at the end of life. Only his wife was aware of his identified gender, and nondisclosure was very important to him. As he continued to decline, the team navigated LGBTQ-sensitive care within the health care setting, insurance inequalities, and support and communication to his family. This case study summarizes clinical recommendations for the LGBTQ individual in the hospice and palliative care setting, suggesting how our patient's care may have been improved. With the changes in social acceptance and attitudes, the LGBTQ community has become more visible and their numbers appear to be growing. It is important, therefore, that hospice and palliative care providers be educated on their needs to provide competent and inclusive health care.

Malignant transformation of endometriosis in a cesarean section abdominal wall scar: a case report.

BACKGROUND: Endometriosis occurring in a cesarean section abdominal wall scar is reported at a rate of 0.03-0.45%. Malignant transformation of this type of endometriosis is exceptionally rare. CASE: A 51-year-old, G3P2012, Black woman presented with a lump in her cesarean section abdominal wall scar that was increasing in size. Biopsy of the mass revealed metastatic adenocarcinoma with poorly differentiated, nonmucinous ovarian primary. She received 3 cycles of neoadjuvant chemotherapy and underwent an interval debulking with the final pathology showing malignant transformation of endometriosis within her abdominal wall scar. She then completed radiotherapy to the area and is disease-free 6 months later. CONCLUSION: Our combination of neoadjuvant chemotherapy and excision of the mass with negative margins followed by adjuvant radiotherapy is a feasible treatment option.

Ectopic production of human chorionic gonadotropin by synovial sarcoma of the hip.

BACKGROUND: Human chorionic gonadotropin (hCG) is a marker of pregnancy and a tumor marker for some gynecologic malignancies, including germ cell tumors and gestational trophoblastic neoplasia. Rarely, hCG is secreted by nongynecologic tumors, confounding the diagnosis. CASE: A 45-year-old woman was evaluated for a persistently elevated ß-hCG. Diagnosis of her primary malignancy, synovial sarcoma of the hip, was delayed as more common etiologies were considered, including ectopic pregnancy and gestational trophoblastic neoplasm. The workup eventually led to the diagnosis using imaging studies but ultimately resulted in a 3-month delay and unnecessary medical and surgical treatments. CONCLUSION: This case highlights the importance of nongynecologic malignancies when evaluating patients with a persistent ß-hCG.

Leg pain and gynecologic malignancy.

Gynecologic malignancies affect more than 83 000 women in the United States, each year. Because the disease involves the pelvis, many patients have side effects distal to this area in their lower extremities. The differential diagnosis of leg pain can be divided into vascular, neurologic, and musculoskeletal causes. In this review article, we address numerous etiologies of leg pain, reviewing the prevalence of disease, physical examination findings, diagnostic as well as treatment modalities.

Hemoglobin A1c and the relationship to stage and grade of endometrial cancer.

OBJECTIVES: To determine if elevated markers of poor glycemic control (HgA1c and fasting glucose levels) in patients surgically staged for type I endometrial cancer is related to a higher stage or higher grade at the time of diagnosis. Also, to assess if these markers impact overall survival. METHODS: A retrospective chart review was performed from January 2000 to June 2010 at three academic medical centers. Patients were included if they underwent surgical staging and had HgA1c drawn within 3 months before surgery. Demographic data, fasting blood glucose levels and overall survival data were also obtained. RESULTS: Eighty-two patients fitting the inclusion criteria were identified during the study period. There was a strong positive correlation between HgA1c and fasting glucose. There was no statistical difference with regard to stage alone, grade alone, or when stratified together with regard to HgA1c or fasting glucose levels. There was a trend toward increased mean HgA1c across increasing stages, but this was not statistically significant. Diabetes, HgA1c and tumor grade did not affect overall survival, but advanced stage was a poor prognostic measure for overall survival. CONCLUSIONS: Elevated preoperative HgA1c has a trend toward a higher stage at the time of diagnosis. Advanced stage is a poor prognostic measure for overall survival.

FIGO staging for carcinosarcoma: can the revised staging system predict overall survival?

OBJECTIVES: The purpose of this study is to detect differences in overall survival between the 1988 FIGO staging and current staging of uterine carcinosarcomas to determine if revised 2009 staging accurately predicts actual patient survival. METHODS: From 1988 until 2010, patients with uterine carcinosarcoma were retrospectively identified from tumor registry records. Patients were grouped in both broad stages (1-4) and all FIGO substages in order to detect differences. Time-dependent receiver operating characteristic curves (ROC) were generated to predict death before the end of the second year post-diagnosis for both the new and revised system. Kaplan Meier estimated median survival time was utilized to compare actual patient survival. RESULTS: Of 112 patients with carcinosarcoma, 37 patients (33%) had FIGO Stage I disease, 15 patients (13.4%) had Stage II disease, 36 patients (32%) were diagnosed as Stage III, and 24 patients (21.4%) had Stage IV disease. 106 of 112 (94.6%) patients underwent lymphadenectomy (pelvic +/- para-aortic). Four patients (3.6%) were downstaged when utilizing broad staging criteria: 2 patients were downstaged from Stage II to I, and 2 patients were downstaged from Stage III to Stage I and II respectively. When looking at substage, the area under the ROC was 0.67 for the former staging system, and 0.65 for the revised staging. Kaplan-Meier estimated median survival time post-diagnosis was 610 days (95% CI [478,930]). CONCLUSION: Based upon our reclassification of 112 patients with uterine carcinosarcoma, the revised FIGO staging system does not predict survival more accurately than former staging. Carcinosarcoma has an overall poor prognosis and better indicators of survival are needed.

Cesarean scar ectopic pregnancy: a case report of failed combination local and systemic methotrexate management requiring surgical intervention.

BACKGROUND: Cesarean scar ectopic pregnancies have been diagnosed with increasing frequency in the last decade. There is no consensus of management for these pregnancies; however, prior reports have suggested best results using either combination methotrexate therapy or surgical excision. CASE: We present a case of failed systemic and local methotrexate therapy requiring operative management, CONCLUSION: Cesarean scar ectopic pregnancies can have disastrous outcomes, including uterine rupture, massive hemorrhage and maternal death. Although this is the first case to report a failure of the combination therapy, major morbidities did not occur. We believe this is due to our choice of expedient surgical management.