Advanced uterine papillary serous cancer: Could there be a role for newer targeted therapeutic approaches or immune checkpoint inhibitors?

BACKGROUND: Although now available in oncology clinics, comprehensive germline mutation testing is being performed only in a minority of patients with advanced uterine papillary serous cancer (UPSC). Some of these patients might harbor various targetable mutations, either heritable or acquired.Data sources: We conducted a retrospective cohort study involving all consecutive patients with UPSC treated at our institution from 2009-2019. Data on epidemiology, with an accent on personal and family history of cancer, clinical presentation, disease stage, employed treatment modalities and cancer-specific survival (CSS) was sought. FINDINGS: Thirteen patients were seventy years of age or younger (≤70) while 15 were older than seventy (>70), and the two arbitrary patient cohorts were well-balanced for the TNM stage. Four UPSC patients >70 had a personal history of metachronous breast cancer. We also identified five cases of breast cancer, two cases of colon cancer, and one of each ovarian and uterine cancer in the first-degree relatives of UPSC patients >70. More than 90% of patients had surgical excision/debulking, and nearly half of the patients in each group received systemic chemotherapy. The most common chemotherapy regimen was carboplatin-paclitaxel every three weeks. Compared to patients ≤70, the UPSC patients >70 were less likely to undergo postoperative radiation therapy (6% vs 61.5%; p = 0.001) and had a worse CSS (21.8 vs. 27.4 months; HR 0.61, p = 0.03). CONCLUSIONS: Personal and family history in a cohort of older UPSC patients identified an excess of second primary cancers, and these patients displayed a shorter CSS. Comprehensive germline and tumor mutation analysis might identify optimal candidates for various targeted agents and immune checkpoint inhibitors, and ultimately improve survival. This may represent an unmet need in the UPSC patients, and further studies are needed to confirm the significance of our findings.

Management and clinical outcomes in uterine malignant mixed Müllerian tumor: Lessons from a single-institution series.

Malignant mixed Müllerian tumor remains an important contributor to morbidity and mortality in women with uterine cancer. Surgery is the primary treatment modality, followed by chemotherapy and/or radiation for advanced disease or high-risk patients. Clinico-epidemiologic characteristics and outcomes in older versus younger women with Malignant mixed Müllerian tumor may differ. We analyzed and now report on 15 consecutive patients with uterine Malignant mixed Müllerian tumor treated at our institution from 2000 to 2018. The mean age at diagnosis was 65 years; 60% (9/15) patients were overweight/obese. Forty-six percent (7/15) had hypercholesterolemia, an association not previously linked with Malignant mixed Müllerian tumor in the literature. All patients but one had surgical excision of the tumor. A third of patients received adjuvant radiation therapy. A majority of patients received chemotherapy; the preferred regimen was carboplatin-paclitaxel. The patients older than 70 had a tendency towards a more advanced disease stage at diagnosis and a significantly shorter cancer-specific survival than their younger counterparts (6 months vs. 102 months (hazard ratio 1.32, p = 0.02)). Our study's conclusions are restricted due to its relatively small size, retrospective design, and some variation in the chemotherapy doses administered in individual patients. Larger studies are needed to confirm the significance of our findings.

Impact of therapeutic modalities on disease-specific survival in older adults with glioblastoma: A single-institution retrospective cohort study.

The standard first-line therapy for glioblastoma consists of maximal surgical resection, followed by concurrent chemoradiotherapy. Optimal management for older glioblastoma patients is unknown as they have not been extensively studied in clinical trials. We report data from a series of 156 consecutive glioblastoma patients treated at our institution from 2007 to 2017. Compared to glioblastoma patients aged 70 or less, the patients older than 70 were less likely to undergo surgical resection (34% vs. 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs. 59%; p = 0.01) or radiation therapy (36% vs. 56%; p = 0.03). Disease-specific survival was significantly shorter in this age group (4.7 vs. 15.3 months; p = 0.002). Nonetheless, when older patients did undergo surgery or chemotherapy, the proportional improvement in cancer-specific survival was similar to the one recorded in younger patients, which is concordant with the findings of other published reports. A multidisciplinary input from neurosurgeons, medical and radiation oncologists, oncology pharmacists and geriatricians remain paramount for the optimal management of glioblastoma in patients older than 70.

Clinico-epidemiologic characteristics and patterns of care in Kaposi's sarcoma: Data from a single-institution series.

In the late 20th to early 21st century, most new Kaposi's sarcoma cases were associated with HIV coinfection and low CD4 T-cell counts. After introduction of effective antiretroviral therapy, the clinical and epidemiologic characteristics of Kaposi's sarcoma may have changed. We analyzed and now report on 27 consecutive Kaposi's sarcoma patients treated at our institution from 2007 to 2017. Most patients were HIV-positive Caucasian men on antiretroviral therapy; the average CD4 T-cell count was above the AIDS-defining level of 200 cells/mm3. Seven patients had Kaposi's sarcoma with mucosal involvement, and 20 had skin-only Kaposi's sarcoma. Mucosal Kaposi's sarcoma patients had a mean CD4 T-cell count of 83 cells/mm3 as opposed to 381 cells/mm3 for patients with skin-only involvement (p = 0.005). Survival was significantly compromised in both groups but even more so in Kaposi's sarcoma patients with mucosal involvement (306 vs. 609 days). Along with other reports, our findings suggest that Kaposi's sarcoma may develop in HIV patients in the modern era despite well-controlled HIV disease. This is significant since Kaposi's sarcoma remains an important contributor to morbidity and mortality in HIV-infected patients.

Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status.

Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed. Compared to Surveillance, Epidemiology, and End Results (SEER) data, our population was entirely Caucasian (100% versus 95%; P=0.11) and male predominant (75% versus 63%; P=0.11). The median age was 76. The patients more often had Tumor-Node-Metastasis (TNM) stage I disease (50% versus 39%; P=0.00003) and a primary tumor size <2cm (57.5% versus 34%; P<0.01). They received more frequently lymph node dissection (70% versus 63%, P=0.002) compared with the SEER findings. We identified a subset of immunocompromised patients (n=10) who presented with more stage III disease (40% versus 33%; P=0.021). Time to death averaged 290.1 days in this subset versus 618.2 days (P<0.001) in immunocompetent patients and their likelihood of death was 5 times higher. As clinical outcomes in MCC patients vary by immunological status, a multidisciplinary tumor-board approach may better optimize individual patient management.

The impact of cognitive distortions, stress, and adherence on metabolic control in youths with type 1 diabetes.

PURPOSE: To investigate the role of cognitive distortions in the relationship between adherence behavior, diabetes-specific stress, general stress, and metabolic control. METHODS: Obtained questionnaire data, glucometer readings, and glycosylated hemoglobin (HbgA(1c)) assays from 143 youths (11-18 years old) with type 1 diabetes. Examined path model of relationships between cognitive distortions, stress, adherence behavior, and metabolic control. Data were analyzed using path analysis. RESULTS: Higher levels of negative cognitive distortions were associated with more stress (both diabetes-specific and general). Higher levels of general stress then led to less adherent behavior and subsequently poorer metabolic control (higher HbgA(1c)). More diabetes-specific stress also led to poorer metabolic control, as well as general stress. CONCLUSIONS: The findings indicate an indirect role of negative cognitive distortions in metabolic control. The current findings suggest that instead of the proposed direct link between cognitive distortions and adherence behavior, an indirect relationship may exist through stress.