The interaction between social determinants of health and cervical cancer survival: A systematic review.

OBJECTIVE: This systematic review aimed to investigate what are the most relevant social determinants of health (SDH), how they are measured, how they interact among themselves and what is their impact on the outcomes of cervical cancer patients. METHODS: Search was performed in PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar databases from January 2001 to September 2022. The protocol was registered at PROSPERO (CRD42022346854). We followed the PICOS strategy: Population- Patients treated for cervical cancer in the United States; Intervention - Any SDH; Comparison- None; Outcome measures- Cancer treatment outcomes related to the survival of the patients; Types of studies- Observational studies. Two reviewers extracted the data following the PRISMA guidelines. Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for risk of bias (ROB) assessment. RESULTS: Twenty-four studies were included (22 had low and 2 had moderate ROB). Most manuscripts analyzed data from public registries (83.3%) and only one SDH (54.17%). The SDH category of Neighborhood was not included in any study. Although the SDH were measured differently across the studies, not being married, receiving treatment at a low-volume hospital, and having public insurance (Medicaid or Medicare) or not being insured was associated with shorter survival of cervical cancer patients in most studies. CONCLUSIONS: There is a deficit in the number of studies comprehensively assessing the impact of SDH on cervical cancer treatment-related outcomes. Marital status, hospital volume and health insurance status are potential predictors of worse outcome.

Nutrition's checkpoint inhibition: The impact of nutrition on immunotherapy outcomes.

OBJECTIVES: To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies. METHODS: A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease. RESULTS: One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10-5). CONCLUSIONS: PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response.

High serum levels of inflammatory markers are associated with early recurrence in patients with high-grade serous ovarian cancer after platinum therapy.

OBJECTIVE: To determine if inflammatory biomarkers can predict the long-term outcome of platinum therapy in patients with high-grade serous ovarian cancer. METHODS: Women diagnosed with high-grade serous epithelial ovarian cancer (n = 70) at a single institution were enrolled in a prospective serum collection study between 2005 and 2020. Seventeen markers of inflammation and oxidative stress were measured in serum samples on a chemistry analyzer. Association was tested for serum levels with progression-free survival (PFS), time to recurrence (TTR), overall survival (OS), and time to death (TTD) using Cox proportional hazards and Kaplan-Meier curves. Patient survival was censored at 10 years. RESULTS: Higher serum levels of LDH were associated with worse PFS (HR 2.57, p = 0.028). High serum levels of BAP (HR 0.38, p = 0.025), GSP (HR 0.40, p = 0.040), HDL-c (HR 0.27, p = 0.002), and MG (HR 0.36, p = 0.017) were associated with improved PFS. Higher expression of LDH was associated with worse OS (HR 2.16, p = 0.023). Higher levels of CK.nac (HR 0.39, p = 0.033) and HDL-c (HR 0.35, p = 0.029) were associated with improved OS. Similar outcomes were found with TTR and TTD analyses. CONCLUSION: General inflammatory biomarkers may serve as a guide for prognosis and treatment benefit. Future studies needed to further define their role in predicting prognosis or how these markers may affect response to therapy.

Uterine Corpus Malignancies in Appalachia Kentucky: Incidence, Survival, and Related Health Disparities.

OBJECTIVES: Uterine cancer is the nation's most common gynecologic malignancy, but it is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). Our aim was to assess the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP) KY. METHODS: This population-based cohort study used Surveillance, Epidemiology, and End Results data and the Kentucky Cancer Registry to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looked at the incidence between diagnoses in AP and NAP. The evaluation criteria included tumor histology (type I, type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance status, and county of residence at diagnosis. RESULTS: The overall age-adjusted incidence rate and survival are similar for US and KY populations; however, histologic types and distribution differ. Compared with the United States, the incidence of corpus cancers in KY is higher for type I (P = 0.03), but lower for type II (P = 0.003), sarcoma (P = 0.006), and mixed (P < 0.001). AP KY has a higher incidence of type I (P < 0.0001) and mixed malignancy (P = 0.04), younger age at diagnosis (P < 0.0001), larger non-Hispanic white population (P < 0.0001), fewer smokers (P = 0.002), and more uninsured and Medicaid recipients (P < 0.0001) compared with NAP KY. The hazard ratio for death is similar in AP and NAP KY (0.896; 95% confidence interval 0.795-1.009). CONCLUSIONS: Type I and mixed uterine corpus cancers have a higher age-adjusted incidence and a younger age at diagnosis in AP compared with NAP KY.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Urinary incontinence and quality of life in endometrial cancer patients after robotic-assisted laparoscopic hysterectomy with lymph node dissection.

To determine the long-term effects of lymph node dissection on lower urinary tract symptoms in patients treated for endometrial cancer. We conducted a retrospective cohort study of 74 patients with International Federation of Gynaecology and Obstetrics (FIGO) Stage I endometrial cancer who underwent surgical intervention with and without lymph node dissection, and evaluated them with the Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). Patients who underwent lymph node dissection reported higher but not statistically different rates of bother by lower urinary tract symptoms compared to those without lymph node dissection. The scores for the lymph node dissection group and the control group were a mean IIQ-7 score of 14.9 ± 23 and 10.5 ± 22.9 (p=.419) and a mean UDI-6 score of 30.0 ± 25.3 and 20.7 ± 22.9 (p=.104), respectively. Lymph node dissection at the time of robotic-assisted surgery did not have a significant effect on lower urinary tract symptoms nor did it affect patient responses on quality of life questionnaires. IMPACT STATEMENT What is already known on this subject? The aetiology of urinary incontinence is multifactorial and there has been debate on how a patient's surgical history affects their risk of developing urinary incontinence. Prior studies have highlighted the relationship between hysterectomy and urinary incontinence (Milsom et al. 1993 ). Additional research has also been done to elucidate the prevalence of pelvic floor disorders in patients who have been surgically treated for endometrial cancer (Erekson et al. 2009 ; Nosti et al. 2012 ). There is limited information on how robotic-assisted lymphadenectomy during surgical staging for endometrial cancer affects patients' urinary function and their quality of life. What do the results of this study add? In this manuscript, we demonstrate that patients who underwent robotic-assisted total laparoscopic hysterectomy (TLH) with lymphadenectomy neither had significant difference in lower urinary tract symptoms nor on quality of life questionnaires as compared to those who did not undergo lymphadenectomy. Worsening of quality of life in regards to urinary incontinence should not be considered a factor of long term surgical morbidity associated with lymph node dissection. What are the implications of these findings for clinical practice and/or further research? There is a need for further studies that focus on the prevalence of pelvic floor disorders in patients after undergoing surgical staging for endometrial cancer and potential interventions that may address these issues.

Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma.

PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma.

OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Significance of venous thromboembolism in women with uterine carcinosarcoma.

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma. METHODS: This multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models. RESULTS: There were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P=0.012), non-Asian race (HR 6.28, P<0.001), large body habitus (HR per kg/m2 1.04, P=0.014), residual disease at surgery (HR 3.04, P=0.003), tumor size ≥5cm (HR 2.73, P=0.003), and stage IV disease (HR 2.12, P=0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P<0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P=0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46, 95%CI 1.05-2.04, P=0.026). CONCLUSION: Our study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

BACKGROUND AND OBJECTIVES: To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. METHODS: This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. RESULTS: The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. CONCLUSION: Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.

Evidence of an epigenetic origin for high-risk 1q21 copy number aberrations in multiple myeloma.

Multiple myeloma is a B-cell malignancy stratified in part by cytogenetic abnormalities, including the high-risk copy number aberrations (CNAs) of +1q21 and 17p(-). To investigate the relationship between 1q21 CNAs and DNA hypomethylation of the 1q12 pericentromeric heterochromatin, we treated in vitro peripheral blood cultures of 5 patients with balanced constitutional rearrangements of 1q12 and 5 controls with the hypomethylating agent 5-azacytidine. Using G-banding, fluorescence in situ hybridization, and spectral karyotyping, we identified structural aberrations and copy number gains of 1q21 in the treated cells similar to those found in patients with cytogenetically defined high-risk disease. Aberrations included 1q12 triradials, amplifications of regions juxtaposed to 1q12, and jumping translocations 1q12. Strikingly, all 5 patients with constitutional 1q12 rearrangements showed amplifications on the derivative chromosomes distal to the inverted or translocated 1q12 region, including MYCN in 1 case. At the same time, no amplification of the 1q21 region was found when the 1q12 region was inverted or absent. These findings provide evidence that the hypomethylation of the 1q12 region can potentially amplify any genomic region juxtaposed to it and mimic CNAs found in the bone marrow of patients with high-risk disease.

Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma.

OBJECTIVE: To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. METHODS: This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. RESULTS: Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). CONCLUSION: Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma.

Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma.

OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. METHODS: We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P<0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P=0.02). When stratified by disease-free interval, women with a disease-free interval ≥6months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a disease-free interval <6months, 2-year SAR rates were similar between the two groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P=0.61). Among women who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). CONCLUSION: Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥6months.

Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma.

BACKGROUND: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. METHODS: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. RESULTS: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36). CONCLUSION: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.

Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.

Pembrolizumab-induced myasthenia gravis: Two patients' experiences.

Checkpoint inhibitors are increasingly used to treat patients with gynecologic malignancies and can cause rare and unusual side effects, also known as immunotoxicities, that are rarely observed in patients receiving traditional immunotherapy. If these are not identified and treated, they can cause disability and even death for patients undergoing treatment. This report describes the range of pembrolizumab-induced myasthenia gravis (MG) immunotoxicity through two cases. The first patient is an 85-year-old woman with recurrent vulvar carcinoma who completed two cycles of pembrolizumab. She had a severe presentation leading to respiratory failure. The second patient is an 80-year-old woman with recurrent serous endometrial carcinoma who developed isolated ocular myasthenia after her second cycle of pembrolizumab. The symptoms and physical examination findings described here illustrate the breadth of symptom severity associated with pembrolizumab-induced MG and importance of early identification and treatment to minimize symptoms and improve outcomes.

Enhancing the effectiveness of follow-up phone calls to improve transitions in care: three decision points.

BACKGROUND: Unavoidable rehospitalizations are frequent, costly, and burdensome for patients and families. The incidence of rehospitalizations within 30 days of discharge can be reduced by improving communication and coordination of care, including enhancing communication with patients and families. Postdischarge follow-up calls are often cited as a cost-effective intervention, yet there is little standardization on how they should be conducted. METHODS: A nonsystematic review of the literature focused on the use of telephone follow-up (TFU) to improve postdischarge processes and reduce avoidable readmissions. Its use was also examined as a component of postdischarge processes among hospitals and organizations participating in the STate Action on Avoidable Rehospitalizations (STAAR) initiative. THE THREE DECISION POINTS: (1) Who Should Make the Call? The decision about who should initiate telephone contact will involve multiple considerations, such as available staff time, level of clinical knowledge required, and financial and practical sustainability. (2) Which Information Is Essential? Care teams should define the follow-up calls' short- and long-term goals and then identify the information needed to achieve them. A standardized assessment sheet may help ensure that patients are always asked the appropriate questions to ascertain whether they require advice and/or intervention, changes in medication, or a visit to their physician or emergency department. (3) What is the Optimal Timing, Frequency, and Duration of Follow-up Calls? The frequency of calls should depend on the patient population, and the duration on the length of the standardized assessment or telephone script and on patient need. CONCLUSION: TFU should continue to be explored as a cost-effective option to reduce readmissions.

A tale of two vulvar angiomyxomas: Two cases and review of literature.

Vulvar angiomyxomas are rare benign mesenchymal neoplasms. Superficial and Aggressive angiomyxomas are two distinct phenotypes that present similarly to other more common vulva-perineal pathologies. Albeit both angiomyxomas carry a risk of recurrence, especially in the setting of incomplete resection, simple excision is insufficient for Aggressive angiomyxoma. It requires wide local excision because of its unique potential for local invasion, infiltration of the paravaginal and pararectal tissue, and more distant metastasis. Here, we present a case of Superficial angiomyxoma and a case of Aggressive angiomyxoma to highlight the diagnostic challenges and management strategies of each tumor. In both cases, angiomyxomas were initially misdiagnosed because of their rarity and nonspecific presentation. Magnetic resonance imaging is the modality of choice for evaluation due to inherent higher spatial resolution of soft tissue anatomical details. Early diagnosis of Aggressive angiomyxoma can prevent incomplete excision and recurrence, spare additional surgery, and offer hormonal therapy options.

Ovarian recurrence risk assessment using machine learning, clinical information, and serum protein levels to predict survival in high grade ovarian cancer.

In ovarian cancer, there is no current method to accurately predict recurrence after a complete response to chemotherapy. Here, we develop a machine learning risk score using serum proteomics for the prediction of early recurrence of ovarian cancer after initial treatment. The developed risk score was validated in an independent cohort with serum collected prospectively during the remission period. In the discovery cohort, patients scored as low-risk had a median time to recurrence (TTR) that was not reached at 10 years compared to 10.5 months (HR 4.66, p < 0.001) in high-risk patients. In the validation cohort, low-risk patients had a median TTR which was not reached compared to 4.7 months in high-risk patients (HR 4.67, p = 0.009). In advanced-stage patients with a CA125 < 10, low-risk patients had a median TTR of 68 months compared to 6 months in high-risk patients (HR 2.91, p = 0.02). The developed risk score was capable of distinguishing the duration of remission in ovarian cancer patients. This score may help guide maintenance therapy and develop innovative treatments in patients at risk at high-risk of recurrence.