Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors.

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions. OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. STUDY DESIGN: This is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumors of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least 1 documented recurrence, and treatment/treatment planning at the MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery, and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier, and were modeled via Cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. RESULTS: Among the 369 patients with adult granulosa cell tumors of the ovary in the registry, 149 patients met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (hazard ratio, 0.37; 95% confidence interval, 0.17-0.81, P=.01) and multivariable analyses (hazard ratio, 0.42; 95% confidence interval, 0.19-0.92; P=.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared with those who did not undergo cytoreductive surgery (181.92 vs 61.56 months, respectively; P=.002). Overall survival benefit remained statistically significant on multivariable analysis (hazard ratio, 0.28; 95% confidence interval, 0.11-0.67; P=.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (hazard ratio, 0.43; 95% confidence interval, 0.26-0.70; P=.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (hazard ratio, 0.74; 95% confidence interval, 0.42-1.26; P=.27). CONCLUSION: Among those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may have a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumors of the ovary.

Integrative Oncology Approaches to Reduce Recurrence of Disease and Improve Survival.

PURPOSE OF REVIEW: After a cancer diagnosis, patients ask what they can do in addition to the recommended treatments to increase their survival. Many turn to integrative medicine modalities and lifestyle changes to improve their chances of survival. Numerous studies have demonstrated that lifestyle changes can significantly improve survival rates for cancer patients. Less support exists for the use of natural products or supplements to improve cancer survival. In this manuscript, we review key findings and evidence in the areas of healthy eating habits, physical activity, stress management and social support, and sleep quality, as well as natural products and supplements as they relate to the cancer recurrence and survival. RECENT FINDINGS: While more research is needed to fully understand the mechanisms underlying the associations between lifestyle changes and cancer survival, findings suggest that lifestyle modifications in the areas of diet, physical activity, stress management and social support, and sleep quality improve clinical cancer outcomes. This is especially true for programs that modify more than one lifestyle habit. To date, outside of supplementing with vitamin D to maintain adequate levels, conflicting conclusion within the research remain regarding the efficacy of using natural products or supplement to improve cancer recurrence of disease or cancer survival. A call for further research is warranted. Lifestyle screening and counseling should be incorporated into cancer treatment plans to help improve patient outcomes. While the scientific community strives for the pursuit of high-quality research on natural products to enhance cancer survival, transparency, dialogue, and psychological safety between patients and clinicians must continue to be emphasized. Proactive inquiry by clinicians regarding patients' supplement use will allow for an informed discussion of the benefits and risks of natural products and supplements, as well as a re-emphasis of the evidence supporting diet and other lifestyle habits to increase survival.

A multilevel intervention to promote HPV vaccination among young adults in Texas: protocol for a randomized controlled trial.

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. METHODS: The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. DISCUSSION: Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. TRIAL REGISTRATION: NCT05057312.

Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study.

OBJECTIVE: To determine whether a non­platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. METHODS: Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1-3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. RESULTS: At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. CONCLUSIONS: Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062.

Clinical outcomes of leuprolide acetate in the treatment of recurrent ovarian granulosa cell tumors.

BACKGROUND: The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach. OBJECTIVE: This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors. STUDY DESIGN: This was a retrospective cohort study of patients enrolled in the Rare Gynecologic Malignancy Registry at a large cancer referral center and affiliated county hospital. Patients meeting inclusion criteria had a diagnosis of recurrent granulosa cell tumor and received either leuprolide acetate or traditional chemotherapy as cancer treatment. Outcomes were separately examined for leuprolide acetate used as adjuvant treatment, maintenance therapy, and the treatment of gross disease. Demographic and clinical data were summarized using descriptive statistics. Progression-free survival was calculated from the initiation of treatment to the date of disease progression or death, and compared between groups with the log-rank test. The 6-month clinical benefit rate was defined as the percentage of patients without disease progression 6 months after starting therapy. RESULTS: Sixty-two patients received a total of 78 leuprolide acetate-containing therapy courses, owing to 16 instances of retreatment. Of these 78 courses, 57 (73%) were for treatment of gross disease, 10 (13%) were adjuvant to tumor reductive surgery, and 11 (14%) were for maintenance therapy. Patients had received a median of 2 (interquartile range, 1-3) systemic therapy regimens before their first leuprolide acetate treatment. Tumor reductive surgery (100% [62/62]) and platinum-based chemotherapy (81% [50/62]) were common before first leuprolide acetate exposure. The median duration of leuprolide acetate therapy was 9.6 months (interquartile range, 4.8-16.5). Nearly half of the therapy courses were single-agent leuprolide acetate (49% [38/78]). Combination regimens most often included an aromatase inhibitor (23% [18/78]). Disease progression was the most common cause of discontinuation (77% [60/78]); only 1 patient (1%) discontinued leuprolide acetate because of adverse events. In the treatment of gross disease, the 6-month clinical benefit rate for first use of leuprolide acetate was 66% (95% confidence interval, 54-82). Median progression-free survival was not statistically different compared with that which followed chemotherapy (10.3 months [95% confidence interval, 8.0-16.0] vs 8.0 months [95% confidence interval, 5.0-15.3]; P=.3). CONCLUSION: In a large cohort of patients with recurrent granulosa cell tumors, the 6-month clinical benefit rate of first-time leuprolide acetate treatment of gross disease was 66% and progression-free survival was comparable to patients treated with chemotherapy. Leuprolide acetate regimens were heterogeneous, but significant toxicity was rare. These results support leuprolide acetate as safe and effective for the treatment of relapsed adult granulosa cell tumors in the second line and beyond.

Integrative Medicine for Ovarian Cancer.

PURPOSE OF REVIEW: Integrative oncology (IO) services provide a wide range of complementary medicine therapies, many of which can augment the beneficial effects of conventional supportive and palliative care for patients with ovarian cancer. This study aims to assess the current state of integrative oncology research in ovarian cancer care. RECENT FINDINGS: We review the clinical research both supporting the effectiveness of leading IO modalities in ovarian cancer care as well as addressing potential safety-related concerns. There is growing amount of clinical research supporting the use of IO and implementation of integrative gynecological oncology models of care within the conventional supportive cancer care setting. Additional research is still needed in order to create clinical guidelines for IO interventions for the treatment of female patients with ovarian cancer. These guidelines need to address both effectiveness and safety-related issues, providing oncology healthcare professionals with indications for which these patients can be referred to the IO treatment program.

Metagenomes of rectal swabs in larger, advanced stage cervical cancers have enhanced mucus degrading functionalities and distinct taxonomic structure.

BACKGROUND: Gut microbiome community composition differs between cervical cancer (CC) patients and healthy controls, and increased gut diversity is associated with improved outcomes after treatment. We proposed that functions of specific microbial species adjoining the mucus layer may directly impact the biology of CC. METHOD: Metagenomes of rectal swabs in 41 CC patients were examined by whole-genome shotgun sequencing to link taxonomic structures, molecular functions, and metabolic pathway to patient's clinical characteristics. RESULTS: Significant association of molecular functions encoded by the metagenomes was found with initial tumor size and stage. Profiling of the molecular function abundances and their distributions identified 2 microbial communities co-existing in each metagenome but having distinct metabolism and taxonomic structures. Community A (Clostridia and Proteobacteria predominant) was characterized by high activity of pathways involved in stress response, mucus glycan degradation and utilization of degradation byproducts. This community was prevalent in patients with larger, advanced stage tumors. Conversely, community B (Bacteroidia predominant) was characterized by fast growth, active oxidative phosphorylation, and production of vitamins. This community was prevalent in patients with smaller, early-stage tumors. CONCLUSIONS: In this study, enrichment of mucus degrading microbial communities in rectal metagenomes of CC patients was associated with larger, more advanced stage tumors.

The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial.

Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibitors in GCT patients. Here, we present a case series of GCT patients treated with pembrolizumab who were enrolled in a phase II basket trial in advanced, rare solid tumors (ClinicalTrials.gov: NCT02721732). Cases We identified 5 patients with recurrent GCT (4 adult and 1 juvenile type); they had an extensive history of systemic therapy at study enrollment (range, 3-10), with most regimens resulting in less than 12 months of disease control. Pembrolizumab was administered in these patients, as per trial protocol. Although there were no objective responses according to the irRECIST guidelines, 2 patients with adult-type GCT experienced disease control for ≥ 12 months (565 and 453 days). In one, pembrolizumab represented the longest duration of disease control compared to prior lines of systemic therapy (565 days vs. 13 months). In the other, pembrolizumab was the second longest systemic therapy associated with disease control (453 days vs. 22 months) compared to prior lines of therapy. In this patient, pembrolizumab was discontinued following withdrawal of consent. PD-L1 expression was not observed in any baseline tumor samples. Pembrolizumab was well tolerated, with no grade 3 or 4 treatment-related adverse events. Conclusions Although our results do not support the routine use of pembrolizumab monotherapy in unselected GCT patients, some patients with adult-type GCT may derive a clinical benefit, with a low risk of toxicity. Future studies should investigate the role of immunotherapy and predictors of clinical benefit in this patient population.

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer.

OBJECTIVE: We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/lenvatinib in recurrent endometrial cancer in a "real-world" clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes. METHODS: Retrospectively, we reviewed toxicity, treatment responses, and survival outcomes of patients with recurrent endometrial cancer who received ≥1 cycle of pembrolizumab/lenvatinib. We compared subgroups based on lenvatinib starting dose (recommended [20 mg] vs reduced [<20 mg]) and histologic type. RESULTS: We analyzed 70 patients (recommended dose cohort, n = 16; reduced dose cohort, n = 54). The most common starting dose was 14 mg daily. Compared to the reduced dose cohort, the recommended dose cohort had a significantly higher mean number of lenvatinib dose reductions due to side effects (1.1 vs. 0.4; p = 0.003) and significantly shorter median time to treatment toxicity (1.3 vs. 3.7 days; p = 0.0001). Response rates did not differ significantly between the recommended and reduced dose cohorts (28.6% vs. 38.3%, respectively; p = 0.752). Two patients, both in the reduced dose cohort, had complete responses. Patients with carcinosarcoma histology had response and clinical benefit rates of 25% (3 of 12) and 58.3% (7 of 12), respectively. There were no differences between the 2 dose cohorts with respect to progression-free (p = 0.245) or overall survival (p = 0.858). CONCLUSION: In clinical practice, a lower starting dose of lenvatinib (14 mg daily) in combination with pembrolizumab was safe and efficacious in recurrent endometrial cancer. The combination produced responses in endometrial carcinosarcomas. Larger studies are required to validate these findings.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation.

PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer.

OBJECTIVE: The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. METHODS: From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2-IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only. RESULTS: 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23-67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients-that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0-68.3). Three patients developed recurrent disease within 2 years of surgery-that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). DISCUSSION: Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

Knowledge matters and empowers: HPV vaccine advocacy among HPV-related cancer survivors.

PURPOSE: To describe knowledge about human papillomavirus (HPV), HPV-related care behavior, and advocacy intent (e.g., vaccine recommendation and willingness to become an advocate for vaccination) and to investigate associations between knowledge, HPV-related care behavior, and advocacy intent among HPV-related cancer survivors. METHODS: A cross-sectional online survey was offered through Qualtrics to HPV-related cancer survivors who were either volunteers at a cancer center or patients of survivorship clinics. RESULTS: A total of 200 survivors responded. Only 33.2% of respondents reported knowing their cancer was HPV-related and 56.8% reported HPV vaccine is safe. Participants who knew that their cancer was caused by HPV were more likely to have vaccinated their children (p < .001). Also, participants who knew that the vaccine is safe were more willing to recommend the vaccine (p < .001), to be a peer mentor for others with HPV-related cancers (43.2% vs. 14.0%, p < .001), and to act as an advocate for increasing vaccination rates (44.1% vs. 24.4%, p = 0.01). Finally, survivors who were aware of the vaccine's effectiveness in decreasing precancerous lesions were more likely to recommend the vaccine (45.7% vs. 12.0%, p = .002). CONCLUSIONS: Raising survivor awareness of the link between HPV and cancer and HPV vaccine safety may increase their willingness to serve as powerful opinion leaders and peer mentors to promote HPV vaccination. Providers may take the simple step of informing patients that their cancer is HPV-related and HPV vaccine is safe to increase the number of informed and empowered survivors.

Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.

Hypomagnesemia and Survival in Patients with Ovarian Cancer Who Received Chemotherapy with Carboplatin.

BACKGROUND: Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. MATERIALS AND METHODS: We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high-grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. RESULTS: The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). CONCLUSION: Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin-containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. IMPLICATIONS FOR PRACTICE: Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum-based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin-containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.

Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls.

OBJECTIVES: The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls. METHODS: We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe). RESULTS: Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas, and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects. CONCLUSION: Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer.

How we use hospice: Hospice enrollment patterns and costs in elderly ovarian cancer patients.

OBJECTIVE: To describe disparities in patterns of hospice use and end-of-life costs among ovarian cancer patients. METHODS: Using Texas Cancer Registry-Medicare data, ovarian cancer patients deceased 2005-2012 with >12 months of continuous Medicare coverage before death were included. Descriptive statistics and multivariable logistic regressions were used to evaluate patterns of hospice use. Cost and resource utilization was obtained from Medicare claims and analyzed using a non-parametric Mann-Whitney test. RESULTS: 2331 patients were assessed: 1788 (77%) white, 359 (15%) Hispanic, 158 (7%) black and 26 (1%) other. 1756 (75%) enrolled in hospice prior to death but only 1580 (68%) died with hospice. 176 (10%) of 1756 patients unenrolled and died without hospice. 346 (20%) unenrolled from hospice multiple times. From 2008 to 2012, patients were less likely to unenroll from hospice prior to death. Black patients were more likely to unenroll from hospice prior to death (OR 2.07 [1.15-3.73]; p = 0.02) compared to white patients. The median amount paid by Medicare during the last six months of life was $38,530 for those in hospice compared to $49,942 if never enrolled in hospice (p < 0.0001) and was higher for black and Hispanic patients compared to white patients. 30% hospice unenrolled patients and 40% multiply enrolled hospice patients received at least one life extending or invasive care procedure following unenrollment from hospice. CONCLUSION: Recently, more patients remain enrolled in hospice, but black patients have a higher risk of unenrollment. Hospice enrollment was associated with lower costs as long as a patient did not unenroll from hospice.

Disseminating universal genetic testing to a diverse, indigent patient population at a county hospital gynecologic oncology clinic.

OBJECTIVE: The universal genetic testing initiative (UGTI) is a quality improvement effort to increase rates of guideline-based genetic counseling (GC) and genetic testing (GT) of patients with potentially hereditary cancers. The UGTI was disseminated to a county hospital gynecologic oncology clinic that serves a diverse, indigent patient population. METHODS: Using the Model for Improvement quality improvement framework, interventions including integrated GC, clinic tracking, assisted GC referrals, and provider education were tested over 26 months. A retrospective data review included patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC) and endometrial cancers (EC) diagnosed between 9/1/12-8/31/16. Statistical analyses were performed to describe the population and to evaluate rates of recommendation and use of immunohistochemistry tumor testing (IHC), GC, and GT. RESULTS: A cohort of 241 patients (57 HGOC, 184 EC) were included. At the conclusion of the study 84.2% of HGOC patients were referred for GC, 89.6% (43/48) completed GC, and 90.7% (39/43) completed GT. Of EC patients, 81.0% were recommended to have IHC and 62.4% (93/149) completed IHC. Patients with HGOC diagnosed during dissemination of UGTI were significantly more likely to receive a recommendation for GC (p = 0.02) and to complete GT (p = 0.03) than those diagnosed before UGTI. Patients with EC were significantly more likely to complete IHC if diagnosed after UGTI than those diagnosed prior to dissemination (p < 0.001). CONCLUSIONS: The UGTI can be adapted to increase use of guideline-based cancer genetics services in a diverse, indigent, gynecologic cancer patient population.

Prognostic factors impacting survival in early stage uterine carcinosarcoma.

OBJECTIVE: Evaluate the impact of clinicopathologic characteristics and adjuvant treatment on survival outcomes in early stage uterine carcinosarcoma patients. METHODS: We performed a retrospective cohort study of women with stage I or II uterine carcinosarcoma at our institution between March 1990 and June 2016. All pathology had been reviewed and confirmed by gynecologic pathologists. Data were extracted from the electronic medical record. Descriptive and comparative statistics were used to compare clinicopathologic characteristics. Univariable and multivariable analyses were performed for survival outcomes. RESULTS: 140 patients were identified. Median age was 67 years (range: 36-91). Median follow-up was 39.1 months (2.9-297.4). The majority of patients had stage IA (67%) versus stage IB (21%) or stage II (11%) disease. The majority of patients (63%) received adjuvant treatment: vaginal brachytherapy only (14%); whole pelvic radiation therapy only (16%); chemotherapy only (n = 13, 9%); combination chemotherapy and vaginal brachytherapy (15%); combination chemotherapy and whole pelvic radiation (9%). 52 patients (37%) received no adjuvant therapy. Median overall survival (OS) was 48.0 months (95% CI 32.7-80.9). On multivariable analysis for OS, advancing age (HR 1.05, 95% CI 1.03-1.08, p < 0.001), higher stage (stage IB: HR 1.64, 95% CI 0.91-2.95, p = 0.10; stage II: HR 3.04, 95% CI 1.51-6.13, p = 0.002), and the presence of a rhabdomyosarcoma component (HR 1.66, 95% CI 1.02-2.70, p = 0.04) were significantly associated with worse OS. CONCLUSIONS: Advancing age, stage, and the presence of a rhabdomyosarcoma component were all associated with worse OS in patients with early stage uterine carcinosarcoma. New treatment algorithms should incorporate factors aside from stage alone.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.