Dietary Magnesium Replacement for Prevention of Hypomagnesemia in Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy.

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.

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.

Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

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.

Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS: There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION: MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

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.

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.

Vulvar Cancer Incidence in the United States and its Relationship to Human Papillomavirus Vaccinations, 2001-2018.

The human papillomavirus (HPV) vaccine was indicated for the prevention of vulvovaginal cancers in 2008, but its impact on the incidence of vulvar cancers within the US is unknown. To determine this, we conducted a secondary analysis of 88,942 vulvar cancer cases among women 20+ years old using the US Cancer Statistics 2001-2018 databases. Data were stratified by tumor behavior (in situ or invasive), age (20-44, 45-64, 65+ years old), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), and US census region (Northeast, South, Midwest, West), and incidence rates and average annual percentage changes (AAPC) were calculated by group. Reversing previous trends, the incidence of vulvar carcinoma in situ significantly decreased between 2001 and 2018 among women from all age groups, races/ethnicities, and regions (combined AAPC,  -4.3; 95% confidence interval (CI), -4.7 to -3.8). The incidence of invasive vulvar squamous cell carcinoma decreased significantly among 20- to 44-year-old women (AAPC, -0.8; 95% CI, -1.3 to -0.3), but significantly increased among those 45 to 64 (AAPC, 2.3; 95% CI, 1.8-2.8) and 65+ years old (AAPC, 1.2; 95% CI, 1.1-1.4). Regardless of tumor behavior, incidence was highest among non-Hispanic Whites and the Midwest region. Overall, the significant declines in vulvar carcinoma in situ among all ages, as well as invasive vulvar cancer among younger women, are encouraging and complement other recent data suggesting HPV vaccinations are already reducing anal and cervical cancer incidence. Over time, further declines in vulvar carcinoma incidence are likely as uptake and completion rates of the HPV vaccine increase in the US. PREVENTION RELEVANCE: We found evidence that HPV vaccinations likely contributed to a decrease in the incidences of vulvar carcinoma in situ and invasive vulvar carcinoma among 20- to 44-year-old women between 2001 and 2018. Our data add to the growing evidence that HPV vaccinations are reducing the incidence of HPV-related anogenital cancers.

Definitive vs palliative pelvic radiation for patients with newly diagnosed stage IVB cervical cancer treated with bevacizumab - An exploratory study.

Objective: Platinum-based chemotherapy and bevacizumab is the standard treatment for stage IVB cervical cancer. When metastases resolve, the benefit of radiating the primary tumor is unclear. We investigate the effect of pelvic radiation on PFS following chemotherapy and bevacizumab in stage IVB cervical cancer. Methods: This is a retrospective series of 29 patients with stage IVB cervical cancer treated with platinum-based chemotherapy and bevacizumab. 3 subgroups were evaluated: definitive pelvic radiation, palliative radiation, and no radiation. The primary outcome was the mean PFS. Progression was determined radiographically. Kaplan-Meier method and the log-rank test for equality analyzed OS and PFS. Results: The median OS was 38.4 months. 11 patients (38%) received definitive radiation, 9 (31%) received palliative and 9 (31%) received no radiation. 7/8 in the palliative group, 7/10 who received no radiation and all in the definitive group experienced progression. The median PFS was 7.5 months and not statistically different (p = 0.62). The median OS was not attained in the definitive group, was 23 months [19.6, -] for the palliative group and 19 months [24.9-45.4] for the no radiation group (p = 0.13). OS was higher in patients receiving definitive radiation vs all others (median OS survival not reached vs 6.6 months, p = 0.04). No difference in PFS between those receiving definitive radiation vs others (12 months vs 5.1 months p = 0.32). Conclusion: Definitive radiation is associated with improved survival among in stage IVB cervical cancer treated with chemotherapy and bevacizumab. This association could be due to treatment, patient, or disease factors associated with improved oncologic outcomes. In absence of higher-level data, shared decision-making with consideration for comorbidities and performance status should be employed.

Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers.

Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumor-specific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16+ patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non-HPV-specific T cells did not. In HPV16+ patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

Evaluation of the Efficacy of a Smoking Cessation Intervention for Cervical Cancer Survivors and Women With High-Grade Cervical Dysplasia: Protocol for a Randomized Controlled Trial.

BACKGROUND: The prevalence of smoking among cervical cancer survivors is strikingly high, yet no smoking cessation interventions to date have specifically targeted this population. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial designed to evaluate the efficacy of a theoretically and empirically based Motivation And Problem Solving (MAPS) approach for promoting and facilitating smoking cessation among cervical cancer survivors. MAPS is a comprehensive, dynamic, and holistic intervention that incorporates empirically supported cognitive behavioral and social cognitive theory-based treatment strategies within an overarching motivational framework. MAPS is designed to be appropriate for all smokers regardless of their motivation to change and views motivation as dynamically fluctuating from moment to moment throughout the behavior change process. OBJECTIVE: This 2-group randomized controlled trial compares the efficacy of standard treatment to MAPS in facilitating smoking cessation among women with a history of high-grade cervical dysplasia or cervical cancer. METHODS: Participants (N=202) are current smokers with a history of high-grade cervical dysplasia or cervical cancer recruited nationally and randomly assigned to one of two treatment conditions: (1) standard treatment (ST) or (2) MAPS. ST consists of repeated letters referring participants to their state's tobacco cessation quitline, standard self-help materials, and free nicotine replacement therapy when ready to quit. MAPS has all ST components along with 6 proactive telephone counseling sessions delivered over 12 months. The primary outcome is abstinence from tobacco at 18 months. Secondary outcomes include abstinence over time across all assessment points, abstinence at other individual assessment time points, quit attempts, cigarettes per day, and use of state quitlines. Hypothesized treatment mechanisms and cost-effectiveness will also be evaluated. RESULTS: This study was approved by the institutional review boards at the University of Texas MD Anderson Cancer Center, the University of Oklahoma Health Sciences Center, and Moffitt Cancer Center. Participant enrollment concluded at Moffitt Cancer Center in January 2020, and follow-up data collection was completed in July 2021. Data analysis is ongoing. CONCLUSIONS: This study will yield crucial information regarding the efficacy and cost-effectiveness of a MAPS approach for smoking cessation tailored to the specific needs of women with a history of high-grade cervical dysplasia or cervical cancer. Findings indicating that MAPS has substantially greater efficacy than existing evidence-based tobacco cessation treatments would have tremendous public health significance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02157610; https://clinicaltrials.gov/ct2/show/NCT02157610. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34502.

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.

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.

A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers.

BACKGROUND: A diverse and abundant gut microbiome can improve cancer patients' treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. MATERIALS AND METHODS: Rectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. RESULTS: Gut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. CONCLUSION: After CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.

Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation.

Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.

An economic and disease transmission model of human papillomavirus and oropharyngeal cancer in Texas.

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC in Texas. Parameters for the Year 2010 were used as the initial values, and the prediction for Year 2012 was compared with the real age-specific incidence rates in 23 age groups for model validation. The validated model was applied to predict 100-year age-adjusted incidence rates. The public health benefits of HPV vaccine uptake were evaluated by computer simulation. Compared with current vaccination program, increasing vaccine uptake rates by 50% would decrease the cumulative cases by 4403, within 100 years. The incremental cost-effectiveness ratio of this strategy was $94,518 per quality-adjusted life year (QALY) gained. Increasing the vaccine uptake rate by 50% can: (i) reduce the incidence rates of OPC among both males and females; (ii) improve the quality-adjusted life years for both males and females; (iii) be cost-effective and has the potential to provide tremendous public health benefits in Texas.