Epithelial ovarian cancer: Evolution of management in the era of precision medicine.

Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.

Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Disparities in clinical trial enrollment at a Canadian comprehensive cancer center: A 15-year retrospective study.

INTRODUCTION: Disparities in clinical trials (CTs) enrollment perpetuate inequities in treatment access and outcomes, but there is a paucity of Canadian data. The objective of this study was to examine disparities in cancer CT enrollment at a large Canadian comprehensive cancer center. METHODS: Retrospective study of CT enrollment among new patient consultations from 2006 to 2019, with follow-up to 2021 (N = 154,880), with the primary outcome of enrollment as a binary variable. Factors associated with CT enrollment were evaluated using multivariable Bayesian hierarchical logistic regression with random effects for most responsible physician (MRP) and geography, adjusted for patient characteristics (sex, age, language, geography, and primary care provider [PCP]), area-level marginalization (residential instability, material deprivation, dependency, and ethnic concentration), disease (cancer site and stage), and MRP (department, sex, language, and training). A sensitivity analysis of the cumulative incidence of enrollment was conducted to account for differences in disease type and follow-up length. RESULTS: CT enrollment was 11.2% overall, with a 15-year cumulative incidence of 18%. Lower odds of enrollment were observed in patients who were female (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.78-0.86), ≥65 years (AOR vs. <40, 0.61; 95% CI, 0.56-0.66), non-English speakers (0.72; 95% CI, 0.67-0.77), living ≥250 km away (AOR vs. <15 km, 0.71; 95% CI, 0.62-0.80), and without a PCP. Disease characteristics accounted for the largest proportion of observed variation (20.8%), with significantly greater odds of enrollment in patients with genitourinary cancers and late-stage disease. CONCLUSION: Significant sociodemographic disparities were observed, suggesting the need for targeted strategies to increase diversity in access to cancer CTs in Canada.

High grade adverse event reporting and enrolment in gynecologic oncology clinical trials.

OBJECTIVE: The primary objective is to assess factors associated with treatment related high grade (CTCAE grade ≥ 3) adverse event (AE) reporting among participants in gynecologic oncology clinical trials. METHODS: All AEs recorded in the Princess Margaret Clinical Trial adverse event database between 01/2016 and 12/2018 were evaluated. Gynecologic oncology clinical trials assessing systemic therapy were included. Inferential statistics on risk factors of related grade ≥ 3 adverse event reporting and GEE logistic models with Odds Ratios (OR) were performed. Multivariable analysis adjusting for age, clinical trial phase, sponsor, and therapy type. RESULTS: The gynecology cancer clinical trials accrued 317 unique patients (359 nested on trials) in 42 systemic therapy trials. In the period, 17,175 related AEs were reported in the gynecological cancer trials, 7.4% were grade ≥ 3. On multivariable analysis, no odds differences of grade ≥ 3 related AEs were detected according to study phase. Patients in immunotherapy clinical trials had lower odds of related grade ≥ 3 AEs than patients on targeted or other therapy (adjusted OR [aOR] 0.43; 95% CI 0.24-0.75). There was greater odds of related grade ≥ 3 AEs in clinical trials assessing combination vs single therapeutics (aOR 2.26, 95% CI 1.34-3.80). Patients aged ≥65 (aOR 1.77; 95% CI 1.08-2.89) had greater odds of related grade ≥ 3 AEs than patients aged 50 to 65 years. When compared to other disease sites, the odds of having a grade  ≥ 3 related AE reported in gynecology clinical trials was no different. CONCLUSIONS: In this cohort, factors influencing the odds of related grade ≥ 3 AE reporting in gynecologic trials included type of therapy and age. The study phase did not correlate with odds of high-grade AE reporting.

Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.

OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

Electronic malignant bowel obstruction symptom monitoring smartphone application for patients with gynecologic cancers.

OBJECTIVES: Implementation of an interprofessional program at Princess Margaret Cancer Centre, including nurse-led proactive calls to support patients with gynecologic cancers with malignant bowel obstruction, demonstrated improved outcomes compared with historical controls. The aim of the study was to convert the proactive calls into an electronic monitoring program to assess it's feasibility and scalability in patients with gynecologic cancers with or at risk of malignant bowel obstruction. METHODS: 'My Bowels on Track' smartphone application included weekly/biweekly electronic patient-reported outcomes (PROs), educational materials, and a secure messaging system. Based on PRO answers, an alerting system flagged patients with symptoms or uncompleted PROs. Nurses tracked and called patients on receiving clinical or compliance alerts. The primary objective was to assess adherence (≥70% PRO completion per patient considered an adherent patient) in the first 2 months on the program. A secondary objective was to assess the positive predictive value (PPV) of the alerts to trigger recommendations. RESULTS: Forty patients were enrolled between August 2021 and September 2022. Median age was 64.5 years (range 29-79 years). Primary diagnosis was ovarian (75%), endometrial (17.5%), or cervical (7.5%) cancer, and 92.5% of patients were receiving systemic therapy. Median duration on the program was 55 days (range 8-121 days). The 2-month adherence was 65% (95% CI 50% to 80%) and the overall adherence was 60% (95% CI 43% to 75%). Sixty-five symptom-related alerts (75% severe, 25% moderate) were reported in 60% (24/40) of patients. There were 59 recommendations triggered by the alerts. The PPV of the alerts to trigger actions was 72% (95% CI 58% to 82%). CONCLUSIONS: This pilot electronic malignant bowel obstruction monitoring program with real-time PRO assessment was feasible, and 65% of participants were adherent during the first 2 months on the program. The PRO response-based alerting system flagged concerning symptoms in 60% of participants, with a PPV of 72% to trigger nurse-led actions and/or management recommendations. TRIAL REGISTRATION NUMBER: NCT03260647.

Optic Nerve MRI T2-Hyperintensity: A Nonspecific Marker of Optic Nerve Damage.

BACKGROUND: MRI abnormalities are common in optic neuropathies, especially on dedicated orbital imaging. In acute optic neuritis, optic nerve T2-hyperintensity associated with optic nerve contrast enhancement is the typical imaging finding. In chronic optic neuropathies, optic nerve T2-hyperintensity and atrophy are regularly seen. Isolated optic nerve T2-hyperintensity is often erroneously presumed to reflect optic neuritis, frequently prompting unnecessary investigations and neuro-ophthalmology consultations. Our goal was to determine the significance of optic nerve/chiasm T2-hyperintensity and/or atrophy on MRI. METHODS: Retrospective study of consecutive patients who underwent brain/orbital MRI with/without contrast at our institution between July 1, 2019, and June 6, 2022. Patients with optic nerve/chiasm T2-hyperintensity and/or atrophy were included. Medical records were reviewed to determine the etiology of the T2-hyperintensity and/or atrophy. RESULTS: Four hundred seventy-seven patients (698 eyes) were included [mean age 52 years (SD ±18 years); 57% women]. Of the 364 of 698 eyes with optic nerve/chiasm T2-hyperintensity without atrophy, the causes were compressive (104), inflammatory (103), multifactorial (49), glaucoma (21), normal (19), and other (68); of the 219 of 698 eyes with optic nerve/chiasm T2-hyperintensity and atrophy, the causes were compressive (57), multifactorial (40), inflammatory (38), glaucoma (33), normal (7), and other (44); of the 115 of 698 eyes with optic nerve/chiasm atrophy without T2-hyperintensity, the causes were glaucoma (34), multifactorial (21), inflammatory (13), compressive (11), normal (10), and other (26). Thirty-six eyes with optic nerve/chiasm T2-hyperintensity or atrophy did not have evidence of optic neuropathy or retinopathy on ophthalmologic examination, and 17 eyes had clinical evidence of severe retinopathy without primary optic neuropathy. CONCLUSIONS: Optic nerve T2-hyperintensity or atrophy can be found with any cause of optic neuropathy and with severe chronic retinopathy. These MRI findings should not automatically prompt optic neuritis diagnosis, workup, and treatment, and caution is advised regarding their use in the diagnostic criteria for multiple sclerosis. Cases of incidentally found MRI optic nerve T2-hyperintensity and/or atrophy without a known underlying optic neuropathy or severe retinopathy are rare. Such patients should receive an ophthalmologic examination before further investigations.

Eccentric Hamstring Strength Imbalance among Football and Soccer Athletes.

OBJECTIVES: Hamstring strain injuries (HSI) are common among football and soccer athletes. Eccentric strength imbalance is considered a contributing factor for HSI. There is, however, a paucity of data on hamstring imbalances of soccer and American football athletes as they age and advance in skill level. High school athletes will display greater interlimb discrepancies compared with collegiate and professional athletes. In addition, soccer athletes will exhibit greater hamstring asymmetry than American football athletes. METHODS: Hamstring testing was performed on soccer and American football athletes using the NordBord Hamstring Testing System (Vald Performance, Albion, Australia). Age, sex, weight, sport specialization, and sport level were recorded. Maximum hamstring forces (N), torque (N · m), and work (N · s) were measured. Hamstring imbalance (%) was calculated by dividing the absolute value of the difference in leg forces divided by their sum. One-way analysis of variance and independent sample t tests compared measurements between athlete groups. RESULTS: A total of 631 athletes completed measurements, including 88 high school male soccer, 25 college male soccer, 23 professional male soccer, 83 high school female soccer, 28 college female soccer, 288 high school football, and 96 college football athletes. High school soccer players displayed significantly greater imbalances for torque (P = 0.03) and work (P < 0.01) than football athletes. Imbalances for maximum force (P = 0.035), torque (P = 0.018), and work (P = 0.033) were significantly higher for male soccer athletes in high school compared with college- and professional-level athletes. Female high school soccer players had significantly higher imbalance in torque (P = 0.045) and work (P = 0.001) compared with female collegiate soccer players. Football athletes did not experience significant changes in force imbalances between skill levels. CONCLUSIONS: High school soccer athletes exhibit greater hamstring imbalances than football athletes. Higher levels of play in soccer, for both male and female athletes, correlate with less hamstring asymmetry.

Patient Self-Reported Allergies and Their Correlation with Thoracic Outlet Syndrome Outcomes.

OBJECTIVES: Thoracic outlet syndrome (TOS) is an uncommon neurovascular disorder that presents as neck and upper extremity pain secondary to brachial plexus trunk or subclavian vasculature compression. The orthopedic literature has correlated patient-reported allergies to postoperative patient-reported outcome (PRO) scores for a variety of surgical procedures. We sought to evaluate patient-reported allergies and PROs following surgical decompression for TOS. METHODS: A chart review was conducted after identifying patients who underwent surgical thoracic outlet decompression by a single surgeon. Patients were contacted and administered five PRO questionnaires via telephone: the QuickDASH Outcome Measure questionnaire (disabilities of the arm, shoulder, and hand [DASH]), the Cervical Brachial Symptom Questionnaire, the Single Assessment Numeric Evaluation, the 12-Item Short Form Survey, and the Numeric Rating Scale (a visual analogue scale). A bivariate analysis of Pearson's correlation coefficient (r) was used to determine the associations of allergies with questionnaires and demographic variables. RESULTS: Of the 393 patients (128 males and 265 females) identified in the study, 75 (24%) responded and completed all of the questionnaires, 18 (24%) males and 57 (76%) females. A significant correlation was found between the number of allergies reported and the QuickDASH Outcome Measure questionnaire (r = 0.375, P < 0.001), the Cervical Brachial Symptom Questionnaire (r = 0.295, P = 0.01), change in the Single Assessment Numeric Evaluation score (r = -0.310, P < 0.01), change in the visual analogue scale (r = 0.244, P = 0.035), sex (r = 0.245, P = 0.034), and the number of medications (r = 0.642, P < 0.001). CONCLUSIONS: The increased frequency of patient-reported allergies is significantly associated with worse PRO scores for women undergoing TOS surgical decompression. Better understanding this association can help physicians counsel patients on expected outcomes.

Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10.

BACKGROUND: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B. METHODS: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1. RESULTS: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (<56 days) and was later for haematological TEAEs (53-84 days). The median duration of grade ≥3 TEAEs was ≤13 days. CONCLUSIONS: In patients with relapsed, platinum-sensitive or platinum-resistant germline BRCA-mutant high-grade ovarian cancer who had received ≥2 prior chemotherapies, rucaparib had robust antitumour activity with a safety profile consistent with prior reports. CLINICAL TRIAL REGISTRATION: NCT01482715.

Variable Association of Physiologic Changes With Electrographic Seizure-Like Events in Infants Born Preterm.

OBJECTIVES: To determine the incidence of seizure-like events in a cohort of infants born preterm as well as the prevalence of associated vital sign changes (heart rate [HR], respiratory rate, and pulse oximetry [SpO2]). STUDY DESIGN: We performed prospective conventional video electroencephalogram monitoring on infants born at 23-30 weeks of gestational age during the first 4 postnatal days. For detected seizure-like events, simultaneously captured vital sign data were analyzed during the pre-event baseline and during the event. Significant vital sign changes were defined as HR or respiratory rate >±2 SD from the infant's own baseline physiologic mean, derived from a 10-minute interval before the seizure-like event. Significant change in SpO2 was defined as oxygen desaturation during the event with a mean SpO2 <88%. RESULTS: Our sample included 48 infants with median gestational age of 28 weeks (IQR 26-29) and birth weight of 1125 g (IQR 963-1265). Twelve (25%) infants had seizure-like discharges with a total of 201 events; 83% (10/12) of infants had vital sign changes during these events, and 50% (6/12) had significant vital sign changes during the majority of the seizure-like events. Concurrent HR changes occurred the most frequently. CONCLUSIONS: Individual infant variability was observed in the prevalence of concurrent vital sign changes with electroencephalographic seizure-like events. Physiologic changes associated with preterm electrographic seizure-like events should be investigated further as a potential biomarker to assess the clinical significance of such events in the preterm population.

How well does neonatal neuroimaging correlate with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy?

BACKGROUND: In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear. METHODS: Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years. RESULTS: Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5-5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury. CONCLUSION: In the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes. IMPACT: Half of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia. Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment. Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI. Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes.

Emerging peptide therapeutics for the treatment of ovarian cancer.

INTRODUCTION: The discovery of therapeutic proteomic targets has resulted in remarkable advances in oncology. Identification of functional and hallmark peptides in ovarian cancer can be leveraged for diagnostic and therapeutic targeting. These targets are expressed in different tumor cell locations, making them excellent candidates for theranostic imaging, precision therapeutics, and immunotherapy. The ideal target is homogeneously overexpressed in malignant cells with no expression in healthy cells, thereby avoiding off-tumor bystander toxicity. Several peptides are currently undergoing extensive evaluation for the development of vaccines, antibody-drug conjugates, monoclonal antibodies, radioimmunoconjugates, and cell therapy. AREAS COVERED: This review focuses on the significance of peptides as promising targets in ovarian cancer. English peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and major conference databases. EXPERT OPINION: Peptides and proteins expressed in tumor cells are an exciting area of research with great potential and may significantly influence precision therapeutics and immunotherapeutic strategies. Accurate utilization of peptide expression as a predictive biomarker has the potential to greatly enhance treatment precision. The ability to measure receptor expression paves the way for its use as a predictive biomarker for therapeutic targeting and requires critical validation of sensitivity and specificity for each indication to guide therapy.

Symptom screening with Targeted Early Palliative care (STEP) versus usual care for patients with advanced cancer: a mixed methods study.

PURPOSE: Although early palliative care is recommended, resource limitations prevent its routine implementation. We report on the preliminary findings of a mixed methods study involving a randomized controlled trial (RCT) of Symptom screening with Targeted Early Palliative care (STEP) and qualitative interviews. METHODS: Adults with advanced solid tumors and an oncologist-estimated prognosis of 6-36 months were randomized to STEP or symptom screening alone. STEP involved symptom screening at each outpatient oncology visit; moderate to severe scores triggered an email to a palliative care nurse, who offered referral to in-person outpatient palliative care. Patient-reported outcomes of quality of life (FACT-G7; primary outcome), depression (PHQ-9), symptom control (ESAS-r-CS), and satisfaction with care (FAMCARE P-16) were measured at baseline and 2, 4, and 6 months. Semi-structured interviews were conducted with a subset of participants. RESULTS: From Aug/2019 to Mar/2020 (trial halted due to COVID-19 pandemic), 69 participants were randomized to STEP (n = 33) or usual care (n = 36). At 6 months, 45% of STEP arm patients and 17% of screening alone participants had received palliative care (p = 0.009). Nonsignificant differences for all outcomes favored STEP: difference in change scores for FACT-G7 = 1.67 (95% CI: -1.43, 4.77); ESAS-r-CS = -5.51 (-14.29, 3.27); FAMCARE P-16 = 4.10 (-0.31, 8.51); PHQ-9 = -2.41 (-5.02, 0.20). Sixteen patients completed qualitative interviews, describing symptom screening as helpful to initiate communication; triggered referral as initially jarring but ultimately beneficial; and referral to palliative care as timely. CONCLUSION: Despite lack of power for this halted trial, preliminary results favored STEP and qualitative results demonstrated acceptability. Findings will inform an RCT of combined in-person and virtual STEP.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers.

OBJECTIVE: Wee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases cytotoxicity when combined with DNA damaging agents. We aimed to evaluate the safety and efficacy of adavosertib in combination with definitive pelvic radiotherapy and concurrent cisplatin in patients with gynecological cancers. METHODS: A multi-institutional, open-label phase I trial was designed to assess dose escalation (3+3 design) of adavosertib in combination with standard chemoradiation. Eligible patients with locally advanced cervical, endometrial or vaginal tumors were treated with a 5-week course of pelvic external beam radiation 45-50 Gy in 1.8-2 Gy daily fractions plus concurrent weekly cisplatin 40 mg/m2 and adavosertib 100 mg/m2 on days 1, 3 and 5 of each week during chemoradiation. The primary endpoint was to determine the recommended phase II dose of adavosertib. Secondary endpoints included toxicity profile and preliminary efficacy. RESULTS: Ten patients were enrolled (nine locally advanced cervical and one endometrial cancer). Two patients experienced a dose-limiting toxicity at dose level 1 (adavosertib 100 mg by mouth daily on days 1, 3 and 5), including one patient with grade 4 thrombocytopenia, and one with treatment hold >1 week due to grade 1 creatinine elevation and grade 1 thrombocytopenia. At dose level -1 (adavosertib 100 mg by mouth daily on days 3 and 5), one out of five patients enrolled had a dose-limiting toxicity in the form of persistent grade 3 diarrhea. The overall response rate at 4 months was 71.4%, including four complete responses. At 2 years follow-up, 86% of patients were alive and progression-free. CONCLUSION: The recommended phase II dose could not be determined due to clinical toxicity and early trial closure. Preliminary efficacy appears promising, yet selecting the adequate dose/schedule in combination chemoradiation warrants further investigation to limit overlapping toxicities.

Gender Disparities Among Professional Team Sports Medicine Physicians.

OBJECTIVE: Although recent trends from the Accreditation Council for Graduate Medical Education (ACGME) present encouraging growth of female representation in sports medicine, the field is still lagging behind other specialties. This study investigates gender disparities among physicians providing care for professional sports teams in male and female sports leagues. DESIGN: Information regarding physicians providing sports medicine care to professional teams obtained by database queries (May 2021). Chi-square analysis compared gender data of orthopaedic team physicians with American Orthopaedic Society for Sports Medicine (AOSSM) and American Academy of Orthopaedic Surgeons (AAOS) membership, residency, and fellowship census data. Primary care sports medicine physicians were compared with American Medical Society for Sports Medicine (AMSSM) and primary-care sports medicine fellowship census data. SETTING: Professional sports health care. STUDY POPULATION: Professional league physicians. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Gender, residency, and fellowship training of professional league physicians. RESULTS: Among a total of 608 team physicians, 572 (93.5%) were male and 40 (6.5%) were female. Orthopedic surgeons comprised 64.7% of the physicians. Fourteen (3.6%) team orthopedic surgeons were female. Thirty-five percent of team physicians were primary care sports medicine physicians. Twenty-six primary care sports medicine physicians (11.6%) were female. Orthopaedic female team physician representation overall was comparable with AOSSM and AAOS membership but significantly less than orthopaedic surgery residents and sports medicine fellows ( P < 0.01). Women's National Basketball Association orthopaedic team physicians were more represented than female membership among AOSSM, AAOS, and orthopaedic sports medicine fellows ( P < 0.01). Except for the WNBA, Premiere Hockey Federation, National Women's Soccer League, and United States Football League, female primary care sports medicine physicians were underrepresented in professional sports compared with AMSSM membership and primary care sports fellows ( P < 0.01). CONCLUSION: Overall, female representation is poor among orthopaedic surgeons and primary care physicians providing sports medicine care to professional teams. Leagues encompassing female athletes tend to have better representation of female physicians. LEVEL OF EVIDENCE: IV.

Elective Hand Surgery Is Delayed among Private Insurance Holders.

OBJECTIVES: Patients with private healthcare plans often defer nonemergent or elective procedures toward the end of the year once they have met their deductible. No previous studies have evaluated how insurance status and hospital setting may affect surgical timing for upper extremity procedures. Our study aimed to evaluate the influence of insurance and hospital setting on end-of-the-year surgical cases for elective carpometacarpal (CMC) arthroplasty, carpal tunnel, cubital tunnel, and trigger finger release, and nonelective distal radius fixation. METHODS: Insurance provider and surgical dates were gathered from two institutions' electronic medical records (one university, one physician-owned hospital) for those undergoing CMC arthroplasty, carpal tunnel release, cubital tunnel release, trigger finger release, and distal radius fixation from January 2010 to December 2019. Dates were converted into corresponding fiscal quarters (Q1-Q4). Using the Poisson exact test, comparisons were made between the case volume rate of Q1-Q3 and Q4 for private insurance and then for public insurance. RESULTS: Overall, case counts were greater in Q4 than the rest of the year at both institutions. There was a significantly greater proportion of privately insured patients undergoing hand and upper extremity surgery at the physician-owned hospital than the university center (physician owned: 69.7%, university: 50.3%; P < 0.001). Privately insured patients underwent CMC arthroplasty and carpal tunnel release at a significantly greater rate in Q4 compared with Q1-Q3 for both institutions. Publicly insured patients did not experience an increase in carpal tunnel releases during the same period at both institutions. CONCLUSIONS: Privately insured patients underwent elective CMC arthroplasty and carpal tunnel release procedures in Q4 at a significantly greater rate than publicly insured patients. This finding suggests private insurance status, and potentially deductibles, influence surgical decision making and timing. Further work is needed to evaluate the impact of deductibles on surgical planning and the financial and medical impact of delaying elective surgeries.

Automated Registration and Color Labeling of Serial 3D Double Inversion Recovery MR Imaging for Detection of Lesion Progression in Multiple Sclerosis.

Automated co-registration and subtraction techniques have been shown to be useful in the assessment of longitudinal changes in multiple sclerosis (MS) lesion burden, but the majority depend on T2-fluid-attenuated inversion recovery sequences. We aimed to investigate the use of a novel automated temporal color complement imaging (CCI) map overlapped on 3D double inversion recovery (DIR), and to assess its diagnostic performance for detecting disease progression in patients with multiple sclerosis (MS) as compared to standard review of serial 3D DIR images. We developed a fully automated system that co-registers and compares baseline to follow-up 3D DIR images and outputs a pseudo-color RGB map in which red pixels indicate increased intensity values in the follow-up image (i.e., progression; new/enlarging lesion), blue-green pixels represent decreased intensity values (i.e., disappearing/shrinking lesion), and gray-scale pixels reflect unchanged intensity values. Three neuroradiologists blinded to clinical information independently reviewed each patient using standard DIR images alone and using CCI maps based on DIR images at two separate exams. Seventy-six follow-up examinations from 60 consecutive MS patients who underwent standard 3 T MR brain MS protocol that included 3D DIR were included. Median cohort age was 38.5 years, with 46 women, 59 relapsing-remitting type MS, and median follow-up interval of 250 days (interquartile range: 196-394 days). Lesion progression was detected in 67.1% of cases using CCI review versus 22.4% using standard review, with a total of 182 new or enlarged lesions using CCI review versus 28 using standard review. There was a statistically significant difference between the two methods in the rate of all progressive lesions (P < 0.001, McNemar's test) as well as cortical progressive lesions (P < 0.001). Automated CCI maps using co-registered serial 3D DIR, compared to standard review of 3D DIR alone, increased detection rate of MS lesion progression in patients undergoing clinical brain MRI exam.

Management of Malignant Bowel Obstruction: An Innovative Proactive Outpatient Nurse-Led Model of Care for Patients With Advanced Gynecologic Cancer.

BACKGROUND: Malignant bowel obstruction (MBO) in patients with advanced gynecologic cancer (GyCa) can negatively impact clinical outcomes and quality of life. Oncology nurses can support these patients with adequate tools/processes. PROBLEM: Patients with GyCa with/at risk of MBO endure frequent emergency or hospital admissions, impacting patient care. APPROACH: Optimizing oncology nurses' role to improve care for patients with GyCa with/at risk of MBO, the gynecology oncology interprofessional team collaborated to develop a proactive outpatient nurse-led MBO model of care (MOC). OUTCOMES: The MBO MOC involves a risk-based algorithm engaging interdisciplinary care, utilizing standardized tools, risk-based assessment, management, and education for patients and nurses. The MOC has improved patient-reported confidence level of bowel self-management and decreased hospitalization. Following education, nurses demonstrated increased knowledge in MBO management. CONCLUSIONS: An outpatient nurse-led MBO MOC can improve patient care and may be extended to other cancer centers, fostering collaboration and best practice.

Carotid-Cavernous Fistula Presenting as Isolated Painful Anisocoria.

A painful isolated third nerve palsy is an uncommon presenting sign of a carotid-cavernous fistula (CCF). It mostly occurs in dural CCFs with posterior drainage into the petrosal sinuses. We present a case of a 50-year-old woman who developed acute right periorbital facial pain in the territory of the first branch of the right trigeminal nerve and was noted to have a right dilated unreactive pupil with very subtle right ptosis. She was subsequently diagnosed with a posteriorly draining dural CCF.