Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.

Coping Strategies and Associated Symptom Burden Among Patients With Advanced Cancer.

BACKGROUND: Few studies examine how patients with advanced cancer cope with stress. The objective of our study was to evaluate coping strategies adopted by patients with cancer and their relationship with symptom burden. METHODS: A secondary data analysis of a prospective cross-sectional survey of patients with cancer and tobacco use was conducted, which examined demographics, symptom burden (Edmonton Symptom Assessment System), and coping strategies (the Brief COPE Questionnaire). Demographic characteristics were summarized by standard summary statistics; we also examined associations between patient characteristics and coping strategies using t-test, rank-sum test, chi-squared test, or Fisher's exact test depending on the distribution of data. RESULTS: Among 399 patients, the majority were female (60%), Caucasian (70%), the mean age was 56.5 (±12.0) years, and the most common malignancies were gastrointestinal (21%) and breast (19%). Patients with cancer adopted multiple adaptive coping strategies, most frequently acceptance (86.7%) and emotional support (79.9%), with humor (18.5%) being the least. Common maladaptive strategies included venting (14.5%) and self-distraction (36.6%), while substance use (1.0%) was infrequently reported. Of the adaptive strategies, female gender was significantly associated with higher engagement with emotional and instrumental support, positive reframing, religious coping, and acceptance (P < .05 for all). College educated patients reported significantly higher implementation of humor, planning, and acceptance. Maladaptive coping strategies such as denial were associated with increased pain and depression, while patients adopting emotional-focused strategies rated decreased emotional distress. CONCLUSIONS: The majority of patients with advanced cancer reported adopting multiple, adaptive coping strategies, and a minority utilized maladaptive or avoidant strategies, rarely substance use, and may need additional psychological support.

Detection and Management of Perioperative Hyperglycemia at a Tertiary Cancer Center.

INTRODUCTION: To improve the detection and management of perioperative hyperglycemia at our tertiary cancer center, we implemented a glycemic control quality improvement initiative. The primary goal was to decrease the percentage of diabetic patients with median postoperative glucose levels > 180 mg/dL during hospitalization by 15% within 2 years. METHODS: A multidisciplinary team standardized preoperative screening, preoperative, intraoperative, and postoperative hyperglycemia management. We included all patients undergoing nonemergent inpatient and outpatient operations. We used a t test, rank sum, chi-square, or Fisher's exact test to assess differences in outcomes between patients at baseline (BL) (10/2018-4/2019), during the first phase (P1) (10/2019-4/2020), second phase (P2) (5/2020-12/2020), and maintenance phase (M) (1/2021-10/2022). RESULTS: The analysis included 9891 BL surgical patients (1470 with diabetes), 8815 P1 patients (1233 with diabetes), 10,401 P2 patients (1531 with diabetes) and 30,410 M patients (4265 with diabetes). The percentage of diabetic patients with median glucose levels >180 mg/dL during hospitalization decreased 32% during the initiative (BL, 20.1%; P1, 16.9%; P2, 12.1%; M, 13.7% [P < .001]). We also saw reductions in the percentages of diabetic patients with median glucose levels >180 mg/dL intraoperatively (BL, 34.0%; P1, 26.6%; P2, 23.9%; M, 20.3% [P < .001]) and in the postanesthesia care unit (BL, 36.0%; P1, 30.4%; P2, 28.5%; M, 25.8% [P < .001]). The percentage of patients screened for diabetes by hemoglobin A1C increased during the initiative (BL, 17.5%; P1, 52.5%; P2, 66.8%; M 74.5% [P < .001]). CONCLUSIONS: Our successful initiative can be replicated in other hospitals to standardize and improve glycemic control among diabetic surgical patients.

Comparative analysis of hormonal therapy in low-grade endometrial stromal sarcoma: A retrospective study.

OBJECTIVE: To evaluate the disease course of patients with low grade endometrial stromal sarcoma (LG-ESS) and compare oncologic outcomes associated with hormonal therapy in primary and recurrent disease. METHODS: This is a retrospective study of patients with LG-ESS who underwent active treatment between January 2000 and July 2023. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier product-limit estimator and modeled via Cox proportional hazards regression. RESULTS: A total of 221 patients were included; 58 % of patients (91/157) were stage I, 12 % (19/157) stage II, 13 % (20/157) stage III, and 17 % (27/157) stage IV. Surgery was the primary treatment for 98 % (213/218). Only 79 patients received hormonal adjuvant therapy, 58 % (46/79) Megace, 24 % (19/79) Letrozole, and 18 % (14/79) received other hormonal therapy. There was no significant difference in RFS (p = 0.159) and OS (p = 0.167) between patients receiving Megace versus Letrozole as adjuvant therapy. At first recurrence, patients given Megace had a similar RFS to those on Letrozole (p = 0.302), but a better OS (27 vs 10 months, p = 0.018).  Negative status of estrogen, smooth muscle actin, and desmin were associated with lower RFS (p = 0.039, p = 0.002, and p = 0.015, respectively) and OS (p = 0.008, p = 0.012, and p = 0.013, respectively). Lymphovascular invasion was associated with lower RFS (p = 0.033), and negative status of progesterone was associated with lower OS (p = 0.003). CONCLUSION: There was no difference in oncologic outcomes between Megace and Letrozole in patients who received adjuvant therapy for LG-ESS. Megace may have potential survival advantage in recurrent disease. Further study is warranted to determine the most effective agents and their sequence in the treatment of LG-ESS.

A colostomy for large bowel obstruction at the end of life: What do patients gain from palliative surgery?

OBJECTIVES: Malignant large bowel obstruction (LBO) is a frequent complication affecting women with gynecologic cancers and is an indication for emergent surgery. However, the life expectancy and subsequent medical care utilization are unknown. We sought to estimate overall survival (OS) following colostomy and describe subsequent healthcare utilization among patients with advanced gynecologic malignancies. METHODS: We conducted a retrospective analysis of patients with advanced gynecologic cancers who underwent colostomy with palliative intent due to LBO at our institution between March 2014 and January 2023. Summary statistics were used to describe the clinical and demographic characteristics of the study population. OS was estimated using the Kaplan-Meier method, and we defined healthcare utilization at the end-of-life using criteria published by the National Quality Forum. RESULTS: A total of 78 patients were included. The median age at the time of surgery was 61 (range: 34-83), and most patients had recurrent ovarian, fallopian tube, or primary peritoneal cancer (n = 51, 65.4%), followed by cervical cancer (n = 16, 20.5%), and uterine cancer (n = 10, 12.8%). The median Charlson comorbidity index was 3 and median postoperative length of stay was five days (range: 1-26). The median follow-up for all patients was 4.5 months (range: 0.07-46.2), and the median OS was 4.5 months (95% CI: 2.9-6.0), including 12 patients (15.4%) with <30-day OS and 21 (26.9%) with <60-day OS. In the last 30 days of life, 62.7% of patients were re-admitted to the hospital, 53.0% were seen in the emergency department, and 18.5% were admitted to an intensive care unit. CONCLUSIONS: A significant proportion of patients died within 60 days of surgery, and many had high healthcare utilization at the end of life.

Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.

OBJECTIVE: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes. METHODS: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures. RESULTS: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%). CONCLUSIONS: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.

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.

Effect of Digital Health Coaching on Self-Efficacy and Patient-Reported Outcomes in Individuals with Acute Myeloid and Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial.

INTRODUCTION: Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy. METHODS: Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score. RESULTS: A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p = 0.219). There were no significant associations between the intervention and other patient-reported outcomes for patients with CLL. CONCLUSION: There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.

The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy.

OBJECTIVES: In patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess whether the chemotherapy response score predicts homologous recombination status. METHODS: We identified patients with advanced epithelial ovarian cancer (diagnosed January 2019 to 20 June 2023) who received neoadjuvant chemotherapy, underwent interval surgery, and for whom a chemotherapy response score was reported (1=no or minimal tumor response, 2=appreciable tumor response, 3=complete or near complete response with no residual tumor). Comparisons were made using ANOVAs or Kruskal-Wallis test for continuous variables and χ2 or Fisher's exact test for categorical variables. RESULTS: The cohort consisted of 234 patients with advanced ovarian cancer who underwent interval surgery following neoadjuvant chemotherapy. Of those who underwent germline genetic testing, 22% (51/232) had a pathogenic BRCA1 or BRCA2 mutation and of those with tumors sent for testing, 65% were found to have homologous recombination deficiency (66/146). With increasing chemotherapy response scores, a higher likelihood of a complete gross resection was observed (50% (chemotherapy response score, CRS 1) vs 77% (CRS 2) vs 88% (CRS 3), p<0.001). On multivariable analysis, CRS 2 (adjusted odds ratio=3.28, 95% CI 1.12 to 9.60, p=0.03) and CRS 3 (5.83, 1.79 to 18.93, p=0.003) were independently associated with homologous recombination deficiency compared with CRS 1. CONCLUSION: A positive response to chemotherapy at the time of interval tumor reductive surgery defined by the chemotherapy response score was associated with homologous recombination status and the likelihood of achieving a complete gross resection.

TERT promoter mutations and survival outcomes in adult-type granulosa cell tumors.

OBJECTIVES: T0 evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations. METHODS: This is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for TERT promoter and FOXL2 c.C402G mutations were included. We used descriptive statistics to compare demographic and clinical variables and estimated progression-free and overall survival with Kaplan-Meier curves. Cox proportional hazards regression and log-rank tests were employed for comparisons, with multivariable analyses adjusting for various factors. RESULTS: Among 70 patients, 28 (40%) had TERT+ tumors. The median age at diagnosis was 40 years (range 12-71) for TERT- patients and 46 years (range 25-76) for TERT+ patients. At diagnosis, 22 (63%) of 35 TERT- patients were stage I, 10 (29%) stage II, and 3 (9%) stage III, while in the TERT+ group, 17/23 (74%) were stage I, 3 (13%) stage II, and 3 (13%) stage II. Univariable analysis showed no difference in time from diagnosis to first recurrence (p=0.19) and from first recurrence to second recurrence (p=0.24) based on tumor TERT status. The median time from first to second recurrence in the TERT- group was 27.3 months (95% CI 14.1 to 40.0) and in the TERT+ group was 14.8 months (95% CI 8.1 to 21.0). There was no observed difference in overall survival between the groups (HR=0.53; 95% CI 0.19 to 1.45; p=0.21). Multivariable analysis adjusting for age at diagnosis, TERT promoter mutation status, systemic chemotherapy, and stage demonstrated a significant difference in progression-free survival based on TERT mutation status (HR=2.89; 95% CI 1.32 to 6.36). CONCLUSIONS: After adjustment for covariates, patients with adult granulosa cell tumors and TERT+ tumors had shorter progression-free survival after first recurrence. TERT promoter mutations may identify a subset of patients with recurrent adult granulosa cell tumors and less favorable outcomes.

Scaling cervical cancer screening in Mozambique: analysis of loop electrosurgical excision procedure (LEEP) specimens.

OBJECTIVES: As cervical cancer screening programs are implemented and expanded, an increasing number of women require loop electrosurgical excision procedure (LEEP) for treatment of pre-invasive cervical disease. Our objective was to describe the pathological results of LEEP specimens performed as part of the MULHER study and identify factors associated with positive LEEP margins. METHODS: The MULHER study enrolled 9014 women who underwent HPV testing followed by visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) and thermal ablation for those with positive results. Participants with lesions ineligible for ablation underwent LEEP. Pathology reports were reviewed for specimen size/volume, number of fragments, pathological diagnosis and margin status. Multivariable regression analysis was performed to identify variables associated with positive LEEP margins. RESULTS: 169 participants underwent LEEP. The median age was 38 years (range 30-49). 65.1% were women living with HIV. Pathological diagnosis was available for 154 patients and included cancer (n=6, 3.9%); cervical intraepithelial neoplasia (CIN) 2/3 (n=75, 48.7%); CIN 1 (n=67, 43.5%); and normal/benign findings (n=6,3.9%). 31.8% of LEEP specimens were removed in more than one fragment. The mean specimen volume was 2.9 cm3 (range 0.2-15.0). LEEP margin status was available for 130 patients. Positive margins (ectocervical/endocervical only, or both) were noted in 76 (58.5%) patients and associated with HIV+status (p=0.0499) and a diagnosis of CIN 2 or worse (p=0.0197). There were no associations between margin status and age, number of fragments or specimen volume. CONCLUSION: Our results showed a high number of LEEP specimens with positive margins. Additional evaluation is needed to better understand the characteristics of precancerous cervical lesions in this high-risk population. As cervical cancer screening programs are scaled in Mozambique and other lower-resource countries, there is a need to train providers to perform high-quality LEEP and for accurate and timely pathological interpretation.

Sleep disturbances based on patient reported outcomes in patients with breast cancer.

PURPOSE: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders. METHODS: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed. Clinical characteristics, PROs using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and PSG data were reviewed. RESULTS: 404 patients were identified with 43% early, 30% locally advanced and 17% metastatic disease. PSQI revealed poor sleep in 75%, and ESS demonstrated daytime sleepiness in 55%. Sleep aid use was reported by 39%, and pain medication use in 22%. Most patients (50.2%) had multiple sleep disorders. Insomnia (54.5%) was the most frequent sleep disorder, followed closely by obstructive sleep apnea (OSA) (53.7%). PSG was performed in 74%. Multivariate analysis linked poor sleep to use of sleep aids [OR 7.7, 95% CI 3.9 to 15.2], anxiety disorder [OR 4.8, 95% CI 1.7 to 14.0], and metastatic disease [OR 2.8, 95% CI 1.1 to 6.6]. Daytime sleepiness correlated with known diagnosis of OSA [OR 1.9, 95% CI 1.0 to 3.3] and sleep aid use [OR 0.6, 95% CI 0.4 to 0.9]. CONCLUSIONS: Poor sleep was associated with sleep aid use, anxiety disorder and metastatic disease. Insomnia was the most common sleep disorder, followed by OSA (mostly mild). Education about sleep health and proactive screening for sleep symptoms would be beneficial in patients with breast cancer.

A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas.

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment. DESIGN: Retrospective cohort study. INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO. MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation. RESULTS: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation. CONCLUSIONS: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.

Frequency of vaccine hesitancy among patients with advanced cancer.

BACKGROUND: Vaccine hesitancy has become prevalent in society. Vulnerable populations, such as those with cancer, are susceptible to increased morbidity and mortality from diseases that may have been prevented through vaccination. OBJECTIVES: Our objective was to determine patient perception of vaccine efficacy and safety and sources of information that influence decisions. METHODS: This study was a prospective cross-sectional survey trial conducted from March 10, 2022, to November 1, 2022, at a Supportive Care Clinic. Patients completed the survey with a research assistant or from a survey link. Vaccine hesitancy was defined as a response of 2 or more on the Parent Attitudes About Childhood Vaccines (PACV-4). Perception on vaccine safety and efficacy along with the importance of sources of information were determined by a questionnaire. RESULTS: Of the 72 patients who completed the PACV-4, 30 were considered vaccine-hesitant (42%). Of those who completed the survey alone (35), 23 (66%) were vaccine-hesitant; and of those who completed the survey with the help of a study coordinator (37), 7 (19%) were vaccine-hesitant. The most important source for decision-making was their doctor (82%, 95% CI 73-89), followed by family (42%, 95% CI 32-52), news/media (31%, 95% CI 22-41), and social media (9%, 95% CI 4-16). Clinical and demographic factors including age, gender, race/ethnicity, education level, and location of residence were not associated with vaccine hesitancy. SIGNIFICANCE OF RESULTS: Vaccine hesitancy is present among patients with advanced cancer. The high value given to the doctor's recommendation suggests that universal precautions regarding vaccine recommendation may be an effective intervention.

Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer.

BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer. METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival. RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma. CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools. PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.

Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers.

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. RESULTS: Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. CONCLUSIONS: The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.

Ablative Margins of Colorectal Liver Metastases Using Deformable CT Image Registration and Autosegmentation.

Background Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need. Purpose To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation. Materials and Methods This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones on CT images was applied for MAM quantification retrospectively. The per-tumor incidence of local disease progression was defined as residual tumor or local tumor progression. Factors associated with local disease progression were evaluated using the multivariable Fine-Gray subdistribution hazard model. Local disease progression sites were spatially localized with the tissue at risk for tumor progression (<5 mm) using a 3D ray-tracing method. Results Overall, 213 ablated CLMs (mean diameter, 1.4 cm) in 124 consecutive patients (mean age, 57 years ± 12 [SD]; 69 women) were evaluated, with a median follow-up interval of 25.8 months. In ablated CLMs, an MAM of 0 mm was depicted in 14.6% (31 of 213), from greater than 0 to less than 5 mm in 40.4% (86 of 213), and greater than or equal to 5 mm in 45.1% (96 of 213). The 2-year cumulative incidence of local disease progression was 72% for 0 mm and 12% for greater than 0 to less than 5 mm. No local disease progression was observed for an MAM greater than or equal to 5 mm. Among 117 tumors with an MAM less than 5 mm, 36 had local disease progression and 30 were spatially localized within the tissue at risk for tumor progression. On multivariable analysis, an MAM of 0 mm (subdistribution hazard ratio, 23.3; 95% CI: 10.8, 50.5; P < .001) was independently associated with local disease progression. Conclusion Biomechanical deformable image registration and autosegmentation on CT images enabled identification and spatial localization of colorectal liver metastases at risk for local disease progression following ablation, with a minimal ablative margin greater than or equal to 5 mm as the optimal end point. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sofocleous in this issue.

Doing the hard work of learning: oncologists' enduring impressions of a year-long communication skills training program.

PURPOSE: Few studies have examined the long-term impact of communication skills training for oncologists. We developed a year-long communication skills curriculum for medical oncology fellows with the primary goals of fostering life-long learning of patient-centered communication skills and internalization of associated attitudes and beliefs. We engaged learners through reflection, narrative methods, and action methods, thereby creating a non-threatening, team-based environment. The purpose of the current study was to determine whether learners perceived that they had acquired enduring skills, attitudes, and knowledge years after they participated. METHODS: Former fellows completed an online cross-sectional survey from June to July 2019 that included demographic information, 21 items on a numerical scale, and 3 narrative prompts. Survey items pertained to 4 domains, including skills, attitudes, confidence with specific scenarios, and overall impressions. The numerical scale ranged from "strongly agree" = 1 to "strongly disagree" = 5. RESULTS: A total of 114 fellows, including 27 teaching assistants, participated in the communication skills training over 8 years. The average time between the end of the training program and completion of the survey was 5.2 years. The response rate was 68/114 (64%). Forty-one (60%, 95% CI: 49.3-73.8) fellows agreed or strongly agreed that the curriculum profoundly impacted their practice of medicine. Forty-three (64%, 95% CI: 51.5-75.5) fellows strongly agreed or agreed that they often found themselves informally sharing lessons they learned during the series. Overall average domain scores were 1.89 (SD = 0.84) for skills, 2.16 (0.79) for attitudes, 2.05 (0.81) for confidence with specific challenges, and 2.38 (0.94) for lasting impressions. Results were significantly more favorable for teaching assistants than for others. CONCLUSION: Engaging, interactive, safe, and learner-centered communication skills training has an enduring and favorable impact on oncologists' self-perceived skills, confidence with specific challenges, and attitudes.

Characterizing morphologic subtypes of high-grade serous ovarian cancer by CT: a retrospective cohort study.

OBJECTIVE: A novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features unique to each morphologic subtype. METHODS: This retrospective study included 109 patients with high-grade serous ovarian cancer who underwent pre-operative computed tomography (CT) scanning and laparoscopic assessment of disease burden between 1 April 2013 and 5 August 2015. Gross morphologic subtype had been previously assigned by laparoscopy. Two radiologists independently reviewed CT images for each patient, categorized disease at eight anatomic sites, and assessed for radiographic characteristics of interest: large infiltrative plaques, mass-like metastases, enhancing peritoneal lining, architectural distortion, fat stranding, calcifications, and lymph node involvement. Demographic and clinical information was summarized with descriptive statistics and compared using Student's t-tests, χ² tests, or Fisher exact tests as appropriate; kappa statistics were used to assess inter-reader agreement. RESULTS: Certain radiographic features were found to be associated with gross morphologic subtype. Large infiltrative plaques were more common in type 1 disease (88.7% (47/53) vs 71.4% (25/35), p=0.04), while mass-like metastases were more often present in type 2 disease (48.6% (17/35) vs 22.6% (12/53), p=0.01). Additionally, radiographic presence of disease at the falciform ligament was more common in type 1 morphology (33.9% (19/56) vs 13.2% (5/38), p=0.02). CONCLUSION: Morphologic subtypes of high-grade serous ovarian cancer were associated with specific CT findings, including the presence of large infiltrative plaques, mass-like metastases, and falciform ligament involvement.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.