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Objective: While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses. Design: Cost‐effectiveness study Population: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management. Methods: The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings. Main outcome measures: The primary outcome was the cost‐effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost‐effectiveness ratios (ICERs). Results: MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer‐related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses. Conclusion: MIS constitutes a cost‐effective management strategy for women with suspicious ovarian masses. MIS is a cost‐effective management strategy for women with suspicious ovarian masses. MIS is a cost‐effective management strategy for women with suspicious ovarian masses. [ABSTRACT FROM AUTHOR]

Purpose: The past decade has seen an increase in oral anticancer drug (OACD) approvals. Polypharmacy and drug-drug interactions (DDIs) likely contribute to OACD toxicity. We assessed a one-time pharmacist-led video consultation to identify DDIs., Methods: We conducted a single-arm telehealth intervention of a one-time 30-minute pharmacist-led video consultation among patients initiating OACDs. The visit focused on identifying polypharmacy and DDIs. Feasibility was defined as ≥50% completion of all study interventions. We determined the prevalence, characteristics, and severity of OACD-related potential DDIs. We also assessed the prevalence of medication list inaccuracies, polypharmacy, patient satisfaction, and patient perception of intervention acceptability, appropriateness, and feasibility., Results: Of 58 eligible patients, 43 (74%) completed the intervention and 33 (57%) completed all evaluations. Median medication per patient was nine (range 4-21), and 98% of patients had at least five prescriptions. The median number of medication list errors was two (range 0-16), with at least one error for 76% and >1 for 52%. Pharmacists identified OACD-related interactions in 18 cases (42%), including change in drug metabolism (eight), elimination (one), and absorption (three). Interactions were classified as Lexicomp categories C (13), D (five), or X (one) requiring close monitoring or a change in treatment. All patients expressed high satisfaction with the intervention and agreed or completely agreed that it was acceptable, appropriate, and feasible., Conclusion: Polypharmacy, medication list errors, and DDIs are prevalent among patients initiating OACDs. A one-time remote pharmacist-led video consultation can address OACD-related DDIs, which may decrease medication complexity and improve adherence.

Objective: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery., Methods: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests., Results: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001)., Conclusions: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions. Both OncoTarget, which identifies high-affinity inhibitors of individual master regulator (MR) proteins, and OncoTreat, which identifies drugs that invert the transcriptional activity of hyperconnected MR modules, produced highly significant 30-day disease control rates (68% and 91%, respectively). Moreover, of 18 OncoTreat-predicted drugs, 15 induced the predicted MR-module activity inversion in vivo. Predicted drugs significantly outperformed antineoplastic drugs selected as unpredicted controls, suggesting these methods may substantively complement existing precision cancer medicine approaches, as also illustrated by a case study., Significance: Complementary precision cancer medicine paradigms are needed to broaden the clinical benefit realized through genetic profiling and immunotherapy. In this first-in-class application, we introduce two transcriptome-based tumor-agnostic systems biology tools to predict drug response in vivo. OncoTarget and OncoTreat are scalable for the design of basket and umbrella clinical trials. This article is highlighted in the In This Issue feature, p. 1275., (©2023 American Association for Cancer Research.)

Purpose: Implementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center., Methods: We developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry. A 2-item assessment in English or Spanish was administered to patients through the electronic medical record portal or using paper forms. We evaluated completion rates and mode of completion. Through feedback from patients, clinicians, and staff, we identified strategies to improve completion rates and acceptability., Results: From March, 2021, to February, 2022, 3,500 patients were seen in the breast oncology clinic. Of them, 39% (n = 1,349) responded to the screening items, either by paper or portal, 12% (n = 437) preferred not to answer, and the remaining 49% (n = 1,714) did not have data in their electronic health record, meaning they were not offered screening or did not complete the paper forms. Young adults (18-39 years) were more likely to respond compared with patients 70 years or older (61% v 30%, P < .01). English-preferring patients were more likely to complete the screening compared with those who preferred Spanish (46% v 28%, P < .01). Non-Hispanic White patients were more likely to respond compared with Non-Hispanic Black patients and with Hispanic patients (46% v 39% v 32%, P < .01). Strategies to improve completion rates included partnering with staff to facilitate paper form administration, optimizing patient engagement with the portal, and clearly communicating the purpose of the screening., Conclusion: Systematic financial screening is feasible, and electronic data capture facilitates successful implementation. However, inclusive procedures that address language and technology preferences are needed to optimize screening.

Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy. Thus, we designed a phase 1b dose-escalation clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in patients with metastatic BC (MBC) (NCT02632071). Study results showed that the two agents can be safely combined, that clinical activity is identified in patients with HR + /HER2 - disease and that the HDAC6 score has potential as predictive biomarker. Analysis of other tumor types also identified multiple cohorts with predicted sensitivity to HDAC6i's. Mechanistically, we have linked the anticancer activity of HDAC6i's to their ability to induce c-Myc hyperacetylation (ac-K148) promoting its proteasome-mediated degradation in sensitive cancer cells., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy., Design: Cost-effectiveness study., Population: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer., Methods: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values., Main Outcome Measures: The primary outcome was the incremental cost-effectiveness ratio (ICER)., Results: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses., Conclusions: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle., (© 2022 John Wiley & Sons Ltd.)

Objective: To estimate trends in use of laparoscopic power morcellators in women undergoing minimally invasive hysterectomy and to examine use of containment systems in these patients in relation to safety guidance from the U.S. Food and Drug Administration (FDA)., Methods: We examined data that were recorded in the Premier Healthcare Database from patients who underwent laparoscopic supracervical hysterectomy from 2010 to 2018. Patients were stratified based on use of laparoscopic power morcellators. The cohort was further stratified as either pre-FDA guidance (2010 quarter 1-2014 quarter 1) or post-FDA guidance (2014 quarter 2-2018 quarter 2). Interrupted time series analyses were performed to determine the effect of FDA guidance on the use of laparoscopic power morcellators and containment bags., Results: Among 67,115 patients, laparoscopic power morcellator use decreased from 66.7% in 2013 quarter 4 to 13.3% by 2018 quarter 2. The likelihood of laparoscopic power morcellator use decreased by 9.5% for each quarter elapsed in the post-FDA warning period (risk ratio [RR] 0.91, 95% CI 0.90-0.91). Containment bag use rose from 5.2% in 2013 quarter 4 to 15.2% by 2018 quarter 2. The likelihood of containment bag use increased by 3% for each quarter elapsed in the post-FDA warning period (RR 1.03, 95% CI 1.02-1.05). Among women who had laparoscopic power morcellator use, uterine cancers or sarcomas were identified in 54 (0.17%) before the FDA guidance compared with seven (0.12%) after the guidance ( P =.45). Containment bags were used in 11.1% of women with uterine cancers or sarcomas before the FDA guidance compared with 14.3% after the guidance ( P =.12). The perioperative complication rate was 3.3% among women who had laparoscopic power morcellator use without a containment bag compared with 4.5% ( P =.001) in those with a containment bag (aRR 1.35, 95% CI 1.12-1.64)., Conclusion: Use of laparoscopic power morcellators has decreased over time. Containment bag use increased after the FDA's 2014 guidance; however, most procedures employing laparoscopic power morcellators are still performed without a containment bag., Competing Interests: Financial Disclosure Dr. Wright has received royalties from UpToDate and received research support from Merck. Dr. Hou has served as a consultant for Foundation Medicine and Natera. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures., Methods: Women aged 18-64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation., Results: From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2., Conclusion: Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level., Competing Interests: Financial Disclosure: Jason D. Wright has received royalties from UpToDate and received research support from Merck. June Y. Hou has served as a consultant for Foundation Medicine and Natera. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Cervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30-65 years. We examined the use of cervical cancer screening among average-risk Medicaid beneficiaries., Design: Retrospective cohort study., Population: Women age 30-64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co-testing or primary HPV testing from 2013 to 2016., Methods: The IBM Watson Health Multi-State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined., Main Outcome Measure: The rate of repeat cervical cancer screening was analysed using a cumulative incidence function., Results: A total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co-testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24-36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3., Conclusion: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination., Tweetable Abstract: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused., (© 2021 John Wiley & Sons Ltd.)

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19., Significance: Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171., (©2022 American Association for Cancer Research.)

Objective: To examine the use of estrogen therapy (ET) and patterns of follow-up evaluation for sequelae of estrogen deprivation among women who were premenopausal who underwent bilateral salpingo-oophorectomy (BSO) for benign gynecologic diseases., Methods: The IBM Watson Health MarketScan Research Databases were used to identify women between age 18 and 50 years who underwent BSO from 2008 to 2019. Estrogen therapy was defined as any prescription of estrogen filled from 6 weeks before BSO to 36 months after BSO. Patterns of follow-up testing including bone mineral density and lipid testing were examined., Results: We identified a total of 61,980 women who underwent BSO for benign indications. Overall, 64.5% (95% CI 64.1-64.9%) of women received ET. The rate of ET use within 36 months of surgery declined from a peak of 69.5% in 2008 to 58.2% in 2016. The median duration of continuous ET was 5.3 months. Estrogen therapy use declined with increasing age. The cumulative rate of ET use at 36 months after surgery was 79.1% (95% CI 76.9-81.1) in those aged 18-29 years, 75.9% (95% CI 74.5-77.3%) in those aged 30-34 years, 70.2% (95% CI 69.1-71.2%) in those aged 35-39 years, 66.1% (95% CI 65.3-66.9%) in those aged 40-44 years, and 60.0% (95% CI 59.4-60.6%) in those aged 45-50 years. In a multivariable model, women who underwent surgery more recently and those with medical comorbidities were less likely to receive ET, whereas younger women, those with Medicaid insurance, those outside of the northeast, and those who underwent concurrent hysterectomy were more likely to receive ET., Conclusion: Estrogen therapy use in women who are premenopausal who underwent BSO for benign gynecologic diseases has declined substantially over the past decade., Competing Interests: Financial Disclosure Dr. Wright has received royalties from UpToDate and research support from Merck. Dr. Hou has served as a consultant for Foundation Medicine. The other authors did not disclose any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses., Design: Cost-effectiveness study POPULATION: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management., Methods: The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings., Main Outcome Measures: The primary outcome was the cost-effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost-effectiveness ratios (ICERs)., Results: MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer-related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses., Conclusion: MIS constitutes a cost-effective management strategy for women with suspicious ovarian masses., Tweetable Abstract: MIS is a cost-effective management strategy for women with suspicious ovarian masses., (© 2021 John Wiley & Sons Ltd.)

Objective: To examine access to high-volume surgeons in comparison with low-volume surgeons who perform hysterectomies within high-volume hospitals and to compare perioperative morbidity and mortality between high-volume and low-volume surgeons within these centers., Methods: Women who underwent hysterectomy in New York State between 2000 and 2014 at a high-volume (top quartile by volume) hospital were included. Surgeons were classified into quartiles based on average annual hysterectomy volume. Multivariable models were used to determine characteristics associated with treatment by a low-volume surgeon in comparison with a high-volume surgeon and to estimate the association between physician volume, and morbidity and mortality., Results: A total of 300,586 patients cared for by 5,505 surgeons at 59 hospitals were identified. Women treated by low-volume surgeons, in comparison with high-volume surgeons, were more often Black (19.4% vs 14.3%; adjusted odds ratio [aOR] 1.26; 95% CI 1.09-1.46) and had Medicare insurance (20.6% vs 14.5%; aOR 1.22; 95% CI 1.04-1.42). Low-volume surgeons were more likely to perform both emergent-urgent procedures (26.1% vs 6.4%; aOR 3.91; 95% CI 3.26-4.69) and abdominal hysterectomy, compared with minimally invasive hysterectomy (77.8% vs 54.7%; aOR 1.91; 95% CI 1.62-2.24). Compared with patients cared for by high-volume surgeons, those operated on by low-volume surgeons had increased risk of a complication (31.0% vs 10.3%; adjusted risk ratios [aRR] 1.84; 95% CI 1.71-1.98) and mortality (2.2% vs 0.2%; aRR 3.04; 95% CI 2.20-4.21). In sensitivity analyses, differences in morbidity and mortality remained for emergent-urgent procedures, elective operations, cancer surgery, and noncancer procedures., Conclusion: Socioeconomic disparities remain in access to high-volume surgeons within high-volume hospitals for hysterectomy. Patients who undergo hysterectomy at a high-volume hospital by a low-volume surgeon are at substantially greater risk for perioperative morbidity and mortality., Competing Interests: Financial Disclosure Ana I. Tergas received funds from Auro vaccines. Dr. Wright has served as a consultant for Clovis Oncology and received research funding from Merck and royalties from UpToDate. Dr. Hou has served as a consultant for Foundation Medicine. No other authors have any conflicts of interest or disclosures. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer., Methods: Patients with metastatic HER2+ breast cancer progressing on at least 2 lines of HER2-directed therapy were eligible. The phase I portion determined the tolerable dose of ruxolitinib in combination with trastuzumab. The primary objective of the phase II was to assess the progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab compared to historical control., Results: Twenty-eight patients were enrolled, with a median number of prior therapies of 4.5. Ruxolitinib 25 mg twice daily was the recommended phase II dose with no dose limiting toxicities (DLTs). Of 26 evaluable patients in phase II, the median PFS was 8.3 weeks (95% CI 7.1, 13.9). Among the 14 patients with measurable disease, 1 patient had a partial response and 4 patients had stable disease. Most of the adverse events were hematologic., Conclusion: While well tolerated with a strong preclinical rationale, the combination of ruxolitinib and trastuzumab did not lead to an improvement in PFS compared to historical control in patients with trastuzumab-resistant metastatic HER2+ breast cancer., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Propranolol regulates angiogenesis in pre-clinical models and reduces distant breast cancer (BC) metastases in observational studies. We assessed the feasibility of combining propranolol with neoadjuvant chemotherapy (NAC) in patients with BC., Methods: Women with clinical stage II-III BC undergoing NAC [weekly paclitaxel × 12, followed by dose-dense adriamycin/cyclophosphamide (AC) × 4] started propranolol 20 mg PO BID with paclitaxel #1, and increased to 80 mg extended release (ER) PO daily, as tolerated. The primary endpoint was to assess feasibility, defined as at least 75% of patients having at least 80% adherence to propranolol as prescribed. Secondary endpoints included identifying safety, rate of dose holds and modification, and rate of reaching 80 mg ER daily. The proposed sample size was 20 patients., Results: From November 2012 to September 2015, ten patients were enrolled. Median age was 50.5 years (range, 44-67). All patients had hormone receptor-positive/HER2-negative breast cancer. Three women had grade I bradycardia that resulted in a 1-week delay in increasing the propranolol dose. Ninety percent of women reached the target propranolol dosing of 80 mg ER daily, and 70% took the target propranolol dose until the night before surgery. Of the 4 women who dose-reduced propranolol, 1 increased to the target propranolol dose. Mean adherence to propranolol dosing was 96% (range: 91-100%). All patients went to surgery., Conclusion: Our results support the feasibility of combining propranolol (up to 80 mg ER) with neoadjuvant taxane/anthracycline-based chemotherapy.

Importance: Increased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently., Objective: To examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures., Design, Setting, and Participants: This cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020., Main Outcomes and Measures: Receipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively., Results: Among 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180-day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50)., Conclusions and Relevance: In this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.

Background and Objectives: Twenty percent of the patients affected with stage IV antropyloric stomach cancer are hospitalized with a gastric outlet obstruction syndrome (GOOS) requiring its resolution to improve the quality of life (QoL). We present our preliminary short- and mid-term results regarding the influence of endoscopic placement of self-expandable metal stent (SEMS) or open stomach-partitioning gastrojejunostomy in QoL., Materials and Methods: In this prospective randomized longitudinal cohort trial, we randomly assigned 27 patients affected with stage IV antropyloric stomach cancer into two groups: Group 1 (13 patients) who underwent SEMS positioning and Group 2 (14 patients) in whom open stomach-partitioning gastrojejunostomy was performed. The Karnofsky performance scale and QoL assessment using the EQ-5D-5L™ questionnaire was administered before treatment and thereafter at 1, 3, and 6 months. Results : At 1-month, index values showed a statistically significant deterioration of the QoL in patients of Group 2 when compared to those of Group 1 ( p = 0.004; CI: 0.04 to 0.21). No differences among the groups were recorded at 3-month; whereas, at 6-month, the index values showed a statistically significant deterioration of the QoL in patients of Group 1 ( p = 0.009; CI: -0.25 to -0.043)., Conclusions: Early QoL of patients affected with stage IV antropyloric cancer and symptoms of GOOS is significantly better in patients treated with SEMS positioning but at 6-month the QoL significantly decrease in this group of patients. We explained the reasons of this fluctuation with the higher risk of re-hospital admission in the SEMS group.

Importance: While cervical cancer screening with cytologic and human papillomavirus (HPV) testing has reduced mortality from cervical cancer, overuse of these tests is associated with downstream psychological and medical consequences, as well as significant costs. Guidelines now recommend less frequent testing, although adherence to these recommendations is uncertain., Objective: To determine the frequency of overuse of cervical cancer screening tests., Design, Setting, and Participants: This cohort study included 2 299 177 women aged 30 to 65 years recorded in the MarketScan database who underwent cervical cancer screening with cervical cytologic testing, cotesting, or primary HPV testing in 2013 through 2014. Women were followed-up for 3 years, and use of repeat testing during this period was noted. Clinical and demographic characteristics associated with overuse of screening and the association between screening and performance of routine gynecologic examinations were recorded. Data were analyzed from June 15 to September 15, 2020., Main Outcomes and Measures: Cumulative performance of overuse of cervical cancer screening with repeat cytologic or HPV testing within 36 months of the index screening test., Results: A total of 2 299 177 women with a median (interquartile range) age of 47 (39-54) years were identified. Initial cervical cancer screening consisted of cytologic testing alone in 1 286 179 women (55.9%), cotesting in 991 583 women (43.1%) and HPV testing in 21 415 women (0.9%). The cumulative incidence of repeat cervical cancer screening was 17.7% (95% CI, 17.6%-17.7%) at 12 months, 51.1% (95% CI, 51.0%-51.2%) at 24 months and 65.8% (65.7%-65.8%) at 36 months. Repeat screening was less common in older women (32 198 women [60.2%] aged 60-64 years vs 194 665 women [67.8%] aged 30-39 years; P < .001), women with medical comorbidities (125 197 women [64.1%] with ≥2 comorbidities vs 423 012 women [64.7%] with no comorbidities; P < .001), women screened in 2014 (176 734 women [53.4%] in 2014 vs 555 767 women [69.4%] in 2013; P < .001), and those screened with cotesting (277 032 women [56.9%] for cotesting vs 450 438 [71.2%] for cytologic testing; P < .001). In contrast, overuse of testing was more common in the Northeastern US (143 916 women [68.1%] in the Northeast vs 81 552 women [51.6%] in the West; P < .001), in women with more frequent outpatient visits (238 510 women [71.1%] with ≥6 visits vs 279 412 [58.7%] with ≤2 visits; P < .001). Women with a sexually transmitted infection after their index testing were also more likely to undergo repeat testing (adjusted odds ratio, 1.42 [95% CI, 1.21-1.68]). Women who did not undergo repeat screening were significantly less likely to undergo a gynecological exam after the index screening test: during year 2 of follow-up, 657 749 women (96.7%) who underwent repeating screening had a gynecological examination compared with 203 566 women (26.2%) who did not undergo a gynecological examination., Conclusions and Relevance: These findings suggest that among commercially insured women with average risk, cervical cancer screening tests were frequently overused.

Importance: Patients with cancer are at risk for unplanned hospitalizations during treatment which can increase the cost of care., Objectives: To determine demographic and clinical factors associated with healthcare utilization and costs among clinical trial participants., Design, Setting, and Patients: We conducted a retrospective analysis among breast cancer patients over the age of 65 treated on SWOG clinical trials from 1999 to 2011 with trial data linked to Medicare claims., Main Outcomes and Measures: The outcomes were healthcare utilization (emergency room visits (ER), hospitalizations) and costs from Medicare Claims. Demographic, clinical, and prognostic factors were captured from clinical trial records. We identified cardiovascular comorbidities/risk factors (CVD-RFs) of diabetes, hypertension, hypercholesterolemia, and coronary artery disease (CAD) from Medicare claims. Multivariable logistic and linear regression were used to assess the association between CVD-RFs and outcomes., Results: Among the 708 patients included in the analysis, 160 (22.6%) experienced 234 separate hospitalizations, and 193 (27.3%) experienced 311 separate ER visits. Black race was associated with an increase in hospitalizations (OR [95% CI], 2.52 [1.10-5.79], p = 0.03), but not emergency room visits compared to white race. Diabetes, hypertension, hypercholesterolemia, and CAD were all independently associated with increased risk of both hospitalizations and ER visit. Hypertension had the strongest association, with more than a threefold risk of hospitalization for those with hypertension compared to those without (OR [95% CI], 3.16 [1.85-5.40], p < 0.001). For those with ≥ 3 RFs, the risk of hospitalization was nearly 3 times greater compared to 0 or 1 CVD-RFs (OR [95% CI], 2.74 [1.71-4.38], p < 0.001). Similar results were seen for ER visits. In the first 12 months after trial registration, patients with diabetes ($38,324 vs $30,923, 23.9% increase, p = 0.05), hypercholesterolemia ($34,168 vs $30,661, 11.4% increase, p = 0.02), and CAD ($37,781 vs $31,698, 19.2% increase, p = 0.04) had statistically significantly higher total healthcare costs. Additionally, those with ≥ 2 significant CVD-RFs ($35,353 vs. $28,899, 22.3% increase, p = 0.005) had statistically significantly higher total healthcare costs., Conclusions: Among participants treated on clinical trials, black race and presence of multiple cardiovascular comorbidities was associated with a substantial increase in ER visits, hospitalizations and healthcare costs. Efforts to reduce unplanned hospitalizations should focus on this high-risk group.

Background: Prior work has shown that the competitiveness of the market in which hospitals operate is associated with use of surgical procedures. This study examined the association between regional market competition and use of breast reconstruction for women with breast cancer and ductal carcinoma in situ undergoing mastectomy., Methods: Women who underwent mastectomy from 2010 to 2011 recorded in the National Inpatient Sample were selected. The competitive market environment for each hospital in which patients were treated was estimated using the Herfindahl-Hirschman Index. Multivariable models were developed to examine the association between regional market competition and breast reconstruction, with adjustment for other clinical, demographic, and structural variables., Results: Immediate breast reconstruction was performed for 9902 (45%) of 22,011 women. The rate of immediate breast reconstruction was 34.5% at hospitals in non-competitive markets, 49% at hospitals in moderately competitive markets, and 56.4% at hospitals in highly competitive markets (P < 0.0001). In a multivariable model, women in moderately competitive markets were 24% (risk ratio [RR] 1.24; 95% confidence interval [CI] 1.10-1.41) more likely to undergo immediate breast reconstruction than women in noncompetitive markets, whereas those in competitive markets were 25% (RR 1.25; 95% CI 1.11-1.41) more likely to have reconstruction. Later year of treatment, higher census tract income level, and residence in an urban area were associated with an increased likelihood of reconstruction (P < 0.05 for all). In contrast, older age, non-white race, and non-commercial insurance were associated with a lower likelihood of reconstruction (P < 0.05 for all)., Conclusion: Patients who undergo mastectomy at hospitals in competitive markets are more likely to undergo immediate breast reconstruction.

Background: The selective estrogen receptor modulator tamoxifen is now widely used for the treatment and prevention of breast cancer. Tamoxifen use has been associated with a variety of gynecologic problems. Despite the frequency with which hormonal therapy is used for the treatment of breast cancer, limited population-level data are available to describe the occurrence of gynecologic conditions and the use of surveillance testing in women receiving tamoxifen and aromatase inhibitors., Objective: We performed a population-based analysis among women with breast cancer receiving hormonal therapy with tamoxifen, a drug commonly used in premenopausal and sometimes postmenopausal women, to determine the frequency of gynecologic abnormalities and use of diagnostic and surveillance testing. We compared these findings to women treated with aromatase inhibitors, agents commonly used in postmenopausal women., Study Design: The MarketScan database was used to identify women diagnosed with breast cancer from 2009 through 2013 who underwent mastectomy or lumpectomy. Women receiving tamoxifen (age <50 vs ≥50 years) were compared to women ≥50 years of age treated with aromatase inhibitors. We examined the occurrence of gynecologic symptoms and diseases (vaginal bleeding, endometrial polyps, endometrial hyperplasia, and endometrial cancer) and gynecologic procedures and interventions (transvaginal ultrasound, endometrial biopsy, hysteroscopy/dilation and curettage, and hysterectomy). Time-dependent analyses were performed to examine symptoms and testing., Results: A total of 75,170 women, including 15,735 (20.9%) age <50 years treated with tamoxifen, 13,827 (18.4%) age ≥50 years treated with tamoxifen, and 45,608 (60.7%) age ≥50 years treated with aromatase inhibitors were identified. The cumulative incidence of any gynecologic symptom or pathologic diagnosis during the study period was 20.2%, 12.3%, and 3.5%, respectively (P < .001), while the cumulative incidence of any gynecologic procedure or intervention during the study period was 34.2%, 20.9%, and 9.0%, respectively (P < .0001). Among women without symptoms or pathology, interventions were performed in 20.0%, 11.0%, and 6.8%, respectively (P < .0001)., Conclusion: Compared to women taking aromatase inhibitors, gynecologic symptoms, procedures, and pathology are higher for both premenopausal and postmenopausal women with breast cancer on tamoxifen. Increased efforts to curb use of gynecologic interventions in asymptomatic women are needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: While adjuvant hormonal therapy (HT) reduces mortality for women with nonmetastatic breast cancer, nonadherence to HT is common., Objective: We investigated the association between patterns of prior nonadherence to medications for chronic conditions with HT nonadherence., Design, Setting, and Participants: For this retrospective cohort study, the MarketScan database was scanned for women 18 years and older who had been diagnosed with nonmetastatic breast cancer between January 1, 2010, and December 31, 2012, and who filled 2 or more prescriptions for tamoxifen and/or an aromatase inhibitor., Main Exposures and Outcomes: Nonadherence to medications for 6 chronic conditions (hypertension, hyperlipidemia, gastroesophageal reflux disease, thyroid disease, diabetes, osteoporosis) in the 12 months before diagnosis was defined as a medication possession ratio (MPR) less than 80%. Nonadherence to HT was defined as an MPR less than 80% between the first and last prescription for HT up to 2 years., Analysis: Multivariable logistic regression was used to determine the association between prior medication nonadherence and HT nonadherence., Results: Of 21 255 women treated with adjuvant HT, 3314 (15.6%) were nonadherent, and age (<55 or ≥75 years vs 55-64 years), higher 30-day out-of-pocket costs, and increased comorbidities were associated with nonadherence. Women without prior medications for 1 of the chronic conditions (n = 7828 [37%]) had an 18.4% nonadherence rate to HT. Those who used 1 or more medication prior to HT and were adherent (n = 9223 [43%]) had a 9.8% nonadherence rate to HT (relative to those without prior medications: odds ratio [OR] 0.56; 95% CI, 0.50-0.61), while those who were nonadherent to their chronic medications (n = 4214 [20%]) had a 23.1% nonadherence rate to HT (OR 1.43; 95% CI, 1.30-1.58). Adherence and nonadherence for medications for each of the 6 medical conditions was associated with adherence or nonadherence for HT, respectively., Conclusions and Relevance: We found that nonadherence to medications for chronic conditions prior to HT was associated with greater nonadherence to oral HT in patients with breast cancer. Medication nonadherence history may play an important role in determining patients at risk for nonadherence to a subsequent medication for a different illness, such as HT, and a potential target for future interventions.

Purpose: Nonadherence to oral endocrine therapy is common among women with breast cancer (BC). Less is known about nonadherence to medications for other chronic conditions among survivors of BC., Methods: We used the MarketScan Database to identify women older than 18 years who had nonmetastatic BC diagnosed between January 1, 2009, and December 31, 2013. Prescriptions were identified for the following six non-cancer-related conditions: hypertension, thyroid disease, hyperlipidemia, gastroesophageal reflux disease, diabetes, and osteoporosis. The study period was defined as 1 year before BC diagnosis (index date) through 1.5 years after the index date, with a 6-month washout period after the index data to control for adherence during the preoperative period and during chemotherapy if necessary. Adherence was defined as a medication possession ratio ≥ 80%. Change in adherence was defined as a 20% decrease in the medication possession ratio from the time before diagnosis compared with after treatment. Factors associated with change in adherence were evaluated in multivariable logistic models., Results: Among 36,149 patients diagnosed with BC, the average adherence to these medications before BC was 91.4%. However, after BC treatment, adherence decreased to 77.9% (P < .001). Looking at drugs for each condition, nonadherence ranged from 15.6% to 38% (P < .001). Factors associated with an increase in nonadherence included older age, insurance type, number of medications, and comorbid conditions., Conclusion: Decreased adherence to medications for chronic diseases was found in the first year after breast cancer treatment. Breast cancer survivors may need additional interventions to improve their adherence to their medications for chronic conditions., (Copyright © 2016 by American Society of Clinical Oncology.)

Patients with breast cancer, which lacks ER, PR, and HER2; "triple negative" (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single-institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC. Women diagnosed with early stage TNBC from January 1, 1998 to December 31, 2007 were identified through institutional databases. Electronic medical records were reviewed to assess patterns of recurrence, treatment, and survival. In total, 1,323 patients, median age 53 years (range 20-91), were identified. There were 298 patients (23%) who developed metastatic disease, of whom, 99 (33%) developed BMs, representing 7.5% of the entire cohort. Following BM diagnosis, treatment consisted of: radiotherapy 87 (88%) patients, resection 26 (26%) patients, and systemic chemotherapy 70 (71%) patients, with a median of 1.0 (range 0-8) chemotherapy regimens. The actuarial median survival from diagnosis of BMs is 5 months (95% CI 4-7 months). This single-institution, retrospective study confirms that the prognosis for patients with BMs from TNBC remains poor. This group of patients urgently needs improved therapies., (© 2012 Wiley Periodicals, Inc.)

Late clinical outbreak in patients with right colon cancer translates into very advanced stage of the tumour. Nevertheless, long term results of radical surgery are favourable, even if susceptible of improvements. While earlier diagnoses are not easy to achieve, a greater surgical radicality can be obtained both by extending resections to the surrounding structures and organs, and by enlarging lymphadenectomy to all the inframesocolic compartment and to the main lymph nodes located at the level of superior mesenteric vessels. A series of 60 right hemicolectomies performed from 1968 to 1990 to treat right colonic cancer is presented. Intraoperative mortality was of 4 cases (6.6%). Lymph node "mapping" was drawn, and in 26 cases (43%) metastases were found. Paracolic nodes were involved in 96% of cases, intermediate in 42%, and principal ones in 34%. Forty four patients, surgically treated up to 1985 and eligible for a 5 year follow up, were all verified. Overall free of disease survival was assessed in 28 cases (63.6%). Survival in relation to Dukes staging was 81.8% (9/11) in C. According to presence (LN+) or absence (LN-) of lymphatic spread, 5 year survival was found to be 70.3% (19/27) in LN-, and 52.9 (9/17) in LN+. Difference between the two groups is 17.4%, much smaller than the mean one of 45% reported by world literature. This figure, together with the finding of a 12, 10 and 5 year survival in patients with principal nodes involvement, suggests that extended lymphadenectomy might play a principal role in improving long term survival rates of advanced right colon cancer.

A retrospective analysis is reported of 131 symptomatic patients for gastro-esophageal reflux, comparing the radiological diagnosis to endoscopic, manometric and pH-metric results. A low incidence of x-ray examination is found. The role of radiology in gastro-esophageal reflux is considered and discussed.