A Phase I trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies.

PURPOSE: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared to sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers. PATIENTS AND METHODS: A 3+3 phase I trial was conducted with 3 potential dose levels in patients with previously treated endometrial (EC), cervical (CC), and platinum-resistant ovarian cancer (OC) patients to ascertain the recommended Phase II dose (RP2D). AB160 was administered intravenously on Days 1, 8 and 15 of a 28-day cycle (ABX 75-175 mg/m2, BEV 30-70 mg/m2). Pharmacokinetic analyses were performed. RESULTS: No dose-limiting toxicities (DLTs) were seen among the 3 DLs tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% CI: 16.3%-61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies. CONCLUSIONS: The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2).

Breast cancer and gender-affirming hormone therapy for transgender and gender-diverse (TGD) individuals.

Transgender and gender-diverse (TGD) individuals are at risk for breast cancer, but are less likely to undergo screening mammograms and appear to suffer poorer cancer-related outcomes than cisgender women. Gender-affirming hormone therapy (GAHT) may be lifesaving for TGD individuals from the perspective of affirming their core identities; however, the effects of GAHT on cancer development, progression, and outcomes are poorly understood.

Baclofen for hiccups: a large mixed methods multisite study.

OBJECTIVE: Hiccups can be bothersome and spawn morbidity. Although oral baclofen is perhaps the most prescribed agent for hiccups, a paucity of data supports its use. METHODS: This multisite, single institution study examined the medical records of patients who had hiccups and had been prescribed baclofenas noted in a clinical encounter. Mixed methods were used to assess baclofen's palliative efficacy. In view of the sometimes transient nature of hiccups and other such factors, cessation or palliation of hiccups in 75% of patients was sought to indicate true palliation. RESULTS: A total of 301 patients with a median age of 61 years (range 20-87 years) and a male predominance are the focus of this report. Baclofen was most often prescribed at 10 mg orally three times a day. Only 105 patients (35%) (95% CI: 30% to 41%) acquired hiccup palliation. Corroborative medical record quotations included, 'Still has hiccups.'Quotations such as, 'Responding to baclofen this AM', were also recorded. Baclofen appeared more likely to benefit patients with hiccups of >48 hours (chronic) duration in univariable analyses (OR for benefit: 0.51 (95% CI: 0.29 to 0.91; p=0.02) with similar conclusions drawn from multivariable analyses. Adverse events occurred in 15 patients with drowsiness the most common. CONCLUSIONS: Baclofen did not meet this study's a priori threshold for successful hiccup palliation, but further study is indicated to learn whether baclofen might help patients with chronic hiccups.

Vitamin and Mineral Supplementation, Weight Gain, and Poor Appetite in Patients With Cancer: Many Questions and Fewer Answers.

Patients with cancer or with a history of cancer often seek nutritional advice. In turn, cancer health care providers are often asked questions related to nutrition and cancer. Should I take high-dose vitamins or other high-dose supplements? Should I take a regular-dose vitamin or other regular-dose nutritional supplements? Will I experience weight loss during postoperative chemotherapy? What should be my weight goals during and after adjuvant therapy? In the setting of advanced cancer, what should I do to keep my appetite and weight up? This review attempts to provide data-driven answers to some of these commonly posed questions.

A TGF-ß/KLF10 signaling axis regulates atrophy-associated genes to induce muscle wasting in pancreatic cancer.

Cancer cachexia, and its associated complications, represent a large and currently untreatable roadblock to effective cancer management. Many potential therapies have been proposed and tested-including appetite stimulants, targeted cytokine blockers, and nutritional supplementation-yet highly effective therapies are lacking. Innovative approaches to treating cancer cachexia are needed. Members of the Kruppel-like factor (KLF) family play wide-ranging and important roles in the development, maintenance, and metabolism of skeletal muscle. Within the KLF family, we identified KLF10 upregulation in a multitude of wasting contexts-including in pancreatic, lung, and colon cancer mouse models as well as in human patients. We subsequently interrogated loss-of-function of KLF10 as a potential strategy to mitigate cancer associated muscle wasting. In vivo studies leveraging orthotopic implantation of pancreas cancer cells into wild-type and KLF10 KO mice revealed significant preservation of lean mass and robust suppression of pro-atrophy muscle-specific ubiquitin ligases Trim63 and Fbxo32, as well as other factors implicated in atrophy, calcium signaling, and autophagy. Bioinformatics analyses identified Transforming growth factor beta (TGF-ß), a known inducer of KLF10 and cachexia promoting factor, as a key upstream regulator of KLF10. We provide direct in vivo evidence that KLF10 KO mice are resistant to the atrophic effects of TGF-ß. ChIP-based binding studies demonstrated direct binding to Trim63, a known wasting-associated atrogene. Taken together, we report a critical role for the TGF-ß/KLF10 axis in the etiology of pancreatic cancer-associated muscle wasting and highlight the utility of targeting KLF10 as a strategy to prevent muscle wasting and limit cancer-associated cachexia.

Social determinants of health: a need for better data capture in Asian American patients with hepatocellular cancer.

BACKGROUND: Social determinants of health lead to better cancer care. This multi-site, single-institution study sought to capture data on social determinants of health data in Asian Americans with hepatocellular carcinoma; this group constitutes 60% of patients with this malignancy and are often undertreated or not treated at all. METHODS: This study took advantage of an institutional initiative designed to capture and integrate social determinants of health data into the electronic medical record for all patients. Medical records of Asian Americans with hepatocellular cancer were reviewed to acquire data on housing instability, lack of transportation, financial concerns, and social isolation; a score of 1 indicated poor social determinants of health. RESULTS: Of 112 adult Asian American patients with hepatocellular cancer, 22 (20%) were Southeast Asian, and 74 (67%) described English proficiency/preference. Total noncompletion per domain (no question answered within that domain) was observed in 90 patients (80%) for housing instability; 90 (80%) for lack of transportation; 92 (82%) for financial hardship; and 90 (80%) for social isolation. A score of 1 (highest risk) was observed in 1 patient (0.9%) for housing instability; 1 (0.9%) lack of transportation; no patient for financial hardship; and 1 (0.9%) for social isolation. Of note, institution-wide benchmark total noncompletion rates were 0.3%, 0.3%, 47%, and 39% for these respective domains. CONCLUSION: High total noncompletion rates make social determinants of health data challenging to interpret and underscore the need for evidence-based guidelines on how best to capture such data in underserved patients.

Completion of Genetic Testing and Incidence of Pathogenic Germline Mutation among Patients with Early-Onset Colorectal Cancer: A Single Institution Analysis.

Over the past 20 years, rates of early-onset colorectal cancer (eoCRC), defined as <50 years of age at diagnosis, have increased, with 16-25% associated with a pathogenic germline variant (PGV) resulting in a hereditary cancer syndrome. In the present study, we sought to further characterize PGVs observed in patients with eoCRC. We conducted a retrospective analysis of patients with a history of CRC referred for genetic counseling at Mayo Clinic Rochester between April 2019 and April 2022. Three hundred and three CRC patients were referred to medical genetics, including 124 with a history of eoCRC. Only 84 patients (68%) with eoCRC referred for genetic counseling completed genetic testing, with an average of 48 genes evaluated. PGVs were identified in 27.4% with eoCRC, including 8.3% with Lynch syndrome (LS). Other detected PGVs known to increase the risk of CRC included MUTYH (4.8%), CHEK2 (3.6%), APC, BMPR1A, and TP53 (1.3% each). Among those with aoCRC, 109 patients (61%) completed genetic testing, among which 88% had either a dMMR tumor, personal history of an additional LS malignancy, or family history of LS malignancy, with PGVs detected in 23% of patients. This study reinforces the importance for all patients with CRC, especially those with eoCRC, to undergo germline testing.

Measuring symptoms and toxicities: a 35-year experience.

PURPOSE: When conducting trials aimed at the improvement of cancer-related and/or cancer treatment-related toxicities, it is important to determine the best means of measuring patients' symptoms. METHODS: The authors of this current manuscript have an extensive experience with the conduct of symptom-control clinical trials. This experience is utilized to provide insight into the best means of measuring symptoms caused by cancer and/or cancer therapy. RESULTS: Patient-reported outcome data are preferable for measuring bothersome symptoms, for determining toxicities caused by treatment approaches, and offer more accurate and detailed information compared with health care practitioners recording their impressions of patient experiences. Well-validated patient friendly measures are recommended when they are available. When such are not readily available, face-valid, single-item numerical rating scales are effective instruments to document both treatment trial outcomes and cancer treatment side effects/toxicities. CONCLUSION: The use of numerical rating scales are effective means of measuring symptoms caused by cancer, by cancer treatments, and/or alleviated by symptom control treatment approaches.

Loss of appetite in patients with cancer: an update on characterization, mechanisms, and palliative therapeutics.

PURPOSE OF REVIEW: Over the past year, loss of appetite in patients with cancer has continued to be an area of active investigation. This review provides an update of recently published findings. RECENT FINDINGS: Despite the emergence of new cancer therapeutic agents, this symptom of loss of appetite continues to trouble patients, and it continues to be associated with poor survival. Recent preclinical research promises to lead to newer approaches and newer, more effective palliative agents. Recent clinical research shows that agents such as olanzapine, anamorelin, and cannabis either do or might palliate this symptom. SUMMARY: Loss of appetite in patients with cancer remains an important area of clinical and research focus. Recent published data provide greater clarity with respect to how to palliate this symptom. Today, although clinicians have more options to palliate cancer-associated loss of appetite than ever before, questions remain unanswered about how to palliate this symptom optimally and how to improve the quality of life of patients who suffer from it.

Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival.

BACKGROUND: Bevacizumab-induced gastrointestinal perforation is a rare but potentially devastating adverse event that has generated limited data on overall survival. Yet, such survival data are critical in guiding management. METHODS: This multi-site, single-institution retrospective study focused on all cancer patients who had received bevacizumab and who had suffered a well-documented gastrointestinal perforation from January 1, 2004 through January 20, 2022.The main goal was to report survival outcomes; Kaplan Meier curves and Cox survival models were used for this purpose. RESULTS: Eighty-nine patients are included in this report with a median age of 62 years (range 26-85). Colorectal cancer was the most common malignancy (n = 42). Thirty-nine patients underwent surgery for the perforation. Seventy-eight were deceased at the time of reporting with an overall median survival of all patients of 2.7 months (range 0-45 months), and 32 (36%) died within 30 days of perforation. In univariable survival analyses, no statistically significant associations were observed for age, gender, corticosteroid use, and time since last bevacizumab dose. However, surgically treated patients manifested a better survival (hazard ratio (HR) 0.49 (95% CI 0.31-0.78); p = 0.003). In multivariable analyses, surgery continued to be associated with improved survival (HR 0.47 (95% CI 0.29-0.74); p = 0.002), and corticosteroid use was associated with worse survival (HR 1.75 (95% CI 1.02-2.99); p = 0.04). CONCLUSION: Although gastrointestinal perforation after bevacizumab should be managed on a case-by-case basis, these descriptive survival data can help inform patients, their families, and healthcare providers as challenging management decisions arise.

Rates of and Factors Associated With Patient Withdrawal of Consent in Cancer Clinical Trials.

Importance: Patient withdrawal of consent from a cancer clinical trial is defined as a patient's volitional cessation of participation in all matters related to a trial. It can undermine the trial's purpose, make the original sample size and power calculations irrelevant, introduce bias between trial arms, and prolong the time to trial completion. Objective: To report rates of and baseline factors associated with withdrawal of consent among patients in cancer clinical trials. Design, Setting, and Participants: This multisite observational cohort study was conducted through the Alliance for Clinical Trials in Oncology. Patient withdrawal was defined as a patient's voluntary termination of consent to participate anytime during trial conduct. Baseline patient- and trial-based factors were investigated for their associations with patient withdrawal within the first 2 years using logistic regression models. All patients who participated in cancer therapeutic clinical trials conducted within the Alliance for Clinical Trials in Oncology from 2013 through 2019 were included. The data lock date was January 23, 2022. Main Outcomes and Measures: The percentage of patients who withdrew consent in 2 years and factors associated with withdrawal of consent. Results: A total of 11 993 patients (median age, 62 years; 67% female) from 58 trials were included. Within 2 years, 1060 patients (9%) withdrew from their respective trials. Two-year rates of withdrawal were 5.7%, 7.6%, 8.5%, 7.8%, 8.4%, 9.5%, and 9.8% for each of the respective years from 2013 through 2019. In multivariable analyses, Hispanic ethnicity (odds ratio [OR], 1.67; 95% CI, 1.30-2.15; P < .001), randomized design with placebo (OR, 1.64; 95% CI, 1.38-1.94; P < .001), and patient age 75 years and older (OR, 1.39; 95% CI, 1.12-1.72; P = .003) were associated with higher likelihood of withdrawal by 2 years. Use of radiation was associated with patient retention (OR, 0.68; 95% CI, 0.54-0.86; P = .001). Conclusions and Relevance: In this cohort study, rates of withdrawal of consent were less than 10% and appeared consistent over time. Factors that are associated with withdrawal of consent should be considered when designing trials and should be further studied to learn how they can be favorably modified.

Developing & integrating a mobile application tool into a survivorship clinic for esophageal cancer patients.

Esophageal cancer (EC) patients are living longer due to enhanced screening and novel therapeutics, however, the post-esophagectomy long-term management remains challenging for patients, caregivers, and providers. Patients experience significant morbidity and have difficulty managing symptoms. Providers struggle to manage symptoms, affecting patients' quality of life and complicating care coordination between surgical teams and primary care providers. To address these patient unique needs and create a standardized method for evaluating patient reported long-term outcomes after esophagectomy for EC, our team developed the Upper Digestive Disease Assessment tool, which evolved to become a mobile application. This mobile application is designed to monitor symptom burden, direct assessment, and quantify data for patient outcome analysis after foregut (upper digestive) surgery, including esophagectomy. It is available to the public and enables virtual and remote access to survivorship care. Patients using the Upper Digestive Disease Application (UDD App) must consent to enroll, agree to terms of use, and acknowledge use of health-related information prior to gaining access to the UDD App. The results of patients scores can be utilized for triage and assessment. Care pathways can guide management of severe symptoms in a scalable and standardized method. Here we describe the history, process, and methodology for developing a patient-centric remote monitoring program to improve survivorship after EC. Programs like this that facilitate patient-centered survivorship should be an integral part of comprehensive cancer patient care.

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer.

Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)-based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Outcomes of Older Adults With AML Treated in Community Versus Academic Centers: An Analysis of Alliance Trials.

PURPOSE: Clinical trials are important for managing older patients with AML. We investigated differences in outcomes of older patients with AML on the basis of whether patients participated in intensive chemotherapy trials at community versus academic cancer centers. METHODS: We used data from the Alliance for Clinical Trials in Oncology phase III trials that enrolled patients age ≥ 60 years with newly diagnosed AML between 1998 and 2002 in the Cancer and Leukemia Group B (CALGB) 9720 trial and between 2004 and 2006 in the CALGB 10201 trial. Centers funded by the NCI Community Oncology Research Program were identified as community cancer centers; others were designated as academic cancer centers. Logistic regression models and Cox proportional hazards models were used to compare 1-month mortality and overall survival (OS) by center type. RESULTS: Seventeen percent of the 1,170 patients were enrolled in clinical trials in community cancer centers. The study results demonstrated comparable rates of grade ≥3 adverse events (97% v 93%), 1-month mortality (19.1% v 16.1%), and OS (43.9% v 35.7% at 1 year) between community versus academic cancer centers, respectively. After adjusting for covariates, 1-month mortality (odds ratio, 1.40; 95% CI, 0.92 to 2.12; P = .11) and OS (hazard ratio, 1.04; 95% CI, 0.88 to 1.22; P = .67) were not statistically different among patients treated in community versus academic cancer centers. CONCLUSION: An older patient population, who have complex health care needs, can be successfully treated on intensive chemotherapy trials in select community cancer centers with outcomes comparable with that achieved at academic cancer centers.

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden.

BACKGROUND: Pembrolizumab confers minimal benefit to most patients with pancreas cancer. We explored survival and patient treatment burden (for example, death within 14 days of therapy) in a subgroup who had early access to pembrolizumab . METHODS: This multisite study examined consecutive pancreas cancer patients, who received pembrolizumab from 2004 through 2022. Median overall survival of > 4 months was to be deemed favorable. Patient treatment burden and medical record quotations are presented descriptively. RESULTS: Forty-one patients (median age 66 years; range 36, 84) are included. Fifteen (37%) had dMMR, MSI-H, TMB-H, or Lynch syndrome; and 23 (56%) received concurrent therapy. The median overall survival was 7.2 months (95% confidence interval (CI): 5.2, 12.7 months); 29 were deceased at the time of reporting. Patients with dMMR, MSI-H, TMB-H, or Lynch syndrome had a lower risk of death: hazard ratio (HR): 0.29 (95% CI: 0.12, 0.72); p = 0.008. Medical record phrases ("brilliant response") aligned with the above. One patient died within 14 days of therapy, and one was in an intensive care unit within 30 days of death. Fifteen patients enrolled in hospice; four of these died < 3 days later. CONCLUSIONS: These unexpectedly favorable findings underscore the need for healthcare providers-including palliative care providers-to knowledgeably guide patients about cancer therapy even near the end of life.