The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

Computed Tomography Angiography and Conventional Angiography for the Diagnosis and Treatment of Non-variceal Gastrointestinal Bleeding at a Tertiary Cancer Center.

INTRODUCTION: To evaluate the diagnostic value of computed tomography angiography (CTA) and conventional angiography (CA) and the therapeutic value of transarterial embolization for acute gastrointestinal bleeding in patients with malignancy. METHODS: A retrospective review of 100 patients who underwent CTA and/or CA for gastrointestinal bleeding at a comprehensive cancer center between the years 2011-2021 was performed. Clinical and patient outcome data were collected and analyzed using Kruskal-Wallis tests for continuous variables and chi-square tests or Fisher's exact tests (whichever is appropriate) for categorical variables in univariate analysis. All tests were two-sided at a significance level of 0.05. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Fifty-two percent of our patients underwent CTA alone, 29% underwent CA alone, and 19% underwent both procedures. Overall, CTA was positive in 11.3% (8/71) of patients and CA was positive in 22.9% (11/38) of patients. Of patients who underwent both studies, 52.6% (10/19) were positive for both. ICU admission was associated with CTA and/or CA positivity (p=0.015). Of 48 patients with data for embolization, 50% of patients underwent transarterial embolization for bleeding, 11 patients had identifiable bleeding on CA, and 13 patients underwent prophylactic embolization at the site of suspected bleeding. Rebleeding following embolization was found in 33.3% (8/24) of patients, including six patients who underwent prophylactic embolization and two patients who were treated for visualized bleeding. CONCLUSION: CTA and CA are two critical studies for patients with GI bleeding and a history of malignancy. Neither alone can effectively exclude an identifiable source of bleeding. In patients with a history of malignancy, transarterial embolization may be an effective treatment of both angiographically visible and occult sources of GI bleeding.

Comparison of allelopathic effects of two typical invasive plants: Mikania micrantha and Ipomoea cairica in Hainan island.

Mikania micrantha and Ipomoea cairica are two invasive plants widely distribute and seriously damage in Hainan island. In this study, the leaves extracts of two weeds were collected and determined for their allelopathic potentials on Chrysanthemum coronarium. The phytotoxicity bioassay showed that when the extract concentration was 50 and 100 mg/ml, the inhibited effects of M. micrantha on growth of C. coronarium were greater than by I. cairica. However, when the extract concertation at 400 mg/ml, the opposite inhibited effects were observed. We speculated this phenomenon was caused by different allelopathic compounds. Therefore, using gas chromatography-mass spectrometry, 19 and 23 compounds were identified respectively, benzoic acid and cinnamic acid were the main components in the two leaves extracts, which were selected to carry out the further bioassays. Subsequent bioassay results showed the effects of two allelochemicals on morphological index and chlorophyll content and POD activity were all negative to C. coronarium, whereas the content of MDA and activity of SOD, CAT represented adverse changes. Moreover, the inhibitions by cinnamic acid were generally greater than those by benzoic acid. Thus, the phenolic acids played the most crucial roles in the allelopathic effccts of M. micrantha and I. cairica leaves extracts.

Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors.

BACKGROUND: Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. METHODS: This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. RESULTS: Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). CONCLUSIONS: Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report.

BACKGROUND: It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes. METHODS: We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score. RESULTS: Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82). CONCLUSIONS: Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.

The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors--results of a prospective study.

BACKGROUND: Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors. METHODS: In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users. RESULTS: Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR=1.28, 95% CI=0.62-2.64) and breast cancer (33 deaths, RR=1.78, 95% CI=0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (P=0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, P=0.02). CONCLUSIONS: Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.