Side Effects Of Cancer Therapy Research Articles

Anti-inflammatory effects of Radix Aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluorouracil in mice

Ethnopharmacological relevance5-Fluorouracil (5-FU) is a chemotherapy agent that is widely used in clinical oncologic practice. However, intestinal mucositis is the most frequently occurring side effect of cancer therapy with 5-FU. Based on a literature survey, Radix Aucklandiae herbal preparation potentially ameliorates intestinal mucositis in 5-FU-treated mice. Aim of the studyThe aim of this study was to investigate the inflammation and gastrointestinal regulation of intestinal mucositis induced by 5-FU, including the intestinal morphology, as well as the reduction in food intake, body weight loss, and diarrhea. Materials and methodsIntestinal mucositis was induced in mice by 5-FU (30 mg/kg, i.p., for 5 consecutive days). The dose-dependent Radix Aucklandiae herbal preparation (0.3, 1, and 3 g/kg/day, p.o.), loperamide (3 mg/kg/day, p.o.) or celecoxib (40 mg/kg/day, p.o.) was concurrently administered until the 7th day. Physical status observation, diarrhea assessment, serum proinflammatory cytokine levels, intestinal villus height and crypt depth, and total goblet cells from tissues were assessed. ResultsThe dosage regimen of 5-FU administration caused severe intestinal mucositis in mice, including damage to the intestinal morphology, accompanied by a reduction in food intake, body weight loss, and diarrhea. The high-dose Radix Aucklandiae herbal preparation significantly relieves 5-FU-induced intestinal mucositis by enhancing proliferative activity in epithelial crypts; improving anepithymia, body weight loss, and diarrhea; and displaying protective effects on goblet cells in intestinal mucosal epithelia. Activation of NF-κB in the intestinal mucositis model was also suppressed by the Radix Aucklandiae herbal preparation, suggesting that it is a potent inhibitor of NF-κB and proinflammatory cytokines, such as IL-1β, IL-6, TNF-α, and COX-2. ConclusionsOur data support the conclusion that the Radix Aucklandiae herbal preparation could effectively ameliorate 5-FU-induced gastrointestinal toxicity and be applied clinically for the prevention of intestinal mucositis during chemotherapy.

Hormone replacement therapy after breast cancer: Yes, No or maybe?

Over nine million breast cancer survivors worldwide suffer compromised quality of life attributable to estrogen depletion related symptoms of menopause and side effects of cancer therapy. Hormone Replacement Therapy (HRT) is very effective in managing these symptoms in general population and in breast cancer survivors. However, the concern of breast cancer recurrence as a result of HRT use keeps many oncologists from using this approach in symptom management. Evidence from randomized trials, observational studies and met-analyses on the impact of HRT use on breast cancer recurrence and survival remains controversial. Climacteric symptoms in breast cancer survivors should be delineated for type and severity for methodical management. Lifestyle modifications are effective for mild symptoms, while non-hormonal pharmaceutical approaches can be used as second-line therapy for control of hot flashes, vulvo-vaginal atrophy, arthralgia, mood swings, sleep disturbance, and depression. Evidence does not conclusively render HRT, as a contraindicated approach for these patients; informed consent and shared-decision-making is a reasonable approach for HRT use in symptomatic breast cancer survivors.

Eficacy of Cryotherapy in the Prevention of Oral Mucosistis in Adult Patients with Chemotherapy.

Oral mucositis (OM) is a common side effect of cancer therapies. It causes ulcerative, painful lesions in the oral cavity that can provoke malnutrition, increased risk of infection, longer hospital stays, and seriously affect the quality of life. Cooling the mucosa with oral cryotherapy (OC) during and/or after chemotherapy is the most accessible and tolerable intervention available. The aim of this study is to define the efficacy of OC for preventing OM induced by chemotherapy/radiotherapy in adult patients with cancer. Secondary endpoints include associated problems as pain. A systematic search was performed using the Pubmed, WOS (Web of Science), Cochrane Library, CINAHL, and BVS databases for articles published up to 2010. After inclusion and exclusion criteria were applied, a total of eight articles were analyzed in this review. In seven of the eight articles, the incidence of OM of all grades was significantly lower in the OC group compared with the no-OC group. Use of opioids and level of pain were also significantly reduced. OC is an effective intervention to reduce the incidence of OM induced by chemotherapy as well as the associated severity and pain. Based on these results, OC with only water or with chamomile, associated or not with other mouthwash therapies, is an effective intervention to reduce the incidence of OM induced by chemotherapy as well as the associated severity and pain.

Effect of antioxidants coenzyme Q10 and β-carotene on the cytotoxicity of vemurafenib against human malignant melanoma.

Melanoma is a type of highly invasive skin cancer derived from melanocytes with poor prognosis. Vemurafenib (PLX4032) is a clinically approved targeted therapeutic for BRAF mutant melanoma that has a high therapeutic response rate and significantly prolongs the overall survival time of patients with melanoma. Antioxidants have been widely used as supplements for cancer prevention and for decreasing the side effects of cancer therapy. However, antioxidants can also protect cancer cells from oxidative stress and promote cancer growth and progression. The present study aimed to examine the effect of the antioxidants coenzyme Q10 (CoQ10) and β-carotene on melanoma cell growth and invasiveness and on the cytotoxicity of vemurafenib against both vemurafenib-sensitive (SK-MEL-28) and vemurafenib-resistant (A2058) human malignant melanoma cell lines. MTS assay and wound-healing assay demonstrated that CoQ10 alone significantly reduced the viability and migration of melanoma cells, respectively, and synergistically worked with vemurafenib to decrease the viability and migration of human melanoma cells. In contrast, MTS assay and flow cytometry revealed that β-carotene alone did not affect the viability and apoptosis induction of melanoma cells; however, it inhibited cell migration and invasiveness. Wound-healing and Transwell assay demonstrated that β-carotene alleviated the cytotoxicity of vemurafenib and mitigated the inhibitory effect of vemurafenib on cell migration and invasion. Both CoQ10 and β-carotene protected melanoma cells from undergoing apoptosis induced by vemurafenib. Immunoblotting demonstrated that β-carotene at physiological concentration worked synergistically with vemurafenib to suppress the Ras-Raf-Mek-Erk intracellular signaling pathway. The present study aimed to add to the evidence of the in vitro effects of CoQ10 and β-carotene on the antimelanoma effects of vemurafenib.

Self-efficacy in symptom management for adolescents and young adults with cancer: a systematic review.

Adolescents and young adults (AYAs) have more frequent and intense adverse effects from cancer therapy than other age groups. Self-efficacy, the ability for persons to maintain health-related behavior change, may assist with symptom management but the role it plays in AYAs with cancer has not been thoroughly investigated. This review explores the role that self-efficacy has in symptom management for AYAs with cancer and provides guidance for clinicians to utilize self-efficacy as a means to reduce side effects of therapy. A systematic review of peer-reviewed literature was conducted to identify works discussing self-efficacy and symptom management for AYAs with cancer. Five databases were searched with key terms and articles that discussed relationships between self-efficacy and cancer therapy symptoms were retained for analysis. Twelve manuscripts representing 1180 individuals age 12 to 43years were identified. Self-efficacy was found to be related to (1) health management behaviors, (2) psychosocial health, (3) sexual and reproductive health, and (4) physical symptoms. Self-efficacy had direct correlations with physical activity, nutritional intake, symptom regulation, mental health, sexual health, and fertility preservation. The included studies did not find significant relationships with medication adherence or pain management. Self-efficacy is an attribute that impacts behavior change, health maintenance, and overall wellness and can be changed over time and through interventions to improve symptoms of cancer therapy. Self-efficacy should be evaluated as a construct in relevant studies aimed at improving side effects of cancer therapy to better understand outcomes from interventions. Symptoms, toxicities, and adverse effects of cancer therapy may be improved by increasing self-efficacy of patients.

Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.

Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools.

Early detection strategies and improvements in cancer treatment have dramatically reduced the cancer mortality rate in the United States (US). However, cardiovascular (CV) side effects of cancer therapy are frequent among the 17 million cancer survivors in the US today, and cardiovascular disease (CVD) has become the second leading cause of morbidity and mortality among cancer survivors. Circulating biomarkers are ideal for detecting and monitoring CV side effects of cancer therapy. Here, we summarize the current state of clinical studies on conventional serum and plasma CVD biomarkers to detect and prevent cardiac injury during cancer treatment. We also review how novel exploratory tools such as genetic testing, human stem cell-derived cardiomyocytes, Omics technologies, and artificial intelligence can elucidate underlying molecular and genetic mechanisms of CV injury and to improve predicting cancer therapy-related cardiotoxicity (CTRC). Current regulatory requirements for biomarker qualifications are also addressed. We present generally applicable lessons learned from published studies, particularly on how to improve reproducibility. The combination of conventional circulating biomarkers and novel exploratory tools will pave the way for precision medicine and improve the clinical practice of prediction, detection, and management of CTRC.

The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

Sodium selenite is often given to moderate the side effects of cancer therapy to enhance the cellular defence of non-cancerous cells. To determine whether sodium selenite during radiotherapy protects not only normal cells but also cancer cells, which would imply a reduction of the desired effect of irradiation on tumour during radiotherapy, the effect of the combined treatment of irradiation and sodium selenite was investigated. Human bronchial cells from carcinoma (A549) and normal tissue (BEAS-2B) were treated with sodium selenite and effects on growth and in combination with radiation on metabolic activity and cell cycle distribution were studied. The influence on radiosensitivity was determined via colony forming assays using different solvents of sodium selenite and treatment schedules. It was shown that sodium selenite inhibits growth and influences cell cycle distribution of both normal and tumour cells. Metabolic activity of normal cells decreased more rapidly compared to that of cancer cells. The influence of sodium selenite on radiation response depended on the different treatment schedules and was strongly affected by the solvent of the agent. It could be shown that the effect of sodium selenite on radiation response is strongly dependent on the respective experimental in vitro conditions and ranges from lead to an initially suspected but ultimately no real radioprotection to radiosensitizing up to no effect in one and the same cell line. This might be a reason for controversially described cell responses to radiation under the influence of sodium selenite in studies so far.

Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology.

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in <1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

Current progress in cancer immunotherapy based on natural killer cells.

One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still isno definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the meansof immunotherapy. As innate lymphocytes, NKcells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen-specific. Latest insights into thebiology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell-dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T-cell-targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy.

THE IMPACT OF CLUSTERING OF ORAL SYMPTOMS IN THE PATHOGENESIS OF RADIATION CARIES: A NARRATIVE REVIEW

Objective: Radiation caries (RC) is a dental disease with a high potential for teeth destruction, which impairs quality of life in head and neck cancer (HNC) patients who undergo radiotherapy (RT). The aim of this study was to discuss how the indirect effects of cancer therapy side effects have a pivotal role in the pathophysiology and progression of RC in light of the recently described of oral theory. Study Design: The present narrative review assessed studies regarding specific head and neck radiation-related symptom clusters. The search was performed with PubMed/Medline and manual search. Results: HNC treatment generates clusters of oral symptoms encompassing specific conditions (oral mucositis, radiodermatitis, pain, dysphagia, taste disturbances, dry mouth, and fatigue) and gastrointestinal manifestations (nausea, vomiting, and dehydration), which lead to dietary changes, deficient oral hygiene, enamel fragility, and a highly cariogenic oral environment, impacting the risk for RC onset and progression. Conclusions: A better understanding of the clustering of oral symptoms could be of considerable clinical significance for the oral health and quality of life of HNC patients; therefore, contemporary protocols of RC prevention have to take into account this broader treatment scenario of clustering of oral side effects.

Resveratrol exerts anti-oxidant and anti-inflammatory actions and prevents oxaliplatin-induced mechanical and thermal allodynia

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a frequent and devastating side effect of cancer therapy. No preventive strategies are currently available. We investigated the use of resveratrol (RESV) in the prevention of CIPNP and evaluated key components of the antioxidant defense system and neuroinflammatory factors as possible mediators contributing to RESV actions. Male rats were injected with oxaliplatin (OXA) and received daily oral RESV. Paw mechanical and thermal allodynia, oxidative stress, antioxidant, pro-inflammatory and neuronal injury/activation markers were evaluated in the sciatic nerve (SN), lumbar dorsal root ganglia (DRG) and spinal cord (SC). OXA-injected animals developed mechanical and thermal allodynia, while those receiving OXA + RESV showed patterns of response similar to control animals. Higher TBARS levels and lower GSH/GSSG ratios were observed in the SN of animals receiving OXA. The mRNA levels of the transcription factor NFκB and the pro-inflammatory cytokine TNFα were found to be upregulated both in lumbar DRG and SC. In addition, the antioxidant enzymes NQO-1 and HO-1 and the neuronal injury marker ATF3 showed increased levels of expression in lumbar DRG. In the dorsal SC the neuronal activation marker c-fos and the transcription factor Nrf2, main regulator of antioxidant defenses, were found to be upregulated. RESV early and sustained administration prevented NFκB, TNFα, ATF3 and c-fos upregulation, while increasing the expression of Nrf2, NQO-1, HO-1 and the redox-sensitive deacetylase SIRT1. RESV treatment was also able to restore TBARS levels and GSH/GSSG ratio. Thus, RESV administration resulted in the upregulation of antioxidant mediators, suppression of pro-inflammatory parameters and prevention of OXA-induced mechanical and thermal allodynia.

Abstract 593: Ocular drops of palonosetron reduce chemotherapy-induced acute nausea and vomiting in the dog

Abstract Background: Nausea and vomiting are common side effects of cancer therapies thereby seriously affecting the quality of life of patients. Therefore, the prevention or treatment of chemotherapy-induced nausea and vomiting has become an important part of the comprehensive treatment of cancer. Several 5-HT3 receptor antagonists have been developed in the treatment of nausea and vomiting using mainly the oral route of administration (which is not convenient due to vomiting) or the intravenous route. In this study we tested whether ocular administration of the 5-HT3 receptor antagonist palonosetron (eye drops) could prevent nausea and vomiting associated with intravenous cisplatin injection in dogs. Methods: Six adult male Beagle dogs (10-13 kg) were included in a randomized crossover study. This study was carried out in AAALAC facilities in strict accordance with the European and French animal welfare regulations for animal use in experimentation. Dogs were administered 18 mg/m2 cisplatin intravenously over a 20-min period, followed 45 min later by ocular administration (eye drops, 200µL/eye) of either placebo (2% povidone in saline) or palonosetron (30 or 120 µg/kg). The number of vomits and nausea associated behaviours, scored on a visual analogue scale (VAS), were recorded every 15 min for 7 h following cisplatin administration. Blood samples were collected to measure plasma levels of palonosetron. Results: The placebo treated group vomited an average number of 10.2±2.1 times (range 5-17) over the 7-h period following cisplatin infusion. Ocular administration of palonosetron at 30 μg/kg in cisplatin-treated dogs very strongly and significantly decreased vomiting episodes, with only 1 vomiting episode in 2 dogs overall (p&amp;lt;0.0001). After ocular administration of palonosetron at 120 μg/kg, no vomiting episodes were observed in any dog throughout the observation period (p&amp;lt;0.0001). With regards to the VAS, in the placebo-treated group the nausea-associated behaviour started between 2.5 and 2.75 h after the end of the cisplatin infusion and peaked between 3.75 and 4.25 h after the end of the cisplatin infusion. The area under the curve (AUC) of VAS was 7344 ± 1050 mm*min in the placebo-treated group. Ocular administration of palonosetron at 30 or 120 µg/kg in cisplatin-treated dogs decreased the VAS score strongly. The VAS AUCs were 320 ± 268 (p&amp;lt;0.0001) and 0 ± 0 mm*m (p&amp;lt;0.0001) in 30 µg/kg and 120 µg/kg palonosetron groups, respectively. Plasma palonosetron concentration reached 10.3 ± 3.9 ng/mL, 5 min after ocular administration of palonosetron at 30 µg/kg and 2.8 ± 0.5 ng/mL and 0.9 ± 0.2 ng/mL at 2 h and 6 h post dosing, respectively. Conclusions: This study demonstrates for the first time that palonosetron administered via ocular route produces a rapid clear-cut anti-emetic and anti-nausea effect in conscious dogs exposed to cisplatin. This finding points out the tremendous interest of this novel and convenient route of administration which could help improving the quality of life of patients. Citation Format: Sandra Nourry, Minja Hyttila-Hopponen, Pierre Montagne, Lasse Saloranta, Sari Pappinen, Jouko Levijoki, Christophe Drieu La Rochelle. Ocular drops of palonosetron reduce chemotherapy-induced acute nausea and vomiting in the dog [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 593.

Imipridone enhances vascular relaxation via FOXO1 pathway.

Cardiovascular complications are a side effect of cancer therapy, potentially through reduced blood vessel function. ONC201 (TIC10) is currently used in phase 2 clinical trials to treat high-grade gliomas. TIC10 is a phosphatidylinositol 3-kinase (PI3K)/AKT/extracellular signal-regulated kinase (ERK) inhibitor that induces apoptosis via upregulation of TNF-related apoptosis-inducing ligand, which via stimulation of FOXO and death receptor could increase eNOS upregulation. This has the potential to improve vascular function through increased NO bioavailability. Our aim was to investigate the role of TIC10 on vascular function to determine if it would affect the risk of CVD. Excised abdominal aorta from White New Zealand male rabbits were cut into rings. Vessels were incubated with TIC10 and AS1842856 (FOXO1 inhibitor) followed by cumulative doses of acetylcholine (Ach) to assess vessel function. Vessels were then processed for immunohistochemistry. Incubation of blood vessels with TIC10 resulted in enhanced vasodilatory capacity. Combination treatment with the FOXO1 inhibitor and TIC10 resulted in reduced vascular function compared to control. Immunohistochemical analysis indicated a 3-fold increase in death receptor 5 (DR5) expression in the TIC10-treated blood vessels but the addition of the FOXO1 inhibitor downregulated DR5 expression. The expression of DR4 receptor was not significantly increased in the presence of TIC10; however, addition of the FOXO1 inhibitor downregulated expression. TIC10 has the capacity to improve the function of healthy vessels when stimulated with the vasodilator Ach. This highlights its therapeutic potential not only in cancer treatment without cardiovascular side effects, but also as a possible drug to treat established CVD.

Amino acid mixture (enterade) as a new approach to reducing cancer therapy-induced gastrointestinal toxicity: A retrospective study.

e24107 Background: Gastrointestinal toxicity is a common side effect of cancer therapy. Pre-clinical studies using a proprietary mixture of amino acids, demonstrated a reduction in mucositis and gastrointestinal toxicity following irradiation via tightening of the mucosal barrier, increasing proliferation of crypt cells, increasing villous height and increasing absorption of fluid, electrolytes and nutrients. A novel 5-amino acid mixture “enterade” was previously evaluated in a Phase II clinical trial for anti-diarrheal effects in post bone marrow transplant patients at Dana Farber Cancer Institute (NCT02919670). Signs of anti-diarrheal efficacy were found in treatment-compliant patients.Enterade is currently being tested in two prospective Phase II studies (NCT03722511 and NCT04073017) in neuroendocrine tumor patients with quality of life limiting diarrhea. We conducted a pilot study to evaluate early antidiarrheal signals in oncologic treatment-induced diarrhea. Methods: An IRB-approved retrospective chart review was conducted at Markey Cancer Center between Sept 2019 and Dec 2019. Medical records were retrospectively reviewed for all solid tumor patients who received enterade for chemotherapy or immunotherapy-induced diarrhea. Patients were instructed to consume one 8-oz bottle of enterade twice a day for at least one week in addition to standard of care antidiarrheal medications. Results: A total of 46 patients were offered enterade. Antidiarrheal efficacy data was available on 17 patients. 11 were female and the mean age of the cohort was 64 years. Six out of 17 patients had a previous history of bowel resection. Four patients had immune checkpoint induced colitis. Three patients developed diarrhea from TKI use and rest were on cytotoxic chemotherapy at the time of the diarrheal episode. Eighty-eight percent (15/17) of patients reported a reduction in diarrhea frequency after consuming enterade. On average, patients noticed an improvement in diarrhea frequency after 3.6 days of enterade consumption, with 86% (13/15) of responders reporting at least 50% reduction in diarrhea frequency. Conclusions: Patient-reported diarrheal improvement after enterade consumption is consistent with pre-clinical data. Results suggest the amino acid mixture may alleviate symptoms of cancer therapy-induced gastrointestinal toxicity (i.e. diarrhea). A prospective clinical trial is warranted to substantiate the observed improvement in chemotherapy and immunotherapy induced diarrhea.

The evolution of financial toxicity in patients with lung cancer.

e19406 Background: Financial toxicity (FT), or the cost-related side effect of cancer therapy, has been linked to poor clinical outcomes, greater symptom burden, and worse quality of life. While the repercussions of FT have been thoroughly explored, the longitudinal patient relationship with FT in the initial course of therapy is unknown. Methods: Patients with stage II – IV lung cancer were recruited in a prospective longitudinal non-interventional study between July 2018 and January 2020. FT was measured via the COST score, a validated questionnaire for benchmarking FT, at a) the time of cancer diagnosis and then later at b) 6-month follow up (6MFU). In this model, a lower COST score indicates increased financial hardship. Completed 6MFU data was compared to corresponding baseline data for each patient. Linear regression analysis was used to compare patient characteristics with baseline COST (COSTbase) and 6-month COST (COST6M) scores. Results: At the time of analysis, 209 patients were screened and 194 (95.1%) patients agreed to participate and complete the baseline survey. Subsequently, 93 patients completed the 6MFU survey, 32 patients had died, and 7 patients were lost to follow up. The remaining 62 patients have not met the study end point to date. Of the 93 patients that completed the 6MFU and baseline survey, the median age was 65 (range 35-89), 50.5% were male, and 76.3% were Caucasian. Over the first six months of therapy 36.5% overestimated OOP expenses by &gt; $1000 and 22.5% reported a decrease in total monetary savings, but only 4.3% of patients made decisions about health care based on cost of care. FT was present at both time points but was worse at diagnosis than at 6MFU (median COSTbase 25 [range 1-44] vs. median COST6M 27 [range 0-44]; p = 0.04). Linear regression correlated risk factors with FT at baseline ( &lt; 1 month monetary savings, employed but on sick leave, and inability to afford basic necessities; all p &lt; 0.001) that were different from risk factors at 6MFU (paying much more than expected OOP and sacrificing spending to meet medical costs; p &lt; 0.001). There was no significant difference between estimated OOP costs at baseline (median $2550 [range $0 - $500,000]) and actual OOP costs (median $2496 [range $0 – 25,900]; p = 0.25). Conclusions: FT toxicity is pervasive at both diagnosis and at 6-month follow up, however, the magnitude of toxicity changes with time. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, suggesting that different groups may benefit from financial intervention at diagnosis versus 6MFU.

Chemotherapy remote care monitoring program (CRCMP): Integration of an SMS text patient-reported outcome (PRO) in the electronic health record (EHR) to identify patients needing pharmacist intervention for chemotherapy-induced nausea and vomiting (CINV).

2001 Background: CINV is a feared side effect of cancer therapy. Despite advances in management, CINV is a common cause for emergency department (ED) evaluation and other unplanned health care utilization. The University of Michigan Rogel Cancer Center initiated the CRCMP to proactively identify patients (pts) experiencing CINV and intervene prior to the need for urgent evaluation. Methods: Pts receiving highly emetogenic chemotherapy are identified by administration of a NK1 antagonist. Once enrolled in the CRCMP, pts receive a daily text message survey for 7 days after treatment. The survey is based on the validated MASCC anti-emesis tool (MAT). Responses are stored within a flowsheet in the EHR. Responses above a set threshold trigger a message to the team pharmacist for intervention. Data presented was reviewed from EHR and claims data. Results: In 8 mo, 652 pts received a NK-1 antagonist (2244 total cycles) and 387 pts enrolled in the CRCMP (59%). Each pt enrolled for an average of 1.8 cycles of chemo (range 1-8). Of patients enrolled, 61.4% were female and 86.2% were Caucasian. Chemotherapy intent was curative for 51.7% and palliative for 48.3% of pts. Pts enrolled most commonly received cisplatin-based (29.7%) followed by carboplatin-based (22.5%), and 5-fluoruracil-based (20.9%) therapy. Text message response rate was 94% (N=18,143 responses of 19,256 total messages sent). During 861 cycles of therapy, 7% of responses noted vomiting and 33% of responses noted nausea. Since implementation of CRCMP, total hospitalization, ED, and urgent care use has decreased (p=0.029) compared to historical data. When utilization for nausea-related diagnoses was considered, the reduction was more notable (Table). Conclusions: Pts engaged in the CRCMP for CINV, allowing for rapid assessment of PROs by a pharmacist. Health care utilization related to nausea was reduced following implementation of CRCMP. While these changes were numerically small, reduction in unnecessary care utilizing PROs can contribute to high value care for cancer patients. [Table: see text]

Chinese Herbal Medicine and Its Regulatory Effects on Tumor Related T Cells.

Traditional Chinese medicine is an accepted and integral part of clinical cancer management alongside Western medicine in China. However, historically TCM physicians were unaware of the chemical constituents of their formulations, and the specific biological targets in the body. Through HPLC, flow cytometry, and other processes, researchers now have a much clearer picture of how herbal medicine works in conjunction with the immune system in cancer therapy. Among them, the regulation of tumor-related T cells plays the most important role in modulating tumor immunity by traditional Chinese medicine. Encouraging results have been well-documented, including an increase in T cell production along with their associated cytokines, enhanced regulation of Tregs and important T cell ratios, the formation and function of Tregs in tumor microenvironments, and the promotion of the number and function of normal T Cells to reduce conventional cancer therapy side effects. Chinese herbal medicine represents a rich field of research from which to draw further inspiration for future studies. While promising agents have already been identified, the vast majority of Chinese herbal mechanisms remain undiscovered. In this review, we summarize the effects and mechanisms of specific Chinese herbs and herbal decoctions on tumor related T cells.

Speckle-Tracking Echocardiography in Cardio-Oncology and Beyond.

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer therapy, but also in patients with a variety of other clinical conditions. This review and case series examine the clinical applications and overall usefulness of speckle-tracking echocardiography in cardio-oncology and, more broadly, in clinical cardiology.

MP38-03 EFFECTS OF HAEMATOLOGICAL MALIGNANCY TREATMENT TO FERTILITY IN YOUNG MALES

INTRODUCTION AND OBJECTIVE: Haematological malignancies are one of the prominent groups of cancers effecting adolescents and young adults. The side-effects of cancer therapies to fertility in this patient group is poorly understood by clinicians. Consequently, patients are left feeling confused and unsatisfied after treatment due to inadequate physician counselling. It is therefore the aim of this review to provide information on the risks to fertility from common blood cancer treatments. METHODS: Three databases (Medline via PUBMED, SCOPUS, Cochrane Library) were searched for randomized-controlled trials, non-randomized studies of interventions (NRSIs), and other observational studies. This review included male patients at their most fertile age, taken to be 13-51 years old and diagnosed with haematological malignancies. Markers reflecting gonadal function were monitored to identify changes to male fertility. These included sperm characteristics such as sperm count and morphology alongside the sex hormones testosterone and FSH. Analysis of studies was performed following a satisfactory risk of bias assessment using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS) tool. RESULTS: After relevant studies were excluded from the initial search seven studies featuring 1482 patients with haematological malignancies were included for analysis. 1353 of the patients had Hodgkin’s Lymphoma and patients featuring ABVD (n=4) and BEACOPP (n=3) treatment regimes were reviewed. Patients treated with BEACOPP were more prone to oligospermia and those who received fewer cycles had a greater likelihood of sperm production recovering. Evidence shows that both ABVD and BEACOPP impair male fertility, but the use of BEACOPP and an increased number of cycles is associated with greater impairment. CONCLUSIONS: Substantial evidence identifies the risks to fertility from ABVD and BEACOPP in Hodgkin lymphoma patients to help guide clinicians and patients in making appropriate fertility sparing decisions (Figure 1). This review also identifies a significant gap in literature necessitating high-quality studies to accurately record fertility changes in respond to cancer treatment in males.Source of Funding: None