Management Of Treatment-related Toxicities Research Articles

The impact of fibre and prebiotic interventions on outcomes in cancer and haematopoietic stem cell transplantation: a systematic review

Background & aimsCancer therapy is associated with a range of toxicities that severely impact patient well-being and a range of clinical outcomes. Dietary fibre/prebiotics characteristically improve the gastrointestinal microenvironment, which consequently elicits beneficial downstream effects that could be relevant to the prevention and management of treatment-related toxicities. Despite the compelling theoretical scientific rationale there has been limited effort to synthesise the available evidence to conclude such scientific underpinning to the clinical use of fibre/prebiotics in cancer patients. Therefore, this systematic review aimed to evaluate the clinical impact of fibre/prebiotic-based interventions on gastrointestinal-side effects; gastrointestinal-microbiome; clinical outcomes; nutrition status and body composition; and quality-of-life in children and adults being treated for cancer or undergoing a haematopoietic stem cell transplant (HSCT). MethodsThis study was conducted in adherence to PRISMA guidelines, and the protocol was published prospectively with PROSPERO (CRD42022299428). Three databases (MEDLINE (Ovid), CINHAL, EMBASE) were searched from inception to December 2023. All articles were assessed for bias using the Cochrane risk-of-bias tool RoB 2.0 (for RCTs) and ROBINS-I (for non-RCTs). ResultsA total of 9989 de-duplicated records were identified, of these, 14 (paediatrics [n= 1], adults [n=13]) met the inclusion criteria (randomised controlled trials (RCT) [n = 11], observational or non-RCTs [n = 3]). The risk-of-bias was graded to be serious/high (n=6); moderate/some concerns (n=7); low (n=1). Interventions included prebiotic supplement (n=8), nutrition supplement/formula with added fibre/prebiotic (n=3) and dietary modification (n=3). The dose of fibre intervention ranged from 2.4g-30g per day. Substantial heterogeneity of target parameters was identified across a range all outcome categories, precluding definitive conclusions. ConclusionThe scientific rationale for fibre/prebiotics-based interventions for the prevention or management of cancer treatment-related toxicities is compelling. However, it is clear that the scientific and clinical field remains disconnected in how to effectively translate this approach to improve cancer outcomes. High-quality intervention studies translatable to clinical practice are now evidently crucial to determine if and how fibre/prebiotics should be used to support people undergoing cancer or HSCT therapy.

Trends in hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) from 2004-2019.

6535 Background: Many patients with AML achieve remission after induction chemotherapy, but the relapse rates remain high. For patients with intermediate and adverse-risk AML that have achieved complete remission, HCT often presents the best option for cure. HCT, usually reserved for fit patients with good disease control, comes with different operational, financial, and technical challenges, even in eligible patients. Our study analyzed HCT use in patients with AML from 2004 to 2019 to determine whether the use of HCT has improved in more recent years and identify study subpopulations with an increase in the use of HCT. Methods: Patients with AML from the National Cancer Database were divided into two primary cohorts: patients diagnosed from 2004-2010 and 2011-2019. Logistic regression was used to estimate the effect of patient and disease characteristics on the odds of receiving HCT and evaluate differences between the constructed patient cohorts. Results: Of 78,092 patients with AML, 7204 (9.2%) received HCT. HCT use increased continuously over the years: 6.5% in 2004, 8.4% in 2010, and 10.6% in 2015. There was a slight decrease in HCT from 13.1% in 2018 to 12.2% in 2019. The receipt of HCT declined with increasing age with higher use of HCT in all groups in 2011-2019 compared to 2004-2010: 71-80 years= 2 vs. 0.4 %, 60-70 years= 13 vs 6%, 41-59 years= 18 vs 15%, and 18-40 years = 19 vs 16%. HCT use declined with higher Charlson Deyo Comorbidity Index (CCI) with higher use of HCT in all groups in 2011-2019 compared to 2004-2010: CCI: 2-3= 4 vs 2%, CCI 1= 7% vs 5%, CCI 0= 12% vs 9%. HCT use was higher in patients who traveled longer distances to hospitals with higher HCT use in 2011-2019 compared to 2004-2010: travel distance ≥38.4 miles= 15 vs. 13%, 12-34.7 miles= 12 vs 9%, 5-11.9 miles= 8 vs 5%, and 0-4.9 miles= 5 vs 3%. On multivariable analysis, the odds of receiving HCT increased significantly in 2011-2019 compared to 2004-2010, particularly in older patients, patients with higher CCI, and patients who traveled longer distances for treatment. Black race, lower income, no insurance, and lower educational attainment were associated with a lower likelihood of receiving HCT; however, the odds of receiving HCT did not improve over the two time periods based on these variables. Conclusions: To our knowledge, this is the largest-scale analysis of HCT utilization in patients with AML in the United States. The increase in HCT utilization from 2004-2010 to 2011-2019, particularly in older adults and those with more comorbidities, may reflect improvement in risk-stratification models, better supportive care, and better management of treatment-related toxicity. However, despite a modest increase in HCT use over the years, significant disparities exist based on race, insurance type, income, and education. Innovative strategies are necessary to increase HCT and make it accessible to all patients regardless of socioeconomic and demographic factors.

Time on treatment is prolonged in patients utilizing an ePRO based digital symptom monitoring platform in the community setting.

1528 Background: Earlier and more effective management of cancer-related symptoms and treatment-related toxicities might improve the survival of patients receiving systemic anti-cancer therapy. One potential mechanism for improved outcomes could be prolonging time on therapy. We have previously reported on the successful real-world implementation of an electronic patient-reported outcomes (ePRO) tool in a community oncology practice. We now report on the impact of the tool on time on therapy for common anti-cancer treatments. Methods: We evaluated time on treatment across three community oncology practices that have implemented Expain, an EMR-integrated ePRO system which enables remote symptom monitoring during therapy. We compared drug-specific cohorts of patients that had been enrolled on the ePRO tool with a concurrent cohort of patients not enrolled on the ePRO platform. We examined time on treatment using a Kaplan Meier (KM) approach. Analysis was confined to patients with no prior administration of the parenteral therapeutic agent or a 90-day treatment-free washout period; and to patients with at least three months of potential follow-up. Analysis was only conducted for drugs with at least 80 patients in the Expain arm. Results: In each drug-specific cohort, the distribution of age, sex, and primary cancer diagnosis was similar in patients enrolled vs not enrolled on the ePRO (Mann-Whitney and Chi-square p > 0.05 except for the rituximab cohort which had more males in the ePRO cohort [67 vs 52%]). The impact of the ePRO-based symptom monitoring system on time on therapy was statistically significant for 5 agents. Conclusions: We confirm in the community setting the observation that digital symptom monitoring can increase time on therapy. We believe this is due to more effective management of treatment related toxicities, as well as more effective management of malignancy related or comorbid medical emergencies which might interrupt or lead to the discontinuation of therapy. We are evaluating the robustness of these results after using various methods to address any potential non-comparability of the cohorts. We are also examining the impact of prolonging time on treatment on survival. [Table: see text]

P43-9 A 10-year marathon, race against time: Challenges in management of metastatic colon cancer

This poster illustrates the management of initially locally advanced colon carcinoma and followed by metastatic disease over a course of 10 years. It reflects our challenges in managing not only the cancer itself but also the toxicities related to treatment. In the last 10 to 15 years there are major advancements in treatment of metastatic colorectal carcinoma. With 5-Fluorouracil (5-FU) alone, the median survival has been reported as 11 to 12 months. However with more new agents other than 5-FU, for example other new cytotoxic agents, biologic agents targeting angiogenesis and the epidermal growth factor receptor (EGFR), the average median survival is approaching 3 years (Heinemann et al). Past and current treatment history was obtained retrospectively through electronic medical records. Madam L was first diagnosed with Dukes C Transverse Colon Carcinoma pT3N2M0 in 2010. However she developed metastatic disease subsequently in 2011. She failed a total 11 lines of chemotherapy and targeted therapy, including XELOX, XELIRI, FOLFIRI, TS-1, Regarofenib used with combination of Cetuximab, Panitumumab, Aflibercept. She suffered from side effects of both chemotherapy and targeted therapy, which some has been managed medically and some disabling enough to lead to cessation of the agent. She was given multiple chemo-holidays in between treatments. Over the course of 10 years, with advancement in treatment and new laboratory investigations for mutation, this patient has been on newer treatments. She is still undergoing palliative chemotherapy and is asymptomatic now. This patient has beaten the odds, by proper sequencing of chemotherapy and targeted therapy, besides adequate management of treatment related toxicity.

Geographic and demographic disparities in breast cancer outcomes: A population-based study.

7028 Background: Breast cancer (BC) is one of the leading causes of cancer-related mortality worldwide, with over 2 million new cases diagnosed each year. Area of residence has been shown to affect survival, but its impact on BC is unknown. The purpose of this study is to address the potential disparities in BC outcomes between the urban area (UA) and rural area (RA). Methods: We obtained data based on BC patients’ (pts) area of residence; UA vs RA, using the Surveillance, Epidemiology, and End Results (SEER) database treated from 1975-2016. Different socio-demographic variables and tumor characteristics (cts) from both groups were analyzed. Disease specific survival (DSS) and overall survival (OS) were analyzed by Kaplan-Meier methods. Multivariable analyses were conducted using Cox regression models. Results: A total of 99,339 and 872,742 pts were analyzed from RA and UA respectively. Pt cts, including age, sex, marital status, insurance status were similar across both RA and UA. There were a higher number of Black and Hispanic pts in the UA compared to RA. A total of 264,191 pts had receptor subtype data available. A slightly higher percentage of triple negative BC (TNBC) pts was seen in the RA compared to UA (13.5% v 12.7%) whereas UA had a higher percentage of HER2+ BC (18% v 17.3%). There were 95.4% early/locally advanced (stage I-III) and 4.6% metastatic pts. UA pts had significantly improved DSS and OS regardless of stage, grade or other tumor cts compared to RA pts. When stratified by receptor subtype, UA had significantly improved DSS and OS in hormone positive (HR+) (OS HR of 0.86; DSS HR of 0.87; p < 0.05) and HER2+ pts (OS HR of 0.87; DSS HR of 0.83; p < 0.05). However, there were no significant differences seen between UA and RA pts with TNBC. Conclusions: To our knowledge, this is the first study to report BC outcomes based on geographic disparities. Interestingly, HR+ and HER2+ UA pts had better outcomes than RA pts, whereas TNBC pts had similar survival regardless of residence area. Perhaps this disparity is partly due to the longer duration of treatment needed with hormonal therapy in the adjuvant setting making compliance an important factor to take into account in RA pts, in addition to complicated decision making with upcoming data in HER2 + cancer in the early stage setting. Access to healthcare, differences in surgical and systemic approaches of pt care, management of treatment-related toxicities and environmental factors are all potential factors that may affect outcomes in BC pts. Based on the above data, further studies are needed to further evaluate and reduce such disparities.

Patient-reported outcomes on treatment-related side effects in renal cell carcinoma.

654 Background: Effective management of treatment related toxicities is crucial to maximizing patient outcomes and enhancing quality of life in renal cell carcinoma. Little is known about patient perception and reporting of side effects in a real world setting outside clinical trials. We sought to gather independent data from online patient communities to estimate gaps in communication and reporting. Methods: KCCure conducted an anonymous online survey from 07/19 to 09/19 using questions related to side-effect experience and management. Results: 1,136 patients (median age 57 years [range 28-86], 54% male) participated, 411 patients on systemic therapy were asked about side-effects. 47% of patients reported bothersome side effects impacting their daily lives. The most poorly managed side-effect was fatigue (25%), followed by taste alteration (15%) and loss of appetite (15%). Only 50% of patients are confident their medical oncologist will offer help for side effects, and 20% are worried that reporting side effects may result in dose reduction or treatment discontinuation. 6% of patients don’t talk about their side effects. Patients who identified as non-white (Hispanic, African American, Asian/Pacific Islander and Native American) were three times less likely to talk about side effects. 51% indicated the best advice on managing treatment related side effects was provided by their medical oncologist; 40% seek advice from online patient communities and 35% from advocacy organizations. Only 8% used manufacturer support websites. 13% had never had any concomitant medication prescribed to manage side effects. Major unreported side effects are sexual dysfunction, cognitive impairment and vision disturbances. Conclusions: The majority of patients experience treatment related side-effects on a regular basis, but underreporting may be significant due to a variety of factors, including fear of dose-reduction or discontinuation. Sexual side-effects are underreported. Future studies need to explore differences in reporting for minority populations as well as side effect experiences according to the class of agent prescribed, and the setting in which treatment occurs.

Management of treatment-related toxicities in advanced medullary thyroid cancer.

Tyrosine kinase inhibitors (TKI), predominantly vandetanib and cabozantinib, are increasingly used for management of advanced medullary thyroid cancer. This review aims to discuss the major and serious adverse events associated with TKI. The choice of TKI depends on the patient's existing comorbidities. Patients who have long QT interval should avoid vandetanib and those at risk of gastrointestinal perforation should avoid cabozantinib. Hypertension is common during the first 3 months. Treatments include ACE inhibitors, calcium channel blockers (avoiding verapamil and diltiazem, which are CYP3A4 inhibitors), and beta blockers. Diuretics should be second line because of derangement of electrolytes, which may exacerbate QT interval. As nitric oxide (NO) blockade and ET1 are implicated in the mechanism of hypertension, nitrates and endothelin receptor antagonists may be used. Thromboembolism may require anticoagulation or revascularization procedures. Prolonged QT interval should be treated by dose interruption and reduction, correction of electrolytes, and avoidance of medications, which prolong QTc interval. Diarrhoea is managed symptomatically and with electrolyte replacement, dermatological adverse events with avoidance of exacerbating factors and topical therapies. Thyroid function should be monitored. Toxicities are common with TKI use, and management involves symptomatic treatment, avoidance of triggers, dose interruption, and dose reduction.

Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy.

The impressive disease response observed with chimeric antigen receptor (CAR) T-cell therapy is accompanied by the potential for unique and severe toxicities. Cytokine release syndrome (CRS) and neurologic toxicities have emerged as prominent toxicities associated with this treatment modality. This article presents an overview of pathophysiology, assessment, and evidence-based management of CAR T-cell therapy-associated toxicities, with particular attention paid to CRS and neurologic toxicity management. Implications for nursing practice are included for prominent toxicities to guide clinical practice. An overview of recent guidelines and evidence for CAR T-cell therapy toxicity assessment and management is provided. Evidence-based approaches to CAR T-cell therapy toxicities continue to evolve. As organizational and institutional guidelines emerge, nurses must be aware of anticipated toxicities and interventions used in clinical practice to provide timely and effective care.

Management of treatment-related toxicity caused by multi kinase inhibitors administered due to advanced thyroid carcinoma

Management of treatment-related toxicity caused by multi kinase inhibitors administered due to advanced thyroid carcinoma

Implementing a patient-centered approach to immunotherapy treatment on an inpatient step-down unit.

38 Background: Executing an innovative investigational therapy within a pre-existing infrastructure, while incorporating the organizational mission and vision is a complex process. Literature supports the use of patient-centered framework and integration of evidence in standardizing nursing practice to promote efficient workflow, accountability, and ultimately, optimal patient-care outcomes. The aim of this presentation is to describe the experience of a step-down unit at a comprehensive cancer center in developing and implementing processes to safely administer immunotherapy. Methods: A multidisciplinary workgroup reviewed the pre-existing infrastructure, determined the financial impact of new clinical trials and availability of resources, distinguished roles and stakeholder responsibilities, and developed staff education and technology utilization. A unit-prospective analysis, using the Strengths, Weaknesses, Opportunities, and Threats (SWOT) methodology was performed to assist in planning and reducing variations in processes during initial implementation. Results: This initiative resulted in the standardization of immunotherapy treatment workflow and development of patient care tools. The workflow consisted of patient education and treatment pathways, whereas the tools included the treatment calendar and nursing assessment forms comprised of daily handwriting sentence construction and CAR-T Toxicity (CARTOX) Grading Assessment. EHR collaboration resulted in the incorporation of CARTOX into nursing documentation in EMR. These workflow and tools are essential in ensuring timely assessment and management of treatment-related toxicities, escalation of care needs, and reduction of potential missed care and adverse events that impact staffing needs and health care costs. Conclusions: A patient-centered approach provides a framework in implementing innovative changes that promote patient safety. Engaging the frontline staff throughout the journey promoted empowerment and accountability. Multidisciplinary planning and nursing leadership transparency in orchestrating multi-level routines for actualization of competence proved immensely invaluable.

Optimizing outcome for patients with mantle cell lymphoma

Intensive multidrug regimens,such as rituximah plus fractionated cyclophsphamide,vincristine,doxorubicin,and dexamethasone(R-HyperCVAD),are now being used to improve outcomes in patients with mantle cell lymphoma(MCL).In addition to these combinations,novel targeted agents,including bortezomib,bendamustine,and lenalidomide,are also being integrated into the treatment paradigm.Given the wide array of therapies available,making and implementing treatment decisions has become a complex process,requiring interdisciplinary collaboration.This article discussesed the pharmacist's role in this collaboration,as well as the administration of standard and novel therapies for MCL and the management of treatment related toxicities. Key words: Lymphoma, mantle-cell; Targeted therapy; Antitumor drugs

Results from the Multi-institutional, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Efficacy of a Mucoadhesive Hydrogel Rinse in Mitigating Oral Mucositis (OM) in Chemoradiation-Treated (CRT) Head-and-Neck Cancer (HNC) Patients

Conclusions: Acute GI toxicity during definitive RT for anal cancer was most significant during weeks 4-5, while rectal bleeding improved during treatment. The discrepancies in patient and clinician reported symptoms of proctitis are consistent with studies in rectal cancer, and demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments. Additional research is needed to explore ways these assessments can improve management of treatment-related toxicity. Author Disclosure: A. Tom: None. A. Bennett: None. D. Rothenstein: None. S. Milgrom: None. E. Law: None. E. Mangarin: None. A. Wu: None. K.A. Goodman: None.

Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities

SummaryTreatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the last two decades as major pathways involved in pathogenesis have been elucidated. These include the vascular endothelial growth factor (VEGF) axis and mammalian target of rapamycin (mTOR). Therapies targeting the VEGF pathway include bevacizumab, sorafenib, sunitinib, pazopanib, and axitinib, whereas temsirolimus and everolimus inhibit the mTOR pathway. All of these novel therapies—VEGF and mTOR inhibitors—are associated with a variety of unique toxicities, some of which may necessitate expert medical management, treatment interruption, or dose reduction. Common adverse events with newer drugs include hypertension, skin reactions, gastrointestinal disturbances, thyroid dysfunction, and fatigue. Skilled management of these toxicities is vital to ensure optimal therapeutic dosing and maximize patient outcomes, including improved survival and quality of life. This review describes and compares the toxicity profiles of novel molecularly targeted agents used in the treatment of mRCC and presents guidance on how best to prevent and manage treatment-related toxicities. Particular attention is given to axitinib, the newest agent to enter the armamentarium. Axitinib is a second-generation receptor tyrosine kinase inhibitor with potent VEGF receptor inhibition that provides durable responses and superior progression-free survival in advanced RCC compared with sorafenib.

Multiple myeloma: management of adverse events

The combination of conventional chemotherapy or dexamethasone with new drugs, such as immunomodulatory agents and proteasome inhibitors, has substantially changed the treatment paradigm of myeloma patients. New drugs have been incorporated in pre-transplant induction regimens and post-transplant consolidation and maintenance strategies for young patients; in elderly patients, standard melphalan and prednisone (MP) plus thalidomide or plus bortezomib are now considered standards of care, and ongoing trials are assessing if lenalidomide plus standard MP or plus low-dose dexamethasone may be other options. The efficacy of these drugs needs to be balanced against their toxicity. Different drugs have a different toxicity profile. The choice for the best treatment strategy for every single patient should be based on results of scientific randomized studies but tailored to account for patient's biological age, comorbidities, and the expected toxicity profile of different regimens. Prompt dose reduction and accurate management of treatment-related toxicity can greatly reduce early discontinuation rate and significantly improve treatment efficacy. This chapter will focus on frequency and management of main adverse events in newly diagnosed and relapsed myeloma patients and will provide guidelines for dose reductions and supportive therapy.

Management of treatment-related toxicity in advanced ovarian cancer.

Recognition of recurrent ovarian cancer as a disease with significant secondary responses and remissions has led to an increase in the need for oncologists to plan for the long-term therapy of patients. However, many of the currently available front-line and salvage agents used in advanced ovarian cancer are associated with cumulative and/or irreversible toxicities that pose challenges in long-term planning. The irreversible effects associated with some of these therapies may render patients less tolerant to subsequent treatments and lead to a cycle of diminishing treatment options with each remission and disease relapse. Additionally, the potential for patients to experience cumulative toxicity must be carefully weighed against the goals of prolonging the disease-free interval and improving patient quality of life. A number of agents are available in the treatment armamentarium (platinum, paclitaxel, gemcitabine, etoposide, liposomal doxorubicin, and topotecan), many, but not all of which are associated with cumulative toxicity. For instance, cumulative neurotoxicity associated with cisplatin as first-line therapy may diminish the option for retreatment with platinum at first relapse. In contrast, the main toxicity associated with topotecan is noncumulative, manageable myelosuppression. In this review, the major toxicities associated with the predominant chemotherapy agents used in advanced ovarian cancer are discussed along with selected management approaches in the context of long-term treatment planning and sequencing.

Management of Treatment-Related Toxicity in Advanced Ovarian Cancer

Management of Treatment-Related Toxicity in Advanced Ovarian Cancer