Chemotherapy-related Side Effects Research Articles

Immune-related adverse events in patients treated with immunotherapy according to corticosteroid exposure.

e14709 Background: Patients with cancer require treatment with corticosteroids for multiple reasons, including prevention of chemotherapy-related side effects. Although corticosteroid use has been associated with lower efficacy of immune checkpoint inhibitors (ICI) in some studies, whether corticosteroid exposure affects the presence and severity of immune-related adverse events (irAEs) remains unclear. Methods: Retrospective single-center study of patients diagnosed with solid tumors treated with ICI. Eligible patients were those who received at least one cycle of ICI and had at least 1 month of follow-up post-ICI initiation. Patient data were extracted from electronic medical records. Comparisons between groups were made based on steroid exposure (defined as the administration of >10 mg of prednisone or its equivalent for >10 days within a 30-day period or at any point during ICI treatment, excluding steroid treatment for irAEs). Associations between variables were assessed using independent samples T-test, Chi-square, and Fisher’s exact tests. Results: We included 135 patients (mean age 61 years, SD 13); 72 (54%) were male. Forty-two (31%) had been exposed to steroids (mean prednisone equivalent of 427 mg, SD 298). Most patients received ICI as palliative treatment for advanced disease (105/135; 78%), primarily as first-line therapy (79/105; 75%). Patients exposed to corticosteroids were more likely to have received ICI with chemotherapy (76% vs 1%, p<0.001), were younger (56 vs. 63 years, p=0.009), more likely to be female (62% vs. 39, p=0.014), and had lower median Charlson Comorbidity Index scores (2 vs. 3, p=0.026). Steroid-exposed patients were more likely to have employed ICI in the neoadjuvant or adjuvant settings (36 vs. 16%, p=0.024) or as third or subsequent line therapy (26 vs. 8%, p=0.044). There were no statistically significant differences in the frequency of irAEs of any grade based on steroid exposure (31% vs 41%, p=0.252). However, patients who were exposed to steroids were significantly less likely to delay or suspend ICI (10% vs. 32%, p=0.005). No other parameters were associated with the rate or severity of irAEs. Conclusions: Our findings suggest that corticosteroid exposure does not increase the frequency of irAEs in patients treated with ICI, but it is associated with a reduced likelihood of discontinuing ICI due to irAEs. These observations suggest that corticosteroids may play a beneficial role in managing patients undergoing immunotherapy, particularly in sustaining treatment continuity despite irAEs. This study underscores the need for further investigation into optimal steroid use strategies to enhance patient outcomes with immunotherapy, especially in situations when they are commonly prescribed, such as premedication for chemotherapy.

Pathologic Response Rates in Patients with Gastric Cancer Following FLOT Neoadjuvant Chemotherapy

Background: Gastric adenocarcinoma is among the most prevalent cancers associated with a high mortality rate. The multidrug neoadjuvant chemotherapy administered before and after surgery has attracted attention as a beneficial standard of care for managing this malignancy. Objectives: This study assessed the pathologic response of patients with gastric cancer who were treated with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). Methods: Patients with pathologically confirmed gastric adenocarcinoma without distant metastases were enrolled in this retrospective cohort study conducted at Imam Reza and Ghaem hospitals in Mashhad. Data regarding demographics, tumor status, treatment toxicity, and pathology results were collected using a predesigned questionnaire after four cycles of FLOT neoadjuvant chemotherapy. SPSS-26.0 was utilized to analyze the data, and a significance level of P < 0.05 was applied. Results: We evaluated data from 53 cases with a mean age of 51.1 ± 9.7 years. Diffuse adenocarcinoma was the most common finding in histology (54.7%). Pathologic complete response was observed in 16 (30.2%) patients. Most (69.8%) patients received only 7 out of 8 planned cycles. Concerning surgical margin, 46 (86.8%) patients achieved R0 tumor resection. Pathologic complete response was not significantly linked with age (P = 0.91), sex (P = 0.65), performance status (P = 0.2), tumor histology (P = 0.14), tumor grading (P = 0.07), tumor location (P = 0.8), and the number of neoadjuvant chemotherapy cycles (P = 0.9). Conclusions: Our findings demonstrated the relative clinical efficacy of neoadjuvant chemotherapy with the FLOT regimen administered before and after surgery. However, due to chemotherapy-related side effects, patients may not adhere to all eight prescribed cycles of chemotherapy.

D-CRSE: Diminishing chemotherapy-related side effects through patient education, a mixed-methods pilot study

Objectives Patient education materials regarding self-management of chemotherapy-related side effects are limited, which may result in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address problems themselves, and guidance on when to contact their oncologist or seek emergency care. This mixed-methods study conducted at Penn State Cancer Institute evaluates the feasibility of using an educational brochure to improve patient outcomes through education. Methods Chemotherapy naïve patients with breast or gastrointestinal (GI) cancer were enrolled in a single-arm clinical trial from December 2021 to 2022. Participants received the educational brochure and were asked to provide their initial impressions. They completed The Emotional Thermometer Scale (ETS) and the Memorial Symptom Assessment Scale (MSAS) to measure changes in patient symptoms and mental health throughout their chemotherapy course at 0, 6, and 12-week intervals. The drop-out rate was recorded as a measure of study feasibility. Results The study participants were split between the following cancer types: 77.8% breast and 22.2% GI cancer. A significant decrease in overall mean ETS score was observed between baseline and week 6 (p = 0.001) and 12 (p = 0.0004), respectively. Moreover, the mean MSAS psychological symptoms decreased significantly at week 12 compared to baseline (p = 0.005), while no change was observed in physical symptoms (p = 0.101). Of the 40 participants who completed baseline surveys, 37 had at least one additional visit for a drop-out rate of 7.5%. Conclusion This mixed-methods pilot study was successful in demonstrating the feasibility of distributing a standardized educational brochure as an intervention for chemotherapy patients. While participants’ emotional scores and psychological symptoms decreased over time, physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden.

Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. DERR1-10.2196/55662.

Изучение опыта работы с химиопрепаратами специалистов сестринского дела в онкологических клиниках Казахстана

The purpose of the study to describe the nursing practices related to the administration of chemotherapy and aims to assess the level of competence among nursing professionals, identify challenges encountered while working with chemotherapy, and evaluate the safety conditions in their workplace. Methods. This study presents a cross-sectional design using a quantitative method. The participants in this study are nursing specialists actively engaged in handling chemotherapy drugs in three prominent clinics in the Republic of Kazakhstan, which offer medical care to patients with oncohematological and oncological conditions affecting the respiratory, urinary, and digestive systems. A total of 70 completed questionnaires were collected from nursing professionals working in these clinics. The data collected was statistically analyzed using STATA 14 statistical software. The analysis focused on assessing educational qualifications, workload, workplace safety climate, and the complexity of nursing practices for patients undergoing chemotherapy. Results. The majority of participants are relatively young professionals with limited experience in working with chemotherapy drugs and no specialized training in this field. Overall, participants displayed a reasonable understanding of breeding conditions, the effects of chemotherapy drugs, the use of PPE and the implementation of preventive measures when handling them. However, there was a lack of awareness regarding the proper transportation of chemotherapy drugs and the requisite protocols for the disposal of medical and biological waste generated by patients receiving chemotherapy. The study revealed that clinics where participants were interviewed offered mentoring and peer support programs. According to participants, the primary challenges in working with chemotherapy revolved around caring for patients experiencing chemotherapy-related side effects, mainly due to the high workload and the inherent toxicity of chemotherapy. Nevertheless, most participants indicated that workplace safety conditions were maintained at a high level. Conclusion. This study provides valuable insights into the practices of nursing specialists involved in administering chemotherapy in multiple oncology clinics within the Republic of Kazakhstan. It sheds light on the experiences of these professionals and offers a comprehensive understanding of the existing conditions and challenges faced when delivering chemotherapy to patients.

Budget Impact of the Oncotype DX Breast Recurrence Score® Test in Patients with Early Primary Hormone-Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in Germany

Background: Gene expression tests can inform decisions on whether to recommend or omit chemotherapy for patients with early HR+, HER2− breast cancer. The benefit of these tests is well established and fully reimbursed by sickness funds for lymph node-negative (pN0) patients in Germany. A budget impact model was built to evaluate the effect of using the Oncotype DX Breast Recurrence Score^® test also for node-positive (pN1: 1–3 positive lymph nodes) patients. Methods: The prospective randomized clinical trial, RxPONDER, defined conditions (Recurrence Score result 0–25 for postmenopausal patients with 1–3 positive lymph nodes) under which omitting chemotherapy does not significantly impact invasive disease-free survival with results currently reported for 5-year follow-up. The present budget impact model calculates average total cost per node-positive patient versus no testing from a sickness funds perspective, taking into account not only the budgetary impact of avoiding chemotherapy and associated side effects, but also the costs of treating those patients who develop distant metastasis. The stability of the results was investigated by probabilistic multivariate sensitivity analysis. Results: After deducting testing cost, applying the Oncotype DX Breast Recurrence Score test yielded an average savings per node-positive patient of EUR 4,272. Without the test costs, the greatest savings resulted from reductions in direct treatment costs and costs arising from the treatment of chemotherapy-related side effects, which together averaged EUR 6,677. The targeted use of chemotherapy after testing also resulted in slightly lower costs for treatment of distant metastasis, if it did occur. The multivariate sensitivity analysis also almost exclusively resulted in cost savings. Conclusion: Analogous to the pN0 situation, this budget impact model demonstrates that the Oncotype DX Breast Recurrence Score test can also reduce healthcare costs in Germany in treatment of node-positive (pN1: 1–3 positive lymph nodes) patients by minimizing both unnecessary chemotherapy and undertreatment. Additional benefits to patients would include reduced morbidity and improved quality of life for those patients who can safely avoid chemotherapy or undertreatment.

Permissibility of an Intermittent Fasting in Patients with Chronic Lymphocytic Leukemia in the Era of Novel Therapies :a Pharmacology Based Review

Introduction Chronic Lymphocytic Leukemia (CLL) is a mature neoplasm characterized by the proliferation of immunologically dysfunctional B cells. Inhibitors of BCL2 (venetoclax) and Bruton Tyrosine Kinase (BTK) (ibrutinib, acalabrutinib and zanubrutinib) are novel agents that have revolutionized outcomes in CLL patients in the newly diagnosed and relapsed/refractory settings. Nevertheless, tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) remains concerning adverse events. In clinical trials, fasting has demonstrated reductions in chemotherapy-related side effects and improved treatment tolerability . However, with novel agents in CLL this can be challenging with the need for aggressive hydration in fluid-restricting fasting practices and the higher risk for GI bleeding and peptic ulcer disease complications with fasting. This review aims to explore the literature available to answer the permissibility of intermittent fasting (IF) in CLL patients who are being treated with first line novel agents (FLNAs). Methods Literature exploration was performed to identify IF practices and the effects of fasting conditions and fluid-restriction on the pharmacokinetics (PK) of FLNAs. Literature was also scoped for data on TLS and GIB risk associated with FLNAs in CLL patients as well as the effects of fasting and or fluid-restricted states on GIB and TLS risks. Lastly, the identified risks were accumulated to build a pathway for permissibility of IF in this patient population. Results Venetoclax has amplified the historical low risk of TLS in patients with CLL to a significant degree. Approaches to prevent TLS such as aggressive hydration and use of uric acid reducing drugs hinder patients wishing to practice fluid restricting IF ( See Table 1 and Figure 1), especially during ramp-up phase. Moreover, venetoclax should be administered with food and on daily basis. Hence, only fluid liberal IF practices with daily food intake and medication administration may be possible in venetoclax CLL patients. Furthermore, studies have indicated a possible increased baseline risk of GIB in patients who practice IF. Also, FDA reporting system for adverse events (AE) had higher GIB events among ibrutinib patients compared to other FLNAs. Overall, there was scarcity in the clinical data available on the effects of IF on treatment outcomes with FLNA in CLL patients. There was also evident variability in the number of reported AE between the relatively older (ibrutinib and venetoclax) and newer medications (acalabrutinib and zanubrutinib), which may be causing an underestimation of treatment risks. Conclusion Until further data is available, patients on BTK inhibitors should refrain from practicing IF for GI bleeding risk. However, it may be possible for patients on venetoclax to practice fluid liberal IF conditionally and conservatively for TLS risk. This is on the conditions that adequate hydration and daily administration with food are achieved. Fasting's risks and benefits must be discussed with patients . Further prospective clinical trials, including exploration of different forms of IF, are needed to better elucidate the effect of IF on FLNAs treatment -related outcomes in CLL patients .

Effect of Adjuvant Chemotherapy in Highly Malignant Non-Metastatic Prostate Cancer: An Interim Analysis of Non-Randomized Comparative Trials.

Gleason grade group 5 (GG5) prostate cancers is aggressive with high metastatic rates and is not sensitive to androgen deprivation therapy (ADT). Even the presence of a limited (tertiary) Gleason pattern 5 component may have high aggressive biological behavior. This study aims to prospectively evaluate whether a non-androgen receptor pathway therapy - adjuvant chemotherapy could improve clinical outcomes among non-metastatic prostate cancer with the above highly malignant characters. This prospective non-randomized clinical trial included non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or tertiary Gleason pattern 5. Each subject was allowed to decide whether to receive four to six cycles chemotherapy of docetaxel after receiving a standard treatment (i.e., radical surgery ± radiotherapy or radical radiotherapy combined with long-term ADT). The primary endpoint was event-free survival (EFS). Event was defined as any of biochemical failure or imaging failure, or change of systemic therapy due to PSA arises, or death. The secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. A total of 188 consecutive patients were enrolled from November 2019 to November 2022. Median prostate-specific antigen was 26.6 ng/ml. 52% had T3b to T4 disease, 27% had N1 disease. 140 patients received standard therapy only, and 48 patients received adjuvant chemotherapy after radical therapy. The median follow-up time was 18.4 (3.0-36.7) months. The estimated 36-month EFS of the chemotherapy group and the control group were 94.7% vs. 72.8% (p = 0.044). There were 1 event who added novel endocrine therapy in the chemotherapy group, and 21 events in the control group, including 6 cases of biochemical recurrence and 9 cases of lymph node and distant metastasis, 4 cases that changed systemic therapy and 2 cases died. The MFS of the two groups at 36 months were 100% and 90.7%, respectively (P = 0.143). After the 1:1 propensity score match, the EFS and MFS of the two groups were 94.7% and 80.8% (P = 0.069), and 100% and 93.1% (P = 0.132), respectively. The urinary toxicity of grade 2 and 3 in the chemotherapy group and the control group were 4.2% and 7.1% (P = 0.134) while the grade 2 rectal toxicity were 5.0% and 10.4% (P = 0.317), respectively. No grade 4 toxicity occurred. Considering the chemotherapy-related side effects, grade 3 or above toxicity were leukopenia (41.7%), alopecia (27.1%), thrombocytopenia (2.1%) and edema (2.1%). Results of this interim analysis shows that the addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall recurrence and metastasis free survival of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Development and pilot study of “Smart Cancer Care”: a platform for managing side effects of chemotherapy

BackgroundAs outpatient chemotherapy treatment increases, cancer patients receiving chemotherapy spend more time at home. In addition, since the types of chemotherapy are gradually expanding, it will be essential to prepare patient self-management strategies for various chemotherapy-related side effects. This study aimed to develop a platform (called Smart Cancer Care) to implement a chemotherapy side effect management program and to evaluate its feasibility.MethodsSmart Cancer Care comprises an application for patients and a dashboard for medical staff. Thirty-two symptoms to be managed using Smart Cancer Care were summarized through a literature review and Delphi. Management guidelines were developed based on the severity of each symptom (3 stages), and installed in Smart Cancer Care according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 guidelines. To evaluate the feasibility of the developed application and medical dashboard, cancer patients and cancer treatment medical staff used Smart Cancer Care for 2 to 3 weeks and subsequently reported the experience of using them.ResultsThe patient application provided a list of symptoms according to the cancer type and anticancer drug enabling presence and severity of each symptom to be evaluated. Patients received management guidelines for symptoms based on the symptom evaluation results. On the medical staff dashboard, administrators and authorized medical personnel could access and assess information regarding side effects and symptom severity submitted by the patient. The feasibility and usefulness of Smart Cancer Care were confirmed through a pilot test targeting 30 patients and 24 chemotherapy-related medical staff. For patients, the evaluation score for the “The program will be helpful when seeing medical staff” item was the highest. For medical staff, the score for the “By checking the patient’s symptoms using the program, it helps to take appropriate measures for the patient” item was the highest. Although minor corrections were raised, most patients and medical staff expected that Smart Cancer Care would help their treatment.ConclusionsThe configuration of the application and dashboard of Smart Cancer Care detailed in this study could be used for the development of a widely accepted platform to implement a chemotherapy side effect management program.

Family caregivers’ experiences of caring for children diagnosed with haematological malignancies receiving chemotherapy in Ethiopia: A qualitative study

PurposeStudies from different countries show that caregivers of children with haematological cancer receiving chemotherapy encounter substantial distress when witnessing their children's suffering from the illness and chemotherapy side effects, alongside experiencing psychosocial problems and financial difficulties. However, no studies for this are available from Ethiopia in its specific cultural background and health care system. Thus, this study aimed to explore and bring into light the experiences of Ethiopian family caregivers of children with haematological malignancies receiving chemotherapy. MethodsA qualitative descriptive study was conducted using a maximum variation purposive sampling method among 20 caregivers. Semi-structured in-depth face-to-face interviews were conducted until no new themes discovered. The data were analysed through qualitative thematic analysis. ResultsParticipants believed cancer comes from different reasons and chemotherapy is ineffective in curing cancer. They identified various chemotherapy-related side effects, and psychosocial problems. The lack of health insurance, loss of job or income, and high cost of treatments were the major financial challenges. Adhering to treatments, acceptance and reassurance, religious and spiritual therapies, traditional medicine, and a support system were the major coping strategies. They had needs for improved support in information and education, psychosocial support, and in the availability of medications. ConclusionsSystematic health assessment, provision of targeted information and education, psychosocial support, nursing care respecting the caregivers' positive coping strategies, improvement in chemotherapy medication availability, and facilitating connections with supporting organisations would help improve child outcomes and address caregiver needs.

Therapeutic Fasting in Reducing Chemotherapy Side Effects in Cancer Patients: A Systematic Review and Meta-Analysis.

The aim of this study was to assess the available evidence regarding the effect of a variety of fasting-like regimens on preventing chemotherapy-related side effects. PubMed, Scopus and Embase were used to select the studies for this review, which concluded on 24 November 2022. All types of clinical trials and case series reporting chemotherapy toxicity associated with fasting regimens and any comparison were considered. A total of 283 records were identified, of which 274 were excluded, leaving only nine studies that met the inclusion criteria. Five of these trials were randomized. Overall, moderate to high-quality evidence showed that several fasting regimens did not provide benefits compared to a conventional diet or other comparators in reducing the risk of adverse events. The overall pooled estimate for a variety of fasting regime when compared to non-fasting, indicated no significant difference in the side effects (RR = 1.10; 95% CI: 0.77-1.59; I2 = 10%, p = 0.60), including neutropenia alone (RR = 1.33; 95% CI: 0.90-1.97; I2 = 0%, p = 0.15). A sensitivity analysis confirmed these results. Based on our systematic review and meta-analysis, there is currently no evidence supporting the superiority of therapeutic fasting over non-fasting in preventing chemotherapy toxicity. The development of cancer treatment that do not entail toxicities remains imperative.

D-CRSE: Diminishing chemotherapy related side effects through patient education.

e24148 Background: Patient (pt) education materials regarding self-management of cytotoxic chemotherapy related side effects are lacking at Penn State Cancer Institute (PSCI), resulting in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address the problems themselves, information on when to contact their oncologist, and guidance on when to visit the ED. The aim of our pilot study is to evaluate the feasibility at PSCI and subsequently improve pt related outcomes and quality of life through pt education. Methods: Chemotherapy naïve pts with breast or gastrointestinal (GI) cancer were enrolled from November 2021-December 2022. At the baseline visit, pts were consented, given the brochure and asked to complete surveys. The Emotional Thermometer Scale (ETS) evaluates mental health, measuring distress, anxiety, depression, and anger while the Memorial Symptom Assessment Scale (MSAS) evaluates symptoms commonly seen with chemotherapy. MSAS means were also broken down into physical, psychological, and global distress index (GDI) subsets. Pts filled out the same surveys at their 6 and 12 week visits to assess change over time. Results: 40 pts completed the baseline surveys, and 36 of them had at least one additional visit. Some key demographics were: 82.2% female, 17.8% male, 22.2% GI cancer (71.4% colonic adenocarcinoma, 14.3% rectal adenocarcinoma, 14.3% anal squamous cell carcinoma), 77.8% breast cancer (81.8% ductal carcinomas, 9.1% lobular carcinomas, 9.1% invasive metaplastic carcinoma, 52.5% ER+, 42.5% PR+, 22.5% HER2+), and 27.5% of patients underwent concurrent therapies with chemotherapy. Table 1 summarizes the mean score comparisons from baseline to 6 and 12 weeks for the ETS and MSAS. We observed significantly decreased psychological symptoms at week 12 compared to baseline (p = 0.023), while physical symptoms did not change significantly (p = 0.21). Conclusions: We successfully conducted a pilot study distributing a standardized educational brochure, thus demonstrating feasibility of this intervention. Measured psychological symptoms decreased over time, while physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden. We plan to expand standardized pt education materials to other cancer types, incorporate digital educational tools, and further explore pt education barriers. Clinical trial information: NCT04694794 .[Table: see text]

A nurse versus a chatbot ‒ the effect of an empowerment program on chemotherapy-related side effects and the self-care behaviors of women living with breast Cancer: a randomized controlled trial

BackgroundThe high levels of unmet needs in relation to provision of self-care information reported by women living with breast cancer suggests that pre-chemotherapy education is suboptimal. Chatbots are emerging as a promising platform to provide education to patients helping them self-manage their symptoms at home. However, evidence from empirical studies on the effect of chatbots education on women living with breast cancer self-care behaviors and symptoms management are scarce.MethodsThis three-arm randomized controlled trial was performed in a chemotherapy day care center within an oncology center in Egypt. A total of 150 women living with breast cancer were randomly selected and randomized into three groups: the ChemoFreeBot group (n = 50), the nurse-led education group (n = 50), and the routine care group (n = 50). In the ChemoFreeBot group, women were given a link to interact with ChemoFreeBot and ask questions about their symptoms and self-care interventions by typing questions or keywords at any time. On the same day as their first day of chemotherapy, the nurse-led education group received face to face teaching sessions from the researcher (nurse) about side effects and self-care interventions. The routine care group received general knowledge during their chemotherapy session about self-care interventions. The self-care behaviors effectiveness and the frequency, severity and distress of chemotherapy side effects were measured at baseline and postintervention for the three groups. The ChemoFreeBot’s usability was assessed.ResultsThe mixed design repeated measures ANOVA analyses revealed a statistically significant both group effect and interaction effect of group*time, indicating a significant difference between the three groups in terms of the physical symptoms frequency (F = 76.075, p < .001, F = 147, p < .001, respectively), severity (F = 96.440, p < .001, F = 220.462, p < .001), and distress (F = 77.171, p < .001, F = 189.680, p < .001); the psychological symptoms frequency (F = 63.198, p < .001, F = 137.908, p < .001), severity (F = 62.137, p < .001), (F = 136.740, p < .001), and distress (F = 43.003, p < .001, F = 168.057, p < .001), and the effectiveness of self-care behaviors (F = 20.134, p < .001, F = 24.252, p < .001, respectively). The Post hoc analysis with Bonferroni adjustment in showed that women in the ChemoFreeBot group experienced a statistically significant less frequent, less severe and less distressing physical and psychological symptoms and higher effective self-care behaviors than those in the nurse-led education and routine care groups (p > .001).ConclusionChemoFreeBot was a useful and cost-effective tool to improve increase self-care behavior and reduce chemotherapy side effects in women living with breast cancer through the provision of personalized education and the improvement of the accessibility to real-time and high-quality information compared to “one size fits all” approach used by nurses to provide the information. ChemoFreeBot can be an empowering tool to assist nurses to educate women with breast cancer and allow women to take an active role in managing their symptom.Trial registrationThis study was retrospectively registered in the University hospital Medical Information Network (UMIN) Center, Clinical Trials Registry on 26/09/2022; Registration No:R000055389,Trial ID:UMIN000048955.

Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant

BackgroundGut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs.MethodsLGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle.ResultsWe demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action.ConclusionOverall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients.

Abstract OT3-06-01: Diminishing Chemotherapy Related Side Effects through Patient Education

Abstract Background At the Penn State Cancer Institute (PSCI), there is currently a lack of patient education materials regarding self-management of cytotoxic chemotherapy related side effects, thus leading to use of disreputable sources (online searches) by cancer patients. A standardized brochure developed by our team aims to educate patients about commonly experienced chemotherapy related side effects. It also provides patients with tools to address these problems themselves, information on when to contact their medical oncologist, and brief guidance on when it is appropriate to visit the Emergency Department. We hypothesize that effective patient education through the brochure will improve patient related outcomes and quality of life. Moreover, empowering patients with such a trustworthy resource will decrease anxiety and distress related to their treatments. If this intervention is found to be impactful, it could be expanded to other cancer types within PSCI and eventually to other institutions across the country. Trial design • Recruitment and Screening: Chemotherapy naïve patients with breast cancer are recruited from our institution, screened, and enrolled on a rolling basis • Baseline Visit: Consent, receive the brochure, and complete the following questionnaires: the Patient Education Material Assessment Tool (PEMAT), Emotional Thermometer Scales (ETS), and Memorial Symptom Assessment Scale (MSAS) • PEMAT is utilized to evaluate if a teaching material is understandable and promotes action, which will help determine if the brochure itself is an effective education tool • ETS is utilized to evaluate the mental health, specifically measuring distress, anxiety, depression, and anger • MSAS is a validated patient rated instrument for evaluation of diverse group of symptoms commonly seen with chemotherapy • Follow Up Visits: Fill out the same 3 surveys again at their 6-week and 12-week visits • Patients will fill out the same questionnaires to assess changes over time, a surrogate for effectiveness of the brochure • Surveys take about 12 minutes to complete on average Eligibility Criteria 1. Adult with Breast cancer &amp;gt;18 years of age 2. Chemotherapy naive, will either start cytotoxic chemotherapy in the next 6 weeks or have started cytotoxic chemotherapy in the past 6 weeks prior to enrollment 3. May receive multiple forms of therapy such as immunotherapy, targeted treatment, endocrine therapy or radiation as long as they receive concurrent cytotoxic chemotherapy 4. Ability to understand and read written English or Spanish without any functional difficulty 5. ECOG performance status 0-3 6. May be involved with other cancer trials being offered at the PSCI Specific Aims • Primary Outcome: Determine if effective patient education through a standardized brochure will improve patient related outcomes and quality of life • Secondary Outcome: Drop-out rate after the baseline visit Statistical methods • Outcome variables from survey-based questionnaires will be measured at all three time points • Their distribution at time points will be summarized using numerical and graphical methods • Paired-sample tests will be used to compare the difference between visits’ data • Linear mixed-effect models for repeated measures will be used to examine the overall pattern by using data from all three time points • All tests will be two-sided with a significance level of 0.05 • We do not plan to do adjustments for multiple testing Present accrual and target accrual: • 24 total accrued, 14 completed • 60 target accrual • Plan to approach 70-75 patients and anticipate a 10-15% dropout rate which was considered in determining accrual goals Contact: • Corresponding Author: Shelby Labe SLabe1@pennstatehealth.psu.edu • PI: Monali Vasekar, MD MVasekar@pennstatehealth.psu.edu Citation Format: Shelby Labe, Monali Vasekar, Daniella Mikhail, Gavin Jones, Joanna Bhasker, Pritika Singh, Rhea Kanwar, Sonia Hafiz, Junjia Zhu, Hannah Dailey. Diminishing Chemotherapy Related Side Effects through Patient Education [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-06-01.

A comprehensive review of the preventive action of Natural Nutraceutical Ingredients in reducing Chemotherapy – Induced Side effects

Cancer is an umbrella term for more than 100 diseases, having the ability to access every part of the body. Chemotherapy drugs used to treat cancer can harm cells in the body including the nervous system and main functioning parts like the heart, lungs, and kidney, according to the American Cancer Society(2020).This re-evaluation aims to give a detailed synopsis of the evidence supporting the effectiveness of natural nutraceutical ingredients and their role in minimizing chemotherapy-related side effects by reviewing several published studies.Research Gap gives ideas for searching for an ingredient with greater efficacy and fewer or no side effects.This study focuses on natural nutraceutical ingredients as opposed to synthetic ingredients because the latter are poorly absorbed by the body and have more negative side effects. This study recommends using natural nutraceutical ingredients as supportive care supplements to treat chemo-related side effects and strengthen patients’ immune systems to fight the disease by regenerating their tissues.The main purpose of the study is to combine conventional medical practices with nutritionally enhanced autonomous human body recovery using natural ingredients in cancer patients.This review will provide an overview based on the fact that natural ingredients, including bioactive components, enriched fractions, and extracts in both raw and pristine form, are shown as preventive measures for the treatment of cancer.Keywords: Cancer, Chemotherapy-induced side effects, therapeutic benefits, Natural Nutraceutical ingredients, Supportive care, etc.

Folic acid-decorated alginate nanoparticles loaded hydrogel for the oral delivery of diferourylmethane in colorectal cancer

The disease-related suffering in colorectal cancer remains prevalent despite advancements in the field of drug delivery. Chemotherapy-related side effects and non-specificity remain a challenge in drug delivery. The great majority of hydrophobic drugs cannot be successfully delivered to the colon orally mainly due to poor solubility, low bioavailability, pH differences, and food interactions. Polymeric nanoparticles are potential drug delivery candidates but there are numerous limitations to their usefulness in colon cancer. The nanoparticles are removed from the body rapidly by p-glycoprotein efflux, inactivation, or breakdown by enzymes limiting their efficiency. Furthermore, there is a lack of selectivity in targeting cancer cells; nanoparticles may also target healthy cells, resulting in toxicity and adverse effects. The study aimed to use nanoparticles for specific targeting of the colorectal tumor cells via the oral route of administration without adverse effects. Folic acid (FA), a cancer-targeting ligand possessing a high affinity for folate receptors overexpressed in colorectal cancers was conjugated to sodium alginate- nanoparticles by NH2-linkage. The folic-acid conjugated nanoparticles (FNPs) were delivered to the colon by a pH-sensitive hydrogel synthesized by the free radical polymerization method to provide sustained drug release. The developed system referred to as the “Hydrogel-Nano (HN) drug delivery system,” was specifically capable of delivering diferourylmethane to the colon. The HN system was characterized by DLS, FTIR, XRD, TGA, DSC, and SEM. The FNPs size, polydispersity index, and zeta potential were measured. The folic acid-conjugation to nanoparticles' surface was studied by UV–visible spectroscopy using Beer-Lambert's law. In-vitro studies, including sol-gel, porosity, drug loading, entrapment efficiency, etc., revealed promising results. The swelling and release studies showed pH-dependent release of the drug in colonic pH 7.4. Cellular uptake and cytotoxicity studies performed on FR-overexpressed Hela cell lines and FR-negative A-549 cell lines showed facilitated uptake of nanoparticles by folate receptors. A threefold increase in Cmax and prolongation of the mean residence time (MRT) to 14.52 +/− 0.217 h indicated sustained drug release by the HN system. The findings of the study can provide a sufficient ground that the synergistic approach of the HN system can deliver hydrophobic drugs to colorectal cancer cells via the oral route, but further in-vivo animal cancer model studies are required.

Low L3 skeletal muscle index associated with the clinicopathological characteristics and prognosis of ovarian cancer: a meta-analysis.

Sarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass, strength and function, which is one of the most important clinical features of cancer malnutrition, representing a poor prognostic indicator in oncology. Sarcopenia is commonly assessed by measuring the skeletal muscle index (SMI) of the third lumbar spine (L3) using computed tomography (CT). The primary aim of this meta-analysis was to study the association between low SMI and comprehensive clinicopathological characteristics as well as prognosis in patients with ovarian cancer. Data were searched in PubMed, EMBASE and Cochrane databases from inception to 10 June 2022. Studies evaluating the prognostic effect of SMI on ovarian cancer survival or chemotherapy-related side effects were included. The risk of bias and study quality were assessed via the Newcastle-Ottawa Scale (NOS). The search strategy yielded 1286 hits in all three databases combined. Thirteen studies were included for qualitative and quantitative analysis, comprising 1814 patients. Our meta-analysis revealed the significant association between low SMI and progression-free survival (PFS) [P=0.02; hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.06-1.85], as well as 5-year overall survival (OS) [P=0.02; odds ratio (OR): 1.35, 95% CI: 1.05-1.74]. Low SMI was also obviously associated with body mass index (BMI)<25 (P<0.00001; OR: 5.08, 95% CI: 3.54-7.30), FIGO stage (P=0.02; OR: 1.62, 95% CI: 1.06-2.45) and R0 cytoreduction (P=0.04;OR: 1.34, 95% CI: 1.01-1.79). There was no correlation between low SMI and histological types, pathological grades and chemotherapy-related toxicity. The quality of the evidence was relatively high according to NOS. Our meta-analysis indicated that sarcopenia assessed by SMI was associated with poor clinical characteristics and adverse prognosis in patients with ovarian cancer. Consensus should be reached on standardized cut-off values for defining sarcopenia in patients with ovarian cancer.

Short-term fasting and fasting mimicking diets combined with chemotherapy: a narrative review.

Many patients with cancer search for and use alternative and complementary treatments, aiming to improve the effectiveness of their anticancer treatment and a reduction in treatment-associated side effects. Short-term fasting (STF) and fasting mimicking diets (FMDs) are among the most commonly used dietary interventions. In recent years, different trials have reported the promising results of dietary interventions in combination with chemotherapy, in terms of slowing down tumor growth and reduction in chemotherapy-related side effects. In this narrative review, we identify and describe the current evidence about feasibility and effects of STF and FMDs in cancer patients receiving chemotherapy. The studies that examined the effects of STF when combined with chemotherapy suggest potential benefits regarding reduction in side effects and improved quality of life. We also conclude with a list of well-designed studies that are still recruiting patients, examining the long-term effects of STF.

Integrative Oncology's 30-Year Anniversary: What Have We Achieved? A North American Naturopathic Oncology Perspective.

In 1991 the U.S. Congress mandated that the National Institutes of Health (NIH) form the Office of Alternative Medicine to study alternative medical therapies, especially in oncology care. Shortly after, the National Cancer Institute (NCI) created its own division of complementary and alternative medicine (Office of Complementary and Alternative Medicine). At the genesis of the field 30 years ago, what were we hoping to see accomplished by now? In this article we take a look back at milestones, shortfalls and future directions. Exciting opportunities exist to direct our established subspeciality's future directions and we have made valuable advances the field of integrative oncology over the last 30 years: 1, IV high dose ascorbate has clinical research-based applications when used concurrently with some chemotherapeutic agents. 2. Whole body, extracorporeal and locoregional hyperthermia are being applied in treating solid tumors, including brain tumors. 3. PDL-1 tumor microenvironment testing and PDL-1 inhibitor immunotherapies have surprisingly excellent outcomes in a subgroup of cancer patients. 4. Tumor DNA sequencing (resected tumor and circulating tumor DNA in blood) has led to personalized precision targeted treatments. 5. Glucose metabolism's role in cancer progression is better understood and better therapies are available (e.g., intermittent fasting, metformin). 6. Medical cannabis has a larger role in treating chemotherapy-related side effects and shows promise for anti-proliferative effects. 8. Greater understanding has been gained of the interdependence and mutual regulation of processes in psychoneuroendocrinoimmunology (PNEI). The burgeoning field of PNEI has exponentially expanded the discussion of tumorigenesis, apoptosis, and introduced to the field the investigation of more holistic approaches to immune regulation and cancer care. 8. Psychedelic-assisted psychotherapy is gaining traction especially for cancer patients facing demoralization, existential and spiritual distress, anxiety, depression and trauma related to the diagnosis and treatment of their cancer. 9. Spiritual health of cancer patients is more commonly addressed and measurable with an NIH validated scale. 10. Mind-Body therapies are efficacious for reducing cancer-related distress and are included in many cancer care programs.