Adverse Effects Of Chemotherapy Research Articles

Factors Associated with Adverse Effects in Elderly Women Receiving Chemotherapy for Breast Cancer

Objective: To analyze the factors associated with adverse effects in elderly women receiving chemotherapy for breast cancer.
 Study Design: Comparative Cross-sectional Study.
 Place and Duration of Study: Oncology Department, Combined Military Hospital (CMH), Rawalpindi Pakistan, from Dec2020 to Nov 2021.
 Methodology: This study was conducted on 145 female patients (>65 years) with breast cancer who were taking chemotherapy of any type and had undergone one cycle. All the study participants underwent detailed clinical evaluation by a consultant oncologist to assess the presence of various adverse effects of chemotherapy. In addition, the association of Anthracycline use,>3 months of treatment, low haemoglobin at baseline and abnormal liver functions at baseline were studied with adverse effects in the study participants.
 Results: The final analysis included one hundred forty-five elderly female patients with breast cancer receiving chemotherapy.The mean age of the patients was 69.731±8.794 years. 89(61.4%) patients had no adverse effects, while 56(38.6%) had one or more adverse effects during chemotherapy. Anaemia 26(17.9%) was the commonest adverse effect, followed by fatigue 18(12.4%) and abnormal liver function tests 18(12.4%). It was revealed that the use of Anthracycline-based chemotherapy and long duration of chemotherapy were statistically significantly associated with adverse effects (p-value<0.05) in our study participants.
 Conclusion: Considerable number of elderly patients with breast cancer undergoing chemotherapy showed the presence of adverse effects. In addition, patients using Anthracycline-based chemotherapy and taking chemotherapy for more than three months were more at risk of developing adverse effects.

Quinacrine and Curcumin in combination decreased the breast cancer angiogenesis by modulating ABCG2 via VEGF A.

Cancer stem cells (CSCs) cause drug resistance in cancer due to its extensive drug efflux, DNA repair and self-renewal capability. ATP binding cassette subfamily G member 2 (ABCG2) efflux pump afford protection to CSCs in tumors, shielding them from the adverse effects of chemotherapy. Although the role of ABCG2 in cancer progression, invasiveness, recurrence are known but its role in metastasis and angiogenesis are not clear. Here, using in vitro (CSCs enriched side population [SP] cells), ex vivo (patient derived primary cells), in ovo (fertilized egg embryo) and in vivo (patient derived primary tissue mediated xenograft (PDX)) system, we have systematically studied the role of ABCG2 in angiogenesis and the regulation of the process by Curcumin (Cur) and Quinacrine (QC). Cur + QC inhibited the proliferation, invasion, migration and expression of representative markers of metastasis and angiogenesis. Following hypoxia, ABCG2 enriched cells released angiogenic factor vascular endothelial growth factor A (VEGF A) and induced the angiogenesis via PI3K-Akt-eNOS cascade. Cur + QC inhibited the ABCG2 expression and thus reduced the angiogenesis. Interestingly, overexpression of ABCG2 in SP cells and incubation of purified ABCG2 protein in media induced the angiogenesis but knockdown of ABCG2 decreased the vascularization. In agreement with in vitro results, ex vivo data showed similar phenomena. An induction of vascularization was noticed in PDX mice but reduction of vascularization was also observed after treatment of Cur + QC. Thus, data suggested that in hypoxia, ABCG2 enhances the production of angiogenesis factor VEGF A which in turn induced angiogenesis and Cur + QC inhibited the process by inhibiting ABCG2 in breast cancer.

LBODP011 Pembrolizumab Induced Hypophysitis And Resultant Isolated ACTH Deficiency Presenting As Secondary Adrenal Insufficiency.

Abstract Introduction Pembrolizumab is a novel human immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1). It has been approved by the FDA for treatment of many malignancies including breast cancer. Although it has improved survival for many oncological conditions, it has been linked to a variety of endocrinopathies. We present a case of Pembrolizumab induced hypophysitis with isolated ACTH deficiency presenting as secondary adrenal insufficiency. Case presentation A 36 year old female with a history of breast cancer treated with chemotherapy and surgery, presented with intractable nausea and vomiting. She reported not being able to keep anything down for 4-5 days and had experienced multiple episodes of non-bilious, non-bloody emesis. She endorsed dizziness, but denied fever, chills, shortness of breath, abdominal pain, or problems with urination/bowel movements. She had been treated with Pembrolizumab with the last dose being 4 months prior to presentation. On arrival, vitals included temperature 98.4 F, BP 104/62 mm Hg, Heart rate 104 bpm, RR 16 with SpO2 100%. Labs were significant for WBC count 3.65 K/uL (3.81 - 8.94), Eosinophils 10.4% (0.1 - 6; she was noted to have eosinophilia prior to presentation), Hemoglobin 11.6 g/dL (11 - 14.9), Sodium 140 mmol/L (136-145), Potassium 3.4 mmol/L (3.4 - 5.1), Glucose 57 mg/dL (70 - 100), Lactate 0.7 mmol/L (0.2 -2), Lipase 23 U/L (13 - 60), Urine HCG negative, Urinalysis negative for nitrites and leukocyte esterase, TSH 1.22 uIU. ml (0.5 -5.7) and AM cortisol 0.4 ug/dL (6 - 18.4). Endocrinology was consulted and further work up was sought: ACTH <5 pg/ml (7.2 - 63) and Cortisol 30 - 60 minutes after cosyntropin stimulation 3.6 ug/dL. Prolactin, free T4, FSH and LH were within normal limits. MRI brain showed a prominent pituitary gland with enhancement and interval loss of posterior pituitary bright spot representing lymphocytic hypophysitis. She was started on Solu-Cortef and her symptoms resolved. She was discharged on hydrocortisone with education on sick day rules for secondary adrenal insufficiency. Discussion Adrenal insufficiency secondary to immunotherapy is a rare, emergent and dangerous condition. The key to successful management is early recognition. In patients treated with immunotherapy agents, non-specific symptoms such as nausea, vomiting, fatigue (which are common adverse effects of chemotherapy) should prompt urgent evaluation with hormonal workup. Evidence suggests that eosinophilia may be an early indicator before the onset of symptoms which was evident in our case. Radio-graphic imaging is helpful for diagnosis. Treatment entails high dose corticosteroids for acute crisis followed by physiological maintenance dosing. Patients should be educated on sick day rules for adrenal insufficiency. Presentation: No date and time listed

RETRACTED ARTICLE: Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes

BackgroundFertility preservation and restoration in cancer patients/survivors is the need of present times when increased numbers of patients get cured of cancer but face infertility as a serious side effect. Resveratrol has beneficial effects on chemoablated ovaries and testes in mice but has failed to enter the clinics because of extremely poor bioavailability. The present study was undertaken to evaluate the protective and curative effects of Extremely active Resveratrol (XAR™)- a nano-formulation of resveratrol with significantly improved bioavailability- on mouse ovary and testis after chemotherapy. Effects of XAR™ and FSH were compared on stimulation of follicle growth in adult mice ovaries. XAR™ (25 mg/kg) was administered for two days prior to chemotherapy to study the protective effects on the mouse gonads. XAR™ was also administered for 14 days post chemoablation to study the regenerative effects. Besides effect on numbers of primordial and growing follicles and spermatogenesis, the effect of XAR™ was also evaluated on the transcripts specific for ovarian/testicular stem/progenitor/germ cells, their proliferation, differentiation, meiosis, and the antioxidant indices.ResultsSimilar to FSH, XAR™ increased the numbers of primordial follicles (PF) as well as growing follicles. It protected the gonads from the adverse effects of chemotherapy and showed the ability to regenerate non-functional, chemoablated gonads. Besides stimulating follicle growth in adult ovaries similar to FSH, XAR™ also protected the testes from the adverse effects of chemotherapy and improved spermatogenesis. This was accompanied by improved anti-oxidant indices.ConclusionsThe results of the present study potentiate the use of XAR™ in pilot clinical studies to protect gonadal function during oncotherapy and also regenerate non-functional gonads in cancer survivors by improving antioxidant indices and stem cell-based tissue regeneration.

Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer

Mortality from breast cancer is almost exclusively a result of tumor metastasis and resistance to therapy and therefore understanding the underlying mechanisms is an urgent challenge. Chemotherapy, routinely used to treat breast cancer, induces extensive tissue damage, eliciting an inflammatory response that may hinder efficacy and promote metastatic relapse. Here we show that systemic treatment with doxorubicin, but not cisplatin, following resection of a triple-negative breast tumor induces the expression of complement factors in lung fibroblasts and modulates an immunosuppressive metastatic niche that supports lung metastasis. Complement signaling derived from cancer-associated fibroblasts (CAFs) mediates the recruitment of myeloid-derived suppressor cells (MDSCs) to the metastatic niche, thus promoting T cell dysfunction. Pharmacological targeting of complement signaling in combination with chemotherapy alleviates immune dysregulation and attenuates lung metastasis. Our findings suggest that combining cytotoxic treatment with blockade of complement signaling in triple-negative breast cancer patients may attenuate the adverse effects of chemotherapy, thus offering a promising approach for clinical use.

Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs.

Chemotherapy is one of the most effective methods of systemic cancer treatment. Chemotherapy drugs are delivered through the blood circulation system, and they can act at all stages of the cell cycle, and can target DNA, topoisomerase, or tubulin to prevent the growth and proliferation of cancer cells. However, due to the lack of specific targets for chemotherapeutic agents, there are still unavoidable complications of cytotoxic effects. The effect of the microbiome on human health is clear. There is growing evidence of the potential relationship between the microbiome and the efficacy of cancer therapy. Gut microbiota can regulate the metabolism of drugs in several ways. The presence of bacteria in the tumor environment can also affect the response to cancer therapy by altering the chemical structure of chemotherapeutic agents and affecting their activity and local concentration. However, the underlying mechanisms by which the gut and tumor microbiota affect cancer therapeutic response are unclear. This review provides an overview of the effects of gut and tumor microbiota on the efficacy and adverse effects of chemotherapy in cancer patients, thus facilitating personalized treatment strategies for cancer patients.

A REVIEW OF THE ANTICANCER NATURAL PRODUCTS: ALKALOIDS, FLAVONOIDS

According to the international agency for research on cancer 1 in 5 people develop cancer during their lifetime, suggesting that more than 50 million people are living within five years of a past cancer diagnosis (World Health Organization (WHO, 2020, para. 1). Despite novel approaches like nanomedicine, targeted therapy, and immunotherapy in cancer treatments during the last decades, chemoresistance has remained the chief hurdle in eliminating cancerous cells (Elgendy , Alyammahi & Alhamad, 2020, p. 103095). About 9 out of 10 cancer deaths are due to spreading of cancer cells from the primary tumor mass towards close and far tissues (a process called metastasis). Treatment failure followed by consequent recurrence of cancer cells and metastasis is the leading cause of death. Many survivors suffer from serious acute or chronic complications after cancer therapy (Qian, Mei, & Zhang, 2017, p.38). Furthermore, chemotherapy commonly induces a variety of side-effects in patients as a result of nonspecific action against both normal cells and cancerous cells. For instance, chemotherapeutic drugs result in alopecia by affecting not only fast dividing cancer cells, but hair follicles as well. Nausea and vomiting are the most common symptoms induced by chemotherapy, with gastrointestinal symptoms including diarrhea (and in some cases constipation) being another common side effect. Chemotherapy is also known to impair immune function and bone marrow activity (Li et al., 2020, p.599073). The identification of approved doses of anticancer drugs is another point to be given careful attention, especially those with higher cost and administered for a longer duration. Larger doses of chemotherapeutic drugs may increase the risk and severity of the aforementioned side effects, and are not cost-saving. Therefore, phytomedicines should be considered as an option not only for adjuvant therapy, but also in view of their comparatively low toxicity and ability to diminish adverse effects of chemotherapy in cancer patients. Natural products and their derivatives can be used as novel therapeutic interventions with improved pharmacological properties targeting tumor cells (Meriggi & Zaniboni, 2020, pp.1–11).

Analysis of Mexican young women with primary ovarian insufficiency induced by gynaecological and haematological cancer management

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95–5.23, p = .065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09–0.8, p = .18), haematologic cancer (OR 0.11, 95% CI 0.2–0.65, p = .014), radiotherapy (OR 2.62, 95% CI 1.04–6.54, p = .039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01–7.35, p = .049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms. Impact Statement What is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis. What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms. What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.

Cáncer de pene en un hospital de tercer nivel de la Ciudad de México: Descripción de factores de riesgo y frecuencias en población mexicana

Objective: To determine and analyze the prevalence of the principal risk factors in patients with penile cancer in General Hospital “Dr. Eduardo Liceaga” and their survival rate at 24 months. Methods: Cross-sectional, descriptive study. The population (n=93) are hispanic, adult male residents of Mexico City with penile cancer diagnosed. The variables analyzed are: Age, smoking status, HPV status, presence of vascular invasion, treatment and survival status after 24 months. Results: Mean age (n=93) was 57.87. 55.9% were active smokers. 100% were uncircumcised. Only 17.2% were HPV +. Squamous Cell Carcinoma was the predominant type with 86%. 18.3% had vascular invasion. At 24 months after diagnosis with treatment 84.9% patients were alive, 6.5% died of cancer related causes, 6.5% of other causes and (2.2%) of chemotherapy toxicity. Conclusion: This infrequent disease requires a high quality multidisciplinary treatment. Squamous cell carcinomas are the predominant type in Mexico City, risk factors such as smoking, uncircumcised, age and HPV infection were present. HPV vaccines in men could help reduce a proportion of malignancies but there is no data related. Adjuvant therapy should be considered since the survival rate at 24 months of study was lower than first world countries. Periodic evaluation of chemotherapy adverse effects should be considered since a significant proportion died because of toxicity.

Chemotherapy-Related Structural Changes in Cancer: Effect of GnRH Antagonist in the Ovarian Follicles

Objectives: The adverse effect of chemotherapy on the proliferation of granulosa cells has been indicated in recent studies. Gonadotropin-releasing hormone (GnRH) antagonists exert protective effects on granulosa cells against the side effects of chemotherapy. In the present study, we aimed to evaluate the impact of cetrorelix on the proliferation of ovarian granulosa cells following administration of thiotepa in the ovaries of female mice. Materials and Methods: In this experimental study, 30 adult Balb/c female mice (5-8 weeks old, weighing 24-28 g) were divided into three groups (n=10/ each group) (Control group, T. group, and C. group). T. group received 2.5 mg/kg of thiotepa for four consecutive days. The C. group received cetrorelix (0.25 mg/kg) before and at the same time as thiotepa administration and a week after the end of thiotepa administration. Ovaries were used for quantitative and immunohistochemical studies at the end of the investigation. Results: The mean numbers of follicles such as primordial, primary, secondary, and tertiary significantly decreased in the T. group than control group (P=0.02). Cetrorelix treatment exerted a protective effect against thiotepa-induced damage by increasing the mean numbers of follicles in the ovarian cortex (P=0.04). Conclusions: As a GnRH antagonist, cetrorelix can be considered as one of the effective drugs to protect the granulosa cells against chemotherapy-induced damages in cancer disease.

Neoadjuvant chemotherapy for locally advanced esophageal cancer comparing cisplatin and 5-fluorouracil versus docetaxel plus cisplatin and 5-fluorouracil: a propensity score matching analysis.

The standard treatment for locally advanced esophageal cancer is preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), followed by surgery. Although docetaxel plus cisplatin and 5-fluorouracil (DCF) has been reported to have favorable outcomes, no study has compared its therapeutic efficacy to that of standard treatment. This study aimed to compare the therapeutic effects of CF and DCF in the real world by matching patient background factors using propensity scores. We retrospectively reviewed the data of 237 patients with esophageal squamous cell carcinoma who underwent esophagectomy between January 2008 and December 2018. Patients were divided into two groups based on the preoperative chemotherapy regimens of CF (79 patients) or DCF (158 patients), and 49 matched pairs were finally analyzed using propensity score matching. Short- and long-term outcomes were compared between groups. After matching, although no significant differences in survival were observed among the groups, patients receiving DCF showed a significantly high histological response (P < 0.001). Subgroup analyses demonstrated that DCF therapy had better overall survival (P = 0.046) and relapse-free survival (P = 0.010) among pathological T3 and T4 cases. Whereas, adverse effects of chemotherapy were more frequent in the DCF group. Patients receiving DCF had higher pathological response and better survival than those receiving CF, especially in pathological T3 and T4 cases matched using propensity scores. Thus, the DCF regimen might be an effective treatment for locally advanced esophageal cancer. However, the adverse side effects of chemotherapy remain high and should be handled appropriately.

SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer.

BackgroundFluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.MethodsFirstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed In vitro experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.ResultsWe identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.ConclusionThis study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.

A Proposed Link Between Acute Thymic Involution and Late Adverse Effects of Chemotherapy.

Epidemiologic data suggest that cancer survivors tend to develop a protuberant number of adverse late effects, including second primary malignancies (SPM), as a result of cytotoxic chemotherapy. Besides the genotoxic potential of these drugs that directly inflict mutational burden on genomic DNA, the precise mechanisms contributing to SPM development are poorly understood. Cancer is nowadays perceived as a complex process that goes beyond the concept of genetic disease and includes tumor cell interactions with complex stromal and immune cell microenvironments. The cancer immunoediting theory offers an explanation for the development of nascent neoplastic cells. Briefly, the theory suggests that newly emerging tumor cells are mostly eliminated by an effective tissue immunosurveillance, but certain tumor variants may occasionally escape innate and adaptive mechanisms of immunological destruction, entering an equilibrium phase, where immunologic tumor cell death “equals” new tumor cell birth. Subsequent microenvironmental pressures and accumulation of helpful mutations in certain variants may lead to escape from the equilibrium phase, and eventually cause an overt neoplasm. Cancer immunoediting functions as a dedicated sentinel under the auspice of a highly competent immune system. This perspective offers the fresh insight that chemotherapy-induced thymic involution, which is characterized by the extensive obliteration of the sensitive thymic epithelial cell (TEC) compartment, can cause long-term defects in thymopoiesis and in establishment of diverse T cell receptor repertoires and peripheral T cell pools of cancer survivors. Such delayed recovery of T cell adaptive immunity may result in prolonged hijacking of the cancer immunoediting mechanisms, and lead to development of persistent and mortal infections, inflammatory disorders, organ-specific autoimmunity lesions, and SPMs. Acknowledging that chemotherapy-induced thymic involution is a potential risk factor for the emergence of SPM demarcates new avenues for the rationalized development of pharmacologic interventions to promote thymic regeneration in patients receiving cytoreductive chemotherapies.

O-197 Predicting individualised risk of developing amenorrhoea in young breast cancer patients: an international multi-cohort study

Abstract Study question What is the likelihood of developing amenorrhoea after breast cancer treatment in young women with early breast cancer? Summary answer We developed risk prediction model for a web-based tool to provide an individualized risk of developing amenorrhoea of young breast cancer patients at diagnosis. What is known already Young breast cancer survivors have an increased risk of developing premature ovarian insufficiency as a long-term adverse effect of chemotherapy. The potential for developing amenorrhoea is a high priority for these young patients, with some choosing less optimal cancer treatments to minimise the impact on fertility and/or unnecessarily taking on the physical and financial burden of fertility preservation. A key component in good-quality decision-making is understanding the likelihood of outcomes. Yet, current tools to predict individualised ovarian function after breast cancer treatments are imprecise with minimal applicability for clinical practice. Study design, size, duration The FoRECAsT (Fertility after Cancer Predictor) study is a multi-institutional study of 5-year survivors of breast cancer. A literature review addressing the impact of chemotherapy regimens for breast cancer on developing amenorrhoea was conducted. Authors of identified articles and known data registries were contacted and invited to contribute their data to the FoRECAsT database. The FoRECAsT database contains 7473 individuals sourced from Australia, UK, USA, Hong Kong, France, Denmark, Italy, Belgium and International Trial Groups. Participants/materials, setting, methods FoRECAsT cohort includes premenopausal women diagnosed with primary breast cancer, reported history of two or more predictors of developing amenorrhoea and menstrual history information after chemotherapy. Patients with bilateral salpingo-oophorectomy were excluded. Primary outcomes were likelihood of developing amenorrhea at 12 and 24 months. Cross imputation was used to manage missing values. Logistic regression was used to develop risk prediction models and prediction performance was evaluated internally using area under the receiver operating curve (AUC). Main results and the role of chance Out of 7473 individual records from FoRECAsT database, 2833 participants (37.91%) reported menstrual history information at 12 months and 2118 participants (28.34%) reported menstrual history information at 24 months and, thus were included in the analysis. In multivariate logistic regression analyses, common predictors for amenorrhea at 12 and 24 months were older age at diagnosis, lower body mass index, chemotherapy regimens, endocrine therapy and pre-treatment follicle stimulating hormone. In addition, history of smoking and alcohol consumption were also predictors for developing amenorrhea at 12-months. Receiver–operator characteristic analysis produced an estimated AUC of 0.88, sensitivity of 95.75% and specificity of 58.52% for amenorrhoea at 12 months and AUC of 0.92, sensitivity of 94.09% and specificity of 53.58% for amenorrhoea at 24 months. Internal validation with 1000 bootstrap resampling showed good discrimination for both models, C-index of 0·88 (95% CI 0·84–0·91) for amenorrhoea at 12 month and C-index of 0·93 (95% CI 0.90 − 0.94) amenorrhoea at 24 months. Based on these models, a web-based calculator that predicts individualised ovarian function is under development for implementing in clinical practice worldwide. Limitations, reasons for caution The limitations including reliance on self-reported menstrual history, heterogeneity in collecting data in different countries could result in bias and insufficiency. These models require external validation. However, excellent prediction performance of the models and good precision in the estimate of accuracy in internal validation provides reassurance. Wider implications of the findings The model and the associated web application could help clinical discussions and decision-making regarding fertility preservation before chemotherapy when appropriate and to optimise adjuvant endocrine therapy in young women with early breast cancer. Additionally, this tool could be adapted to newer breast cancer treatments and for other cancer treatments. Trial registration number N/A

Abstract 4044: An extract of olive oil wastewater enhances chemotherapy effects on breast cancer cells without exacerbating cardiovascular toxicity

Abstract Background: In cancer patients receiving chemotherapeutic agents, cardiovascular toxicities still remains one of the most undesirable side effects. One of the best known cardiotoxic agents is doxorubicin, a very powerful chemotherapeutic molecules for breast cancer. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, anti-oxidant activities which could exert protective effects on heart cells. A very interesting derivative of EVOO preparation is represented by purified extracts from olive mill waste waters (OMWW) rich in polyphenols. Here, we have investigated the anti-cancer activity of a OMWW preparation, named A009, on breast cancer cells when combined with chemotherapeutics, as well as its potential cardioprotective activities. We had previously reported additive effects with cisplatin in prostate cancer cells. In previous studies we have shown that the combination of A009 with cisplatin or 5-FU was effective in decreasing prostate and colon cancer cell growth, while it did not further reduce growth of rat cardiomyocytes also treated with cisplatin or 5-FU. Here we used 5-fluorouracil as comparison. Methods: Combination of A009 and chemotherapy was investigated in vitro on human breast cancer cell lines BT459, MDA-MB-234. The cardioprotective effects of the A009 extract were tested on H9C2 (cardiomyocytes) cells co-exposed to doxorubicin or 5-fluorouracil and in zebrafish embryos. Results: Adding A009 to doxorubicin or 5-FU was effective in decreasing breast cancer cell growth in monolayer. Breast tumor spheroids morphologically appeared less stable and with reduced diameter when treated with A009 extracts and with the chemotherapeutic agents 5-FU or Doxo, additive effects were observed. A009 mitigated toxicity of doxorubicin or 5-FU on rat cardiomyocytes cells H9C2. Cardioprotective effects were observed by the combination of OMWW extracts with Doxorubicin in Zebrafish embryos. In human cardiomyocytes, we observed 5-FU induced upregulation of the proinflammatory IL6 mRNA, which was reduced by OMWW treatment. Conclusions: Our study demonstrates that the polyphenol rich purified A009 extracts enhance the effect of chemotherapy of doxorubicin and 5-FU on breast cancer cells but mitigates chemotherapy adverse effects on heart in vivo and on cardiomyocytes, appearing as a potential cardio-oncological prevenzion agent. Citation Format: Adriana Albini, Marco M. Festa, Denisa Baci, Nadia Benedetto, Karolina Gutmanska, Nicoletta Macrì, Giovanna Finzi, Fausto Sessa, Serena Zacchigna, Antonino Bruno, Douglas M. Noonan. An extract of olive oil wastewater enhances chemotherapy effects on breast cancer cells without exacerbating cardiovascular toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4044.

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment.

Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy.

Reduced Dose Intensity of Daunorubicin During Remission Induction for Low-Risk Patients With Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of the Chinese Children's Cancer Group.

It is urgently necessary to reduce the adverse effects of chemotherapy while maintaining their cure high rates for children with acute lymphoblastic leukemia (ALL). The present study aimed to determine whether the dose intensity of daunorubicin during the remission-induction phase could be reduced for low-risk patients with ALL. A total of 2396 eligible patients, who participated in CCCG-ALL-2015 study and were provisionally assigned to the low-risk group, were included and divided into single-dose group and double-dose group according to the dosage of daunorubicin during the remission-induction phase. For patients with ETV6-RUNX1 positive ALL or hyperdiploidy ALL, there were no significant differences in outcomes between the two groups. For other patients, the 5-year event-free survival rate was significantly better and the 5-year cumulative risk of any relapse was significantly lower in the double-dose group compared with the single-dose group. Both the 5-year overall survival rate and the risk of early deaths were not significantly different between the two groups. Our results suggested that only B-lineage ALL patients with ETV6-RUNX1 positivity or hyperdiploidy who achieved an early negative minimal residual disease status were suitable candidates for dosage reduction of daunorubicin during the remission-induction phase.Clinical Trial Registration http://www.chictr.org.cn/showproj.aspx?proj=10115, identifier ChiCTR-IPR-14005706.

Quality of life (QoL) of OSE2101 in patients with HLA-A2+ non–small cell lung cancer (NSCLC) after failure to immune checkpoint inhibitors (IO): Final data of phase 3 Atalante-1 randomized trial.

9094 Background: OSE2101 (Tedopi) is an anticancer vaccine increasing overall survival (OS) versus Standard of Care (SoC docetaxel or pemetrexed) in HLA-A2+ NSCLC patients with secondary resistance after sequential Chemo (CT)-IO (ESMO 2021 #47LBA). Here we present the QoL analysis. Methods: EGFR and ALK negative NSCLC patients who failed prior IO, ECOG PS 0-1 were randomized 2:1 to receive either OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was OS; secondary endpoints included time to ECOG PS deterioration and QoL by EORTC QLQ-C30/LC13 questionnaires at baseline and before each treatment administration until the end of treatment (EOT). Changes in QLQ-C30/LC13 scores from baseline to EoT were assessed using mixed-effects model for repeated measures (MMRM). Overall treatment effect and associated p value were estimated using MMRM. Results: 95 out of 118 (81%) patients with secondary resistance to IO completed baseline and ≥ one follow-up questionnaire. Median OS was 11.1 mo for OSE2101 vs 7.5 mo for SoC [HR 0.59; p = 0.02]. Median time to ECOG PS deterioration was 9.0 mo for OSE2101 vs 3.3 mo for SoC [HR: 0.43; p = 0.004]. Global Health Status remained stable with OSE2101 whereas it deteriorated from the 1st cycle with SoC (p = 0.045). Most pronounced effects were observed in the physical (ability to perform activities that require physical effort; p = 0.07) and the role (ability to work and carry out daily activities; p = 0.03) functioning scores (refer table below). Patients had less mouth soreness (p = 0.01), dysphagia (p = 0.01), peripheral neuropathy (p = 0.03), alopecia (p &lt; 0.001) and fatigue (p = 0.06) with OSE2101 than with SoC. The change from baseline of dyspnea, coughing, hemoptysis, and pain were not significantly different between the 2 groups. Conclusions: In advanced HLA-A2+ NSCLC patients with secondary resistance to IO after sequential CT-IO, OSE2101 improves OS and maintains QoL vs. SoC, especially global health status, physical and role functioning scores. Patients presented fewer symptoms typically related to adverse effects of chemotherapy as compared to SoC. Clinical trial information: NCT02654587. [Table: see text]

An elemental diet protects mouse salivary glands from 5-fluorouracil-induced atrophy.

An elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis, in patients with cancer. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In the present study, the protective effects of the ED, Elental®, were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental® (ED group) or saline (control group). After treatment, the mice body weight, salivary gland weight and the histological changes in the salivary gland granular duct area were monitored. The mice body weight remained stable in the ED group, but was significantly decreased in the control group. Moreover, the salivary gland weight was higher in the ED group compared with the control group. In addition, the salivary gland granular duct area cells were larger in the ED group compared with the control group. Whole transcriptome analysis and network analysis were conducted to understand the mechanisms of action of Elental® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis data suggested that Elental® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands. Immunohistochemical analysis of salivary gland tissue demonstrated that the expression of cytochrome c oxidase subunit 4 and epidermal growth factor were higher in the ED group compared with the control group. Next, the rate of apoptosis in the salivary glands was examined using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The number of TUNEL-positive cells in the salivary glands was lower in the ED group compared with the control group. These findings suggested that Elental® may protect mouse salivary glands from 5-FU-induced atrophic changes, which suggests that ED treatment may improve xerostomia and alleviate oral mucositis in patients with cancer receiving 5-FU-based chemotherapy.

Psychocognitive functions among breast cancer survivors

Purpose: Chemotherapy-related cognitive impairments (CRCIs) are one of the adverse effects of chemotherapy, so there is a need to explore alternative measures to maintain normal cognitive functions or to prevent decline in cognitive abilities. This study was conducted to assess the effectiveness of Cognitive Training Interventions Package on cognitive functions among breast cancer survivors (BCSs). Materials and Methods: A total of 59 BCSs were randomly assigned to control and intervention groups. Participants of the intervention group were provided with a Cognitive Training Interventions Package to be practiced from 1st cycle until the completion of 4th cycle of chemotherapy. Both the groups were reassessed on the 4th cycle of chemotherapy. FACT Cog Version-3, Post Graduate Institute Memory Scale (PGIMS), and trail making test were used to assess cognitive functions. Activities of daily livings (ADLs) and depression, stress, and anxiety were measured using Barthel Index Scale and Depression, Anxiety, and Stress Scale-21, respectively. Satisfaction level among participants was measured using a self-structured questionnaire. Results: The mean age was 50.82 ± 10.12 years in the control group and 50 ± 11.24 years in the intervention group. BCSs in the intervention group demonstrated a significant improvement in attention and concentration (P = 0.02); retention for similar pairs (P = 0.001); recognition (P = 0.01); and visual attention, processing speed, and executive functions (P = 0.01). Intervention group also showed a significant improvement in ADLs (P = 0.04). Overall, the participants in the experimental group were more satisfied (mean = 2.00) as compared to those in the control group (mean = 1.896), which is supported by the observed statistical significant difference in the satisfaction levels of the participants (P = 0.04). Reduction in the levels of anxiety and depression was also noticed in both the groups but it was not significant. Conclusion: Cognitive training interventions package was beneficial for BCSs with CRCI to overcome cognitive impairments.