Adverse effects of Systemic Anti-Cancer Therapy (SACT): A study of patients and health care workers exposed to SACT

Adverse effects of Systemic Anti-Cancer Therapy (SACT): A study of patients and health care workers exposed to SACT | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Adverse effects of Systemic Anti-Cancer Therapy (SACT): A study of patients and health care workers exposed to SACT Sudath Shirley Pathmasiri Warnakulasuriya, Meegoda Kankanange Dona Lalitha Meegoda, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8133233/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Despite the therapeutic effectiveness against cancer, Systemic Anti-Cancer Therapy (SACT) causes a wide range of adverse effects (AEs) among both patients and healthcare workers (HCWs). Methods A retrospective cohort and comparative study were conducted among randomly selected patients (n = 400) and HCWs (n = 360), including nurses, pharmacists, doctors, attendants, and cleaning staff. AEs among HCWs were compared with those in the control group (n = 420). A 50-item structured questionnaire was used to assess the prevalence, frequency, severity, and distress caused by AEs. Results A higher mean number of AEs was reported by patients (17.49 ± 2.87) and exposure group nurses (4.53 ± 2.58). Headaches, dizziness, drowsiness, nausea, skin and ocular irritation, and hair loss are more common among both patients and HCWs. The prevalence of common AEs was associated with the selected patient characteristics, and 75% of patients reported more than sixteen of the twenty common AEs. Among HCWs, nurses in the exposure group reported reproductive-related AEs, and the prevalence of AEs varied significantly across the occupational categories. Conclusions The findings of the study indicate that SACT is associated with a broad spectrum of AEs affecting both patients and HCWs. Therefore, effective strategies are required to manage SACT-associated AEs among patients and to strengthen occupational health and safety measures for HCWs exposed to SACT. Clinical Pharmacology Oncology Toxicology Occupational Medicine Adverse effects healthcare workers occupational exposure patients Systemic Anti-Cancer Therapy (SACT) 1. Introduction Cancer is the generic name for a malignant tumor, which is characterized by uncontrolled cell division and the potential to invade surrounding tissues 1 . Cancer causes one in six deaths (16.8%) globally 2 , and 20 million new cases and 9.7 million deaths were reported in 2022 2 . Over 35 million new cases are predicted by 2050 (77% increment from 2022 3 ). Lung (2.5 million; 12.4% new cases) and female breast cancers (2.3 million cases, 11.6%) are predominant globally 3 , and subsequently followed by colorectal cancer (1.9 million cases, 9.6%), prostate cancer (1.5 million cases, 7.3%), and stomach cancer (970,000 cases, 4.9%) 3 . In Sri Lanka, commonly diagnosed cancers among males include oral, trachea, bronchus, lung, colorectal, esophagus, and prostate cancers, while breast, thyroid, colon, ovarian, and cervical cancers are commonly prevalent among women 4 . The primary goal of cancer treatment is to enhance the quality of life and/or overall survival, and the treatment type depends on the specific cancer diagnosis 5–7 . Surgery, radiotherapy, and various drug therapies (chemotherapy, hormone therapy, targeted therapy, immunotherapy, and antibody-drug conjugates) are widely used treatment modalities 7,8 . Drug therapies that mainly target systemic effects are referred to as Systemic Anti-Cancer Therapy (SACT) and are primarily used to treat cancer 1,9–14 and a few other non-oncology indications (rheumatoid arthritis, lupus, nephritis, multiple sclerosis) 15–17 . SACT is generally combined with surgery and/or radiation therapy for therapeutic advances 8,18 . Many drugs used in SACT exhibit cytotoxic properties 1 , non-selective mechanisms, and a narrow therapeutic index 1,19,20 . Thus, despite therapeutic advances, SACT shows a wide range of AEs. Those AEs are generally classified according to drug groups and their mechanisms 1,21 , as well as presentation time (acute vs. chronic) 22 , and physical presentation 23 . Widely reported AEs among patients include nausea 7,20,24,25 , vomiting 7,20,24,25 , diarrhoea 7,20,24–26 , constipation 7,20,24,26 , mucositis 7,20,24–26 , dysapnea 20,26 , hypersensitivity 20,26 , alopecia 19,21,27–32 , fatigue 20,23,26 , bone marrow suppression and related AEs 7,20–23,25–27 , and organ toxicities (nephro 7,25 -, neuro- 7,26,33 , hepato 7,25 -, cardio 7,25,26 -, pulmonary 25 and ototoxicity 7 ), teratogenicity and reproductive effects 7,21,27 . It is reported that gastrointestinal (GI) AEs are prevalent among 80% of patients 7 , and nausea and vomiting are the most troublesome (the most feared and unpleasant AEs) 34 . Moreover, long-term and delayed AEs are identified as cancer-related fatigue (CRF), cognitive impairment, peripheral neuropathy, cardio, pulmonary, and other organ toxicities, sexual dysfunction, infertility, secondary malignancies, anxiety, distress, depression, and fear of recurrence 23,33 . Despite the AEs/ known black box warnings, SACTs are used against cancer due to the therapeutic advances 1,21,22 , and drug group-specific AEs are outlined in Table 8 in the appendix section. Occupational exposure (chronic low dose and accidental exposure) to SACT causes similar AEs among HCWs, and the first concerns regarding this were raised in the 1970s 14 . Subsequently, a vast body of literature has reported surface, environment, and biological sample contamination with drugs and/ or metabolites 35–37 as well as occupational exposure-related AEs among HCWs 13,19,29–32,38,39 . Widely reported AEs among HCWs include headaches 19,29,30,32 , dizziness 19,29,30,32 , nausea 29,30,32 , hair loss 13,19,29–32 , hypersensitivity (skin, eye, mucus membrane irritation) 19,29–32 , fatigue/ weakness 32 , changes in liver/ kidney/ blood counts, and reproductive and teratogenic outcomes (miscarriage 13,29–31,38,39 , pre-term births, still births 38 , congenital abnormalities 29,30,38 , menstrual cycle irregularities 29–32 , fertility-related issues 29,30 ). Due to those AEs, SACT considers hazardous drugs (HDs). Their hazardous characteristics include carcinogenicity, teratogenicity, or other developmental toxicity, reproductive toxicity, organ toxicity at low doses, and genotoxicity. In addition, new drugs share similar structural or toxicological profiles considered HDs according to these criteria 11–14 . Inhalation and dermal contamination are identified as the main occupational exposure routes of SACT 13,14,19,39,40 . Also, inadvertent ingestion and needle-prick injuries are reported as other exposure methods 11,13,14,40 . To minimize the unnecessary occupational exposure to SACT and related AEs among HCWs, safe handling is vital, and it has undergone a five-level hierarchical control consisting of (1) Elimination, (2) Substitution, (3) Engineering controls, (4) Administrative controls, and (5) Personal Protective Equipment (PPE) 16,41,42 . Ensuring occupational health safety and assessing SACT-related AEs among HCWs remain key concerns. Effective management of SACT-related AEs experienced by patients with cancer is essential to enhance treatment compliance and improve quality of life. Therefore, evaluating AEs among both patients and HCWs is vital for developing and implementing protective strategies. Furthermore, there is a notable lack of national literature on the subject. Therefore, the present study aimed to evaluate AEs of SACT among patients and HCWs. 2. Materials and Methods 2.1. Study participants The study adopted a retrospective cohort design with a comparative analysis of patients and HCWs conducted from January to June 2024. The National Cancer Institute (NCI, Apeksha Hospital, Maharagama) was selected as the study setting for both patients and the SACT-exposed HCW cohort. The NCI is the largest tertiary cancer care institution in Sri Lanka, providing comprehensive screening, diagnostic, and therapeutic services to a substantial cancer patient population with over 60,000 annual inpatient admissions and approximately 14,000 new registrations each year 43 . Therefore, the NCI was considered to provide an adequate and representative sample to achieve the objectives of the present study. To evaluate SACT-associated AEs among patients, adult cancer patients (aged >18 years) who had received SACT at the NCI and attended follow-up cancer treatment clinics were recruited. The required sample size of 422 participants was calculated using Daniel's formula for a prevalence study, with 95% confidence interval (Z = 1.96), an expected prevalence of 0.5, and a margin of error (d) of 0.05. The study adopted the simple random sampling method (following the registry of the patients as the sampling frame). During the study period, 400 volunteer patients were recruited. The study excluded in-ward admissions (due to possible acute complications), patients who experienced acute pain/ complications, psychiatric illness, and oral facial cancer manifestations (due to possible communication-related barriers). To assess the SACT-associated AEs among HCWs, a total of 367 HCWs, including nurses, pharmacists, doctors, attendants, and cleaning staff with a minimum of six months of working experience at NCI, were considered. The sample size was calculated using Daniel's formula for prevalence studies, based on a 95% confidence interval (Z = 1.96, a margin of error of 0.05, and an expected prevalence (p) of 0.68. The anticipated population proportion was derived from a previous study that reported 68% of contact exposure to Methotrexate among HCWs in Iran 44 . From the total eligible sample of 367 HCWs, participants from selected occupational categories (excluding pharmacists) were selected using a simple random sampling method proportionate to the workforce distribution at the NCI. The HCWs’ registry was used as the sampling frame for the randomization. The whole sampling method was applied to recruit pharmacists from the exposure group, as the population at the NCI was relatively small (n = 35). Of these, only thirteen pharmacists were directly involved in handling the SACT preparations at the Chemotherapy Reconstitution Unit (CRU), forming the SACT-exposed pharmacists’ group. The remaining pharmacists who work in units other than the CRU at the NCI were classified as non-exposed pharmacists (group 1). Accordingly, a second group of non-exposed pharmacists (group 2) was recruited from the National Hospital, Sri Lanka (NHSL). During the study period, a total of 360 HCWs from selected occupational categories volunteered to participate as SACT-exposed groups (Table 1: The calculated/ achieved sample size for HCWs). To enhance the validity of the findings, the AEs among HCWs were compared with those of a control group. To ensure comparability between the groups, an equal number of HCWs from each occupational category were included in the SACT non-exposed groups. The NHSL, a major tertiary care institution that primarily provides medical and surgical care, was selected as the study setting for the SACT non-exposed groups. A simple random sampling method was employed, using HCW’s registry as the sampling frame. During the study period, a total of 420 HCWs representing the selected occupational categories volunteered to participate in the non-exposed group (Table 1). Due to possible similar AEs to SACT, HCWs with chronic diseases were excluded from both the exposure and non-exposure groups, and HCWs who had been handling or exposed to SACT (or other HDs) six months ago were excluded from the non-exposure groups. Of 35 pharmacists employed at NCI, 33 volunteered to participate during the study period. However, the exposed group was limited to 13 since it included only those directly involved in drug preparation at the CRU. The remaining 20 pharmacists recruited from NCI were categorized as the non-exposed group (group 1). Additionally, 43 pharmacists were recruited from the NHSL to form the non-exposure group (Group 2). 2.2. Study instrument A pre-tested, fifty-item research questionnaire was used to collect data. The instrument included items assessing the prevalence of AEs (yes/no response) as well as their frequency, severity, and level of distress measured using Likert scales (Table 2). The researcher developed the study instrument based on a review of scientific literature. It was validated for content validity (Content Validity Index [CVI] = 0.9) and internal consistency (Cronbach's alpha = 0.9). 3. Results 3.1. Outcomes among patients who underwent the SACT 3.1.1. Baseline characteristics Among the 400 patients, the majority were male (53.3%), of Sinhalese descent (65.3%), employed (53.8%), and were on SACT (99.3%). The mean age of the participants was 47.3 ± 16.09 years (Table 3). 3.1.2. AEs resulting from SACT Patients reported a wide range of AEs after receiving SACT. Among them, the most frequently reported AEs were headache (96%), dizziness (88%), drowsiness (88.8%), vomiting (82.3%), mouth sores (98.5%), hair loss (95.5%), sore throat (90.3%), gastritis (96.3%), fatigue (100%), lack of energy (100%), dry mouth (87.3%), lack of appetite (99%), diarrhea (71%), abdominal bloating (85.8%), and dysuria (76.8%). Among these, headache, skin changes, mouth sores, hair loss, gastritis, lack of energy and appetite, bloating, and dysuria were reported as occurring "frequently or almost always”. In addition, headaches, drowsiness, skin changes, mouth soreness, gastritis, fatigue, lack of energy, and loss of appetite were most often perceived as "severe and/ or very severe". Mouth sores, lack of energy, and loss of appetite were being reported as “very much” distressing for many participants. A detailed summary of the prevalence, frequency, severity, and distress associated with AEs is presented in Table 09. When considering the most common twenty AEs, all patients experienced more than six AEs. Specifically, 74.8% (n = 299) reported more than sixteen AEs, 20.3% reported 11–15 AEs, and 5% reported 6–10 AEs. Overall, patients experienced a mean of 17.49 + 2.87 AEs per individual (Range 9-20) for commonly reported AEs, demonstrating higher frequency, severity, and distress associated with them (Table 4). The total number of AEs showed a statistically significant association with several patient characteristics at the 95% confidence level. These include age, gender, nationality, religion, primary caregiver, education level, and employment status (p = 0.000 for all). Marital status (p = 0.001) and family income (p = 0.003) were also significantly associated with the total number of AEs. 3.2. Outcomes among HCWs 3.2.1. Baseline characteristics Among both SACT-exposed and non-exposed groups of HCWs, the majority were female (except for the pharmacists in the exposure group, who were responsible for drug preparation at the CRU), Sinhalese, and Buddhist across all occupational categories (SACT-exposed vs. non-exposed HCWs), as presented in Table 10. 3.2.2. Duties and responsibilities of handling SACT HCWs in the exposure group performed multiple roles related to the handling of SACT (Table 5). Nurses were primarily involved in administering a mean of 54.58 ± 80.7 intravenous (IV) chemotherapy preparations to a mean of 35.29 ± 45.33 patients. Pharmacists in the exposure group prepared a mean of 634.62 ± 238.38 drug preparations for 284.62 ± 98.71 patients per day. HCWs in the non-exposure group were not involved in handling SACT or any HDs. 3.2.3. AEs resulting from SACT Compared with the control group, nurses in the exposure groups reported a higher prevalence of several AEs including headache (93.9%), dizziness (64.4%), drowsiness (42.4%), nausea (36.4%), skin irritation (96.2%), ocular irritation (37.1%), hair loss (59.1%) and menstrual cycle irregularity (31.9%) with increased frequency, severity and distress. Table 11 in the Appendix summarizes the prevalence, frequency, severity, and distress of AEs experienced by HCWs, categorized by occupational group and compared to the non-exposed groups. Furthermore, nurses in the exposure group reported reproductive AEs including miscarriages (8.6%, n=10), pre-term labor (3%, n=4), low-birth weight and delayed pregnancy (2.6%, n=3), fetal death and subfertility (1.7%, n=2). Those reproductive AEs were very rare or not reported by exposure and non-exposed groups in other occupational categories. Pharmacists in the exposure group experienced a higher prevalence, frequency, severity, and distress of ocular irritation and hair loss. Additionally, they experienced greater severity and distress associated with headaches and dizziness. Among doctors, attendants, and cleaning staff in the exposure group, the prevalence of AEs is relatively low. However, when AEs occurred, those reported more frequently, with higher severity, and greater distress. These findings indicate that nurses are at greater risk of exposure to SACT-related AEs. The mean number of AEs, along with their frequency, severity, and distress, was calculated for the fifteen prominent AEs (Table 6). Nurses in the exposure group experienced a higher mean number of common AEs (4.53 + 2.58) with increased frequency, severity, and distress compared with the control group. Doctors and cleaning staff in the exposure group also reported elevated mean values for frequency, severity, and distress. Moreover, the mean frequency of common AEs was higher among pharmacists and attendants in the exposure group (Table 6). 3.2.4. Comparison of SACT-related AEs Statistically significant differences in the prevalence of common AEs associated with handling SACT were observed between exposed and non-exposed HCW groups across all occupational categories as determined by the independent sample t-test. Furthermore, the frequency, severity, and distress of AEs were significantly higher among nurses and attendants (Table 7). 4. Discussion Cancer is a global health concern 1 , 2 , 6 . SACT is a widely used and effective treatment modality that improves patients’ quality of life and overall survival 6 , 28 . The Cytotoxic properties of SACT agents are therapeutically beneficial in targeting malignant cells 6 , 45 . However, due to the inherent toxicity of many agents, a wide range of AEs have been reported 1 , 21 , 28 , 45 . While the risk associated with these agents is justified for patients, occupational exposure can have a negative impact on HCWs 12 , 13 , 19 , 31 , 32 , 35 , 38 , 39 , 41 . Accordingly, the current study aimed to assess AEs among patients receiving SACT and among HCWs involved in handling these agents, in comparison with a non-exposed cohort of HCWs. The findings are expected to contribute to improving the management of AEs among patients and to strengthening the occupational health and safety among HCWs. The present study identified headaches, dizziness, drowsiness, vomiting, mouth sores, hair loss, sore throat, gastritis, dry mouth, loss of appetite, diarrhoea, bloating, and dysuria as common AEs associated with SACT. Previous literature similarly reported that GI complications, hypersensitivity reactions, skin disorders, hair loss, tumour lysis syndrome, and specific organ toxicities are the most frequent AEs of SACT 1 , 7 , 21 – 25 , 28 , 34 , 46 . Generally, the prevalence of GI AEs is high (approximately 80% 7 ). Chemotherapy-induced nausea and Vomiting (CINV) is considered the most distressing and difficult to manage complication, persisting in about 40% of patients despite prophylactic measures 34 . Consistent with the theoretical evidence, an empirical study in Malaysian patients reported that CINV was the most common and distressing symptom, particularly among those who received moderately or highly emetogenic chemotherapy 23 . In the same cohort, the prevalence of dry mouth or thirst, hair loss, tiredness or weakness, loss of appetite, coldness, numbness in fingers or toes, confusion, loss of concentration, sadness, depression, and reduced sense of touch was notably high 23 . In the present study, fatigue and lack of energy were reported by all patients. Similarly, prospective studies conducted in Australia (85%) 26 and India (87%) 20 reported a considerably high prevalence of fatigue. CRF has been described as both a long-term and delayed AE of SACT as well as a symptom associated with cancer itself 23 . Furthermore, observational studies reported a high rate of GI AEs, including diarrhoea (74% 26 , 49.4% 20 ), constipation (74% 26 ), and loss of appetite (71.4%) 20 . The present study revealed that headache, skin changes, mouth sores, hair loss, gastritis, lack of energy, loss of appetite, bloating, and dysuria were among the most frequently reported AEs of SACT. In addition, headaches, drowsiness, skin changes, mouth soreness, gastritis, fatigue, and lack of energy were predominantly rated as severe or very severe. Mouth sores, lack of energy, and loss of appetite were identified as the most distressing AEs for most patients. In contrast, an Indian study reported that nausea, vomiting, diarrhoea, constipation, mucositis, dyspnoea, rash, and chest pain were generally non-severe²⁰. When considering the twenty most common AEs observed in the present study, patients experienced a minimum of nine AEs, while the majority (74.8%) experienced more than sixteen AEs. The mean prevalence of common AEs (17.49 ± 2.87, range 9–20) indicates a high overall prevalence, frequency, severity, and distress levels. Notably, all patients in the current study reported experiencing more than six AEs, where approximately two-thirds of cancer survivors in India (66.7%)²⁰ and Australia (67%)²⁶ reported more than six AEs, with at least one AE present in 97.4% and 86% of participants in those respective studies. These findings suggest a higher prevalence and burden of AEs among patients in the present study compared with the previously reported data. The number of common AEs was associated with selected personal characteristics (age, gender, nationality, religion, primary caregiver, education level, employment, marital status, and family income). In contrast to the present findings, an Australian study did not report statistically significant associations between AEs and gender, education, socio-economic status, or cancer stage 26 . Similarly, in a retrospective cohort study conducted in India, no significant associations were found between AE frequency and age, socio-economic status, Body Mass Index (BMI), comorbidity, chemotherapy intent, or disease stage 20 . However, other studies have demonstrated significant associations between CINV and gender, chemotherapy regimen 23 , frequency of AEs, and cancer types 20 . The current study did not explore several potential contributing factors, such as drug regimen, nutritional status, alternative medicines, and spiritual aspects. The omission of these variables is acknowledged as a limitation of the present study. Considering the findings among HCWs, the female workforce, the Sinhalese nation, and the Buddhist religion were common in the present study. A prominent female workforce in handling SACT has been similarly reported in other countries, particularly among nurses 19 , 47 , 48 , pharmacists 48 , 49 , and pharmacy technicians 39 . In the present study, nurses in the exposure groups were primarily responsible for administering chemotherapy drugs, reconstituting and dissolving drugs, providing direct patient care, and handling waste materials. Pharmacists were involved mainly in drug preparation, while cleaning and support staff were responsible for environmental sanitation and patient support activities, respectively. Doctors rarely handle SACT in the present study. Comparable role distribution has been documented internationally, with nurses predominantly administering chemotherapy 30 , 47 , 48 , 50 , pharmacists preparing SACT agents 30 , 51 , and other occupational groups responsible for tasks such as cleaning, transport, and waste disposal 30 . Compared with the control group, nurses in the exposure group reported a significantly higher prevalence of headaches, dizziness, drowsiness, nausea, skin irritation, ocular irritation, hair loss, and menstrual cycle irregularity, with increased frequency, severity, and distress levels. Moreover, exposure-group nurses experienced reproductive teratogenic effects such as miscarriages, pre-term labor, low birth weight, delayed pregnancy, fetal death, and subfertility. In contrast, these reproductive AEs were rarely or not reported among non-exposed groups of nurses and HCWs in other occupational categories. Many agents used in SACT are recognized as teratogenic, carcinogenic, and mutagenic 30 . Even minimal exposure can lead to harmful effects 30 . Thus, these substances are classified as HDs and are associated with a broad spectrum of AEs among HCWs 30 , 48 . Reported acute and chronic AEs include headache 19 , 29 , 30 , dizziness 19 , 29 , 30 , nausea, vomiting, diarrhea 29 , 30 , mouth sores 32 , allergy 19 , 29 – 32 , alopecia 19 , 29 – 32 , nail hyperpigmentation 29 , infertility 29 , 30 , 48 , miscarriages 13 , 29 – 31 , 38 , 39 , stillbirths 29 , 38 , menstrual cycle changes 29 – 32 , ectopic pregnancies 29 , preterm and low-birth-weight 29 , congenital anomalies 29 , 30 , 38 , learning disabilities 29 , abnormal blood counts 30 , 31 , liver 31 , kidney damage 30 , 31 , and other organ damage 30 , DNA changes 31 , frequent infections 31 , sore throat 19 , 30 , fatigue and weakness 32 . A meta-analysis reported a significantly increased risk of spontaneous abortions, stillbirth, and congenital malformations among nurses who handled SACT during pregnancy 38 . Similarly, a comparative analysis conducted in Egypt found a higher rate of impaired fertility and oral ulcers among nurses and pharmacists exposed to SACT 48 . As outlined above, a wide range of teratogenic and reproductive AEs are reported by HCWs with SACT. Headache was reported as the most common AE among nurses and nursing assistants in a study conducted in Lativa 19 and it affected only 37.25% of participants 19 . In contrast, the prevalence of headaches in the present study was substantially higher at 93.9%. Other studies have similarly reported increased prevalence of headaches, dizziness, nausea, or a combination of these symptoms among HCWs handling SACT 30 . Compared with the controls, Turkish nurses reported statistically significantly higher rates of weakness, hair loss, and fatigue 32 . Also, hair loss and dizziness were statistically significant among nurses who administered antineoplastic agents 32 . Several factors have been identified as contributing to increased occupational exposure to SACT and related daily activities 29 , 38 insufficient precautions 32 , 52 , insufficient facilities 29 , accidental spills 29 , 52 , limited knowledge on safe handling 52 , increased patient and workload 52 , The involvement of nurses in multiple roles and suboptimal safety practices may similarly contribute to the high prevalence of AEs observed in the present study. However, safety precautions were not evaluated in the current study, representing a limitation. Identification of local factors contributing to occupational exposure and AE is therefore recommended. Among other occupational groups, including doctors, pharmacists, attendants, and cleaning staff, the exposure groups reported increased frequency of getting SACT-associated AEs and statistical significance compared to non-exposed groups. In support, a study conducted in Egypt reported increased prevalence of impaired fertility and oral ulcers among pharmacists exposed to SACT 48 . Nevertheless, there is limited literature examining the prevalence of AEs in these occupational categories relative to nurses. 5. Conclusions The present study highlights that SACT is associated with a wide range of AEs among both patients and HCWs. The patient-reported AEs should be systematically integrated into routine clinical practice as those AEs represent a significant concern for patient safety, treatment compromise, organ damage, secondary malignancy risk, financial burden, psychological distress, and reduced quality of life. Innovative strategies such as enhancing supportive care measures, safe alternative treatments, early detection, and management of AEs are essential to mitigate these risks. Among HCWs, nurses predominantly reported the highest prevalence of SACT-related AEs. Emphasizing the occupational health implications of handling cytotoxic agents. Regular surveillance, periodic studies, and the identification of additional contributing factors are crucial for informing evidence-based interventions. Strengthening institutional policies and implementing comprehensive occupational safety programs remain vital to protecting the health and well-being of HCWs involved in SACT administration. 6. Limitations The mechanism of action of the drug, or drug regimen, can account for many AEs associated with SACT. However, the present study did not evaluate the drug regimen, treatment duration, or chemotherapy cycles and their associations with AEs. Moreover, patients receiving SACT as inpatients may experience and report AEs with greater intensity, frequency, severity, or distress compared to outpatients. Additionally, recall bias cannot be excluded, as patients may have underreported or misremembered their symptoms. These factors represent limitations related to the patient sample. Among HCWs, a relatively high prevalence of common AEs was reported even among those not directly exposed to SACT, except nurses. These findings may be influenced by unexamined variables such as exposure to other HDs, presence of chronic diseases, workload, number of night shifts, fatigue, and environmental factors. The lack of evaluation of these potential confounders constitutes another limitation of the present study. Furthermore, the exposure group of HCWs was limited to those employed at the NCI; including HCWs from other regional centers across Sri Lanka would be advantageous. However, such expansion should ensure sample homogeneity regarding workload exposure level and AE profile. If maintaining homogeneity across centers is not feasible, integrating a qualitative component could provide valuable insight into contextual and experiential factors influencing occupational exposure and ARE perception. Appendix AEs – Adverse Effects AKI – Acute Kidney Insufficiency BMI – Body Mass Index CHF – Congestive Heart Failure CINV – Chemotherapy Induced Nausea and Vomiting CKD – Chronic Kidney Disease CRF – Cancer-Related Fatigue CRU – Chemotherapy Reconstitution Unit CVD – Cardio-Vascular Disease CVI – Content Validity Index DNA – Deoxyribonucleic acid GI – Gastrointestinal HDs – Hazardous drugs HCWs – Healthcare workers HF – Heart Failure HUS – Hemolytic Uremic Syndrome IV – Intravenous MI – Myocardial Infarction MRI – Medical Research Institute NDI – Nephrogenic Diabetes Insipidus NHSL – National Hospital Sri Lanka NCI – National Cancer Institute SACT – Systemic Anti-Cancer Therapy SIADH – Syndrome of Inappropriate Anti-Diuretic Hormone Secretion SOS – Sinusoidal Obstruction Syndrome TMA – Thrombotic microangiopathy VOD – Veno-Occlusive Disease Abbreviations AEs Adverse Effects AKI Acute Kidney Insufficiency BMI Body Mass Index CHF Congestive Heart Failure CINV Chemotherapy Induced Nausea and Vomiting CKD Chronic Kidney Disease CRF Cancer–Related Fatigue CRU Chemotherapy Reconstitution Unit CVD Cardio–Vascular Disease CVI Content Validity Index DNA Deoxyribonucleic acid GI Gastrointestinal HDs Hazardous drugs HCWs Healthcare workers HF Heart Failure HUS Hemolytic Uremic Syndrome IV Intravenous MI Myocardial Infarction MRI Medical Research Institute NDI Nephrogenic Diabetes Insipidus NHSL National Hospital Sri Lanka NCI National Cancer Institute SACT Systemic Anti–Cancer Therapy SIADH Syndrome of Inappropriate Anti–Diuretic Hormone Secretion SOS Sinusoidal Obstruction Syndrome TMA Thrombotic microangiopathy VOD Veno–Occlusive Disease Declarations Ethics approval and consent to participate: The study was conducted in accordance with the principles of the Declaration of Helsinki, and it was approved by the Ethics Review Committees of the University of Sri Jayewardenepura (35/21) and the Medical Research Institute (25/2020), Sri Lanka. Consent for publication: Participants’ consent was obtainedto publish research findings . Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: “The authors declare no conflicts of interest.” Authors must identify and declare any personal circumstances or interests that may be perceived as inappropriately influencing the representation or interpretation of reported research results”. Funding: This research was funded by the Medical Research Institute (MRI), Sri Lanka (25/2020) and the University of Sri Jayewardenepura (RC/URG/AHS/2024/94). Authors' contributions: Sudath S.P. Warnakulasuriya and Sudheera S. Jayasinghe conceived this study. Samanthi N. Senarath searched the literature, collected data and initially drafted the paper. Except the Samanthi N. Senarath, all authors supervised the whole process and revised the manuscript. Dharshana De Silva and Wasantha K. Rathnayake facilitated resources, and Lalitha Meegoda was involved in funding acquisition. Lalitha Meegoda and Sudath S.P Warnakulasuriya were involved in the project administration. Acknowledgements: National Cancer Institute (NCI) (Apeksha Hospital), Sri Lanka References Basak D, Arrighi S, Darwiche Y, Deb S (2021) Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile. Life 12(48). 10.3390/life12010048 Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229–263. 10.3322/caac.21834 World Health Orgnization. Global cancer burden growing, amidst mounting need for services. Updated February 1, 2024. 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Pediatr Blood Cancer 52(4):497–502. 10.1002/pbc 21835 Chan HK, Ismail S (2014) Side effects of chemotherapy among cancer patients in a Malaysian general hospital: Experiences, perceptions, and informational needs from clinical pharmacists. Asian Pac J Cancer Prev 15(13):5305–5309. http://dx.doi.org/10.7314/APJCP.2014.15.13.5305 McQuade RM, Stojanovska V, Abalo R, Bornstein JC, Nurgali K (2016) Chemotherapy-induced constipation and diarrhoea: pathophysiology, current and emerging treatments. 7(November):1–14. 10.3389/fphar 2016.00414 Lai E, Persano M, Dubois M et al (2022) Drug-related toxicity in breast cancer patients: a new path towards tailored treatment? A narrative review. Precis Cancer Med 5:15. https://dx.doi.org/10.21037/pcm-21-38 Pearce A, Haas M, Viney R et al (2017) Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS ONE 12(10):1–12. https://doi.org/10.1371/journal.pone.0184360 Rang HP, Ritter JM, Flower RJ, Henderson (2016) G.RANG & DALE'S Pharmacology. Elsevier Kluwer W, Williams L, Wilkins L (2009) Clinical Pharmacology . 3rd ed Eisenberg S (2016) A Call to Action for Hazardous Drug Safety: Where we have been and where we are now. Clin J Oncol Nurs 20(4):377–384. 10.1188/16.CJON.20-04AP Simons A, Toland S (2017) Perceived adverse effects from handling systemic anti-cancer therapy agents. Br J Nurs 26(16):S38–S44. 10.12968/bjon.2017.26.16.s38 Samra GHE, Gaballah IM, Rashed LA, Shehata RA (2018) Adverse health effects of occupational exposure to cisplatin among healthcare workers. Egypt J Occup Med 42(2):181–194. 10.21608/ejom.2018.6802 Unsar S, Kurt S, Kostak AM, Yaman R, Özcan M (2016) Determination of antineoplastic drug exposure of nurses at a university hospital. Int J Caring Sci 9(1):314–320. https://www.internationaljournalofcaringsciences.org/docs/30_Unsar_original_9_1.pdf Patel UH, Mir MA, Sivik JK et al (2015) Central neurotoxicity of immunomodulatory drugs in multiple myeloma. Hematol Rep 7(1):12–14. 10.4081/hr.2015.5704 Smith P, Lavery A, Turkington RC (2020) An overview of acute gastrointestinal side effects of systemic anti-cancer therapy and their management. Best Pract Res Clin Gastroenterol 48–49. 10.1016/j.bpg.2020.101691 Leso V, Sottani C, Santocono C, Russo F, Grignani E, Iavicoli I (2022) Exposure to Antineoplastic drugs in occupational settings: a systematic review of biological monitoring data. Int J Environ Res Public Health 19(3737):1–25. 10.3390/ijerph19063737 Palamini M, Dufour A, Therrien R et al (2020) Quantification of healthcare workers’ exposure to cyclophosphamide, ifosfamide, methotrexate, and 5-fluorouracil by 24-h urine assay: A descriptive pilot study. J Oncol Pharm Pract 26(8):1864–1870. 10.1177/1078155220907129 Le LMM, Reitter D, Sophie H et al (2017) Safety Analysis of Occupational Exposure of Healthcare Workers to Residual Contaminants of Cytotoxic Drugs Using the FMECA Security Approach. Sci Total Environ May599–600. 10.1016/j.scitotenv.2017.05.066 Liu S, Huang Y, Huang H et al (2023) Influence of occupational exposure to antineoplastic agents on adverse pregnancy outcomes among nurses: A meta-analysis. Nurs Open 10(9):5827–5837. 10.1002/nop2.1853 Rocha SD, Gomes ANH, Zen PRG, Bica CG (2020) Handling of antineoplastic drugs: A health concern among health care workers. Rev Bras Med do Trab 18(4):407–414. 10.47626/1679-4435-2020-527 United States Pharmacopoeia. USP General Chapter Hazardous Drugs: Handling in Health Care Settings. Updated January 21 (2025) Accessed March 20, 2025. https://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare Polovich M (2020) USP General Chapter : Considerations for Oncology Nursing Practice. Semin Oncol Nurs 36:1–20. 10.1016/j.soncn.2020.151022 Work Safe (2023) Accessed December 21, 2024. https://www.worksafebc.com/en/resources/health-safety/books-guides/safe-work-practices-handling-lead?lang=en Hospital Performance Report- (2019) Medical Statistics Unit, Apeksha Hospital (National Cancer Institute), Maharagama, Sri Lanka. 2019. https://www.ncisl.health.gov.lk/wp-content/uploads/2020/03/Hospital-Performance-Report-2019.pdf Shahrasbi AA, Afshar M, Shokraneh F et al (2014) Risks to health professionals from hazardous drugs in Iran: A pilot study of understanding of the healthcare team to occupational exposure to cytotoxics. EXCLI J 13:491–501 Srivastava N, Majumder A, Rastogi S (2019) Adverse Drug Reactions of Anti-Cancer Drugs and their Management. Rev 1(1):19–27 Nurgali K, Jagoe RT, Abalo R, Editorial (2018) Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae? Front Pharmacol 22(09):245. 10.3389/fphar.2018.00245 Sargidy AAW, Yahia A, Ahmad M et al (2022) Knowledge of safe handling, administration, and waste management of chemotherapeutic drugs among oncology nurses working at Khartoum Oncology Hospital, Sudan. PeerJ 10. 10.7717/peerj.14173 Elshaer N (2017) Adverse health effects among nurses and clinical pharmacists handling antineoplastic drugs: Adherence to exposure control methods. J Egypt Public Health Assoc 92(3):144–155. 10.21608/EPX.2018.16148 Kadhim MQ, Kadhim DJ (2024) Assessment of the Knowledge and Practice on Safe Handling of Anticancer Drugs among Pharmacists in Iraqi Healthcare Settings. Al-Rafidain J Med Sci 7(1):85–92. 10.54133/ajms.v7i1.1040 Zakaria MM, Alaa SM, Desoky GM (2022) Oncology Nurses’ Knowledge and Practices regarding Safe Administration of Intravenous Chemotherapy. Egypt J Heal Care 13(1):1218–1231. 10.21608/ejhc.2022.225111 Campos D, Silva I, Rego M, Correia P, Moreira F (2024) Characterization of education, technical practices and attitudes of Portuguese pharmacy technicians towards manipulation of cytotoxic drugs. J Oncol Pharm Pract 30(5):893–901. 10.1177/10781552231190025 Abu-Alhaija D, Bakas T, Shaughnessy E, Miller E (2023) The Factors That Influence Chemotherapy Exposure Among Nurses: An Integrative Review. Work Heal Saf 71(5):212–227. 10.1177/21650799221140583 Xiangyu Meng Y, Lei X, Zhang K, Sun Liming Zhang, Zhifei Wang Cancer immunotherapy Classification, therapeutic mechanisms, and nanomaterial-based synergistic therapy. Appl Mater Today (2021) ;24:101149. https://doi.org/10.1016/j.apmt.2021.101149 Tables Tables 1 to 7 are available in the Supplementary Files section Additional Declarations The authors declare no competing interests. Supplementary Files Appendix.docx Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Introduction","content":"\u003cp\u003eCancer is the generic name for a malignant tumor, which is characterized by uncontrolled cell division and the potential to invade surrounding tissues\u003csup\u003e1\u003c/sup\u003e. Cancer causes one in six deaths (16.8%) globally\u003csup\u003e2\u003c/sup\u003e, and 20 million new cases and 9.7 million deaths were reported in 2022\u003csup\u003e2\u003c/sup\u003e. Over 35 million new cases are predicted by 2050 (77% increment from 2022\u003csup\u003e3\u003c/sup\u003e). Lung (2.5 million; 12.4% new cases) and female breast cancers (2.3 million cases, 11.6%) are predominant globally\u003csup\u003e3\u003c/sup\u003e, and subsequently followed by colorectal cancer (1.9 million cases, 9.6%), prostate cancer (1.5 million cases, 7.3%), and stomach cancer (970,000 cases, 4.9%)\u003csup\u003e3\u003c/sup\u003e. In Sri Lanka, commonly diagnosed cancers among males include oral, trachea, bronchus, lung, colorectal, esophagus, and prostate cancers, while breast, thyroid, colon, ovarian, and cervical cancers are commonly prevalent among women\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe primary goal of cancer treatment is to enhance the quality of life and/or overall survival, and the treatment type depends on the specific cancer diagnosis\u003csup\u003e5\u0026ndash;7\u003c/sup\u003e. Surgery, radiotherapy, and various drug therapies (chemotherapy, hormone therapy, targeted therapy, immunotherapy, and antibody-drug conjugates) are widely used treatment modalities\u003csup\u003e7,8\u003c/sup\u003e. Drug therapies that mainly target systemic effects are referred to as Systemic Anti-Cancer Therapy (SACT) and are primarily used to treat cancer\u003csup\u003e1,9\u0026ndash;14\u003c/sup\u003e and a few other non-oncology indications (rheumatoid arthritis, lupus, nephritis, multiple sclerosis)\u003csup\u003e15\u0026ndash;17\u003c/sup\u003e. SACT is generally combined with surgery and/or radiation therapy for therapeutic advances\u003csup\u003e8,18\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eMany drugs used in SACT exhibit cytotoxic properties\u003csup\u003e1\u003c/sup\u003e, non-selective mechanisms, and a narrow therapeutic index\u003csup\u003e1,19,20\u003c/sup\u003e. Thus, despite therapeutic advances, SACT shows a wide range of AEs. Those AEs are generally classified according to drug groups and their mechanisms\u003csup\u003e1,21\u003c/sup\u003e, as well as presentation time (acute vs. chronic)\u003csup\u003e22\u003c/sup\u003e, and physical presentation\u003csup\u003e23\u003c/sup\u003e. Widely reported AEs among patients include nausea\u003csup\u003e7,20,24,25\u003c/sup\u003e, vomiting\u003csup\u003e7,20,24,25\u003c/sup\u003e, diarrhoea\u003csup\u003e7,20,24\u0026ndash;26\u003c/sup\u003e, constipation\u003csup\u003e7,20,24,26\u003c/sup\u003e, mucositis\u003csup\u003e7,20,24\u0026ndash;26\u003c/sup\u003e, dysapnea\u003csup\u003e20,26\u003c/sup\u003e, hypersensitivity\u003csup\u003e20,26\u003c/sup\u003e, alopecia\u003csup\u003e19,21,27\u0026ndash;32\u003c/sup\u003e, fatigue\u003csup\u003e20,23,26\u003c/sup\u003e, bone marrow suppression and related AEs\u003csup\u003e7,20\u0026ndash;23,25\u0026ndash;27\u003c/sup\u003e, and organ toxicities (nephro\u003csup\u003e7,25\u003c/sup\u003e-, neuro-\u003csup\u003e7,26,33\u003c/sup\u003e, hepato\u003csup\u003e7,25\u003c/sup\u003e-, cardio\u003csup\u003e7,25,26\u003c/sup\u003e-, pulmonary\u003csup\u003e25\u003c/sup\u003e and ototoxicity\u003csup\u003e7\u003c/sup\u003e), teratogenicity and reproductive effects\u003csup\u003e7,21,27\u003c/sup\u003e. It is reported that\u0026nbsp;gastrointestinal (GI) AEs are prevalent among 80% of patients\u003csup\u003e7\u003c/sup\u003e, and nausea and vomiting are the most troublesome (the most feared and unpleasant AEs)\u003csup\u003e34\u003c/sup\u003e. Moreover, long-term and delayed AEs are identified as cancer-related fatigue (CRF), cognitive impairment, peripheral neuropathy, cardio,\u0026nbsp;pulmonary, and other organ toxicities, sexual dysfunction, infertility, secondary malignancies, anxiety, distress, depression, and fear of recurrence\u003csup\u003e23,33\u003c/sup\u003e. Despite the AEs/ known black box warnings, SACTs are used against cancer due to the therapeutic advances\u003csup\u003e1,21,22\u003c/sup\u003e, and drug group-specific AEs are outlined in Table 8 in the appendix section.\u003c/p\u003e\n\u003cp\u003eOccupational exposure (chronic low dose and accidental exposure) to SACT causes similar AEs among HCWs, and the first concerns regarding this were raised in the 1970s\u003csup\u003e14\u003c/sup\u003e. Subsequently, a vast body of literature has reported surface, environment, and biological sample contamination with drugs and/ or metabolites\u003csup\u003e35\u0026ndash;37\u003c/sup\u003e as well as occupational exposure-related AEs among HCWs\u003csup\u003e13,19,29\u0026ndash;32,38,39\u003c/sup\u003e. Widely reported AEs among HCWs include headaches\u003csup\u003e19,29,30,32\u003c/sup\u003e, dizziness\u003csup\u003e19,29,30,32\u003c/sup\u003e, nausea\u003csup\u003e29,30,32\u003c/sup\u003e, hair loss\u003csup\u003e13,19,29\u0026ndash;32\u003c/sup\u003e, hypersensitivity (skin, eye, mucus membrane irritation)\u003csup\u003e19,29\u0026ndash;32\u003c/sup\u003e, fatigue/ weakness\u003csup\u003e32\u003c/sup\u003e, changes in liver/ kidney/ blood counts, and reproductive and teratogenic outcomes (miscarriage\u003csup\u003e13,29\u0026ndash;31,38,39\u003c/sup\u003e, pre-term births, still births\u003csup\u003e38\u003c/sup\u003e, congenital abnormalities\u003csup\u003e29,30,38\u003c/sup\u003e, menstrual cycle irregularities\u003csup\u003e29\u0026ndash;32\u003c/sup\u003e, fertility-related issues\u003csup\u003e29,30\u003c/sup\u003e).\u003c/p\u003e\n\u003cp\u003eDue to those AEs, SACT considers hazardous drugs (HDs). Their hazardous characteristics include carcinogenicity, teratogenicity, or other developmental toxicity, reproductive toxicity, organ toxicity at low doses, and genotoxicity. In addition, new drugs share similar structural or toxicological profiles considered HDs according to these criteria\u003csup\u003e11\u0026ndash;14\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInhalation and dermal contamination are identified as the main occupational exposure routes of SACT\u003csup\u003e13,14,19,39,40\u003c/sup\u003e. Also, inadvertent ingestion and needle-prick injuries are reported as other exposure methods\u003csup\u003e11,13,14,40\u003c/sup\u003e. To minimize the unnecessary occupational exposure to SACT and related AEs among HCWs, safe handling is vital, and it has undergone a five-level hierarchical control consisting of (1) Elimination, (2) Substitution, (3) Engineering controls, (4) Administrative controls, and (5) Personal Protective Equipment (PPE)\u003csup\u003e16,41,42\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eEnsuring occupational health safety and assessing SACT-related AEs among HCWs remain key concerns. Effective management of SACT-related AEs experienced by patients with cancer is essential to enhance treatment compliance and improve quality of life. Therefore, evaluating AEs among both patients and HCWs is vital for developing and implementing protective strategies. Furthermore, there is a notable lack of national literature on the subject. Therefore, the present study aimed to evaluate AEs of SACT among patients and HCWs.\u0026nbsp;\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1. Study participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study adopted a retrospective cohort design with a comparative analysis of patients and HCWs conducted from January to June 2024. The National Cancer Institute (NCI, Apeksha Hospital, Maharagama) was selected as the study setting for both patients and the SACT-exposed HCW cohort. The NCI is the largest tertiary cancer care institution in Sri Lanka, providing comprehensive screening, diagnostic, and therapeutic services to a substantial cancer patient population with over 60,000 annual inpatient admissions and approximately 14,000 new registrations each year\u003csup\u003e43\u003c/sup\u003e. Therefore, the NCI was considered to\u0026nbsp;provide an adequate and representative sample to achieve the objectives of the present study.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo evaluate SACT-associated AEs among patients, adult cancer patients (aged \u0026gt;18 years) who had received SACT at the NCI and attended follow-up cancer treatment clinics were recruited. The required sample size of 422 participants was calculated using Daniel\u0026apos;s formula for a prevalence study, with 95% confidence interval (Z = 1.96), an expected prevalence of 0.5, and a margin of error (d) of 0.05. The study adopted the simple random sampling method (following the registry of the patients as the sampling frame). During the study period, 400 volunteer patients were recruited. The study excluded in-ward admissions (due to possible acute complications), patients who experienced acute pain/ complications, psychiatric illness, and oral facial cancer manifestations (due to possible communication-related barriers).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assess the SACT-associated AEs among HCWs, a total of 367 HCWs, including nurses, pharmacists, doctors, attendants, and cleaning staff with a minimum of six months of working experience at NCI, were considered. The sample size was calculated using Daniel\u0026apos;s formula for prevalence studies, based on a 95% confidence interval (Z = 1.96, a margin of error of 0.05, and an expected prevalence (p) of 0.68. The anticipated population proportion was derived from a previous study that reported 68% of contact exposure to Methotrexate among HCWs in Iran\u003csup\u003e44\u003c/sup\u003e. From the total eligible sample of 367 HCWs, participants from selected occupational categories (excluding pharmacists) were selected using a simple random sampling method proportionate to the workforce distribution at the NCI.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe HCWs\u0026rsquo; registry was used as the sampling frame for the randomization. The whole sampling method was applied to recruit pharmacists from the exposure group, as the population at the NCI was relatively small (n = 35). Of these, only thirteen pharmacists were directly involved in handling the SACT preparations at the Chemotherapy Reconstitution Unit (CRU), forming the SACT-exposed pharmacists\u0026rsquo; group. The remaining pharmacists who work in units other than the CRU at the NCI were classified as non-exposed pharmacists (group 1). Accordingly, a second group of non-exposed pharmacists (group 2) was recruited from the National Hospital, Sri Lanka (NHSL). During the study period, a total of 360 HCWs from selected occupational categories volunteered to participate as SACT-exposed groups\u0026nbsp;(Table 1: The calculated/ achieved sample size for HCWs). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo enhance the validity of the findings, the AEs among HCWs were compared with those of a control group. To ensure comparability between the groups, an equal number of HCWs from each occupational category were included in the SACT non-exposed groups. The NHSL, a major tertiary care institution that primarily provides medical and surgical care, was selected as the study setting for the SACT non-exposed groups. A simple random sampling method was employed, using HCW\u0026rsquo;s registry as the sampling frame. During the study period, a total of\u0026nbsp;420 HCWs\u0026nbsp;representing the selected occupational categories\u0026nbsp;volunteered\u0026nbsp;to participate in the non-exposed group\u0026nbsp;(Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDue to possible similar AEs to SACT, HCWs with chronic diseases were excluded from both the exposure and non-exposure groups, and HCWs who had been handling or exposed to SACT (or other HDs) six months ago were excluded from the non-exposure groups. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf 35 pharmacists employed at NCI, 33 volunteered to participate during the study period. However, the exposed group was limited to 13 since it included only those directly involved in drug preparation at the CRU. The remaining 20 pharmacists recruited from NCI were categorized as the non-exposed group (group 1). Additionally, 43 pharmacists were recruited from the NHSL to form the non-exposure group (Group 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2. Study instrument\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA pre-tested, fifty-item research questionnaire was used to collect data. The instrument included items assessing the prevalence of AEs (yes/no response) as well as their frequency, severity, and level of distress measured using Likert scales (Table 2). The researcher developed the study instrument based on a review of scientific literature. It was validated for content validity (Content Validity Index [CVI] = 0.9) and internal consistency (Cronbach\u0026apos;s alpha = 0.9).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1. Outcomes among patients who underwent the SACT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBaseline characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 400 patients, the majority were male (53.3%), of Sinhalese descent (65.3%), employed (53.8%), and were on SACT (99.3%). The mean age of the participants was 47.3 \u0026plusmn; 16.09 years (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.2. AEs resulting from SACT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients reported a wide range of AEs after receiving SACT. Among them, the most frequently reported AEs were headache (96%), dizziness (88%), drowsiness (88.8%), vomiting (82.3%), mouth sores (98.5%), hair loss (95.5%), sore throat (90.3%), gastritis (96.3%), fatigue (100%), lack of energy (100%), dry mouth (87.3%), lack of appetite (99%), diarrhea (71%), abdominal bloating (85.8%), and dysuria (76.8%). Among these, headache, skin changes, mouth sores, hair loss, gastritis, lack of energy and appetite, bloating, and dysuria were reported as occurring \u0026quot;frequently or almost always\u0026rdquo;. In addition, headaches, drowsiness, skin changes, mouth soreness, gastritis, fatigue, lack of energy, and loss of appetite were most often perceived as \u0026quot;severe and/ or very severe\u0026quot;. Mouth sores, lack of energy, and loss of appetite were being reported as \u0026ldquo;very much\u0026rdquo; distressing for many participants. A detailed summary of the prevalence, frequency, severity, and distress associated with AEs is presented in Table 09.\u003c/p\u003e\n\u003cp\u003eWhen considering the most common twenty AEs, all patients experienced more than six AEs. Specifically, 74.8% (n = 299) reported more than sixteen AEs, 20.3% reported 11\u0026ndash;15 AEs, and 5% reported 6\u0026ndash;10 AEs. Overall, patients experienced a mean of 17.49\u003cu\u003e+\u003c/u\u003e2.87 AEs per individual (Range 9-20) for commonly reported AEs, demonstrating higher frequency, severity, and distress associated with them (Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe total number of AEs showed a statistically significant association with several patient characteristics at the 95% confidence level. These include age, gender, nationality, religion, primary caregiver, education level, and employment status (p = 0.000 for all). Marital status (p = 0.001) and family income (p = 0.003) were also significantly associated with the total number of AEs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eOutcomes among HCWs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1. Baseline characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong both SACT-exposed and non-exposed groups of HCWs, the majority were female (except for the pharmacists in the exposure group, who were responsible for drug preparation at the CRU), Sinhalese, and Buddhist across all occupational categories (SACT-exposed vs. non-exposed HCWs), as presented in Table 10. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.2. Duties and responsibilities of handling SACT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHCWs in the exposure group performed multiple roles related to the handling of SACT (Table 5). Nurses were primarily involved in administering a mean of 54.58 \u0026plusmn; 80.7 intravenous (IV) chemotherapy preparations to a mean of 35.29 \u0026plusmn; 45.33 patients. Pharmacists in the exposure group prepared a mean of 634.62 \u0026plusmn; 238.38 drug preparations for 284.62 \u0026plusmn; 98.71 patients per day. HCWs in the non-exposure group were not involved in handling SACT or any HDs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.3. AEs resulting from SACT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with the control group, nurses in the exposure groups reported a higher prevalence of several AEs including headache (93.9%), dizziness (64.4%), drowsiness (42.4%), nausea (36.4%), skin irritation (96.2%), ocular irritation (37.1%), hair loss (59.1%) and menstrual cycle irregularity (31.9%) with increased frequency, severity and distress. Table 11 in the Appendix summarizes the prevalence, frequency, severity, and distress of AEs experienced by HCWs, categorized by occupational group and compared to the non-exposed groups.\u003c/p\u003e\n\u003cp\u003eFurthermore, nurses in the exposure group reported reproductive AEs including miscarriages (8.6%, n=10), pre-term labor (3%, n=4), low-birth weight and delayed pregnancy (2.6%, n=3), fetal death and subfertility (1.7%, n=2). Those reproductive AEs were very rare or not reported by exposure and non-exposed groups in other occupational categories. Pharmacists in the exposure group experienced a higher prevalence, frequency, severity, and distress of ocular irritation and hair loss. Additionally, they experienced greater severity and distress associated with headaches and dizziness. Among doctors, attendants, and cleaning staff in the exposure group, the prevalence of AEs is relatively low. However, when AEs occurred, those reported more frequently, with higher severity, and greater distress. These findings indicate that nurses are at greater risk of exposure to SACT-related AEs.\u003c/p\u003e\n\u003cp\u003eThe mean number of AEs, along with their frequency, severity, and distress, was calculated for the fifteen prominent AEs (Table 6).\u0026nbsp;Nurses in the exposure group experienced a higher mean number of common AEs (4.53\u003cu\u003e+\u003c/u\u003e2.58) with increased frequency, severity, and distress compared with the control group. Doctors and cleaning staff in the exposure group also reported elevated mean values for frequency, severity, and distress. Moreover, the mean frequency of common AEs was higher among pharmacists and attendants in the exposure group (Table 6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.4. Comparison of SACT-related AEs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistically significant differences in the prevalence of common AEs associated with handling SACT were observed between exposed and non-exposed HCW groups across all occupational categories as determined by the independent sample t-test. Furthermore, the frequency, severity, and distress of AEs were significantly higher among nurses and attendants (Table 7).\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eCancer is a global health concern\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. SACT is a widely used and effective treatment modality that improves patients\u0026rsquo; quality of life and overall survival\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The Cytotoxic properties of SACT agents are therapeutically beneficial in targeting malignant cells\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. However, due to the inherent toxicity of many agents, a wide range of AEs have been reported\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. While the risk associated with these agents is justified for patients, occupational exposure can have a negative impact on HCWs\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAccordingly, the current study aimed to assess AEs among patients receiving SACT and among HCWs involved in handling these agents, in comparison with a non-exposed cohort of HCWs. The findings are expected to contribute to improving the management of AEs among patients and to strengthening the occupational health and safety among HCWs.\u003c/p\u003e\u003cp\u003eThe present study identified headaches, dizziness, drowsiness, vomiting, mouth sores, hair loss, sore throat, gastritis, dry mouth, loss of appetite, diarrhoea, bloating, and dysuria as common AEs associated with SACT. Previous literature similarly reported that GI complications, hypersensitivity reactions, skin disorders, hair loss, tumour lysis syndrome, and specific organ toxicities are the most frequent AEs of SACT\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Generally, the prevalence of GI AEs is high (approximately 80%\u003csup\u003e7\u003c/sup\u003e). Chemotherapy-induced nausea and Vomiting (CINV) is considered the most distressing and difficult to manage complication, persisting in about 40% of patients despite prophylactic measures\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Consistent with the theoretical evidence, an empirical study in Malaysian patients reported that CINV was the most common and distressing symptom, particularly among those who received moderately or highly emetogenic chemotherapy\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In the same cohort, the prevalence of dry mouth or thirst, hair loss, tiredness or weakness, loss of appetite, coldness, numbness in fingers or toes, confusion, loss of concentration, sadness, depression, and reduced sense of touch was notably high\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the present study, fatigue and lack of energy were reported by all patients. Similarly, prospective studies conducted in Australia (85%)\u003csup\u003e26\u003c/sup\u003e and India (87%)\u003csup\u003e20\u003c/sup\u003e reported a considerably high prevalence of fatigue. CRF has been described as both a long-term and delayed AE of SACT as well as a symptom associated with cancer itself \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Furthermore, observational studies reported a high rate of GI AEs, including diarrhoea (74%\u003csup\u003e26\u003c/sup\u003e, 49.4%\u003csup\u003e20\u003c/sup\u003e), constipation (74% \u003csup\u003e26\u003c/sup\u003e), and loss of appetite (71.4%)\u003csup\u003e20\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe present study revealed that headache, skin changes, mouth sores, hair loss, gastritis, lack of energy, loss of appetite, bloating, and dysuria were among the most frequently reported AEs of SACT. In addition, headaches, drowsiness, skin changes, mouth soreness, gastritis, fatigue, and lack of energy were predominantly rated as severe or very severe. Mouth sores, lack of energy, and loss of appetite were identified as the most distressing AEs for most patients. In contrast, an Indian study reported that nausea, vomiting, diarrhoea, constipation, mucositis, dyspnoea, rash, and chest pain were generally non-severe\u0026sup2;⁰. When considering the twenty most common AEs observed in the present study, patients experienced a minimum of nine AEs, while the majority (74.8%) experienced more than sixteen AEs. The mean prevalence of common AEs (17.49\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.87, range 9\u0026ndash;20) indicates a high overall prevalence, frequency, severity, and distress levels. Notably, all patients in the current study reported experiencing more than six AEs, where approximately two-thirds of cancer survivors in India (66.7%)\u0026sup2;⁰ and Australia (67%)\u0026sup2;⁶ reported more than six AEs, with at least one AE present in 97.4% and 86% of participants in those respective studies. These findings suggest a higher prevalence and burden of AEs among patients in the present study compared with the previously reported data.\u003c/p\u003e\u003cp\u003eThe number of common AEs was associated with selected personal characteristics (age, gender, nationality, religion, primary caregiver, education level, employment, marital status, and family income). In contrast to the present findings, an Australian study did not report statistically significant associations between AEs and gender, education, socio-economic status, or cancer stage\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Similarly, in a retrospective cohort study conducted in India, no significant associations were found between AE frequency and age, socio-economic status, Body Mass Index (BMI), comorbidity, chemotherapy intent, or disease stage\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, other studies have demonstrated significant associations between CINV and gender, chemotherapy regimen\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e, frequency of AEs, and cancer types\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The current study did not explore several potential contributing factors, such as drug regimen, nutritional status, alternative medicines, and spiritual aspects. The omission of these variables is acknowledged as a limitation of the present study.\u003c/p\u003e\u003cp\u003eConsidering the findings among HCWs, the female workforce, the Sinhalese nation, and the Buddhist religion were common in the present study. A prominent female workforce in handling SACT has been similarly reported in other countries, particularly among nurses\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e, pharmacists\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e, and pharmacy technicians\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the present study, nurses in the exposure groups were primarily responsible for administering chemotherapy drugs, reconstituting and dissolving drugs, providing direct patient care, and handling waste materials. Pharmacists were involved mainly in drug preparation, while cleaning and support staff were responsible for environmental sanitation and patient support activities, respectively. Doctors rarely handle SACT in the present study. Comparable role distribution has been documented internationally, with nurses predominantly administering chemotherapy\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e, pharmacists preparing SACT agents\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e, and other occupational groups responsible for tasks such as cleaning, transport, and waste disposal\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Compared with the control group, nurses in the exposure group reported a significantly higher prevalence of headaches, dizziness, drowsiness, nausea, skin irritation, ocular irritation, hair loss, and menstrual cycle irregularity, with increased frequency, severity, and distress levels. Moreover, exposure-group nurses experienced reproductive teratogenic effects such as miscarriages, pre-term labor, low birth weight, delayed pregnancy, fetal death, and subfertility. In contrast, these reproductive AEs were rarely or not reported among non-exposed groups of nurses and HCWs in other occupational categories.\u003c/p\u003e\u003cp\u003eMany agents used in SACT are recognized as teratogenic, carcinogenic, and mutagenic\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Even minimal exposure can lead to harmful effects\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Thus, these substances are classified as HDs and are associated with a broad spectrum of AEs among HCWs\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. Reported acute and chronic AEs include headache\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, dizziness\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, nausea, vomiting, diarrhea\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, mouth sores\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, allergy\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, alopecia\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, nail hyperpigmentation\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, infertility\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e, miscarriages\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e, stillbirths\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, menstrual cycle changes\u003csup\u003e\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, ectopic pregnancies\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, preterm and low-birth-weight\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, congenital anomalies\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, learning disabilities\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, abnormal blood counts\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, liver\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, kidney damage\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, and other organ damage\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, DNA changes\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, frequent infections\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, sore throat\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, fatigue and weakness\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eA meta-analysis reported a significantly increased risk of spontaneous abortions, stillbirth, and congenital malformations among nurses who handled SACT during pregnancy\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Similarly, a comparative analysis conducted in Egypt found a higher rate of impaired fertility and oral ulcers among nurses and pharmacists exposed to SACT\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. As outlined above, a wide range of teratogenic and reproductive AEs are reported by HCWs with SACT.\u003c/p\u003e\u003cp\u003eHeadache was reported as the most common AE among nurses and nursing assistants in a study conducted in Lativa\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e and it affected only 37.25% of participants\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In contrast, the prevalence of headaches in the present study was substantially higher at 93.9%. Other studies have similarly reported increased prevalence of headaches, dizziness, nausea, or a combination of these symptoms among HCWs handling SACT\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Compared with the controls, Turkish nurses reported statistically significantly higher rates of weakness, hair loss, and fatigue\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Also, hair loss and dizziness were statistically significant among nurses who administered antineoplastic agents\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSeveral factors have been identified as contributing to increased occupational exposure to SACT and related daily activities\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e insufficient precautions\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, insufficient facilities\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, accidental spills\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, limited knowledge on safe handling\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, increased patient and workload\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e, The involvement of nurses in multiple roles and suboptimal safety practices may similarly contribute to the high prevalence of AEs observed in the present study. However, safety precautions were not evaluated in the current study, representing a limitation. Identification of local factors contributing to occupational exposure and AE is therefore recommended.\u003c/p\u003e\u003cp\u003eAmong other occupational groups, including doctors, pharmacists, attendants, and cleaning staff, the exposure groups reported increased frequency of getting SACT-associated AEs and statistical significance compared to non-exposed groups. In support, a study conducted in Egypt reported increased prevalence of impaired fertility and oral ulcers among pharmacists exposed to SACT\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. Nevertheless, there is limited literature examining the prevalence of AEs in these occupational categories relative to nurses.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe present study highlights that SACT is associated with a wide range of AEs among both patients and HCWs. The patient-reported AEs should be systematically integrated into routine clinical practice as those AEs represent a significant concern for patient safety, treatment compromise, organ damage, secondary malignancy risk, financial burden, psychological distress, and reduced quality of life. Innovative strategies such as enhancing supportive care measures, safe alternative treatments, early detection, and management of AEs are essential to mitigate these risks.\u003c/p\u003e\u003cp\u003eAmong HCWs, nurses predominantly reported the highest prevalence of SACT-related AEs. Emphasizing the occupational health implications of handling cytotoxic agents. Regular surveillance, periodic studies, and the identification of additional contributing factors are crucial for informing evidence-based interventions. Strengthening institutional policies and implementing comprehensive occupational safety programs remain vital to protecting the health and well-being of HCWs involved in SACT administration.\u003c/p\u003e"},{"header":"6. Limitations","content":"\u003cp\u003eThe mechanism of action of the drug, or drug regimen, can account for many AEs associated with SACT. However, the present study did not evaluate the drug regimen, treatment duration, or chemotherapy cycles and their associations with AEs. Moreover, patients receiving SACT as inpatients may experience and report AEs with greater intensity, frequency, severity, or distress compared to outpatients. Additionally, recall bias cannot be excluded, as patients may have underreported or misremembered their symptoms. These factors represent limitations related to the patient sample.\u003c/p\u003e\u003cp\u003eAmong HCWs, a relatively high prevalence of common AEs was reported even among those not directly exposed to SACT, except nurses. These findings may be influenced by unexamined variables such as exposure to other HDs, presence of chronic diseases, workload, number of night shifts, fatigue, and environmental factors. The lack of evaluation of these potential confounders constitutes another limitation of the present study.\u003c/p\u003e\u003cp\u003eFurthermore, the exposure group of HCWs was limited to those employed at the NCI; including HCWs from other regional centers across Sri Lanka would be advantageous. However, such expansion should ensure sample homogeneity regarding workload exposure level and AE profile. If maintaining homogeneity across centers is not feasible, integrating a qualitative component could provide valuable insight into contextual and experiential factors influencing occupational exposure and ARE perception.\u003c/p\u003e"},{"header":"Appendix","content":"\u003cp\u003eAEs\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;– Adverse Effects\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAKI \u0026nbsp; \u0026nbsp;\u0026nbsp;– Acute Kidney Insufficiency\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI –\u0026nbsp;Body Mass Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCHF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; –\u0026nbsp;Congestive Heart Failure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCINV\u0026nbsp;\u0026nbsp;– Chemotherapy Induced Nausea and Vomiting\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCKD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;– Chronic Kidney Disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRF\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;– Cancer-Related Fatigue\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRU\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;– Chemotherapy Reconstitution Unit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCVD –\u0026nbsp;Cardio-Vascular Disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCVI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;–\u0026nbsp;Content Validity Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDNA \u0026nbsp;\u0026nbsp;– Deoxyribonucleic acid\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;– Gastrointestinal\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHDs \u0026nbsp; \u0026nbsp;\u0026nbsp;– Hazardous drugs\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCWs \u0026nbsp;– Healthcare workers\u003c/p\u003e\n\u003cp\u003eHF –\u0026nbsp;Heart Failure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHUS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; –\u0026nbsp;Hemolytic Uremic Syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;– Intravenous\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;– Myocardial Infarction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMRI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;– Medical Research Institute\u003c/p\u003e\n\u003cp\u003eNDI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;–\u0026nbsp;Nephrogenic Diabetes Insipidus\u003c/p\u003e\n\u003cp\u003eNHSL\u0026nbsp;– National Hospital Sri Lanka\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNCI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;– National Cancer Institute\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSACT \u0026nbsp;– Systemic Anti-Cancer Therapy\u003c/p\u003e\n\u003cp\u003eSIADH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;–\u0026nbsp;Syndrome of Inappropriate Anti-Diuretic Hormone Secretion\u003c/p\u003e\n\u003cp\u003eSOS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;–\u0026nbsp;Sinusoidal Obstruction Syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTMA\u0026nbsp; \u0026nbsp;–\u0026nbsp;Thrombotic microangiopathy\u003c/p\u003e\n\u003cp\u003eVOD\u0026nbsp; \u0026nbsp;–\u0026nbsp;Veno-Occlusive Disease\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAEs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAdverse Effects\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAKI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAcute Kidney Insufficiency\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBody Mass Index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCHF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCongestive Heart Failure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCINV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChemotherapy Induced Nausea and Vomiting\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChronic Kidney Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCancer\u0026ndash;Related Fatigue\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChemotherapy Reconstitution Unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCVD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCardio\u0026ndash;Vascular Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCVI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eContent Validity Index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDNA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDeoxyribonucleic acid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGastrointestinal\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHDs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHazardous drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHCWs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHealthcare workers\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHeart Failure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHUS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHemolytic Uremic Syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMyocardial Infarction\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMedical Research Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNDI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNephrogenic Diabetes Insipidus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNHSL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNational Hospital Sri Lanka\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNational Cancer Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSACT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSystemic Anti\u0026ndash;Cancer Therapy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSIADH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSyndrome of Inappropriate Anti\u0026ndash;Diuretic Hormone Secretion\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSOS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSinusoidal Obstruction Syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTMA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eThrombotic microangiopathy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVOD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVeno\u0026ndash;Occlusive Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was conducted in accordance with the principles of the Declaration of Helsinki, and it was approved by the Ethics Review Committees of the University of Sri Jayewardenepura (35/21) and the Medical Research Institute (25/2020), Sri Lanka.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eParticipants’ consent was obtainedto publish research findings\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e“The authors declare no conflicts of interest.” Authors must identify and declare any personal circumstances or interests that may be perceived as inappropriately influencing the representation or interpretation of reported research results”.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research was funded by the Medical Research Institute (MRI), Sri Lanka (25/2020) and the University of Sri Jayewardenepura (RC/URG/AHS/2024/94). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eSudath S.P. Warnakulasuriya and Sudheera S. Jayasinghe conceived this study. Samanthi N. Senarath searched the literature, collected data and initially drafted the paper. Except the Samanthi N. Senarath, all authors supervised the whole process and revised the manuscript. Dharshana De Silva and Wasantha K. Rathnayake facilitated resources, and Lalitha Meegoda was involved in funding acquisition. Lalitha Meegoda and Sudath S.P Warnakulasuriya were involved in the project administration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e National Cancer Institute (NCI) (Apeksha Hospital), Sri Lanka\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eBasak D, Arrighi S, Darwiche Y, Deb S (2021) Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile. 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J Oncol Pharm Pract 30(5):893\u0026ndash;901. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/10781552231190025\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAbu-Alhaija D, Bakas T, Shaughnessy E, Miller E (2023) The Factors That Influence Chemotherapy Exposure Among Nurses: An Integrative Review. Work Heal Saf 71(5):212\u0026ndash;227. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/21650799221140583\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eXiangyu Meng Y, Lei X, Zhang K, Sun Liming Zhang, Zhifei Wang\u0026nbsp;\u003c/span\u003e\u003cspan\u003eCancer immunotherapy Classification, therapeutic mechanisms, and nanomaterial-based synergistic therapy. Appl Mater Today (2021) ;24:101149. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.apmt.2021.101149\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 7 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Sri Jayewardanepura","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adverse effects, healthcare workers, occupational exposure, patients, Systemic Anti-Cancer Therapy (SACT)","lastPublishedDoi":"10.21203/rs.3.rs-8133233/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8133233/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eDespite the therapeutic effectiveness against cancer, Systemic Anti-Cancer Therapy (SACT) causes a wide range of adverse effects (AEs) among both patients and healthcare workers (HCWs).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective cohort and comparative study were conducted among randomly selected patients (n\u0026thinsp;=\u0026thinsp;400) and HCWs (n\u0026thinsp;=\u0026thinsp;360), including nurses, pharmacists, doctors, attendants, and cleaning staff. AEs among HCWs were compared with those in the control group (n\u0026thinsp;=\u0026thinsp;420). A 50-item structured questionnaire was used to assess the prevalence, frequency, severity, and distress caused by AEs.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA higher mean number of AEs was reported by patients (17.49\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.87) and exposure group nurses (4.53\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.58). Headaches, dizziness, drowsiness, nausea, skin and ocular irritation, and hair loss are more common among both patients and HCWs. The prevalence of common AEs was associated with the selected patient characteristics, and 75% of patients reported more than sixteen of the twenty common AEs. Among HCWs, nurses in the exposure group reported reproductive-related AEs, and the prevalence of AEs varied significantly across the occupational categories.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe findings of the study indicate that SACT is associated with a broad spectrum of AEs affecting both patients and HCWs. Therefore, effective strategies are required to manage SACT-associated AEs among patients and to strengthen occupational health and safety measures for HCWs exposed to SACT.\u003c/p\u003e","manuscriptTitle":"Adverse effects of Systemic Anti-Cancer Therapy (SACT): A study of patients and health care workers exposed to SACT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 07:44:13","doi":"10.21203/rs.3.rs-8133233/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"acb2e0e9-6812-4c46-8459-ed22f9582b56","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58097194,"name":"Clinical Pharmacology"},{"id":58097195,"name":"Oncology"},{"id":58097196,"name":"Toxicology"},{"id":58097197,"name":"Occupational Medicine"}],"tags":[],"updatedAt":"2025-11-24T22:23:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 07:44:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8133233","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8133233","identity":"rs-8133233","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}