Determination of the Effect of Neuropathic Pain on Quality of Life in Cancer Patients Receiving Chemotherapy

Introduction

Methods

Location and Time of the Study
Data collection was conducted between April 2019 and October 2019 at the outpatient chemotherapy unit and the inpatient oncology-hematology clinic of a private foundation university hospital in Istanbul, as well as at the outpatient chemotherapy unit of a public hospital. At these study sites, patients presenting with neuropathic symptoms were evaluated for peripheral neuropathy by physicians. Although patients were routinely informed about neuropathy as a potential adverse effect of chemotherapy, no structured training was provided regarding its systematic assessment.

Study Population and Sample
The study population comprised patients scheduled to undergo chemotherapy at the outpatient chemotherapy unit and the inpatient oncology-hematology clinic of a private foundation university hospital in Istanbul, as well as at the outpatient chemotherapy unit of a public hospital. No sampling method was employed; instead, all patients meeting the inclusion criteria during the study period were enrolled. Inclusion criteria were: A confirmed diagnosis with no prior chemotherapy, scheduled to receive regular chemotherapy at the study sites, a total Neuropathic Pain Scale (S-LANSS) score of 12 or higher, no ongoing neuropathy treatment, age over 18 years, willingness to communicate and cooperate, literacy, absence of hearing or visual impairments, and voluntary consent to participate. A total of 100 patients who met these criteria were included in the study. Exclusion criteria comprised patients who did not complete the planned treatment regimen, had to discontinue treatment due to health-related reasons, had a diagnosis of diabetes, or had bone metastases.

Data Collection Tools
Four instruments were utilized for data collection in this study. The Chemotherapy-Related Neuropathic Pain Data Collection Form was employed to obtain information on patients" sociodemographic characteristics, disease status, and treatment details. Pain intensity was assessed using the Visual Analog Scale (VAS). The Neuropathic Pain Impact on Quality of Life Questionnaire was administered to evaluate the effect of neuropathic pain on patients" quality of life. To identify the presence of neuropathic pain and determine eligibility for inclusion in the study, the Self-Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) was used.

Chemotherapy-Related Neuropathic Pain Data
Collection Form: The Chemotherapy-Related Neuropathic Pain Data Collection Form was developed by the researchers based on a review of relevant literature. The form comprises two sections. The first section, Patient Characteristics, includes 13 items addressing sociodemographic variables such as gender, age, marital status, educational level, employment status, family structure, identification and description of the caregiver, place of residence relative to the hospital, means of transportation to the hospital, health insurance status, and smoking and alcohol use. The second section, Disease and Treatment Characteristics, consists of 17 items examining clinical and treatment-related factors, including patient diagnosis, time since diagnosis, knowledge about the disease and planned treatment and its side effects, chemotherapy regimen and frequency, source of information, presence, cause, and frequency of pain, conditions accompanying pain, and comorbid chronic diseases along with their treatments. Overall, the form contains a total of 30 items.

VAS: The Visual Analog Scale (VAS), developed by Price et al.,[] is a simple, reproducible, and minimally invasive method for the subjective assessment of pain intensity. It is frequently employed in clinical settings that require rapid evaluation of pain. The VAS consists of a 10 cm line, with one end representing "no pain" and the other end representing "the most severe pain imaginable" (0: No pain; 10: Most severe pain). Patients indicate their pain level by marking the line at the point corresponding to their perceived intensity. Pain severity is generally interpreted as follows: A score of 4 indicates mild pain, 5-6 indicates moderate pain, and 7?10 indicates severe pain. While the VAS is easy to administer, providing clear explanations of the scale endpoints to patients is crucial for obtaining reliable data. The literature supports the VAS as a practical, valid, and widely used tool for assessing cancer-related pain severity.

S-LANSS: The Self-Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) is a modified version of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale, developed by Bennett et al.,[] designed to differentiate neuropathic pain from nociceptive pain. The validity and reliability of the scale were established by Koç.[] Unlike the LANSS Pain Scale, which includes a two-item section completed by a physician, the S-LANSS allows patients to self-report these items without altering the scoring, maintaining equivalence with the original LANSS. Additionally, the S-LANSS incorporates a body map to assist patients in identifying the location of pain. Responses are recorded as "yes" or "no," with total scores ranging from 0 to 24. Patients scoring 12 or above are considered to experience neuropathic pain.

NePIQoL: The Neuropathic Pain Impact on Quality of Life Questionnaire (NePIQoL), developed by Poole et al.[] and validated by Acar,[] was designed to evaluate the impact of neuropathic pain on patients" quality of life. In its original form, the questionnaire is divided into six subscales:

(I) Symptoms - eight items assessing pain symptoms;

(II) Relationships - five items evaluating the effects of neuropathic pain on interpersonal relationships;

(III) Psychological - eight items assessing emotional well-being;

(IV) Social Relationships - eight items examining the influence of neuropathic pain on daily activities;

(V) Physical Activity - seven items assessing the impact of physical activity on pain and related symptoms; and

(VI) Personal Care - six items evaluating self-care in relation to neuropathic pain.

In the present study, analyses were based solely on the total NePIQoL score, and subscale scores were not considered.

The NePIQoL questionnaire comprises a total of 42 items, each rated on a 5-point Likert scale (5: Strongly agree/yes, always; 4: Agree/yes, most of the time; 3: Unsure/ sometimes; 2: Disagree/rarely; 1: Strongly disagree/ no, never). All items, except for items 12, 15, 33, and 34, are scored in descending order from 5 to 1, with the specified four items scored in reverse (1 to 5). The total score is obtained by summing all item scores, yielding a range of 42 to 210, with higher scores indicating a greater impact of neuropathic pain on quality of life. The internal consistency of the questionnaire was reported as 0.86 in the original study, 0.99 in the validity and reliability study, and was determined to be 0.95 in the present study.

Statistical Analysis
Data were analyzed using IBM SPSS Statistics version 25.0. Quantitative variables were summarized as frequencies and percentages. The Kolmogorov-Smirnov test was employed to assess the normality of data distributions. For comparisons between two groups with normally distributed data, the Student's t-test was used, while one-way ANOVA was applied for comparisons among more than two normally distributed groups. For non-normally distributed data, the Mann-Whitney U test was used to compare two groups, and the Kruskal- Wallis test for more than two groups. Relationships between questionnaire scores were examined using Spearman's correlation analysis.

Application of the Study
Information regarding newly diagnosed patients was obtained from ward physicians and nurses. The date of data collection was scheduled based on the patient"s appointment, as confirmed by ward nurses or secretaries. The initial assessment was conducted using the Chemotherapy- Related Neuropathic Pain Data Collection Form prior to the commencement of chemotherapy. The second assessment was performed after the patient had completed at least two cycles of chemotherapy, using the study-specific forms. Prior to data collection, the researcher explained the purpose and procedures of the study to each patient and obtained written informed consent. Data were collected through face-to-face interviews conducted by the researcher during the patients" treatment sessions, with each interview lasting approximately 25 minutes

Ethical Considerations
Prior to conducting the study, written approval was obtained from the University Clinical Research Ethics Committee (April 10, 2019; Approval No: 37068608- 6100-15-1659), followed by written permission from the Istanbul Provincial Health Directorate. The study is conducted according to the Helsinki Declaration. Participation in the study was entirely voluntary, and written informed consent was obtained from all participants after the study purpose and procedures were fully explained. Additionally, written permission was secured for the use of all data collection instruments.

Results

Table 1 Comparison of patients' descriptive characteristics according to vas and nepiqol mean scores

Analysis of mean VAS scores by age revealed a statistically significant difference among groups (p<0.05). Pairwise comparisons indicated that patients aged 50 years and younger had significantly higher VAS pain scores than those over 61 years of age (Kruskal-Wallis test, t=7.301, p=0.036). When analyzed by gender, women had higher mean VAS scores than men, with the difference reaching statistical significance (p<0.05). Although higher mean VAS scores were observed in unmarried patients and those with a high school education, these differences were not statistically significant (p>0.05).

Regarding NePIQoL scores, the mean values tended to decrease with increasing age and increase with lower educational levels; higher scores were also observed among women and married patients. However, differences in NePIQoL scores across demographic groups were not statistically significant (p>0.05).

Comparison of Patients" Disease Characteristics with VAS and NePIQoL Scores

Table 2 presents the comparison of patients" disease characteristics with their mean VAS and NePIQoL scores. Among the participants, 43% were diagnosed with breast cancer, and 51% reported receiving information about their disease, treatment, and potential side effects from both physicians and nurses.

Table 2 Comparison of patients' disease characteristics according to vas and nepiqol mean scores

Although mean VAS and NePIQoL scores were higher in patients with breast cancer and in those who were informed by both healthcare professionals, these differences were not statistically significant (p>0.05).

Table 3 presents the comparison of patients" treatment characteristics with their mean VAS and NePIQoL scores. Among the participants, 35% received alkylating agents as part of their chemotherapy regimen, 40% were at their third chemotherapy cycle during the second assessment, and 55% received treatment at 14-day intervals. Seventy-four percent of patients reported disease-related pain, and 79% experienced pain between chemotherapy sessions.

Table 3 Comparison of patients' treatment characteristics according to vas and nepiqol mean scores

Analysis of mean VAS scores according to the number of chemotherapy cycles revealed a statistically significant difference between groups (p<0.05). Pairwise comparisons indicated that this difference was primarily due to variations in mean VAS scores between patients at different cycles. Specifically, the VAS score of patients receiving the second cycle was lower than that of patients in the fifth cycle (Kruskal-Wallis test, t=10.951, p=0.029). Additionally, patients in the third cycle reported higher VAS scores than those in the fourth (Kruskal-Wallis test, t=10.951, p=0.019) and fifth cycles (Kruskal-Wallis test, t=10.951, p=0.006), with all differences reaching statistical significance.

Comparison of NePIQoL scores by chemotherapy regimen revealed a statistically significant difference between groups (p<0.01). Pairwise analysis indicated that patients in their third chemotherapy cycle had significantly higher NePIQoL scores compared to those in the fifth cycle (One-Way ANOVA, t=4.710, p=0.003).

Although patients receiving alkaloid-based chemotherapy, those treated every 14 days, those identifying disease as the source of pain, and those reporting pain during chemotherapy sessions but not between sessions had higher mean VAS and NePIQoL scores, these differences were not statistically significant (p>0.05).

Table 4 presents the comparison of patients" pain characteristics with mean VAS and NePIQoL scores. Among participants, 91% reported tingling, prickling, or pins-and-needles sensations in the painful area, 73% reported diminished sensation when the area was rubbed, and 70% reported hypersensitivity to touch in the affected region.

Table 4 Comparison of patients' pain characteristics according to vas and nepiqol mean scores

Patients who experienced color changes in the pain area during intensification reported significantly higher NePIQoL scores, with the difference between groups reaching statistical significance (p<0.01).

Analysis of mean VAS scores across pain characteristics indicated that patients generally did not experience throbbing, stinging, or tingling; experienced color changes during pain intensification; reported hypersensitivity to touch; did not feel electric-shock-like, jumping, or bursting sensations at rest; experienced increased heat in the painful area; did not lose sensation when the area was rubbed; and experienced partial loss of sensation when pressing the area. However, differences in mean VAS scores across these pain characteristics were not statistically significant (p>0.05).

Similarly, mean NePIQoL scores were higher among patients who did not report tingling, prickling, or pins- and-needles; experienced hypersensitivity to touch when pain intensified; did not experience electric-shock, jumping, or bursting sensations at rest; experienced increased heat; and did not report loss of sensation when rubbing or pressing the painful area. Nevertheless, these differences were not statistically significant (p>0.05).

Table 5 presents the distribution of patients" mean scores on the VAS, S-LANSS, and NePIQoL questionnaires. The mean VAS score was 6.64±1.96, indicating moderate to severe pain. The mean S-LANSS score was 17.15±4.15, confirming the presence of neuropathic pain in the sample. The mean NePIQoL score was 147.56±62.44, reflecting a substantial impact of neuropathic pain on patients" quality of life.

Table 5 Distribution of patients' VAS, S-LANSS and NePIQoL scores

Table 6 presents the correlation analysis between patients" VAS, S-LANSS, and NePIQoL scores. A positive, weakly significant correlation was observed between VAS and S-LANSS scores (r=0.305, p<0.01). A positive, strongly significant correlation was found between VAS and NePIQoL scores (r=0.728, p<0.01). Additionally, a positive, weakly significant correlation was identified between S-LANSS and NePIQoL scores (r=0.356, p<0.01). These findings suggest that higher pain intensity and neuropathic symptom severity are associated with greater impact on quality of life.

Table 6 Correlation between patients' VAS, S-LANSS and NePIQoL scores

Discussion

In the present study, pain intensity was examined according to age groups among patients with a mean age of 56.73±11.23 years. It was found that patients aged 50 years and younger reported higher pain intensity compared to those aged 61 years and older (p=0.036) (Table 1).

Consistent with these findings, Wong et al.[] investigated age-related differences in subjective (e.g., pain intensity, interference with activities) and objective (e.g., light touch, vibration) measures of chemotherapyrelated peripheral neuropathy in 425 cancer patients with a mean age of 60.9±10.5 years over a three-month period. They reported that patients under 65 years of age (mean age: 54.52±8.01) subjectively experienced more severe pain and activity impairment despite objective measures, whereas patients over 65 years (mean age: 70.90±4.48) reported less severe pain and functional limitations, also contrary to objective assessments.

Similarly, Waddell-Bulls et al.[] examined the relationship between chemotherapy-induced peripheral neuropathy and age in patients with gynecological cancer over a one-year follow-up period. Symptom progression was monitored from the start of chemotherapy until one year post-treatment. Although both age groups exhibited similar neuropathy symptoms during the treatment period, patients under 65 years showed greater symptom reduction after treatment completion compared to those over 65, with no differences in treatment regimens observed between the groups.

The findings of the present study regarding age are consistent with the existing literature. They suggest that the tendency for older patients to report lower levels of neuropathic pain intensity should be carefully considered, and that neuropathy assessment should incorporate both objective and subjective evaluation methods.

In the present study, women reported higher pain intensity than men (p=0.043) (Table 1). This finding aligns with previous research indicating that women generally have a lower neuropathic pain threshold than men and may respond differently to pain due to physiological factors, including hormonal fluctuations during menarche and pregnancy, as well as psychosocial influences such as family and social relationships.[]

Experimental animal studies by Naji-Esfahani et al.[] examining gender differences in chemotherapyinduced neuropathic pain in mice treated with Paclitaxel and Cisplatin reported a higher prevalence of Paclitaxel-related symptoms in female mice. Similarly, large-scale human studies have consistently shown higher pain intensity among women. Mols et al.,[] in a study involving 1.102 patients using the European Organization for Research and Treatment of Cancer questionnaire, found that women experienced greater pain intensity than men. Sacid and Arıkan[] reported similar findings in a sample of 196 cancer patients, where women demonstrated higher pain levels affecting daily activities and quality of life.

In Colombia, Martínez et al.[] investigated chemotherapy- induced peripheral neuropathy (CIPN) in 1.551 patients, of whom 1.094 were women. Among these female patients, 521 (33.6%) had breast cancer and 80 (5.2%) had ovarian cancer; all received Ixabepilone, a chemotherapeutic agent commonly used in breast cancer treatment, and 95.2% developed CIPN. Incidences of CIPN in women treated with Paclitaxel, Docetaxel, Oxaliplatin, and Bortezomib were 52%, 48.5%, 56%, and 65.3%, respectively. In the present study, half of the female patients had breast or ovarian cancer (43% breast cancer, 7% ovarian cancer) (Table 2). The higher pain intensity observed in female patients may be attributed to the greater prevalence of chemotherapy agents in cancer types commonly affecting women, which are known to induce CIPN.

In the present study, a statistically significant difference in pain intensity was observed according to the number of chemotherapy cycles received by patients after the second assessment (p=0.012), with the difference primarily attributable to patients in the second and third cycles reporting pain levels that differed from those in other cycle groups (Table 3).

Consistent with these findings, Sacid and0 Arıkan[] reported that pain intensity increased with the number of chemotherapy cycles in patients undergoing treatment, demonstrating a cumulative effect of chemotherapy on neuropathic pain and its interference with daily activities and quality of life. In the current study, the greater impact on quality of life observed in patients receiving the third cycle was attributed to their higher pain intensity compared to those in the fourth and fifth cycles. Similarly, Shimozuma et al.[] noted that chemotherapy-induced peripheral neuropathy (CIPN) symptoms adversely affected quality of life in breast cancer patients after the seventh cycle, highlighting the progressive influence of cumulative chemotherapy exposure on pain and functional outcomes.

In the present study, contrary to some literature reports, the observed decrease in pain intensity with an increasing number of chemotherapy cycles is thought to reflect patients" initial perception of neuropathic pain and subsequent adaptation over time. Similarly, the reduction in the impact of pain on quality of life with additional cycles may be related to the corresponding decrease in pain intensity. Nevertheless, further studies with robust evidence are needed to clarify the effects of chemotherapy cycle number on neuropathic pain intensity and quality of life, which would substantially inform the clinical management and diagnosis of neuropathic pain.

Additionally, a positive and highly significant correlation was observed between neuropathic pain intensity and its impact on quality of life (p<0.01) (Table 6), indicating that higher pain intensity is associated with a greater negative effect on patients" quality of life.

This study demonstrated that the presence of neuropathic pain adversely affected quality of life and was associated with increased pain intensity. In other words, as neuropathic pain symptoms intensified, both the severity of pain and its negative impact on patients" quality of life increased. Consistent with these findings, Simon et al.[] reported that patients" quality of life decreased as symptom severity increased. A systematic review by Mols et al.,[] encompassing 25 studies, also concluded that chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts quality of life. Similarly, Önsüz[] found that quality of life declined in patients receiving taxane-based chemotherapy as neuropathy severity increased.

In a retrospective study by Streckmann et al.[] involving 188 patients treated with oxaliplatin, chemotherapy- induced neuropathic pain was evaluated, and results indicated a reduction in quality of life with increasing neuropathy severity. Smith et al.[] similarly reported a statistically significant association between peripheral neuropathy and decreased quality of life. Pereira et al.,[] in a study of 58 patients receiving oxaliplatin or taxane-based chemotherapy who experienced neuropathy, found that patients were particularly affected by numbness, tingling, and cold sensations in the extremities, leading to increased dependence on others and a consequent reduction in quality of life.

Limitations of the Study
The findings of this study are based on a sample of volunteer patients who received chemotherapy at two institutions in Istanbul-one private foundation hospital and one public hospital-during a specific time period and who met the inclusion criteria. Therefore, the results may not be generalizable to all patients receiving chemotherapy.

Conclusion

In line with these results; individual and treatment characteristics of patients should be considered in the assessment of neuropathic pain; the assessment and importance of neuropathic pain should be included in patient education and pre- and post-graduate nursing education; quantitative and qualitative studies should be conducted involving different patient groups in terms of individual and treatment characteristics, examining neuropathic pain characteristics and their impact on quality of life.

Ethics Committee Approval: The study was approved by the Yeditepe University Clinical Research Ethics Committee (no: 37068608-6100-15-1659, date: 10/04/2019). Informed Consent: Informed consent was obtained from all participants.

Conflict of Interest Statement: All authors declared no conflict of interest.

Funding: The authors declared that this study received no financial support.

Use of AI for Writing Assistance: No AI technologies utilized. Author Contributions: Concept - T.E., Ş.U.; Design - T.E., Ş.U.; Supervision - Ş.U.; Funding ? T.E.; Data collection and/ or processing - T.E.; Data analysis and/or interpretation - T.E., Ş.U.; Literature search - T.E., Ş.U.; Writing - T.E., Ş.U.; Critical review - Ş.U.

Peer-review: Externally peer-reviewed.

References