Functional assessment of differentiated therapeutic approach effectiveness in ovarian cancer treatment: impact on QoL and survey results

.


Relationship with academic programs, plans and themes
The article is a fragment the overarching research framework of the Odessa National Medical University the Ministry of Health of Ukraine, specifically within the scope of the project titled «Improving the results of diagnosis, multimodal treatment, and rehabilitation of patients with locally disseminated and metastatic tumor diseases of the abdominal cavity, pelvis, tumors of the mammary gland and extremities, precancerous diseases of the cervix», state registration number: 0122U000505, applied, term: 2022-2026, the head is a professor of the radiation department diagnostics, therapy and radiation medicine and oncology Odessa National
Evident from data analysis is the discernible discrepancy in OC incidence across various countries.For instance, Japan reports an incidence rate of 3,1 cases per 100000 women, contrasting starkly with Swedenʼs rate of 21 cases per 100000 women [5].The International Agency for Research on Cancer identifies Scandinavia, Germany, Benelux, Great Britain, Canada, and the United States as regions with the highest rates of ovarian cancer.Conversely, the occurrence of ovarian cancer is notably lower in Asian countries and among migrants from these regions relocating to economically developed nations in the Northern Hemisphere [4].
The risk factors linked to carcinogens and mutagens encompass infertility, nulliparity, early menarche, late menopause, oral contraceptive use, familial history of ovarian and breast tumors, prolonged hormone replacement therapy, lactose consumption, and occupational exposures.In summary, ovarian cancer stands as a medically and socially significant issue [6,7].
To date, the functional assessment of the impact of anticancer therapy on the quality of life (QoL) among ovarian cancer patients remains a relatively unexplored domain within oncology.Quality of life stands as one of the most comprehensive indicators, offering insights into an individualʼs adaptation to evolving circumstances and overall health status.It also aids in assessing the necessity for medical and psychosocial interventions.Recent advancements have seen the emergence of quality of life research as a distinct scientific discipline, complete with its own methodology primarily focused on quantitative analysis, particularly through assessment criteria, and boasting a broad spectrum of applications.
The World Health Organization underscores that quality of life research revolves around the concept of an individualʼs subjective evaluation of their position within society, considering cultural and personal values, aspirations, capabilities, and overall well-being [11].This perception encompasses oneʼs physical, mental, and social well-being, irrespective of external environmental factors, satisfaction with a specific standard of living, or other facets of psychological comfort [10].
To date, there exists limited data regarding the functional implications of various ovarian cancer treatment modalities on patientsʼ quality of life.Specific chemotherapy protocols have shown promise in enhancing the quality of life for ovarian cancer patients by reducing tumor size and lowering the risk of recurrence [9].Conversely, research indicates that certain individuals may experience severe side effects during chemotherapy, resulting in a decline in quality of life and overall well-being [10].This variability in outcomes underscores the necessity to channel research efforts towards comprehending the impact of diverse treatment approaches on quality of life.Establishing optimal therapeutic strategies is imperative, ensuring not only effective tumor management but also enhancing patientsʼ quality of life and general well-being.
Many prior studies investigating the impact of ovarian cancer therapy on quality of life come with several notable limitations that warrant consideration during interpretation.These include the restricted scope of research and brief observation periods.Such constraints pose challenges in generalizing results to the entire ovarian cancer patient population and in analyzing the long-term effects of therapy.Moreover, these limitations may contribute to post-hoc errors and complicate the overall comprehension of therapyʼs effect on quality of life.
The absence of standardized methods for evaluating quality of life in ovarian cancer patients not only hinders the comparison of findings across different studies but also precludes the attainment of consistent conclusions.The dearth of developed or standardized assessment tools may result in subjective or non-comparable results.Furthermore, the divergent trends and variances among different assessment methods further complicate result analysis, underscoring the imperative for standardization in this field [12,13].
Among the foremost tools utilized for assessing quality of life in oncology practice are the EORTC and Due to the substantial influence of quality of life on the overall efficacy of ovarian cancer treatment, further research in this domain holds critical importance.The development of effective therapeutic approaches and enhancements in patientsʼ quality of life necessitate a comprehensive understanding of how various treatment strategies affect their physical, emotional, and social well-being.
The investigation into the impact of platinum-based therapy on the quality of life of ovarian cancer patients becomes particularly intriguing when considering the efficacy of a tailored therapeutic approach.Incorporating research findings underscores the importance of assessing treatment outcomes beyond mere survival rates [16][17][18].A personalized therapeutic strategy, tailored to each patientʼs unique needs and disease characteristics, is increasingly vital for optimizing patient well-being and treatment effectiveness.
By integrating survey outcomes and assessing quality of life metrics, a nuanced understanding emerges regarding the treatmentʼs effect on patientsʼ physical, emotional, and social functionality.This holistic approach to managing ovarian cancer not only enhances clinical decision-making by elucidating the intricate interplay between treatment efficacy and patient quality of life but also fosters patient-centric care and supportive interventions.Ultimately, this approach leads to improved treatment outcomes and enhanced quality of life for patients.
As of now, there is a notable absence of studies systematically analyzing this aspect of quality of life.Therefore, we propose a systematic approach to investigate the influence of therapy on patientsʼ quality of life, contingent upon their sensitivity to platinum drugs.The primary objective is to broaden understanding of this matter through a comprehensive analysis encompassing not only patientsʼ physical, emotional, and social well-being but also examining the correlation between treatment sensitivity and their quality of life.This research endeavor aims to fill the existing gap in knowledge, ultimately offering insights that can inform more effective and tailored therapeutic strategies for ovarian cancer patients.

Research conditions
The study was conducted at the Odessa National Medical University Clinic during 2014-2024.350 patients with stage III-IV ovarian adenocarcinoma who underwent cytoreductive operations were examined.
Examination of patients was carried out in accordance with the requirements of the clinical protocol approved by the order of the Ministry of Health of Ukraine No. 554 of 09.17.2007 «On the approval of protocols for the provision of medical care in the specialty "oncology"» [19].
Data on transvaginal sonography (TVS) and CA-125 biochemical screening were obtained from the medical records of patients who underwent these procedures at the facility.

Methodology of a differentiated treatment strategy
Definition of probable platinum-refractory, resistant and sensitive patients was carried out according to the protocol [20].
Patients were divided into the following clinical groups: Group I (control, GI, n = 50) -patients with OC who received standard first-line adjuvant chemotherapy, including cisplatin at a dose of 75-100 mg/m 2 intravenously with hydration and diuresis every three weeks; II group (experimental, GII, n = 100) -patients with probable platinum refraction who received second-line therapy, including doxorubicin at a dose of 75-100 mg/m 2 intravenously once every three weeks; Group III (experimental, GIII, n = 100) -patients with probable platinum resistance who received medical correction of dysregulatory disorders against the background of standard first-line therapy, including nitric oxide donors, detoxifiers, and antiuricemic agents; IV group (experimental, GIV, n = 100) -patients with predicted platinum sensitivity who received standard first-line therapy after a previous prophylactic course, including 20 mg of dexamethasone 12 and 6 hours before the introduction of platinum drugs, 300 mg of cimetidine or 50 mg of ranitidine and 50 mg of diphenhydramine 30-60 minutes before the introduction of platinum drugs.

Analysis of patients quality of life
Quality of life was assessed 6 and 12 months after completion of treatment with the EORTC QLQ-C30 and FACT-G questionnaires.
The current version of the FACT-G (4) included 27 questions and assessed QOL using 5-point Likerttype subscales: physical (PF or PWB), social or role (RF or RWB), emotional (EF or EWB) functioning and well-being in daily life [15].

Cluster analysis
The study implemented an agglomerative hierarchical clustering algorithm based on Wardʼs method in RStudio [22].This method iteratively merged the two nearest clusters based on the criterion of minimizing within-cluster variation, before generating a dendrogram to display the hierarchical structure of the data.

Statistics
Analysis of comparisons between groups used the nonparametric χ 2 test with Yates correction for pairwise comparisons between binary categories and Bonferroni correction for multiple comparisons in RStudio.The Yates correction was applied to reduce possible random deviations in the case of limited data, while the Bonferroni correction served to control the level of biased deviations in multiple comparisons [23].A nonparametric confidence interval (CI) set at 0,95 for the predicted means accompanied these scores, as well as P-value, an estimate of the probability that a randomly selected score from the experimental sample would have a subscale value higher or lower than a randomly selected one from the control dataset [24].
Common symptoms reported by a significant portion (71,0%) of patients included dyspeptic symptoms, shortness of breath, general weakness, rapid fatigue, weight loss, and a sensation of quick satiety even with small food intake.Edema of the lower extremities was observed in 12,6% of patients, while signs of ascites were present in 5,4%.Remarkably, in 17,4% of patients, the disease manifested without subjective symptoms and was only detected through ultrasound (US) screening.
Biochemical screening revealed elevated CA 125 levels in 44,6% of the participants.The integration of transvaginal ultrasound (TVS) with biochemical screening has emerged as a crucial diagnostic approach for OC.TVS allows for precise evaluation of tumor size and identification of soft tissue abnormalities, including multilocal dense hyperechoic formations and increased intraovarian blood flow.Importantly, this combined approach facilitates early and accurate detection of cancer signs, enabling timely treatment planning.TVS, with its ability to visualize internal organ structures, coupled with biochemical markers such as CA 125 and CA 19-9, demonstrates higher sensitivity and specificity in OC detection compared to standalone biochemical screening [25][26][27].

Analysis of a differentiated therapeutic approach
During the analysis, it was noted that patients in GI-IV frequently reported various symptoms including nausea, taste disturbances, dizziness, and general weakness, often occurring before meals.Visual disturbances were reported by a small percentage of patients (6,0% in GI and 2,0% in GIV).Peripheral polyneuropathy and Lhermitteʼs symptom were observed in some cases.Blood analysis indicated moderate leukopenia and anemia, likely attributed to platinum-based treatment, along with frequent arterial hypotension.Moreover, cough, erythematous rash, and extravasates at injection sites were observed in certain patients undergoing treatment in both GI and GIV stages.
Patients in stage GII undergoing treatment with doxorubicin commonly experienced subfebrile temperatures, palpitations, thrombocytopenia, and leukopenia.Additionally, they reported symptoms such as nausea, vomiting, stomatitis, and diarrhea.At the onset of treatment, these patients often observed a reddish color change in urine, along with frequent complaints of alopecia, darkening of the palms and soles, palmar erythema, nail deformities, skin itching, and rash.Some individuals also reported photophobia and increased lacrimation resembling epiphora.
Itʼs noteworthy that patients who received a pathogenetically determined complex of metabolic support in stages GIII and GIV reported the fewest subjective complaints during treatment.
Further analysis, as depicted in Tables 1 and 2, indicated that the initial values of the subscales of the EORTC QLQ-C30 and FACT-G questionnaires among patients assigned to different clinical groups were comparable.
These differences could be attributed to various treatment-related factors such as therapy side effects, emotional strain, or social support.These factors might influence patientsʼ overall QoL in the long term.
Аналогічна динаміка за субшкалами FACT-G підтверджує той факт, що зміни в ЯЖ та загальному самопочутті пацієнток можуть мати корелюючі особливості та залежати від подібних факторів.Однак значущих кластерів за ієрархією змін показників FACT-G не було сформовано (рис.2, b) [28].functioning (PF), role functioning (RF), and emotional functioning (EF) subscales.This positive trend suggests that the treatment approach had a beneficial impact on the overall well-being of the patients.Additionally, there was a notable decrease in the intensity of nausea (NV) and general weakness (FA) among patients in stages GIII and GIV.This reduction in unwanted symptoms underscores the high efficacy of the treatment strategies employed in alleviating symptoms associated with the disease and its treatment.
Itʼs important to highlight that the observed differences in QoL indicators persisted throughout the entire period of follow-up observation.This underscores the stability of improvement in patientsʼ QoL even after the conclusion of active treatment.Such findings may provide encour agement for the continued use of a similar differentiated approach in future treatments, aiming to sustain and enhance patientsʼ QoL beyond the active treatment phase.
Changes in other indicators according to the subscales of the EORTC QLQ-C30 and FACT-G questionnaire exhibited a fluctuating nature, likely reflecting the heterogeneous composition of the studied population in terms of adaptive response potential and chemotherapy transfer.This suggests individual variations in patientsʼ responses to treatment and the possibility of diverse therapeutic outcomes.Such variability may be attributed to differences in the bodyʼs tolerance to treatment, the impact of drug side effects, and various factors influencing patientsʼ physical and psychological well-being.
The unexpected improvement observed in the control groupʼs functioning index could be attributed to factors such as random variation, regression to the mean, or the relatively small size of the study sample.
Cluster 1 appears to encompass traits associated with physical and social functioning.Overall, group GIV exhibited the most significant improvement across all subscales compared to the other groups after 6 and 12 months of treatment when compared to the control group (Fig. 3).ted to emotional stress and psychological well-being.GIV demonstrated the most favorable performance, followed by GIII, while GII ranked third among the clinical groups in terms of effectiveness compared to the control group within cluster 2 (see Figure 4).Кластер 3 може представляти симптоми та негативні ефекти медичних втручань, які впливають на ЯЖ під час лікування (рис.5).
Cluster 3 likely represents symptoms and adverse effects of medical interventions that impact QoL during treatment (Fig. 5).
Різниця у прирості показників EORTC між групами GII-IV та групою порівняння надала важливе Based on the identified changes in the indicators of each subscale within cluster 3, GIII generally exhibited the most favorable results.However, GIV also demonstrated promising outcomes, albeit with somewhat smaller changes compared to GIII.
Результати дослідження свідчать, що диференційований підхід до лікування РЯ, який враховує індивідуальні особливості пацієнток та забезпечує метаболічну підтримку, може значно покращити клінічні результати та ЯЖ хворих у порівнянні зі стандартними терапевтичними режимами. of a differentiated approach to OC treatment.In the control group, which received chemotherapy without metabolic support, there was a slight increase in the emotional well-being (EWB) subscale and the total score of the FACT-G questionnaire.However, in the experimental groups where differentiated therapy with metabolic support was employed, the increase in these indicators was significantly higher.Moreover, the positive clinical effect on QoL was sustained for at least 12 months (0,95 CI; P < 0,01).
The clinical data further corroborate these findings, indicating a trend where patients who underwent differentiated therapy experienced notable improvements in physical and emotional functioning, alongside a reduction in the severity of side effects, compared to patients who received standard treatment [8,10,27,29,30].
The study results suggest that a differentiated approach to OC treatment, which considers individual patient characteristics and incorporates metabolic support, can lead to significant improvements in clinical outcomes and QoL compared to standard therapeutic regimens.
Despite the heterogeneous nature of the patient population in terms of adaptive response potential and chemotherapy transfer, a differentiated therapeutic approach in the treatment of OC has proven effective in enhancing patientsʼ QoL.This approach, which considers the level of pharmacoresistance and employs various chemotherapy strategies, resulted in significant improvements across multiple domains, including physical, role, and emotional functioning, as well as fatigue, with increases ranging from 8 to 18,5%.Different treatment modalities, including cytoreductive surgeries and diverse chemotherapy regimens, led to varying side effects and symptoms among patients.Importantly, a sustained improvement in QoL was observed after the completion of active treatment, underscoring the importance of an individualized approach with metabolic support to achieve better clinical outcomes.These differences persisted for up to 12 months following the conclusion of the treatment course.
Medical University of the Ministry of Health of Ukraine, Doctor of Medical Sciences, Professor O.V. Bondar.VM, Bondar OV, Rybin AI, Sokolov DV.Functional Assessment of Differentiated Therapeutic Approach Effectiveness in Ovarian Cancer Treatment: Impact on QoL and Survey Results.Ukrainian journal of radiology and oncology.2024;32(2):216-230.DOI: https://doi.org/10.46879/ukroj.2.2024.216-230 Sokolov Український радіологічний та онкологічний журнал.2024.Т. 32.№ 2. С. 216-230 Ukrainian journal of radiology and oncology.2024;32(2):216-230 FACT-G basic questionnaires.These instruments were respectively developed by the Quality of Life Assessment Group of the European Organization for Research and Treatment of Cancer and at the Feinberg School of Medicine of Northwestern University, USA [14, 15].Both questionnaires are modular in nature, facilitating the addition of specific questions tailored to various tumor types and/or treatment regimens onto the core questionnaire.