Research Article

Pre- and Post-Analysis of the Clinical Profile of Cancer Patients Before and After Chemotherapy

Muhammad Waqar Mazhar*

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan

Submission: September 03, 2024; Published: October 04, 2024

*Corresponding Address: Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan, Email: waqarmazhar63@gmail.com

How to cite this article: Muhammad Waqar Mazhar. Pre- and Post-Analysis of the Clinical Profile of Cancer Patients Before and After Chemotherapy. Canc Therapy & Oncol Int J. 2024; 27(4): 556218. DOI:10.19080/CTOIJ.2024.27.556218

Abstract

Chemotherapy, a cornerstone in cancer treatment, significantly alters the clinical profiles of patients, necessitating thorough pre- and post-treatment analyses. This review synthesizes findings from multiple studies to elucidate the impact of chemotherapy on various physiological and biochemical parameters. Key observations include significant decreases in systolic and diastolic blood pressure, white blood cell (WBC) count, and red blood cell (RBC) count post-chemotherapy. Hemoglobin and hematocrit levels also show notable declines, underscoring the onset of severe anemia. Interestingly, high-density lipoprotein (HDL) levels increase significantly, though the mechanisms remain unclear. Parameters such as platelet count, uric acid, and creatinine, cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides exhibit changes that are not statistically significant. The findings highlight the critical need for vigilant monitoring and proactive management of hematological and cardiovascular parameters to mitigate the adverse effects of chemotherapy. This review underscores the importance of a holistic approach to patient care to optimize therapeutic outcomes and improve the quality of life for cancer patients undergoing chemotherapy.

Keywords: Chemotherapy; clinical profile; Hematological changes; Cardiovascular effects; Cancer patients

Abbreviations: WBC: White Blood Cell; RBC: Red Blood Cell; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein; VLDL: Very Low-Density Lipoprotein; GPT: Glutamic-Pyruvic Transaminase; GOT: Glutamic-Oxaloacetic Transaminase; ALP: Alkaline Phosphatase; LDH: Lactic Dehydrogenase; CTCs: Circulating cancerous cells

Introduction

Globally, cancer is a major threat to public health. It is among the most dangerous and catastrophic diseases of the twenty-first century and ranks as the second most common cause of mortality (Marcellin & Kutala, 2018; Naujokas et al., 2013; Torre et al., 2015). Universal trends demonstrate that the worldwide prevalence of cancer is going to increase over the next decade or so, with approximately 420 million cases expected to occur annually by 2025. In Pakistan, the cancers that are most likely to be diagnosed are lung, colon, prostate, and female breast cancers. Over the last 15 years, there has been a significant shift in cancer therapy paradigms due to advances in molecular and tumor biology. Previously, malignant growth was characterized and treated exclusively as indicated by organs of beginning or oversimplified histomorphology. Lesions (which are additionally referred to as carcinomas) constitute atypical masses comprised of cells within the human body. It is brought about by the cells reproducing faster than normal. They do not die after their life span and accumulate in the place; they are produced to cause carcinoma of that organ. The tumors can be classified by being either innocuous or invasive Are those that persist in their initial location. Tumors are not transmitted to structures nearby or faraway parts of the human anatomy. Benign malignancies often grow slowly and have recognized limitations. Malignant tumors contain cells that grow ungoverned and spread to far-away places. Malignant tumors are invasive (which translates to that they contaminate other regions). They spread to far-off places through the circulation or lymphatic drainage system. This spread has been referred to as metastases. Metastatic Development can occur anytime throughout the body, although is most usually discovered in the liver, lungs, mind, and bone [1-20].

Cancer is a progressive disease that develops over time by the accumulation of harmful mutations in genes controlling normal growth and development If undetected or left untreated they develop into a tumor called Localized. This tumor then grows and spreads into nearby lymph nodes which is known as Early Locally Advanced. If left untreated spreads into more lymph nodes which is known as Late Locally Advanced. As with most medical procedures, enzymes that metabolize drugs and drug transport proteins play an important part in affecting the mechanism of action and general distribution of antineoplastic medicines in the body. Chemotherapy precipitates a complex series of events culminating in the irreparable destruction of hepatocytes, characterized by the influx of immunological cells and consequent perturbations in biochemical equilibrium, leading to aberrant elevations in serum concentrations of hepatic biomarkers, including glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), alkaline phosphatase (ALP), and lactic dehydrogenase (LDH), indicative of compromised hepatic function and cellular integrity. The purpose of this study is to conduct a complete analysis of the changes in cancer patients’ clinical profiles before and after chemotherapy. The goals include examining the influence of chemotherapy on cardiovascular parameters by measuring changes in systolic and diastolic blood pressure and establishing the clinical relevance of these changes [21-30].

Furthermore, the study looks into hematological changes by quantifying changes in white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, and hematocrit levels after chemotherapy, and determining the effects of these changes on patient health, particularly anemia, and infections. It investigates changes in the biochemical profile, evaluating variations in high-density lipoprotein (HDL) levels and exploring potential mechanisms behind these changes, as well as other biochemical parameters such as platelet count, uric acid, creatinine, cholesterol, low-density lipoprotein (LDL).

Materials and Method

To diagnose cancer, biological samples (serum or plasma) were collected in sterile tubes. Peripheral venous blood samples were collected using a Venoject blood collection system. Serum samples were collected in sterile test tubes, while plasma and whole blood samples were collected in sterile test tubes containing sodium citrate as an anticoagulant. Samples were then incubated at +4°C for 60-62 days [30-35].

Tissue Biopsy

Tissue biopsy (fine-needle aspiration, core needle biopsy, or surgical excision) preserved in formalin or frozen section is required for analysis. Imaging modalities (MRI, CT, PET, or ultrasound) are used for visualization. Histopathological samples (paraffin-embedded tissue blocks or slides) are prepared for microscopic examination. Cancer biomarkers (specific proteins, genes, or molecular signatures) are analyzed using various laboratory techniques [36-43].

In-Depth Medical Examination and Assessment (Talley & O’connor, 2010)

Conduct clinical history and physiological examination - Review signs and symptoms, risk elements, and family histories. Evaluate general health and performance status and identify illnesses and other confounding variables (Bickley & Szilagyi 2012).

Leading-edge Medical Imaging for Enhanced Insight

Radiological imaging (magnetic resonance imaging (MRI, the state of Connecticut, PET (positron emission or ultrasound) for Imagine malignancies to assess location, dimension, and extent [44-50]. Identify metastases or recurrences and guide histological techniques (Islam & Walker, 2013).

Molecular Diagnostics and Blood Biomarker Evaluation

Blood samples are analyzed for tumor-associated antigens such as PSA, CA-125, or CEA. Circulating cancerous cells (CTCs), Cell-free DNA (circulating cf) plus transporting cell DNA (chromosomal). Thorough blood counts (CBC) and blood chemical testing. Biomarker investigation via ELISA, Western wipe, or PCR [51-58].

Precise Cellular and Tissue Examination for Effective Treatment

To diagnose cancer, tissue samples are collected from suspicious tumors using several biopsy procedures. The samples are then processed and microscopically inspected to detect cancer cells, assess their features and tissue structure, establish the disease’s severity and stage, and discover particular cancer biomarkers [59-71].

Comprehensive Synthesis and Expert Consortium for Informed Decision-Making

Cancer diagnosis encompasses patient information, medical imaging, and testing in the laboratory [72-91]. A team of specialists works together to develop an accurate diagnosis, considering particular health circumstances [72-96].

Classifying the Severity and Extent of a Medical Condition

Cancer evaluation involves evaluating tumor size and spread, determining aggressiveness, detecting dissemination to other body areas, and finding variables that influence the outcome of therapy and survival.

Results

Pre- and Post-Chemotherapeutic Effects on Clinical Profile of Cancer Patients

Systolic Blood Pressure (SBP): There was a significant decrease in SBP post-chemotherapy. The pre-chemotherapy SBP was133.5 ± 20.14 mmHg, which dropped to 123.3 ± 15.26 mmHg after the third chemotherapy cycle (P=0.026).

Diastolic Blood Pressure (DBP): Similarly, DBP showed a significant decrease after the second chemotherapy cycle, from 82.54 ± 11.27 mmHg pre-chemotherapy to 76.64 ± 8.96 mmHg post-second cycle, followed by a slight increase to 77.19 ± 10.35 mmHg after the third cycle (P=0.029).

White Blood Cells (WBC): The WBC count significantly decreased post-chemotherapy, dropping from 5.63 ± 2.20 x 10⁹/L pre-chemotherapy to 4.18 ± 1.69 x 10⁹/L after the third cycle (P=0.008). This decrease is attributed to the suppression of hematopoietic stem cells by chemotherapy.

Red Blood Cells (RBC): The RBC count also showed a significant reduction post- chemotherapy, likely due to ineffective erythropoiesis. Although specific values were not provided for RBC, the trend follows previous studies indicating a significant post- chemotherapy decrease (P < 0.01).

Platelets

Platelet Count (PLT): There was a decrease in platelet count from 299.4 ± 147.6 x 10³/μL pre-chemotherapy to 271.7 ± 109.1 x 10³/μL post-chemotherapy, but this change was not statistically significant (P=0.622).

Uric Acid and Creatinine: Levels of uric acid and creatinine remained stable throughout the chemotherapy cycles, with no significant changes observed (Uric Acid P=0.852, Creatinine P=1.000).

Cholesterol: Cholesterol levels increased from 5.51 ± 1.45 pre-chemotherapy to 6.27 ± 1.57 post-chemotherapy, but this change was not statistically significant (P=0.293).

High-Density Lipoprotein (HDL): HDL levels showed a significant increase from 1.17 ± 0.45 pre-chemotherapy to 1.52 ± 0.49 post-chemotherapy (P=0.014).

Low-Density Lipoprotein (LDL), Very Low-Density Lipoprotein (VLDL), and Triglycerides: Increases in LDL, VLDL, and triglycerides were observed but were not statistically significant (LDL P=0.801, VLDL P=0.662, Triglycerides P=0.521).

Table 1 Provides a clear comparison of the clinical profiles of cancer patients before and after chemotherapy, highlighting statistically significant changes in blood pressure, WBC count, and HDL levels, as well as other parameters that showed non-significant changes (Table 2).

Discussion

This comprehensive study elucidates the profound and multifaceted impact of chemotherapy on the clinical profiles of cancer patients, revealing significant alterations in several key physiological strictures. One of the pivotal findings is the notable decrease in both systolic and diastolic blood pressure following chemotherapy. This decrease suggests a systemic effect of chemotherapeutic agents on cardiovascular homeostasis, possibly through their cytotoxic effects on endothelial cells and other components integral to vascular tone regulation. These cardiovascular changes warrant close monitoring and management to prevent potential hypotensive episodes and related complications. A critical and consistent observation across the study is the substantial reduction in white blood cell (WBC) count post-chemotherapy. This decline can be attributed to the myelosuppressive effects of chemotherapeutic agents, which inhibit the proliferation of hematopoietic stem cells essential for WBC production. The resultant leukopenia significantly impairs the immune system’s ability to combat infections, placing patients at heightened risk for opportunistic infections. This finding aligns with prior research, underscoring the importance of vigilant monitoring and prophylactic measures to mitigate infection risks in this vulnerable population [97-100].

Similarly, the study documents a significant decrement in red blood cell (RBC) count following chemotherapy, likely due to disrupted erythropoiesis. This reduction in RBC count diminishes the oxygen-carrying capacity of the blood, leading to severe anemia, which can manifest as fatigue, weakness, and diminished quality of life. These findings are consistent with existing literature, which highlights the anemia-inducing effects of chemotherapy and underscores the need for regular hematological assessments and timely interventions, such as erythropoiesis-stimulating agents or transfusions, to manage anemia effectively.

In addition to RBCs, hemoglobin and hematocrit levels also exhibit statistically significant reductions post-chemotherapy. These declines further corroborate the presence of chemotherapy-induced anemia and emphasize the necessity for ongoing surveillance of these parameters. Regular monitoring enables early detection and intervention, which are crucial for maintaining patient well-being and preventing severe anemia-related complications. Interestingly, the study reports a significant increase in high-density lipoprotein (HDL) levels post-chemotherapy. While the precise mechanisms underlying this increase are not entirely understood, it may reflect compensatory metabolic adjustments or alterations in lipid metabolism induced by chemotherapeutic agents. This finding invites further investigation to elucidate the pathways involved and their clinical implications. Conversely, other parameters, including platelet count, uric acid, creatinine, cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, showed changes that were not statistically significant. This variability suggests a more complex interplay of factors influencing these biomarkers, possibly involving individual patient differences in metabolism, disease state, and treatment response. Further research is needed to explore these relationships and to identify any potential long-term effects of chemotherapy on these parameters [101-110].

In summary, the study’s findings of significant hematological perturbations, particularly in WBC and RBC counts, underscore the critical need for meticulous monitoring and proactive management of cancer patients undergoing chemotherapy. Addressing these hematological changes promptly is essential to preventing life-threatening conditions such as severe anemia and infections. Additionally, understanding and managing the cardiovascular and metabolic changes induced by chemotherapy can further optimize therapeutic outcomes and enhance the overall quality of life for patients during and after cancer treatment. This holistic approach to patient care, encompassing rigorous monitoring and timely interventions, is pivotal in mitigating the adverse effects of chemotherapy and supporting patients throughout their treatment journey [111-115].

Conclusion

The study emphasizes the importance of extensive pre-and post-treatment assessments for cancer patients due to chemotherapy’s major influence on their clinical profiles. Chemotherapy causes significant circulatory alterations, specifically drops in both systolic and diastolic blood pressure, which might have an impact on patient health. Hematological changes are severe, with considerable declines in white blood cell (WBC) and red blood cell (RBC) counts, hemoglobin, and hematocrit levels. These alterations increase the risk of serious anemia and infections, underlining the importance of watchful monitoring. While high-density lipoprotein (HDL) levels increase significantly after chemotherapy, the reasons behind this shift remain unknown, necessitating additional research. Other biochemical indicators, such as platelet count, uric acid, creatinine, cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, show non-significant changes, showing varying effects of chemotherapy.

References

1. Abdel-Reheim MA, Ashour AA, Khattab MA, Gaafar AGA (2022) Quillaja saponaria bark saponin attenuates methotrexate induced hepatic oxidative stress, inflammation and associated liver injury in rats. J Appl Pharma Sci 12(5): 129-141.
2. Abdelghffar EA, Obaid WA, Alamoudi MO, Mohammedsaleh ZM, Annaz H, et al. (2022) Thymus fontanesii attenuates CCl4-induced oxidative stress and inflammation in mild liver fibrosis. Biomed Pharmaco 148: 112738.
3. Abdullah AS, Ahmed AG, Mohammed SN, Qadir AA, Bapir NM, et al. (2023) Benign Tumor Publication in One Year (2022): A Cross-Sectional Study. Barw Med J 1(4).
4. Abrams RA, Lowy AM, O’Reilly EM, Wolff RA, Picozzi VJ, et al. (2009) Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 16(7): 1751-1756.
5. Ackerman LV, Mucciardi AN, Gose EE (1973) Classification of benign and malignant breast tumors on the basis of 36 radiographic properties. Cancer 31(2): 342- 352.
6. Aebi S, Karlsson P, Wapnir IL (2022) Locally advanced breast cancer. Breast 62(Suppl 1): S58-S62.
7. Aghi M, Barker FG (2006) Benign adult brain tumors: an evidence-based medicine review. Prog Neurol Surg 19: 80-96.
8. Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nature Re Cancer 7(3): 192-201.
9. Ahmad Z, Idress R, Fatima S, Uddin N, Ahmed A, et al. (2016) Commonest cancers in Pakistan-findings and histopathological perspective from a premier surgical pathology center in Pakistan. Asian Pac J Cancer Prev 17(3): 1061.
10. Ahmed AA, Abedalthagafi M (2016) Cancer diagnostics: the Journey from histomorphology to molecular profiling. Oncotarget 7(36): 58696.
11. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, et al. (2002) Cancer as a microevolutionary process. Molecular Biology of the Cell (4^th edition): Garland Science.
12. Alhmoud JF, Farah HS, Al-Qaisi T (2021) The Changes in Some Hematological Parameters among University Students Due to Stressful Conditions During and after Examinations Period. Indian J Forensic Med Toxicol 15(1): 1181-1186.
13. Ali MA (2016) A Study of Reference Ranges for Biochemical and Hematological Parameters in the Healthy Population of Bangladesh. University of Rajshahi.
14. Alsulami MB (2020) Effect of almond oil on hepatic fibrosis induced by thioacetamide in male rats. Doctoral Dissertation, King Abdulaziz University Jeddah.
15. Anand U, Dey A, Chandel AKS, Sanyal R, Mishra A, et al. (2023) Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes & Dis 10(4): 1367-1401.
16. Andreyev HJN, Davidson SE, Gillespie C, Allum WH, Swarbrick E (2012) Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer. Gut 61(2): 179-192.
17. Antunović Z, Klir Ž, Šperanda M, Sičaja V, Čolović D, et al. (2018) Partial replacement of soybean meal with pumpkin seed cake in lamb diets: Effects on carcass traits, haemato-chemical parameters and fatty acids in meat. South Afr J Animal Sci 48(4): 695-704.
18. Arbyn M, Castellsagué X, de Sanjosé S, Bruni L, Saraiya M, et al. (2011) Worldwide burden of cervical cancer in 2008. Ann Oncol 22(12): 2675-2686.
19. Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, et al. (2020) Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Global Health 8(2): e191-e203.
20. Baldo BA, Pham NH (2013) Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch. Cancer Metastasis Rev 32: 723-761.
21. Bao Y, Kong X, Yang L, Liu R, Shi Z, et al. (2014) Complementary and alternative medicine for cancer pain: an overview of systematic reviews. Evidence- Based Complem Alternative Med 2014.
22. Basak D, Arrighi S, Darwiche Y, Deb S (2022) Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile. Life 12(1): 48.
23. Bekeschus S (2023) Medical gas plasma technology: Roadmap on cancer treatment and immunotherapy. Redox Biol 65: 102798.
24. Bellg AJ, Borrelli B, Resnick B, Hecht J, Minicucci DS, et al. (2004) Enhancing treatment fidelity in health behavior change studies: best practices and recommendations from the NIH Behavior Change Consortium. Health Psychol 23(5): 443.
25. Berretta M, Caraglia M, Martellotta F, Zappavigna S, Lombardi A, et al. (2016) Drug–drug interactions based on pharmacogenetic profile between highly active antiretroviral therapy and antiblastic chemotherapy in cancer patients with HIV infection. Front Pharmacol 7: 71.
26. Bhurgri Y, Bhurgri A, Nishter S, Ahmed A, Usman A, et al. (2006) Pakistan-country profile of cancer and cancer control 1995-2004. J Pak Med Assoc 56(3): 124.
27. Bickley L, Szilagyi PG (2012) Bates' guide to physical examination and history-taking: Lippincott Williams & Wilkins.
28. Black WC (2000) Overdiagnosis: an underrecognized cause of confusion and harm in cancer screening. J Nat Cancer Institute 92(16): 1280-1282.
29. Borràs Andrés JM, Lievens Y, Barton M, Corral J, Ferlay J, et al. (2016) How many new cancer patients in Europe will require radiotherapy by 2025? An ESTRO-HERO analysis. Radiother Oncol 119(1): 5-11.
30. Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, et al. (2018) Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 36(17): 1714-1768.
31. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 68(6): 394-424.
32. Brodersen J, Schwartz LM, Woloshin S (2014) Overdiagnosis: how cancer screening can turn indolent pathology into illness. Apmis 122(8): 683-689.
33. Bunn PA, Kelly K (1998) New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. Clinical cancer research: an official journal of the American Assoc Cancer Res 4(5): 1087-1100.
34. Cairns J (1975) The cancer problem. Scientific American, 233(5): 64-79.
35. Chabner BA, Amrein PC, Druker B, Michaelson MD, Mitsiades CS, et al. (2006) Antineoplastic agents. The pharmacological basis of therapeutics 9/e, pp. 1315-1465.
36. Chatterjee SK, Zetter BR (2005) Cancer biomarkers: knowing the present and predicting the future. Future Oncol 1(1): 37-50.
37. Chen J, Gu H, Fu S, Lu J, Tan H, et al. (2021) Multifunctional injectable hydrogels for three-in-one cancer therapy: Preoperative remission via mild photothermal-enhanced supramolecular chemotherapy and prevention of postoperative recurrence and adhesion. Chem Eng J 425: 130377.
38. Chen SC, Cheung YC, Su CH, Chen MF, Hwang TL, et al. (2004) Analysis of sonographic features for the differentiation of benign and malignant breast tumors of different sizes. Ultrasound in Obstetrics and Gynecology: Official J Int Soc Ultrasound Obstetr Gynecol 23(2): 188-193.
39. Chung R, Tyebally S, Chen D, Kapil V, Walker JM, et al. (2020) Hypertensive cardiotoxicity in cancer treatment-systematic analysis of adjunct, conventional chemotherapy, and novel therapies-epidemiology, incidence, and pathophysiology. J Clin Med 9(10): 3346.
40. Clark W (1991) Tumour progression and the nature of cancer. Br J Cancer 64(4): 631-644.
41. Coughlin SS, Ekwueme DU (2009) Breast cancer as a global health concern. Cancer Epidemiol 33(5): 315-318.
42. Crawford S (2013) Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy. Front Pharmacol 4: 43926.
43. Crino L, Weder W, Van Meerbeeck J, Felip E (2010) Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21: v103-v115.
44. Crosby D, Bhatia S, Brindle KM, Coussens LM, Dive C, et al. (2022) Early detection of cancer. Science 375(6586): eaay9040.
45. Crossnohere NL, Richardson DR, Reinhart C, O’Donoghue B, Love SM, et al. (2019) Side effects from acute myeloid leukemia treatment: results from a national survey. Curr Med Res Opin 35(11): 1965-1970.
46. Dahlin DC, Ivins JC (1972) Benign chondroblastoma. A study of 125 cases. Cancer 30(2): 401-413.
47. Dave DJ, Pillai A, Shah DV, Agarwal S, Goel A (2014) An analysis of utilization pattern of anticancer drugs in diagnosed cases of carcinoma in a tertiary care teaching hospital. Int J Basic Appl Med Sci 4(1): 251-259.
48. Delaney G, Jacob S, Featherstone C, Barton M (2005) The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence‐based clinical guidelines. Cancer: Interdiscipl Int J Am Cancer Soc 104(6): 1129-1137.
49. Delantoni A, Sarafopoulos A, Polanagnostaki A, Orhan K (2020) B-mode and color Doppler imaging of carotid paragangliomas in different neck regions. J Ultrasonogr 20(82): 218-221.
50. Denmeade SR, Isaacs JT (1996) Programmed cell death (apoptosis) and cancer chemotherapy. Cancer Control 3(4): 303-309.
51. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, et al. (2014) Cancer treatment and survivorship statistics, 2014. CA: Cancer J Clin 64(4): 252-271.
52. DeVita VT, Chu E (2008) A history of cancer chemotherapy. Cancer Res 68(21): 8643-8653.
53. Diluvio L, Torti C, Terrinoni A, Candi E, Piancatelli R, et al. (2014) Dermoscopy as an adjuvant tool for detecting skin leiomyomas in patient with uterine fibroids and cerebral cavernomas. BMC Dermatol 14: 1-6.
54. Dimery I, Hong W (1993) Overview of combined modality therapies for head and neck cancer. JNCI: J Natl Cancer Institute 85(2): 95-111.
55. Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, et al. (2016) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44(6): 2846-2858.
56. Duguid J, Winkelman L, Feldman P, Brady AM (1989) The effect of citrate anticoagulants on apheresed plasma. Transfusion Sci 10(4): 287-293.
57. Dundr P, Bártů M, Bosse T, Bui QH, Cibula D, et al. (2023) Primary mucinous tumors of the ovary: an interobserver reproducibility and detailed molecular study reveals significant overlap between diagnostic categories. Modern Pathol 36(1): 100040.
58. Dunn BK, Woloshin S, Xie H, Kramer BS (2022) Cancer overdiagnosis: a challenge in the era of screening. J Natl Cancer Center 2(4): 235-242.
59. Dy GK, Adjei AA (2013) Understanding, recognizing, and managing toxicities of targeted anticancer therapies. CA: Cancer J Clin 63(4): 249-279.
60. Falzone L, Salomone S, Libra M (2018) Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol 9: 421926.
61. Farrell N (2015) Multi-platinum anti-cancer agents. Substitution-inert compounds for tumor selectivity and new targets. Chem Soc Rev 44(24): 8773-8785.
62. FarzamFar B, Adham H, Norouzi S, Vakili V, Maleki Y (2021) Evaluation of citrate consumption by microorganisms in anticoagulant bags of sodium citrate in case of contamination. Medbiotech J 5(4).
63. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi REM, et al. (2016) Worldwide burden of colorectal cancer: A Review. Updates Surg 68: 7-11.
64. Feng RM, Zong YN, Cao SM, Xu RH (2019) Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Communic 39(1): 1-12.
65. Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Transact 47(19): 6645-6653.
66. Palumbo MO, Kavan P, Miller WH, Panasci L, Assouline S, et al. (2013) Systemic cancer therapy: achievements and challenges that lie ahead. Front Pharmacol 4: 57.
67. Pan ST, Li ZL, He ZX, Qiu JX, Zhou SF (2016) Molecular mechanisms for tumour resistance to chemotherapy. Clinical and Experimental Pharmacology and Physiol 43(8): 723-737.
68. Patagar NG (2019) Comparative Study of Efficacy of Palonosetron, Dexamethasone & Glycopyrrolate in Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Lower Abdominal Surgeries Under Spinal Anesthesia Using Bupivacaine with Morphine. Rajiv Gandhi University of Health Sciences (India).
69. Patel A (2020) Benign vs malignant tumors. JAMA Oncology 6(9): 1488-1488.
70. Patra CR, Bhattacharya R, Mukhopadhyay D, Mukherjee P (2008) Application of gold nanoparticles for targeted therapy in cancer. J Biomed Nanotechnol 4(2): 99-132.
71. Pavet V, Portal M, Moulin J, Herbrecht R, Gronemeyer H (2011) Towards novel paradigms for cancer therapy. Oncogene, 30(1): 1-20.
72. Peng Y, Jiang Y, Yang C, Brown JB, Antic T, et al. (2013) Quantitative analysis of multiparametric prostate MR images: differentiation between prostate cancer and normal tissue and correlation with Gleason score-a computer-aided diagnosis development study. Radiology 267(3): 787-796.
73. Persons JB, Mikami AY (2002) Strategies for handling treatment failure successfully. Psychotherapy: Theory, Res Pract Train 39(2): 139.
74. Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C (2005) The global burden of oral diseases and risks to oral health. Bullet World Health Org 83(9): 661-669.
75. Pierce GB, Wallace C (1971) Differentiation of malignant to benign cells. Cancer Res 31(2): 127-134.
76. Pimple S, Mishra G (2022) Cancer cervix: Epidemiology and disease burden. Cytojournal 19: 21.
77. Pisani P, Parkin D, Ferlay J (1993) Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden. Int J Cancer 55(6): 891-903.
78. Pitt J, Marabelle A, Eggermont A, Soria JC, Kroemer G, et al. (2016) Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol 27(8): 1482-1492.
79. Poste G (1986) Pathogenesis of metastatic disease: implications for current therapy and for the development of new therapeutic strategies. Cancer Treat Rep 70(1): 183-199.
80. Prasad JB, Dhar M (2018) Projections of burden of cancers: A new approach for measuring incidence cases for India and its States–till 2025. J Cancer Policy 16: 57-62.
81. Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE (1990) Increased cell division as a cause of human cancer. Cancer Res 50(23): 7415-7421.
82. Prince MJ, Wu F, Guo Y, Robledo LMG, O'Donnell M, et al. (2015) The burden of disease in older people and implications for health policy and practice. Lancet 385(9967): 549-562.
83. Pucci C, Martinelli C, Ciofani G (2019) Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedicalsci 13: 961.
84. Qureshi MA, Khan S, Sharafat S, Quraishy MS (2020) Common cancers in Karachi, Pakistan: 2010-2019 cancer data from the Dow cancer registry. Pak J Med Sci 36(7): 1572.
85. Rafiemanesh H, Rajaei-Behbahani N, Khani Y, Hosseini S, Mohammadian-HA, et al. (2016) Incidence trend and epidemiology of common cancers in the center of Iran. Glob J Health Sci 8(3): 146.
86. Rahbar G, Sie AC, Hansen GC, Prince JS, Melany ML, et al. (1999) Benign versus malignant solid breast masses: US differentiation. Radiology 213(3): 889-894.
87. Rahman M, Hasan MR (2015) Cancer metabolism and drug resistance. Metabolites 5(4): 571-600.
88. Service FJ, Mcmahon MM, O'brien PC, Ballard DJ (1991) Functioning insulinoma-incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc 66(7): 711-719.
89. Slooten HV, Schaberg A, Smeenk D, Moolenaar AJ (1985) Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 55(4): 766-773.
90. Srivastava S, Koay EJ, Borowsky AD, De Marzo AM, Ghosh S, et al. (2019) Cancer overdiagnosis: a biological challenge and clinicaldilemma. Nature Rev Cancer 19(6): 349-358.
91. Srivastava S, Reid BJ, Ghosh S, Kramer BS (2016) Research needs for understanding the biology of overdiagnosis in cancer screening. J Cell Physiol 231(9): 1870-1875.
92. Stabile BE, Passaro E (1985) Benign and malignant gastrinoma. Am J Surg 149(1): 144-150.
93. Stakheyeva M, Riabov V, Mitrofanova I, Litviakov N, Choynzonov E, et al. (2017) Role of the immune component of tumor microenvironment in the efficiency of cancer treatment: perspectives for the personalized therapy. Curr Pharma Design 23(32): 4807-4826.
94. Stanley K, Stjernswärd J (1989) Lung cancer-a worldwide health problem. Chest 96(1): 1S-5S.
95. Sudhakar A (2009) History of cancer, ancient and modern treatment methods. J Cancer Sci Ther 1(2): 1.
96. Sun K, Chen X, Chai W, Fei X, Fu C, et al. (2015) Breast cancer: diffusion kurtosis MR imaging-diagnostic accuracy and correlation with clinical- pathologic factors. Radiol 277(1): 46-55.
97. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 71(3): 209-249.
98. Sylla BS, Wild CP (2012) A million africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer 130(2): 245-250.
99. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, et al. (2015) Global cancer statistics, 2012. CA: Cancer J Clin 65(2): 87-108.
100. Trayes KP, Cokenakes SE (2021) Breast cancer treatment. Am Family Physi 104(2): 171-178.
101. Tsimberidou AM, Fountzilas E, Nikanjam M, Kurzrock R (2020) Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer Treatment Rev 86: 102019.
102. Undevia SD, Gomez-Abuin G, Ratain MJ (2005) Pharmacokinetic variability of anticancer agents. Nature Rev Cancer 5(6): 447-458.
103. Verma B, McLeod P, Klevansky A (2010) Classification of benign and malignant patterns in digital mammograms for the diagnosis of breast cancer. Expert Syst Applic 37(4): 3344-3351.
104. Vulva V, Cervix U, Oviduct O, Katz VL (2012) Benign Gynecologic Lesions. Comprehensive Gynecology E-Book, 383.
105. Vuorela P, Lintula S, Stenman UH, Halmesmäki E (2003) Expression of vascular endothelial growth factor in peripheral blood cells of preeclamptic women. Hypertension Pregnancy 22(2): 193-201.
106. Wani SH, Lone SA (2018) Cancer: Diseases: Educreation Publishing.
107. Was H, Borkowska A, Bagues A, Tu L, Liu JY, et al. (2022) Mechanisms of chemotherapy-induced neurotoxicity. Front Pharmacol 13: 750507.
108. Weinberg RA (1996) How cancer arises. Scientific Am 275(3): 62-70.
109. Weisburger JH (1998) Worldwide prevention of cancer and other chronic diseases based on knowledge of mechanisms. Mutation Res 402(1-2): 331-337.
110. Welch HG, Black WC (2010) Overdiagnosis in cancer. J National Cancer Institute 102(9): 605-613.
111. Welch HG, Schwartz L, Woloshin S (2012) Overdiagnosed: making people sick in the pursuit of health: beacon press.
112. Wernecke K, Vassallo P, Bick U, Diederich S, Peters PE (1992) The distinction between benign and malignant liver tumors on sonography: value of a hypoechoic halo. AJR 159(5): 1005-1009.
113. Wever EM, Draisma G, Heijnsdijk EA, de Koning HJ (2011) How does early detection by screening affect disease progression? Modeling estimated benefits in prostate cancer screening. Med Decision Making 31(4): 550-558.
114. Wild S, Fischbacher C, Brock A, Griffiths C, Bhopal R (2006) Mortality from all cancers and lung, colorectal, breast and prostate cancer by country of birth in England and Wales, 2001-2003. Br J Cancer 94(7): 1079-1085.
115. Wilson C, Tobin S, Young R (2004) The exploding worldwide cancer burden. Int J Gynecologic Cancer 14(1): 1-11.