Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Cancer Antigen 125, Prostate-Specific Antigen and Other Cancer Markers: A Primer on Commonly Used Cancer Markers.

Cancer markers are molecules produced by cancer cells which may serve to identify the presence of cancer. Cancer markers can be differentiated as serum-based, radiology-based and tissue-based, and are one of the most important tools in diagnosing, staging and monitoring of treatment of many cancers. The most used cancer markers are serum cancer markers due to its relative ease and lower cost of testing. However, serum cancer markers have poor mass screening utilization due to poor positive predictive value. Several markers such as prostate-specific antigen (PSA), beta-human chorionic gonadotropin (B-hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are used to aid in diagnosis of cancer in cases of high suspicion. Serum markers such as carcinoembryonic antigen (CEA), AFP, carbohydrate antigen 19-9 (CA 19-9), and 5-hydroxyindoleacetic acid (5-HIAA) play a significant role in assessing disease prognosis as well as response to treatment. This work reviews the role of some of the biomarkers in the diagnosis and treatment of cancer.

Unusual presentation of a small cell lung cancer with bilateral breast metastases: Case report and a brief review of the literature.

Small cell lung cancer (SCLC) is a smoker's disease and occurs almost exclusively in smokers. SCLC is a high-grade neuroendocrine tumor and commonly presents as a central tumor with bulky mediastinal adenopathy. It is notorious for causing widespread disease and paraneoplastic syndromes. The usual sites of metastasis include the liver, brain, bone, and adrenals. SCLC presenting with breast metastasis is unusual; however, there are reports of unilateral and bilateral breast metastases. SCLC with bilateral breast metastases is extremely rare, with only five previously reported cases available in the literature. We are taking this opportunity to report and add to the growing literature on the unusual presentation of a small cell lung cancer with bilateral breast metastases.

Increasing Trends in Mortality Rate Among Salivary Gland Tumors in Non-Geriatric African Americans.

Background: The treatment of salivary gland tumors has not changed significantly in the past two decades. However, the increase in the geriatric population with these tumors poses a new challenge for their management. This study explores the incidence-based mortality trends in the geriatric and non-geriatric population for the time period of 2000 - 2014 and compares the trends between races. Methods: Mortality data were extracted from the Surveillance, Epidemiology, and End Results (SEER) Database for the years 2000 - 2014. Incidence-based mortality for all stages of salivary gland tumors was queried and the results were grouped by age (geriatric vs. non-geriatric determined as 65 vs. below 65 years of age) and race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander). All stages and both genders were included in the analysis. T-test was used to determine statistically significant difference between various subgroups. Linearized trend lines were used to visualize the mortality trends between various subgroups (geriatric vs. non-geriatric and Caucasian vs. African American). Results: Incidence-based mortality for salivary gland tumors has worsened since 2000 to 2014 for both geriatric and non-geriatric patients (P < 0.05). There was a statistically significant difference between these two groups in both Caucasian/White patients and African American/Black patients. Notably, the worst incidence-based mortality rates were noted in African American/Black non-geriatric patients followed by Caucasian/White non-geriatric patients. However, there was no statistical difference in incidence-based mortality between Caucasian/White patients and African American/Black geriatric patients. Conclusions: The similarity in incidence-based mortality for geriatric patients with salivary gland tumors in both Caucasian/White patients and African American/Black groups suggests that the effects of race may not be pronounced in the elderly population. The high rate of incidence-based mortality in African American/Black non-geriatric patients may suggest environmental influence and warrants further study.

Advances in the Treatment of Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) represents 10-15% of salivary neoplasms. Due to their low incidence, it is challenging to conduct clinical trials and develop treatment guidelines. Although surgery is the most common approach for a resectable tumor, various treatment options such as chemotherapy, radiotherapy, and immunotherapy have been investigated. There is a need to implement a standardized treatment protocol to effectively manage MEC as it is a common histological subtype. Furthermore, it has become essential to assess chromosomal and genetic abnormalities recently identified with MEC, including alterations of CDKN2A, TP53, CDKN2B, BAP1, etc. These mutations are involved in the transformation of low-grade tumors to high-grade tumors, presenting a vital tool for evaluating the aggressive behavior of this carcinoma. Detailed immunohistochemical and translocation studies can help develop targeted therapies and monitor treatment response. Therefore, biomarker-driven research will immensely improve the outcome, especially in advanced cases. Based on thorough histology and chromosomal translocations, a more personalized treatment plan can improve the overall disease outcome. The purpose of this article is to elaborate on the current treatment advancements, particularly chemotherapy and targeted therapy, as an effective treatment modality for the management of MEC and highlight the comparison with traditional treatment approaches.

Tumor Dormancy: Biologic and Therapeutic Implications.

Metastatic cancer can arise years after treatment of the primary tumor because residual tumor cells can enter dormancy and evade elimination by anti-neoplastic therapies. The mechanisms underlying this phenomenon have been investigated and a number of hypotheses have been proposed. Tumor mass dormancy involves a balance between apoptotic and proliferative cells, keeping a micrometastatic lesion constant in size. This induces a need for blood supply which involves angiogenic dormancy. Cellular dormancy is also considered a mechanism of dormancy, where dormancy is induced due to cells entering a quiescent, reversible, growth-arrested state. In addition to all of these mechanisms, important changes in the tumor microenvironment, including the extracellular matrix, the oxygenation levels of the environment, and endoplasmic reticulum stress, are involved in inducing and maintaining tumor dormancy. Since dormant tumors are commonly known to be resistant to chemotherapy, gaining more knowledge of the mechanism of dormant tumor cells is of importance, as it can lead to the development of future treatment strategies.

Bimodal Age Distribution in Cancer Incidence.

Cancer is caused by accumulation of genetic changes which include activation of protooncogenes and loss of tumor suppressor genes. The age-specific incidence of cancer in general increases with advancing age. However, some cancers exhibit a bimodal distribution. Commonly recognized cancers with bimodal age distribution include acute lymphoblastic leukemia, osteosarcoma, Hodgkin's lymphoma, germ cell tumors and breast cancer. Delayed infection hypothesis has been used to provide explanation for the early childhood peak in leukemias and lymphomas, whereas the peak at an older age is associated with accumulation of protooncogenes and weakened immune system. Further genetic analysis and histopathological variations point to distinctly different cancers, varying genetically and histologically, which are often combined under a single category of cancers. Tumor characteristics and age distribution of these cancers varies also by population groups and has further implications on cancer screening methods. Although significant advances have been made to explain the bimodal nature of such cancers, the specific genetic mechanisms for each age distribution remain to be elucidated. Further distinction among the different cancer subtypes may lead to improvements in individual risk assessments, prevention and enhancement of treatment strategies.

Genetic Polymorphisms in Pharmaceuticals and Chemotherapy.

The study of genetic polymorphisms has significantly advanced the field of personalized medicine. Polymorphism of genes influence the efficacy of drugs used for treating medical conditions such as depression, cardiac diseases, thromboembolic disorders, oncological diseases, etc. The study of genetic polymorphism is beneficial for drug safety as well as for assessing therapeutic outcomes. Understanding and detecting genetic polymorphisms early on in patients can be useful in selecting the correct chemotherapeutic agent and appropriate dosage for a patient. Knowing the genetic profile of a patient and the interindividual response to various drugs significantly influences the proper selection of medication - a key step towards personalized medicine. Polymorphisms also make patients susceptible to certain cancers and identification of these polymorphisms early can be useful for a personalized treatment plan. The Genome-Wide Association Studies (GWAS) project where millions of genetic variants in the genomes of many individuals are studied to identify connections between what is present on the gene and the phenotype of the patient has enhanced the prospect of personalized medicine. GWAS has been used to identify hundreds of diseases associated to genetic polymorphisms. Individual pharmacokinetic profiles of patients to drugs enable the development of early surveillance protocols to prophylactically prevent patients from having adverse reactions. Furthermore, patient-derived cellular organoids are another advancement that allows researchers to screen for polymorphisms of the patient for adverse reactions from chemotherapy and will allow for the development of new medications that are specific to the profile of the patient's tumor. These advances have led to significant progress towards personalized medicine. The functional consequences of genetic polymorphism on cancer drugs and treatment are studied here.

Analysis of Trends in Mortality in Patients with Lymphoepithelial Carcinoma of the Head and Neck.

BACKGROUND: Squamous cell carcinoma is the most common subtype of malignancy found in patients with head and neck malignancy. There are other rare subtypes which are not adequately reported in medical literature. Lymphoepithelial carcinoma consists of lymphocytic infiltration in a background of undifferentiated carcinoma. They are most often seen in salivary glands but can also be found in other structures of the head and neck region. This analysis reports the nation-wide mortality of patients diagnosed with lymphoepithelial carcinoma of the head and neck. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) Database from the years 2000 to 2014. Incidence-based mortality for all stages was queried and results were grouped by gender and race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander). Paired T-test was used to determine statistically significance difference between various subgroups. RESULTS: Incidence-based mortality has been improving for African American/Black patients and has been worsening for Caucasian/White, American Indian/Alaskan native and Asian/Pacific Islander for the period of 2000 to 2014. The differences in mortality trends were statistically different (P < 0.05). The highest mortality rate per 1000 patients was seen in Asian/Pacific Islander population, followed by African American/Black, American Indian/Alaskan native and the least mortality was noted in Caucasian/White patients. When a similar analysis with linearized trend lines on gender was conducted, only African American/Black males and Asian/Pacific Islander females showed an improving trend in mortality. The sample size was a major limitation of this study (Caucasian/White - 134, African American/Black - 30, American Indian/Alaskan native - 5 and Asian/Pacific Islander - 87). CONCLUSION: Lymphoepithelial carcinoma is a rare subtype of head and neck malignancies whose incidence-based mortality showed a worsening trend. This study showed significant race and gender disparity amongst patients with lymphoepithelial carcinoma. Due to its rarity, this subtype warrants further study, especially with regards to its etiology, clinical course and cure rates.

Analysis of Race and Gender Disparities in Mortality Trends from Patients Diagnosed with Nasopharyngeal, Oropharyngeal and Hypopharyngeal Cancer from 2000 to 2017.

BACKGROUND: Squamous cell carcinoma of the nasopharynx, oropharynx and hypopharynx constitutes a majority of head neck malignancies. The incidence-based mortality across different races has been noted to be divergent. This study analyzes the trend in incidence-based mortality from the years 2000 to 2017 amongst both the genders in Caucasian/White and African American/Black patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Database was queried to conduct a nation-wide analysis for the years 2000 to 2017. Incidence-based mortality for all stages of nasopharyngeal, oropharyngeal and hypopharyngeal cancer was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander) and gender. All stages and ages were included in the analysis. t-test was used to determine statistically significant differences between various subgroups. Linearized trend lines were used to visualize the mortality trends of all sub groups. RESULTS: Across all races, the male to female gender disparity in mortality was ~1:3 in patients with nasopharynx and became worse to ~1:4 and ~1:5 for patients with oropharyngeal and hypopharyngeal cancers, respectively. Notably, the highest incidence-based mortality for nasopharyngeal cancers is seen in Asian/pacific Islander males and a similar peak is noted for hypopharyngeal cancers in African American/Black males. Incidence-based mortality rates (per 1000) for nasopharyngeal, oropharyngeal and hypopharyngeal cancer of all races and both the genders was noted to be divergent. CONCLUSION: A significant gender disparity exists in all three pharyngeal cancers across all races. It is unclear if female gender is protective but further study is warranted in a stage-specific and age-specific manner to better understand this disparity.

Cancer stem cells in head and neck cancer.

Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following treatment, and show increased tumorigenic potential when compared to other cancer cells. It is thought that they are responsible for the recurrence of tumors as well as the resistance to treatment that is seen clinically. CSCs are known to be involved in head and neck cancer (HNCs) specifically, as evidence for their existence can be found in head and neck squamous cell carcinoma (HNSCC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC), among others. Here, findings from various approaches to identifying and targeting CSCs and their downstream effectors in HNC are summarized, with an emphasis on recent advancements. Prognostic and therapeutic markers are discussed for each specific type of HNC, and novel treatment strategies and current clinical trials involving CSCs are detailed as well. The information provided here is intended to further the research on this important topic and lead to clinical impact in the battle against HNC.

Management of hepatotoxicity of chemotherapy and targeted agents.

Hepatotoxicity of chemotherapeutic agents such as methotrexate, oxaliplatin, and irinotecan have been well documented and characterized allowing for careful management by oncologists during administration. However, the rapid advance of the field of oncology and introduction of new classes of therapies such as small molecule inhibitors and immunotherapies have introduced new hepatotoxicity challenges and management strategies. This work is a compilation of the hepatotoxicity and recommended management of various chemotherapies and targeted agents, with a focus on the newer classes of targeted anticancer agents.

Unequal allotment of patients in phase III oncology clinical trials.

Patient enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls, however recently some clinical trials have utilized an unequal distribution between the case and control arms. Trends and proportion of phase 3 cancer clinical trials that have an unequal allocation between the years 2010 and 2019 were studied from data extracted from clinicaltrials.gov. 323 trials with two arms and 35 trials with 3 arms were identified as randomized control trials with the primary purpose of a cancer-related treatment that provided allocation data. Amongst the trials with two arms, 238 trials had equal allocation and 85 trials had unequal allocation. Therefore, cancer clinical trials with unequal allocation represent about one in four 2-arm phase 3 trials. Amongst the eligible trials with three arms, 26 trials had equal allocation and 9 trials had unequal allocation. There was no significant difference in the annual proportion of trials with unequal allocation from 2010 to 2019. The categories of cancer which had the highest number of unequally allotted two-arm clinical trials were: gastrointestinal, breast, and genitourinary malignancies. This shift may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs and lower statistical power attached to this method.

Analysis of Trends in Race and Gender Disparities in Incidence-Based Mortality in Patients Diagnosed with Soft Tissue Sarcomas from 2000 to 2016.

BACKGROUND: The clinical course of soft tissue sarcomas is often dependent on the grade of the tumor. The variability of incidence-based mortality in low-grade and high-grade soft tissue sarcomas (STS) with respect to gender and race over the past decade has not been well studied. This study analyzes the rates of incidence-based mortality from the years 2000 to 2016 amongst the grades, genders and racial groups of patients with STS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of low-grade and high-grade soft tissue sarcomas was queried and the results were grouped by race (Caucasian/White vs African American/Black) and gender. All stages and ages were included in the analysis and trend from 2000 to 2016 was analyzed. RESULTS: The incidence-based mortality rates for Caucasians are similar to African Americans in both grades and genders. Rates were not analyzed for American Indian and Asian/Pacific Islanders due to small sample size. Mortality rates of high-grade soft tissue sarcomas were significantly higher compared to low-grade tumors. A higher rate of mortality is noted in Caucasian males compared to African Americans males despite past observations of higher incidence in African Americans. There was no significant change in the rate when trended over the past decade (2007 to 2016). CONCLUSION: This study highlights the higher rate of incidence-based mortality in Caucasian males compared to African American males in the past 15 years despite a lower incidence reported in the 1995 to 2008 period. With no significant change in mortality rates/year noted during this time period, this study implies that soft tissue sarcomas in Caucasian males have worse outcomes. Further research is needed to understand the mechanism underlying this disparity.

Nation-Wide Trends in Incidence-Based Mortality of Patients with Ocular Melanoma in USA: 2000 to 2018.

BACKGROUND: Ocular and orbit melanoma is a rare subtype of melanoma for which outcomes have not been adequately reported. We have analyzed the incidence-based mortality trends of ocular and orbit melanoma over 15 years in USA. Most ocular melanomas originate from the uvea and, to a lesser extent, from the conjunctiva. Primary orbital melanoma is exceedingly rare. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to find the incidence-based mortality for all patients diagnosed with ocular and orbit melanoma for the years 2000 to 2018. Results were grouped by gender and race (Caucasian/White, African American/Black, American Indian/Alaskan Native, and Asian/Pacific Islanders). A paired t-test was used to determine the statistically significant difference between various subgroups (p < 0.05). RESULTS: Incidence-based mortality has been the highest in Caucasian/White patients from 2000 to 2018, followed by African American/Black and Asian/Pacific Islander patients. American Indian/Alaskan native patients appear to have the least mortality. There was a statistically significant difference (p<0.05) in mortality between Caucasian/White patients from 2000 to 2018, and African American/Black and Asian/Pacific Islander patients. The sample size for African American/Black and American Indian/Alaskan native patients was too low to discern a meaningful trend in mortality. Overall, it appears that Caucasian males and females have a far higher and worsening incidence-based mortality compared to other races. CONCLUSION: Ocular melanoma and orbit melanoma are rare entities that are predominantly seen in Caucasian/White patients. This study shows that incidence-based mortality has been worsening for these patients in the past two decades. These entities have a poor prognosis and have not been studied extensively in immunotherapy trials. There is a need for new clinical trials to help improve mortality rates.

Clinical endpoints in oncology - a primer.

Clinical endpoints are essential for assessing the safety and efficacy of new cancer therapies. They are used by oncologists to help guide clinical decision making. While overall survival (OS) has frequently been regarded as the "gold standard" primary clinical endpoint, it's utility is constrained by several disadvantages. The time-consuming nature of trials using OS has led to a recent push to explore surrogate clinical endpoints and their potential to serve as primary clinical endpoints in lieu of OS. Additionally, it is becoming evident that other endpoints add valuable information about quality of life and treatment failure as their use is becoming increasingly prevalent in oncology clinical trials. Without a doubt, the use of clinical endpoints will continue to expand and evolve as new cancer therapies are developed and novel treatments, including immunotherapy, draw interest. This review explores the roles of primary and surrogate clinical endpoints as well as the benefits and drawbacks of each specific endpoint. In addition, it directly compares the unique features of each suggesting some of the specific uses each one fulfills.

Cardiotoxicity of chemotherapy and targeted agents.

The evolution of cancer treatment and development of new classes of anticancer therapies have continued to revolutionize the field of oncology. New therapies including targeted agents, immunotherapies, and adoptive cell transfer have allowed for exciting survival benefit progress for patients. However, the novel nature of these therapies as well as the longer survival periods of patients receiving them has highlighted the various side effects of anticancer therapies. Cardiotoxicity has emerged as a major side effect of anticancer treatment and can present both acutely during treatment and chronically even years after treatment has been completed. This work compiles the cardiotoxic side effects of various chemotherapeutic and targeted anticancer therapies and their management.

Infections in Hospitalized Cancer Patients.

Cancer patients are at an increased risk of developing infections that are primarily treatment-driven but may also be malignancy-driven. While cancer treatments such as chemotherapy, radiotherapy, and surgery have been known to improve malignancy morbidity and mortality, they also have the potential to weaken immune defenses and induce periods of severe cytopenia. These adverse effects pave the way for opportunistic infections to complicate a hospitalized cancer patient's clinical course. Understanding the risk each patient inherently has for developing a bacterial, fungal, or viral infection is critical to choosing the correct prophylactic treatment in conjunction with their scheduled cancer therapy. This review discusses the most common types of infections found in hospitalized cancer patients as well as the current guidelines for prophylactic and antimicrobial treatment in cancer patients. In addition, it describes the interaction between antibiotics and cancer therapies for consideration when treating infection in a cancer patient.

Analysis of Demographics and Outcomes of Surgical Resection in the Central Nervous System of Patients With Metastatic Melanoma.

BACKGROUND: Patients with melanoma frequently develop central nervous system metastases. Oligometastatic disease is often treated either by surgical resection or by stereotactic radiotherapy. This study investigates the trends and clinical outcomes of patients with melanoma who have undergone surgical procedures on the central nervous system during their hospitalization. METHODS: A retrospective study was performed based on admissions of adult patients who underwent craniotomy for metastatic melanoma from 2000 to 2014 using the Nationwide Inpatient Sample database. The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included hospital length of stay (LOS) and discharge disposition (home/home with health care and skilled nursing facilities/long-term acute care (SNFs/LTAC)). Factors associated with in-hospital mortality were examined by multivariable logistic regression. We adjusted for patient and hospital characteristics, payer, and comorbid conditions. We also examined trends of mortality for the study years. RESULTS: There were an estimated 1,216 discharges of patients with melanoma undergoing craniotomy during the study period. Patients undergoing surgical interventions were typically males (69%) and whites (79%). Ninety-eight percent of procedures were performed at teaching hospitals. Unadjusted all-cause in-hospital mortality was 3.1%. There was no significant difference in mortality over 13 years. Age, gender, and race were not associated with increased in-hospital mortality. LOS was longer in elderly and those with higher Charlson Comorbidity Index. Of the survivors, 76% were discharged to home or with home healthcare while 24% were discharged to SNFs/LTAC. Patients with age > 65 (odds ratio (OR): 2.9; 95% confidence interval (CI): 2.2 - 3.9, P < 0.001) and those with higher Charlson Comorbidity Index (OR: 1.2; 95% CI: 1.1 - 1.3) had higher odds for being discharged to SNFs/LTAC. CONCLUSIONS: Patients who undergo craniotomy for metastatic melanoma have a low in-hospital mortality rate. One quarter of patients were discharged to SNFs/LTAC.

Analysis of Race and Gender Disparities in Incidence-Based Mortality in Patients Diagnosed with Thyroid Cancer from 2000 to 2016.

BACKGROUND: Well-differentiated thyroid cancer has better outcomes compared to undifferentiated/anaplastic thyroid cancer. The incidence of well-differentiated thyroid cancer is known to be more in women whereas it is approximately the same in both genders for anaplastic thyroid cancer. The variability of incidence-based mortality across gender in the context of race has not been studied. This study analyzes the rates of incidence-based mortality from the years 2000 to 2016 amongst both the genders in four racial groups. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was utilized to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of well-differentiated and undifferentiated thyroid cancer was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan Native and Asian/Pacific Islander) and gender. All stages and ages were included in the analysis. Two sample t-test was used to determine statistically significant difference between various subgroups. RESULTS: Incidence-based mortality rates (per 100,000) for well-differentiated and undifferentiated thyroid cancer for all races and both the genders were calculated. The incidence-based mortality rates for both genders are approximately the same despite a 2-3:1 difference in incidence. Anaplastic thyroid cancer has a higher mortality rate in Caucasian and Asian/Pacific Islander women compared to men despite an equal ratio in incidence. As expected, the mortality rates of anaplastic thyroid cancer were significantly higher compared to well-differentiated cancer across all races and genders. Also, Asian/Pacific Islander women have a higher rate of mortality compared to both the genders of Caucasian and African American races. CONCLUSION: Incidence-based mortality for anaplastic thyroid cancer is higher in women in all races whereas there is no difference in mortality between men and women for well-differentiated thyroid cancer. This is divergent from the incidence ratios noted in these malignancies. In the context of increasing incidence of thyroid cancer for the past few decades, this data suggests that additional resources may be devoted to decreasing the disparity of mortality in this gender.

Trends in the crossover of patients in phase III oncology clinical trials in the USA.

BACKGROUND: The incorporation of crossover in randomised controlled trials is accepted as an ethical obligation, especially in cancer clinical trials. The more common type of crossover is crossover allowance, which allows patients assigned to one arm to switch to another arm if there is an established benefit in the crossover arm. In contrast, crossover-designed studies involve switching patients from all arms to a different arm as part of the study design. Crossover allowance may have advantages in patient recruitment and incorporating crossover after initial positive results fulfil ethical requirements. However, crossover can also contribute to confounding major endpoints of studies, such as overall survival or the second progression-free survival interval. For this reason, it is important to investigate and identify potential trends of crossover in clinical trials testing novel therapies. METHODS: Data about cancer clinical trials were extracted from clinicaltrials.gov. The search query was limited to completed phase III studies in adult populations. Location was limited to the USA. Date range extended from 1990 to 2019. Search query included the terms: cancer; completed- recruitment status; age: 18-65+ years; sex: all; location: USA; and study phase: phase 3. Studies were then excluded if they were not randomised controlled trials (RCTs) with the primary purpose of treatment and if they did not test cancer-related interventions. RESULTS: A total of 744 clinical trials were identified. There were 459 RCTs aimed at treatment, and of those, 35 utilised crossover. The start dates of these crossover trials ranged from 1997 to 2012. Thirty studies utilised crossover allowance. Prostate, breast and gastrointestinal stromal tumour cancers were the most represented cancer types in crossover studies. Among the 30 studies, the median proportion of patients who crossed over relative to the original arm assignment ranged from 2% to 88%, with a median of 57.5%. CONCLUSIONS: The proportion of identified clinical trials with crossover compared to those without is extremely small. Crossover in clinical trials studying cancer treatment does not appear to be a widespread practice. Even though statistical approaches to mitigate confounding exist, crossover can still skew accurate reporting of the impact of experimental therapies on overall survival.