Head and Neck Cancer of Unknown Primary: A Multicenter Retrospective Cohort study in Northern Thailand, an Endemic Nasopharyngeal Cancer Area.

OBJECTIVE: This study aimed to evaluate the characteristics and oncological outcomes of head and neck carcinoma of unknown primary (HNCUP) patients in an endemic nasopharyngeal cancer (NPC) area. METHODS: One hundred and forty-four HNCUP patients curatively treated between January 1995 and December 2022 from 5 centers were retrospectively recruited onto the study to analyze the clinicopathological characteristics and oncological outcomes and compare them with historical data. A multivariate Cox proportional hazards model analysis was performed to evaluate factors affecting survival outcomes. A propensity-matched pair analysis of the patients with positive and negative EBV-encoded small RNA (EBER) staining was applied to compare the characteristics and outcomes between the two groups. RESULTS: The median follow-up time was 45 months. Most patients (88.2%) received total mucosal irradiation (TMI). Primary tumor emergence (PTE) was detected in 6 patients (4.2%) who did not have TMI. The 5-year overall survival (OS), disease-free survival, and locoregional recurrence-free survival were 51.3%, 64.9%, and 72.7%, respectively. Extranodal extension and N3 compared with the N1 stage were the significant independent predictors for OS (HR 2.90, 95% CI 1.12-7.51, p = 0.028 and HR 3.66, 95%CI 1.23-11.89, p = 0.031, respectively). The matched-pair analysis demonstrated comparable all survival outcomes between the EBER-positive and -negative groups. All patients in the matched pair analysis received TMI, and no PTE was detected. CONCLUSION: Our survival outcomes were comparable to previous studies with a low rate of PTE. The matched pair analysis of EBER-positive and -negative groups revealed similar oncological outcomes and no primary tumor emergence when total mucosal irradiation was administered.

Cancer of unknown primary and the «seed and soil¼ hypothesis.

The worldwide incidence rate of cancer of unknown primary (CUP) reaches 5% (Kang et al, 2021; Lee, Sanoff, 2020; Yang et al, 2022). CUP has an alarmingly high mortality rate, with 84% of patients succumbing within the first year following diagnosis (Registration and Service, 2018). Under normal circumstances, tumor cell metastasis follows the «seed and soil¼ hypothesis, displaying a tissue-specific pattern of cancer cell homing behavior based on the microenvironment composition of secondary organs. In this study, we questioned whether seed and soil concept applies to CUP, and whether the pattern of tumor and metastasis manifestations for cancer of known primary (CKP) can be used to inform diagnostic strategies for CUP. We compared data from metastatic and primary CUP foci to the metastasis patterns observed in CKP. Furthermore, we evaluated several techniques for identifying the tissue-of-origin (TOO) in CUP profiling, including DNA, RNA, and epigenetic TOO techniques.

Health Economic Consequences Associated With COVID-19-Related Delay in Melanoma Diagnosis in Europe.

Importance: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet. Objective: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe. Design, Setting, and Participants: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022. Exposure: COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks. Main Outcomes and Measures: Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure. Results: There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario. Conclusions and Relevance: This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

Detecting undetectable - epidemiology, etiology, and diagnosis of carcinoma of unknown primary - systematic review.

Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.

Cancers of Unknown Primary: A Descriptive Study in the U.S. Military Health System.

INTRODUCTION: Cancers of unknown primary (CUP) are defined as histologically confirmed metastatic cancers that do not have an identified primary site of origin despite an appropriate diagnostic workup. Although accessibility to and quality of medical care influence diagnosis of cancer including CUP, previous studies describing CUP have generally been conducted in patients with various accessibilities to care. This study aimed to describe the demographic, histologic, and temporal trend characteristics of CUP patients in the DoD Cancer Registry of the Military Health System (MHS), which provides universal health care access, reducing the potential effects of accessibility to care on research results. MATERIALS AND METHODS: The data were obtained from the DoD's Automated Central Tumor Registry (ACTUR), which collects cancer data from beneficiaries who were diagnosed or received treatment in the MHS. We described the demographic and histologic distributions in CUP patients aged 18 years or older diagnosed from 1987 to 2013. We calculated the proportion of CUP patients among all metastatic cancers and the most common histologic categories of those tumors. We then evaluated whether the proportion of histologic types changed over time. RESULTS: CUP comprised 13.3% of all metastatic cancers in ACTUR during the study period. The majority of CUP within ACTUR was moderately and well-differentiated adenocarcinoma (51.3%) and poorly differentiated carcinomas (23.2%) followed by squamous cell carcinomas (12.5%). The percentages of CUP among metastasized cancers of the same histologic category ranged 12%-15% for moderately and well-differentiated adenocarcinomas, squamous cell, and poorly differentiated carcinomas, and 41%-46% for malignant neuroendocrine carcinomas and undifferentiated neoplasms. However, the percentages varied by sex, race, and age for certain pathologies. The proportion of CUP patients among all metastatic cancer patients has steadily declined from 22.4% to 8.3% from 1987 to 2013. CONCLUSION: The proportion and trends of CUP in the ACTUR were generally consistent with other descriptive CUP studies. This study provides a description of CUP in a health care system with universal access in the USA and provides a foundation for future studies on CUP.

Sarcoma of unknown primary: myth or reality?

BACKGROUND: Sarcoma of unknown primary (SUP) designates an enigmatic entity with histologic confirmation of a metastatic tumor without an identifiable primary after a thorough diagnostic workup. The term "unknown primary" is heavily debatable given that sarcomas can arise from any tissue that harbors its histological structure. In this review, we discuss the validity of SUP as a distinct entity. Medline/PubMed and Google Scholar were searched from 1990 until April 2020 for publications in the English language reporting on SUP. We excluded articles reporting on cases with sarcomas from known organ sites such as lung or uterine sarcomas as well as synovial sarcomas. The Kaplan-Meier method was used to compute the median overall survival. A total of 26 patients with SUP were identified. The median age at diagnosis was 17.5 years with a similar prevalence among men and women. The tumors most commonly reported were alveolar rhabdomyosarcoma and rhabdomyosarcoma not otherwise specified. Almost two-thirds of the patients were reported to have more than one metastatic site. Among the 13 patients with survival data, the median overall survival was 10.0 months. Two patients underwent autopsy and had their primary culprit identified in the chest wall and paravertebral. CONCLUSIONS: This review showed that SUP shares with sarcomas of known primary similar clinical features including an aggressive clinical course, generally poor response to chemotherapy, and dismal patient outcomes. Thus, SUP does not appear to display a different natural history and biological properties that would allude to a distinct entity.

[Screening for cancer in case of venous thromboembolism: when and how?] / Quand et comment rechercher un cancer en cas de maladie thromboembolique veineuse ?

Screening for cancer in case of venous thromboembolism: when and how? Cancer associated thrombosis (cat) is an important challenge. When venous thromboembolism (vte) occurs without any identified risk factors, the risk of cat raises the question of a hidden cancer and the need for an extensive screening or not. Several series have shown a prevalence between 5% and 10% of cancer when non provoqued vte is diagnosed. Most of cancers occur during the following year of vte. If we consider diagnosing the cancer in early stage, we might improve the patient outcome and reduce cancer mortality. A simple screening, including clinical examina¬tion, personal and familial history of cancer, basic laboratory tests and recommended age and sex testing is mandatory. Other exams are considered as useless at present time. Whether a tep-scan, prescribed in patients older than 50, brings a clinical benefit, is still unresolved. Screening for cancer in case of venous thromboembolism: when and how? Cancer associated thrombosis (cat) is an important challenge. When venous thromboembolism (vte) occurs without any identified risk factors, the risk of cat raises the question of a hidden cancer and the need for an extensive screening or not. Several series have shown a prevalence between 5% and 10% of cancer when non provoqued vte is diagnosed. Most of cancers occur during the following year of vte. If we consider diagnosing the cancer in early stage, we might improve the patient outcome and reduce cancer mortality. A simple screening, including clinical examina¬tion, personal and familial history of cancer, basic laboratory tests and recommended age and sex testing is mandatory. Other exams are considered as useless at present time. Whether a tep-scan, prescribed in patients older than 50, brings a clinical benefit, is still unresolved.

Quand et comment rechercher un cancer en cas de maladie thromboembolique veineuse ? L'association thrombose et cancer est connue depuis longtemps et pose des problèmes diagnostiques et thérapeutiques spécifiques. La maladie thromboembolique veineuse (mtev) peut précéder le cancer et servir de signe d'alerte. Plusieurs publications font état d'une prévalence comprise entre 5 et 10 % de cancer occulte en cas de mtev non provoquée. La plupart des cancers apparaissent dans l'année qui suit le diagnostic de mtev. Dépister un cancer au stade infraclinique, au moment du diagnostic de la thrombose, permettrait de diminuer le risque d'extension du cancer et d'améliorer le pronostic des patients. Une recherche de cancer, simple, incluant interrogatoire, examen clinique et bilan biologique minimal, sans examens complémentaires inutiles et adaptée aux facteurs de risque, doit donc être effectuée. La question est aujourd'hui de savoir si une stratégie plus extensive, comprenant un tep-scan, notamment chez les patients de plus de 50 ans, apporte un bénéfice clinique.

Real-world experience with limited screening for occult malignancy in patients presenting with spontaneous venous thromboembolism: a single-centre, retrospective cohort study.

Spontaneous venous thromboembolism (VTE) may represent the first manifestation of previously undiagnosed malignancy; however, contemporary international guidelines call for a limited approach to screening for malignancy in such patients. This retrospective cohort study of 328 patients presenting to the Auckland City Hospital Thrombosis Unit identified 17 patients who were subsequently diagnosed with some form of malignancy within 12 months of their presentation. Review of their history, physical examination and limited age and gender-appropriate cancer screening investigations as described by the National Institute for Clinical Excellence and International Society of Thrombosis and Haemostasis guidelines revealed that all 17 would have been safely diagnosed by the 'limited' screening approach endorsed by these guidelines, thus presenting a 'real-world' basis for clinicians to pursue 'limited' screening for malignancy in their everyday practice in patients with spontaneous VTE.

Type 2 diabetes mellitus and cancer of unknown primary risk: results from the Netherlands Cohort Study.

OBJECTIVE: Cancer of unknown primary (CUP) is a metastatic malignancy with an unidentifiable primary tumour origin. Previous studies suggest that type 2 diabetes mellitus (T2DM) and CUP risk are associated. This study examines the association in greater depth by investigating T2DM status, T2DM duration, T2DM age at diagnosis, and medication that was being used in relation to CUP. METHODS: Data were utilized from the Netherlands Cohort Study, a prospective cohort that includes 120 852 participants aged 55-69 years at baseline in 1986. All participants completed a self-administered questionnaire on cancer risk factors. CUP cases were identified through record linkage with the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow-up, 963 incident CUP cases and 4288 subcohort members were available for case-cohort analyses. Proportional hazards models were employed to estimate multivariable-adjusted hazard ratios (HRs). RESULTS: Overall, we observed a nonsignificant positive association between T2DM status and CUP risk [HR, 1.35; 95% confidence interval (CI), 0.92-1.99], which increased in women after stratification for sex (HR, 1.55; 95% CI, 0.90-2.64). For participants who were aged less than 50 years at diagnosis of T2DM, a statistically significant positive association was found in relation to CUP (HR, 2.42; 95% CI, 1.26-4.65), compared with participants without T2DM. CONCLUSION: Our findings indicate that there is a nonsignificant positive association between T2DM and CUP risk and that the association became stronger in women in stratified analyses.

Adherence to the World Cancer Research Fund and the American Institute for Cancer Research lifestyle recommendations for cancer prevention and Cancer of Unknown Primary risk.

BACKGROUND & AIMS: The World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) updated their cancer prevention recommendations in 2018. Adherence to these recommendations has been associated with lower cancer risk and mortality. However, adherence in relation to Cancer of Unknown Primary (CUP) risk has not been studied. This study investigates whether adherence to the WCRF/AICR recommendations is associated with CUP risk. METHODS: Data from the prospective Netherlands Cohort Study on diet and cancer was used to measure adherence to the recommendations in relation to CUP risk. The cohort includes 120 852 participants (aged 55-69 years), who completed a self-administered questionnaire on cancer risk factors at baseline. Adherence was investigated with respect to body fatness, physical activity, plant foods, meat consumption and alcohol. Incident CUP cases were identified through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. A follow-up of 20.3 years, resulted in 856 incident CUP cases and 3911 subcohort members with complete information available for case-cohort analyses. Multivariable adjusted hazard ratios were estimated using proportional hazards models and were adjusted for age at baseline, sex, cigarette smoking (status, frequency, and duration) and total energy intake. RESULTS: Highest adherence appeared to be associated with decreased CUP risk in the age-sex adjusted model (HR: 0.76, 95% CI: 0.62-0.92). After additional adjustment for cigarette smoking (status, frequency, and duration), the association attenuated and was no longer statistically significant. No multiplicative interactions were observed between sex nor smoking status and overall adherence in relation to CUP. CONCLUSION: Within this cohort, highest adherence to the WCRF/AICR recommendations is not statistically significantly associated with decreased CUP risk after multivariable adjustment.

Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer of unknown primary.

A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital polymerase chain reaction. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66-92) and 100% (95% CI = 88-100), 85% (95% CI = 69-94) and 94% (95% CI = 73-100), and 93% (95% CI = 81-99) and 97% (95% CI = 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI = 1-72) and 100% (95% CI = 3-100), 0% (95% CI = 0-52) and 100% (95% CI = 3-100), and 100% (95% CI = 54-100) and 100% (95% CI = 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP.

Incidence of cancers of unknown primary origin in India and their trends during 1986-2014: A joinpoint regression analysis.

Background: Cancer of unknown primary (CUP) origin is cancer in which malignant cancer cells are in the body but the site of cancer where it began is unknown. Detailed incidence and time trends of these cancers, specific to various regions in India is needed. This paper aims to summarize and report the incidence of other and unknown (O&U) cancers across India in 27 population-based cancer registries (PBCRs) and to study the trends among these cancers using joinpoint regression analysis. Methods: Data on the incidence of CUP were obtained from the published reports on 27 PBCRs of the National Cancer Registry Programme (NCRP) of the Indian Council of Medical Research (ICMR). A joinpoint regression model was used to analyze the long-term trends of incidence related to CUP based on published data from PBCRs between 1986 and 2014. Annual Percent Change (APC) in incidence rate was estimated for various registries. Results: The northeast region had the highest age-adjusted rate (AAR) for both men (1.76-29.7) and women (1.99-14.68). Age-specific rate (ASR) for both men (39.8-855.7) and women (48.2-470.4) was highest in the northeast region. There is an increase in the incidence rate for all six major registries over the past decade with an exception of women in the Delhi Cancer Registry. There is a decline in incidence rate by 0.14 during 1990-2012 in the female population of the Delhi registry. Conclusion: The increasing incidence trends of CUP is a matter of concern for the healthcare professionals and researchers. There is a need for research and advanced and improved diagnostic tools for the improvement of the status of O&U cancers.

Real-world data analysis of patients with cancer of unknown primary.

Cancer of unknown primary (CUP) is a heterogeneous malignancy in which the primary site of the tumor cannot be identified through standard work-up. The survival outcome of CUP is generally poor, and there is no consensus for treatment. Here, we comprehensively analyzed the real-world data of 218 patients with CUP (median age, 62 years [range, 19-91]; male, 62.3%). Next-generation sequencing was conducted in 22 (10%) patients, one of whom showed level 1 genetic alteration. Most (60.3%) patients were treated with empirical cytotoxic chemotherapy, and two patients received targeted therapy based on the NGS results. The median OS was 8.3 months (95% confidence interval [CI] 6.2-11.4), and the median progression-free survival of patients treated with chemotherapy was 4.4 months (95% CI 3.4-5.3). In multivariate Cox regression analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 and localized disease were significantly associated with favorable survival outcomes. Collectively, we found that CUP patients had a poor prognosis after standard treatment, and those with localized disease who received local treatment and those with better PS treated with multiple lines of chemotherapy had better survival outcomes. Targeted therapies based on NGS results are expected to improve survival outcomes.

Characterisation and outcomes of patients referred to a regional cancer of unknown primary team: a 10-year analysis.

BACKGROUND: In the United Kingdom, national guidance published in 2010 recommended the establishment of specialist teams to improve clinical pathways for patients presenting with malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This study sought to define outcomes of patients referred to a regional MUO/CUP service. METHODS: Data were collected prospectively on all patients (n = 1225) referred to a regional CUP team over a 10-year period. Patient demographics, clinical, pathological and outcome data were recorded and analysed. RESULTS: Confirmed CUP (cCUP) was diagnosed in 25% of patients. A primary metastatic cancer was identified in 36%, 5% were diagnosed with provisional CUP (pCUP), 27% retained the diagnosis of MUO and in 8% a non-cancer diagnosis was made. Median survival was low in all patients with a final malignant diagnosis: primary identified 9.0 months, cCUP 4.0 months, pCUP 1.5 months and MUO 1.5 months. CONCLUSIONS: Patients presenting with MUO have poor outcomes irrespective of the final diagnosis. These patients need a patient-centred, streamlined, rapid diagnostic pathway. There are clear benefits to primary and secondary care teams having access to a dedicated, multidisciplinary MUO/CUP service, with clinical nurse specialists supporting the patients, to help facilitate this pathway and ensure early oncology review.

[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center]. / Chirurgie de réduction de risque mammaire et découverte fortuite de cancer : dix ans d'expérience dans un centre de lutte contre le cancer.

INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers. METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts. RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%). DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.

Descriptive epidemiology of cancer of unknown primary in South Korea, 1999-2017.

BACKGROUND: Cancers of unknown primary (CUPs) are tumors found after metastasizing from unidentified primary sites; these tumors generally have unknown treatment strategies, expected treatment results, and prognosis. We assessed the epidemiological characteristics of CUPs in Korea. METHODS: We extracted records for 1999 through 2017 from the Korea Central Cancer Registry using the International Statistical Classification of Diseases and Related Health Problems (10th revision) codes for CUP as defined by the International Agency for Research on Cancer. Age-standardized rates and relative survival rates were calculated. RESULTS: The CUPs constituted 2.1 % of the total number of cancer registrations in 1999, declining to 0.7 % in 2017. The incidence rate decreased for both sexes (5.35 to 2.20 for men, 3.15 to 1.77 for women). Patients aged 80 years and older had the highest incidence rate at 40.2, and 86.3 % of CUPs occurred in those 50 years of age or older. The cases of retroperitoneum and peritoneum sites increased over time. Cases diagnosed by microscopic methods and death certification only were 62.3 % and 7.9 %, respectively. The malignant neoplasm of the retroperitoneum and peritoneum and unknown primary site had the highest and lowest survival rates, respectively. The 5-year relative survival rate increased over time from 14.2 % (1999-2002) to 27.3 % (2013-2017). CONCLUSIONS: Our analysis of data from the Korea Central Cancer Registry found decreasing rates of CUP, although with consistent disparities by patient age and sex. Advancements in diagnostic technology may be decreasing the number of CUP diagnoses. Expanding the amount of information recorded in the registry may further improve diagnostic accuracy.

Outcome of two-week head and neck cancer pathway for the otolaryngology department in a tertiary centre.

BACKGROUND: The two-week-wait head and neck cancer referral pathway was introduced by the Department of Health, and refined through National Institute for Health and Care Excellence guidelines which were updated in 2015. METHODS: A retrospective study was conducted of two-week-wait referrals to out-patient ENT from January to June 2018. The analysis included demographics, referral symptoms according to National Institute for Health and Care Excellence 2015 guidelines, cancer pick-up rates and positive predictive values. RESULTS: A total of 1107 patients were referred for suspected head and neck cancer over six months, with 6 per cent diagnosed with cancer. Neck lump, persistent hoarseness and throat pain were the most common presenting symptoms. Neck lump had the highest positive predictive value, followed by oral swelling. Oral bleeding and persistent unilateral sore throat showed significant positive predictive values. Investigation for metastatic head and neck cancer of an unknown primary or the involvement of other multidisciplinary teams could hinder the achievement of a 62-day treatment target. CONCLUSION: The cancer pick-up rate from two-week-wait referrals is only 1.5 times higher than routine referrals. The 'red flag' symptoms given in the 2015 National Institute for Health and Care Excellence update would benefit from further review.

Family history of cancer in first degree relatives and risk of cancer of unknown primary.

OBJECTIVE: Cancer of Unknown Primary (CUP) refers to the presence of metastatic lesions, with no identifiable primary site during the patient's lifetime. Poor survival and lack of available treatment highlight the need to identify potential CUP risk factors. We investigated whether a family history of cancer is associated with increased CUP risk. METHODS: We performed a case cohort analysis using data from the Netherlands Cohort Study, which included a total of 963 CUP cases and 4,288 subcohort members. A Cox Proportional Hazards Regression was used to compare CUP risk in participants who reported to have a family member with cancer to those who did not, whilst adjusting for confounders. RESULTS: In general, we observed no increased CUP risk in those who reported a family history of cancer. CUP risk appeared slightly increased in those who reported cancer in a sibling (HR: 1.16, 95% CI: 0.97-1.38), especially in those with a sister with cancer compared with those without (HR: 1.23, 95% CI: 0.99-1.53), although these findings are not statistically significant. CONCLUSION: Having a family history of cancer is not an independent risk factor of CUP.

Occult Malignancy in Adult Tonsillectomy for Benign Indication.

OBJECTIVE: National pathology guidelines recommend full pathologic analysis for all adult tonsillectomy specimens. We evaluated the available data on occult malignancy in adult tonsillectomy for benign indication, and created a screening system to reduce the risk of missed malignancies if routine histopathologic examination were to be discontinued. STUDY DESIGN: Retrospective chart review and systematic review of the literature. SETTING: Tertiary care academic hospital and multi-hospital private healthcare system. SUBJECTS AND METHODS: A systematic literature review identified case series of adult tonsillectomy. Retrospective chart review at our institutions from 2000 to 2016 produced an additional case series. The pooled rate of occult malignancy was determined, and re-analyzed using criteria based on preoperative risk factors designed to identify patients requiring full pathologic analysis. The predicted effects of prospective application of the proposed criteria were calculated. Pooled occult malignancy prevalence was estimated. RESULTS: Literature review and our own case series yielded 12,094 total cases. Occult malignancy prevalence in the combined data was 0.033%, representing four occult malignancies. Three out of the four would have been selected for full pathology preoperatively with use of the proposed criteria. Statistical analysis indicates that the predicted frequency of occult malignancy incidence in cases negative for the criteria is 0.01%, or 1/10,000. CONCLUSION: Application of the proposed criteria to adults undergoing tonsillectomy for benign indication identifies a subset of patients with an estimated incidence of occult malignancy similar to that reported for pediatric tonsillectomy, and potentially may permit safe elimination of pathologic analysis of their tonsil specimens. LEVEL OF EVIDENCE: Pooled analysis of case series from the literature and a single institution, level 4.

A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Unknown Primary.

OBJECTIVE: The aim of the study was to provide a real-world, population-based assessment of the incidence and outcomes of neuroendocrine neoplasms (NENs) of unknown primary. METHODS: Surveillance, Epidemiology, and End Results registry was accessed, and cases with NENs of unknown primary were reviewed. Rates of NENs diagnosis 1975-2017 according to primary tumor site were also reviewed. Survival outcomes of patients with NENs of unknown primary compared to metastatic NENs with known primary were determined through Kaplan-Meier estimates and multivariable Cox regression analysis. Overall and cancer-specific survival analyses were stratified by primary site and histology (neuroendocrine tumor vs. neuroendocrine carcinoma). RESULTS: A total of 3,550 cases (7%) were diagnosed with NENs of unknown primary within the study duration. The annual percent change for NENs of unknown primary was 3.4 (95% CI: 2.6-4.2). Within the cohort of metastatic neuroendocrine tumor patients (carcinoid tumor histology), the following factors were associated with a lower risk of death; younger age (HR: 0.477; 95% CI: 0.443-0.513), female sex (HR: 0.922; 95% CI: 0.860-0.989), and small intestinal primary (HR for unknown primary vs. small intestinal primary: 1.532; 95% CI: 1.408-1.668). Within the cohort of metastatic neuroendocrine carcinoma, the following factors were associated with a lower risk of death in this cohort; younger age (HR: 0.646; 95% CI: 0.612-0.681), female sex (HR: 0.843; 95% CI: 0.801-0.888), and small intestinal primary (HR for unknown primary vs. small intestinal primary: 2.961; 95% CI: 2.586-3.391). CONCLUSIONS: The diagnosis of NENs of unknown primary has increased across the past 4 decades. Outcomes of individuals with metastatic small intestinal NENs seem to be better than those with metastatic NENs of unknown primary (for both carcinoid tumors and neuroendocrine carcinomas).