Cancer In Asymptomatic Individuals Research Articles

Cancer screening with multicancer detection tests: A translational science review.

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

Applying ONCO-RADS to whole-body MRI cancer screening in a retrospective cohort of asymptomatic individuals

BackgroundWhole-body magnetic resonance imaging (WB-MRI) has emerged as a valuable tool for cancer detection. This study evaluated the prevalence rates of cancer in asymptomatic individuals undergoing WB-MRI according to the Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) classifications in order to assess the reliability of the classification method.MethodsWe retrospectively enrolled 2064 asymptomatic individuals who participated in a WB-MRI cancer screening program between 2017 and 2022. WB-MRI was acquired on a 3-T system with a standard protocol, including regional multisequence and gadolinium-based contrast agent-enhanced oncologic MRI. Results of further examinations, including additional imaging and histopathology examinations, performed at our institute were used to validate the WB-MRI findings. Two radiologists blinded to the clinical outcome classified the WB-MRI findings according to the ONCO–RADS categories as follows: 1 (normal), 2 (benign finding highly likely), 3 (benign finding likely), 4 (malignant finding likely), and 5 (malignant finding highly likely). Firth logistic regression analysis was performed to determine the associations between participant characteristics and findings of ONCO-RADS category ≥ 4.ResultsOf the 2064 participants with median age of 55 years, 1120 (54.3%) were men, 43 (2.1%) had findings of ONCO-RADS category ≥ 4, and 24 (1.2%) had confirmed cancer. The cancer prevalence rates were 0.1%, 5.4%, 42.9%, and 75% for ONCO-RADS categories 2, 3, 4, and 5, respectively. In the multivariable model, older age (OR: 1.035, p = 0.029) and history of hypertension (OR: 2.051, p = 0.026), hepatitis B carrier (OR: 2.584, p = 0.013), or prior surgery (OR: 3.787, p < 0.001) were independently associated with the findings for ONCO-RADS category ≥ 4.ConclusionsThe ONCO-RADS categories for cancer risk stratification were validated and found to be positively correlated with cancer risk. The application of ONCO-RADS facilitates risk-based management after WB-MRI for cancer screening.

Clinical validation of a ctDNA-based assay for multi-cancer detection: An interim report from a Vietnamese longitudinal prospective cohort study of 2795 participants.

135 Background: Cancer is a major public health and economic issue and is the leading cause of death worldwide. Up to 80% of cancer patients in Vietnam were diagnosed at stage III or stage IV, leading to a a low 5-year survival rate compared to other countries. Early cancer screening assays capable of identifying early-stage cancer patients among high-risk or asymptomatic individuals are essential to achieve better treatment outcomes and reduced mortality. We previously developed a multimodal LB-based assay named Screening for the Presence Of Tumor by Methylation And Size (SPOT-MAS) to detect the five most common cancer types in Vietnam (liver, breast, colorectal, gastric, and lung cancer). To be successfully applied as a population-wide screening test, the clinical performance of SPOT-MAS needs to be validated in a prospective study. Methods: Herein, we launched a prospective cohort study named K-DETEK (ClinicalTrials.gov identifier: NCT05227261) at 13 major hospitals and one research institute in Vietnam to assess the feasibility and performance of SPOT-MAS in a multi-center clinical trial setting. Our study recruited 10,000 asymptomatic participants participants aged 40 years or older and followed-up for 6 and 12 months. The performance was assessed by computing the number of cases with the detection of a signal (n, %), including a positive predictive value (PPV) and accuracy in detecting tumor tissue-of-origin (TOO). Results: At the time of abstract submission, our analysis of 2795 participants demonstrated its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. Furthermore, we presented a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment. Conclusions: Our study has demonstrated the clinical application of a multi-cancer blood test in a low- and middle-income country like Vietnam, where a nationwide cancer screening program is urgently needed but currently not available. Beyond detecting cancer signals, our test predicted the tumor location, allowing clinicians to fast-track the follow-up diagnostic and guide any necessary treatment. Keywords: liquid biopsy, ctDNA, clinical validation, prospective trial, cancer screening. Clinical trial information: NCT05227261 .

Are we ready to endorse new multiple cancer early-detection tests?

Cancer detection tests open a new era of developing cancer markers, allowing early detection and improving cancer treatments. Existing cancer detection technologies, for example, CA125, CA 19.9, CT, MRI, and others, are either not highly sensitive or specific enough for early detection. Recent technological development of “liquid biopsy” research led to more sensitive biomarkers. Newly developed multiple-cancer early-detection tests can screen up to multiple cancers in asymptomatic individuals with one blood draw. These tests, however, might pose significant challenges in our clinical practice. This paper highlights the issues we face and how to solve their problems.

Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery.

The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis. Currently, there are no designated diagnostic or screening tests for pancreatic cancer in clinical use. Thus, identifying risk groups, preclinical risk factors or surveillance strategies to facilitate early detection is a target for ongoing research. Hereditary genetic syndromes are a obvious, but small group at risk, and warrants close surveillance as suggested by society guidelines. Screening for pancreatic cancer in asymptomatic individuals is currently associated with the risk of false positive tests and, thus, risk of harms that outweigh benefits. The promise of cancer biomarkers and use of 'omics' technology (genomic, transcriptomics, metabolomics etc.) has yet to see a clinical breakthrough. Several proposed biomarker studies for early cancer detection lack external validation or, when externally validated, have shown considerably lower accuracy than in the original data. Biopsies or tissues are often taken at the time of diagnosis in research studies, hence invalidating the value of a time-dependent lag of the biomarker to detect a pre-clinical, asymptomatic yet operable cancer. New technologies will be essential for early diagnosis, with emerging data from image-based radiomics approaches, artificial intelligence and machine learning suggesting avenues for improved detection. Early detection may come from analytics of various body fluids (eg 'liquid biopsies' from blood or urine). In this review we present some the technological platforms that are explored for their ability to detect pancreatic cancer, some of which may eventually change the prospects and outcomes of patients with pancreatic cancer.

Clinical validation of a ctDNA-based assay for multi-cancer detection: An interim report from a Vietnamese longitudinal prospective cohort study of 2,795 participants

ABSTRACT The SPOT_MAS assay ‘Screening for the Presence Of Tumor by Methylation And Size’ detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2,795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Detection of stage I HPV-driven oropharyngeal cancer in asymptomatic individuals in the Hamburg City Health Study using HPV16 E6 serology - A proof-of-concept study.

SummaryBackgroundThe lack of detectable precancerous lesions poses challenges to the early detection of human papillomavirus-driven oropharyngeal cancer (HPV-OPC). Antibodies against HPV16 early proteins, especially E6, are uniquely sensitive and specific biomarkers detectable years prior to HPV-OPC diagnosis. Thus, HPV16 early protein serology warrants clinical investigation for HPV-OPC screening.MethodsUsing multiplex serology, we analyzed HPV16 serum antibodies of the first 5000 participants (n=4,424 sera, recruited 2016-2017) of the Hamburg City Health Study, a population-based prospective cohort (45-74 years). Participants seropositive for HPV16 E6 and at least one additional early protein (E1, E2, E7) were considered at high risk for HPV-OPC development and invited to six-monthly non-invasive head and neck follow-up (FU) examinations (visual inspection, endoscopy, ultrasonography, performed 2019-2020). Participants with suspicious lesions were examined by magnetic resonance imaging and panendoscopy with biopsy. Histologically confirmed OPC cases were treated according to standard of care.FindingsIn total, 35 out of 4,424 study participants (0·8%, 95% confidence interval (CI) 0·6-1·1%) were HPV16 E6 seropositive. Among these, eleven (0·3%, 95%CI 0·1-0·5%) were considered at high risk for HPV-OPC of which nine were successfully re-contacted and invited to regular clinical FU examinations. Two males and one female were diagnosed with stage I HPV-OPC within 1·3 years of clinical FU (3-4 years after initial blood draw), representing one diagnosis of prevalent advanced disease, one incident diagnosis of advanced disease, and one incident diagnosis of early disease. The remaining participants showed no detectable signs of cancer, and undergo regular examinations (median clinical FU: 1·0 years, median total FU from blood draw to last clinical FU visit: 4·7 years).InterpretationHPV16 early antibodies allowed identifying three asymptomatic stage I HPV-OPC patients, out of eleven participants considered at high risk. However, two of the three cases already showed signs of advanced disease at diagnosis. Targeting multiple early proteins may considerably improve the positive predictive value of HPV16 serology and may have clinical utility for HPV-OPC screening.FundingThis work was funded by DKFZ and UKE intramural funding.

Cancer-associated gene analysis of cervical cytology samples and liquid-based cytology significantly improve endometrial cancer diagnosis sensitivity.

To the best of our knowledge, there are no useful screening methods for early detection of endometrial cancer in asymptomatic individuals. The present study evaluated the usefulness of genetic analysis of liquid-based cytology (LBC) specimens by assessing whether pathological genetic mutations detected in cancer tissue sections were detected in LBC specimens from the cervix and uterus. The primary endpoint was genetic analysis of cervical cytology specimens and LBC for the detection of endometrial cancer. Endometrial thickening (>11 mm) assessed using transvaginal ultrasonography was present in 60% of cases and adenocarcinoma assessed using cervical cytology was present in 50% of cases. In 70% of cases, pathogenic mutations detected in cancer tissue sections were also detected in cervical and/or endometrial LBC specimens. The pathogenic variants identified were PTEN in four cases, tumor protein P53, PI3K catalytic subunit α and fibroblast growth factor receptor 2 in two cases each and APC regulator of WNT signaling pathway, KRAS and catenin β1 in one case each. In the present study, a combination of endometrial thickening assessed by transvaginal ultrasonography, cervical cytology and genetic analysis resulted in a high sensitivity of 90% for detection of endometrial cancer. The combination of these tests is more expensive than conventional methods, but delayed detection of uterine cancer requires multidisciplinary treatment, which increases healthcare costs. Increased spending on early detection of uterine cancer is better economically and may improve patient quality of life.

Interventions to increase mammography screening uptake among women living in low-income and middle-income countries: a protocol for a systematic review.

IntroductionBreast cancer is the most prevalent cancer and the second leading cause of cancer-related deaths among women in low and middle-income countries (LMICs), including sub-Saharan Africa. Mammography screening is the most effective screening method for the early detection of breast cancers in asymptomatic individuals and the only screening test that decreases the risk of breast cancer mortality. Despite the perceived benefits, it has a low utilisation rate in comparison with breast self-examination and clinical breast examination. Several interventions to increase the uptake of mammography have been assessed as well as systematic reviews on mammography uptake. Nonetheless, none of the published systematic reviews focused on women living in LMICs. The review aims to identify interventions that increase mammography screening uptake among women living in LMICs.Methods and analysisRelevant electronic databases will be systematically searched from 1 January 1990 to 30 June 2021 for published and grey literature, including citation and reference list tracking, on studies focusing on interventions to increase mammography screening uptake carried out in LMICs and written in the English language. The search will incorporate the key terms: mammography, interventions, low- and middle-income countries and their associated synonyms. Randomised controlled trials, observational studies and qualitative and mixed methods studies of interventions (carried out with and without comparison groups) reporting interventions to increase mammography screening uptake in LMICs will be identified, data extracted and assessed for methodological quality by two independent reviewers with disagreements to be resolved by consensus or by a third author. We will use narrative synthesis and/or meta-analysis depending on the characteristics of the data.Ethics and disseminationEthical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42021269556.

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21–1 (CYFRA 21–1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20 –2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80 –0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up.

Circulating microtumors: A functional hallmark for cancer detection and management.

3544 Background: There are presently no accepted non-invasive means for detection of cancers in asymptomatic individuals or suspected cases. Radiological and serological investigations, though non-invasive, are not confirmatory and necessitate an invasive biopsy to establish malignant status of suspected findings. Invasive biopsies, in turn, face challenges due to non-representative tumor tissue or in cases where biopsy is impossible or unviable. We hypothesized that Circulating Microtumors (also called as C-ETACs: Circulating Ensembles of Tumor Associated Cells) in peripheral blood are universally present in solid organ cancers and their detection can be linked to malignant status. Methods: We obtained peripheral blood from 14,138 patients with various solid organ cancers as well as 10,625 asymptomatic individuals with age associated elevated risk of cancer. Out of the 14,138 patients with cancer, 25.1 % had local (non-metastatic) disease and 56.4% had metastatic disease as confirmed by radiological evaluation. C-ETACs were enriched and harvested from PBMCs using an epigenetically activating medium that is cytotoxic towards non-malignant epithelial and hematolymphoid cells in blood but confers survival benefit on apoptosis resistant circulating cells of tumorigenic origin and their heterotypic clusters (C-ETACs) in peripheral blood. Viable C-ETACs were identified and further characterized by immunocytochemistry (ICC) profiling. Results: C-ETACs were detected in 89.7% of samples from solid organ cancers irrespective of stage, treatment or present radiological status. C-ETACs were rarely detected (3.0%) in asymptomatic individuals. The asymptomatic individuals where C-ETACs were detected are being followed up periodically so as to enable detection of cancer based on clinical or radiological manifestation of symptoms. Conclusions: C-ETACs are ubiquitous in cancers and unexpected in asymptomatic individuals. Detection of C-ETACs in asymptomatic individuals may be indicative of risk of latent undiagnosed malignancy. The non-invasiveness of this approach makes it convenient for screening large populations for cancer.

Does low-dose computed tomography screening improve lung cancer-related outcomes?—a systematic review

: Screening with low-dose computed tomography (LDCT) can potentially decrease the mortality rate of lung cancer by detecting tumors at earlier stages. Although a number of guidelines exist on the implementation of screening and the management of screening-detected lesions, the field has progressed since those were written in terms of the clinical data now available and the greater range of surgical options now on offer to patients. This systematic review aims to provide an updated assessment of how LDCT screening may impact lung cancer-related outcomes in light of such recent data and surgical progress. A systematic literature search was conducted to identify articles focused on the use of LDCT to screen for primary non-small cell lung cancer in asymptomatic individuals. Of 2,880 articles identified, high quality papers reporting the results of 27 major studies were selected for in-depth analysis—including 17 observational studies (15 prospective and 2 retrospective), and 11 randomised-controlled trials. LDCT screening detected lung cancer in 0–8.2% of asymptomatic adults subject. These rates were demonstrated in most studies to be significantly higher than the lung cancer detection rate with no screening. Invasive procedures for benign lesions were performed in 0.07–1.9% of LDCT-screened subjects. Most LDCT screening-detected lung cancers presented in stage I, and 52–100% of patients with LDCT-detected lung cancer received surgery. Two large randomized-controlled trials showed that LDCT screening was associated with a 20.0% reduction in mortality when compared to chest X-ray (CXR) screening, and a 26% reduction in mortality when compared to no screening. LDCT screening is associated with: higher rates of lung cancer detection; diagnosis of lung cancer at an earlier stage; greater likelihood of surgical therapy being given; and lower mortality from lung cancer. The rate of ‘unnecessary’ interventions as a result of LDCT screening is low.

Minimally invasive surgery for the management of iatrogenic colon perforation in the elderly

Aim: Colonoscopy is the most commonly used diagnostic tool for screening for colorectal cancer in asymptomatic individuals and for surveillance in patients with a history of colonic disease. The procedure has several drawbacks, including acute colon perforation. As elderly individuals with aging immune systems frequently respond inadequately to physiologic stress, this life-threatening complication requires meticulous management in this patient cohort. We aimed to evaluate a minimally invasive surgical approach to iatrogenic colon perforation (ICP) in this vulnerable age group.Material and Methods: This is a retrospective study. We reviewed data from all patients ≥ 65 years of age diagnosed with iatrogenic colon perforation (ICP) between January 2012 and June 2019 at Gaziosmanpasa University Hospital. Results: Seventeen cases of ICP were identified (mean age was 76.5 years); 16 patients were treated surgically and one was managed conservatively. The most frequent site of perforation was the sigmoid colon (58.8%) and surgical management was primarily laparoscopic (93.7%). Twelve of the 16 patients who were managed with surgical intervention underwent laparoscopic primary repair and three patients underwent laparoscopic colectomy due to a primary diagnosis of colorectal malignancy. One patient with delayed diagnosis underwent laparotomy and proctosigmoidectomy (Hartmann procedure); this patient did not survive beyond the immediate post-operative period.Conclusion: Our findings suggest that early recognition is critical for the successful treatment of ICP in the elderly. Most patients respond well to a minimally invasive laparoscopic approach. This approach can be considered for large perforations and is safe and effective when carried out by an experienced surgeon.

Development of a blood-based cancer screening assay with a novel multivariate cancer risk score (MCRS) model by integrating shallow WGS data and plasma protein markers.

45 Background: Despite the increase of our knowledge about carcinogenesis and recent successful development of innovative cancer drugs, cancer mortality has only slightly decreased in the past decades. Cancer early detection is probably the most cost-effective means to reduce cancer mortality as prognosis is much better when cancer is detected and treated at the early stage. Recently studies have demonstrated that blood-based mutation detection approaches may be effective to identify asymptomatic cancer patients from general population. Methods: Here we reported a novel multivariate cancer risk score (MCRS) model that interrogates shallow whole genome sequencing (WGS) data from cell-free DNA (cfDNA) and protein markers results in a single blood draw. Results: In a prospective clinical study consisting of 76 stage I-IV cancer patients and 152 normal individuals, the MCRS model demonstrated 60% sensitivity at 98.5% specificity. In order to validate clinical utility of the MCRS model in detection of cancer patients, we collated the data from a previous study of occult maternal malignancies from 1.93 million pregnant women undergoing NIPT test between 2016 and 2017. 466 out of the 639 pregnant women who tested positive for multiple chromosomal aneuploidies (MCAs) in the initial NIPTs (i.e. 0.06 - 0.1x WGS), have also underwent the protein markers test. Out of the 466 subjects, 39 maternal malignant cancer cases were diagnosed with a median follow-up of 399 days (IR, 303 - 487 days) by imaging and histology. The cancer patients presented a wide spectrum of cancer types, the most frequent being breast cancer (10 cases), liver cancer (8) and lymphoma (8), at stage II to IV. This subgroup of 466 subjects was selected as an independent validation cohort for our study. Through our new method, we analyzed shallow WGS and proteins data. The MCRS model allowed 28 of the 39 (71.8%) cancer cases to be identified with a positive predictive value of 73.7% and specificity of 97.7%. Conclusions: Taken together, these data demonstrate the MCRS model holds promise for detecting cancer in asymptomatic individuals, particularly in the populations at high risk of cancer.

Screening to Detect Precursor Lesions of Pancreatic Adenocarcinoma in High-risk Individuals: A Single-center Experience.

Objective of the workPancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer.Research aimPancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer.MethodsBetween 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described.ResultsThree patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings.ConclusionsAdherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.

Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a...

Cancer screening fantasies

The use of circulating tumour DNA to screen for cancer in asymptomatic individuals is the goal of Grail, initially set up by Illumina. This company is now raising a large amount of capital to develop this project on a much longer time scale than initially announced. Although it has access to cutting edge technology and is led by excellent scientists, the prospect for success in this application is rather bleak, mainly because of the extreme requirements for specificity in order to avoid overdiagnosis.

Issue Highlights

Issue Highlights

Familial Gastric and Pancreatic Cancers: Diagnosis and Screening

Screening for gastric and pancreatic cancers in asymptomatic individuals is not routinely practiced in the United States. While there is insufficient evidence that general population screening would reduce morbidity and/or mortality associated with these cancers, the utility of screening for individuals at increased risk warrants further study. Clinical challenges include identifying high risk individuals who would be most likely to benefit from screening and determining which screening modalities and intervals would be most effective.

Symptoms do not predict colorectal cancer in an FOB screened population

The Scottish Bowel Screening Programme aims to detect cancer in asymptomatic individuals. We aimed to measure the prevalence of lower gastrointestinal symptoms in faecal occult blood (FOB) screen-positive patients, to correlate the symptoms with neoplasia and to compare the predictive value of FOB screening with urgent symptomatic referrals in Ayrshire and Arran. Data were collected prospectively on FOB screen-positive patients undergoing colonoscopy. Patients completed a symptom questionnaire. Positive predictive values (PPVs) for detecting neoplasia were calculated and a chi-square test was performed to determine any influence of symptoms in diagnosing neoplasia. Symptomatic patients undergoing colonoscopy via a general practice fast-track system were compared. A total of 378 FOB screen-positive patients were included. In all, 198 (52%) had colorectal symptoms. Overall, 32 were diagnosed with colorectal cancer and 93 had polyps . FOB positivity and symptoms gave a PPV of 34% for neoplasia. FOB positivity without symptoms gave a PPV of 32% for neoplasia. Urgent referral of symptomatic patients had a lower PPV of 21% for neoplasia (p < 0.001). Half the FOB screen-positive patients had bowel symptoms. Symptoms in these patients had no correlation with an increased rate of neoplasia. The PPV for neoplasia is superior in symptomatic and asymptomatic screen-positive patients when compared to conventional urgent symptom-based referral.