Asymptomatic Cancer Survivors Research Articles

Effect of insulin resistance on CAC scores in cancer survivors.

e24056 Background: Many cancer (ca) survivors exhibit signs of insulin resistance (IR), an important risk factor for the development of coronary artery disease (CAD). Paramount in survivorship care is prevention of cardiovascular disease. Coronary artery calcium (CAC) scans offer a risk assessment of cardiovascular (CV) disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors. We hypothesized that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors. Methods: We enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. Patients were tested for fasting insulin, -glucose, HgbA1c and lipids. Patients without evidence for prediabetes or diabetes also underwent an oral glucose tolerance test (oGTT). All patients received a CAC scan. Results: 32 patients were IS, 29 patients were IR/prediabetic and 29 patients were IR/diabetic. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant ( p=0.005) where as the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups: the IS group had a mean of 5.3, the IR/prediabetic group had a mean of 7.3, and the IR/diabetic group had a mean of 11.0 ( p < 0.001). The two IR groups did not differ statistically (p=0.076). Conclusions: Our study showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. Survivors with IR also have less frequent zero CAC scores than insulin-sensitive survivors. Survivors disproportionately exhibit insulin resistance, partly due to the association of certain types of cancer with IR. This trial highlights the importance of screening survivors for IR. Survivors diagnosed with IR should be screened for CAD more frequently than the general population. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.

Effect of insulin resistance on CAC scores in cancer survivors

BackgroundMany ca. survivors exhibit signs of IR, an important risk factor for the development of CAD. CAC scans offer a risk assessment of CV disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors.ObjectivesThe aim of this study was to show that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors.MethodsWe enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. All patients received a CAC scan.Results70% of asymptomatic survivors overall and 81% of asymptomatic IR patients show CAD on CAC scans. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant (p = 0.005) whereas the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups (p < 0.001). The two IR groups did not differ statistically (p = 0.076).ConclusionsSurvivors with IR including prediabetes have less frequent zero CAC scores than insulin-sensitive survivors. Our study also showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. This trial highlights the importance of screening survivors for IR and draws attention to the association of IR to CAC not only in diabetes but also in prediabetes. The high fraction of asymptomatic survivors with CAD is concerning and calls for further investigation. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.

Evaluation of the Impact of Magnetic Resonance Imaging with Susceptibility-weighted Imaging for Screening and Surveillance of Radiation-induced Cavernomas in Long-term Survivors of Malignancy

AimsRadiation-induced cavernomas (RIC) are common late toxicities in long-term survivors of malignancy following cerebral irradiation. However, the natural history of RIC is poorly described. We report the first series of long-term surveillance of RIC using modern magnetic resonance imaging (MRI) including highly sensitive susceptibility-weighted imaging (SWI). The aims of this research were to better characterise the natural history of RIC and investigate the utility of MRI-SWI for screening and surveillance. Materials and methodsEligibility required long-term survivors of malignancy with previous exposure to cerebral irradiation and RIC identified on MRI-SWI surveillance. The number and size of RIC were reported on Baseline MRI-SWI and last Follow-up MRI-SWI. ResultsIn total, 113 long-term survivors with RIC underwent MRI-SWI surveillance; 109 (96%) were asymptomatic at the time of RIC diagnosis. The median age at cerebral irradiation was 9.3 years; the median radiotherapy dose was 50.4 Gy. The median time from cerebral irradiation to Baseline MRI-SWI was 17.9 years. On Baseline MRI-SWI, RIC multiplicity was present in 89% of patients; 34% had >10 RIC; 65% had RIC ≥4 mm. The median follow-up from Baseline MRI-SWI was 7.3 years. On Follow-up MRI-SWI, 96% of patients had multiple RIC; 62% had >10 RIC; 72% had RIC ≥4 mm. Of the 109 asymptomatic patients at RIC diagnosis, 96% remained free from RIC-related symptoms at 10 years. Only two required neurosurgical intervention for RIC; there was no RIC-related mortality. ConclusionsRIC are commonly multiple, asymptomatic and typically increase in size and number over time. Our findings suggest that MRI-SWI for screening of RIC is unlikely to influence longer term intervention in asymptomatic cancer survivors. In the absence of neurological symptoms, assessment or monitoring of RIC are insufficient indications for MRI-SWI surveillance for long-term survivors of malignancy with past exposure to cerebral irradiation.

Echocardiography for the 10-year prediction of cardiomyopathy in long-term survivors of childhood cancer

Abstract Background Childhood cancer survivors (CCS) treated with anthracyclines and/or chest-directed radiotherapy receive life-long echocardiographic surveillance to detect cardiomyopathy early. Current risk stratification and surveillance frequency recommendations are based on anthracycline- and chest-directed radiotherapy dose. We assessed the added prognostic value of an initial left ventricular ejection fraction (EF) measurement at &amp;gt;5 years after cancer diagnosis. Patients and methods Echocardiographic follow-up was performed in asymptomatic CCS from the Emma Children's Hospital (derivation; n=299; median time after diagnosis, 16.7 years [inter quartile range (IQR) 11.8–23.15]) and from the Radboud University Medical Center (validation; n=218, median time after diagnosis, 17.0 years [IQR 13.0–21.7]) in the Netherlands. CCS with cardiomyopathy at baseline were excluded (n=16). The endpoint was cardiomyopathy, defined as a clinically significant decreased EF (EF&amp;lt;40%). The predictive value of the initial EF at &amp;gt;5 years after cancer diagnosis was analyzed with multivariable Cox regression models in the derivation cohort and the model was validated in the validation cohort. Results The median follow-up after the initial EF was 10.9 years and 8.9 years in the derivation and validation cohort, respectively, with cardiomyopathy developing in 11/299 (3.7%) and 7/218 (3.2%), respectively. Addition of the initial EF on top of anthracycline and chest radiotherapy dose increased the C-index from 0.75 to 0.85 in the derivation cohort and from 0.71 to 0.92 in the validation cohort (p&amp;lt;0.01). The model was well calibrated at 10-year predicted probabilities up to 5%. An initial EF between 40–49% was associated with a hazard ratio of 6.8 (95% CI 1.8–25) for development of cardiomyopathy during follow-up. For those with a predicted 10-year cardiomyopathy probability &amp;lt;3% (76.9% of the derivation cohort and 74.3% of validation cohort) the negative predictive value was &amp;gt;99% in both cohorts. Conclusion The addition of the initial EF &amp;gt;5 years after cancer diagnosis to anthracycline- and chest-directed radiotherapy dose improves the 10-year cardiomyopathy prediction in CCS. Our validated prediction model identifies low-risk survivors in whom the surveillance frequency may be reduced to every 10 years. Calibration in both cohorts Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation

Perceived value drives use of routine asymptomatic surveillance PET/CT by physicians who treat head and neck cancer.

Why physicians use surveillance imaging for asymptomatic cancer survivors despite recommendations against this is not known. Physicians surveilling head and neck cancer survivors were surveyed to determine relationships among attitudes, beliefs, guideline familiarity, and self-reported surveillance positron-emission-tomography/computed-tomography use. Among 459 responses, 79% reported using PET/CT on some asymptomatic patients; 39% reported using PET/CT on more than half of patients. Among attitudes/beliefs, perceived value of surveillance imaging (O.R. 3.57, C.I. 2.42-5.27, P = <.0001) was the strongest predictor of high imaging, including beliefs about outcome (improved survival) and psychological benefits (reassurance, better communication). Twenty-four percent of physicians were unfamiliar with guideline recommendations against routine surveillance imaging. Among physicians with high perceived-value scores, those less familiar with guidelines imaged more (O.R. 3.55, C.I. 1.08-11.67, P = .037). Interventions to decrease routine surveillance PET/CT use for asymptomatic patients must overcome physicians' misperceptions of its value. Education about guidelines may modify the effect of perceived value.

Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials

Circulating tumor cells (CTCs) have been detected by us and others in cancer patient blood. However, little is known about how to specifically capture and deactivate CTCs in vivo, which may lead to successful metastasis prevention in asymptomatic cancer survivors after surgery. We hypothesize that the dual antibody conjugates may have the advantage of capturing CTCs specifically over their single antibody counterparts. Here we show that the surface-functionalized dendrimers can be sequentially coated with two antibodies directed to surface biomarkers (EpCAM and Slex) of human colorectal CTCs. The dual antibody-coated dendrimers exhibit a significantly enhanced specificity in capturing CTCs in the presence of interfering blood cells, and in both eight-patient bloods and nude mice administered with the labeled CTCs in comparison to their single antibody-coated counterparts. The dual antibody-coated conjugates down-regulate the captured CTCs. This study provides the first conceptual evidence that two antibodies can be biocompatibly conjugated to a nanomaterial to capture and down-regulate CTCs in vivo with the enhanced specificity.

Imaging and cancer survivorship: challenges and changing concepts

The widening gap between cancer incidence and mortality testifies to the increasing success of cancer treatment. For example, in Queensland Australia, there are now more than 7 cancer survivors for each patient newly diagnosed with cancer. These individuals represent a population at risk for recurrent malignancy for whom there is a growing demand for imaging services. Imaging for suspected recurrence may be prompted by symptoms or rising tumour markers, whilst for some tumours, imaging contributes to regular surveillance. The benefits of early detection of recurrence through imaging surveillance need to be balanced against cost, patient anxiety and radiation exposure. A recent study has estimated the absolute risk of second cancer induction resulting from use of radiological examinations in this context to be between 0.1% and 10% [1]. Targeting patients at greatest risk of recurrence would improve the balance between risk and benefit for imaging surveillance and is potentially achievable through the use of prognostic imaging biomarkers derived from imaging procedures performed at staging or post-treatment [2]. Increasingly sophisticated treatments for recurrent disease present further challenges to the use of imaging in cancer survivorship. There are now more therapeutic options for patients with localised disease or recurrence to a few sites (oligometastatic disease). Although well established for hepatic metastases from colorectal cancer, surgical resection of localised recurrence is increasingly adopted for alternative sites of recurrence and for other tumour types. For tumour sites unamenable to surgery, stereotactic body radiotherapy can allow focal delivery of high-dose radiation with single or few fractions with promising local control and overall survival rates [3]. These developments create new questions for imaging. Firstly, should imaging surveillance programmes of asymptomatic cancer survivors be developed to allow identification of the oligometastatic state prior to disseminated disease? The potential benefits of surveillance are highlighted by a study of patterns of distant failure and progression in breast cancer which found oligometastatic disease to be more common amongst asymptomatic patients [4]. Secondly, how can imaging be optimised to distinguish oligometastatic from disseminated disease? Imaging in this context must have high sensitivity and specificity on a lesion-by-lesion basis because an accurate assessment of the number of metastases is required to avoid the morbidity of inappropriate oligometastatic treatment, as well as the possibility of oligometastatic treatment being wrongly withheld due to the presence of benign lesions that are indistinguishable from additional metastases. Hybrid imaging techniques that combine modalities with complementary sensitivity and specificity are likely to offer the greatest opportunities for accurate assessment of oligometastatic disease. Higher accuracy for skeletal metastases can be achieved by diphosphonate SPECT/CT or fluoride PET/CT in place of planar scintigraphy [5] whilst integrated FDG-PET/MRI has the potential to optimise detection of skeletal and hepatic recurrence in a single examination [6,7]. The new PET tracer Gallium-68 Prostate Specific Membrane Antigen demonstrates high accuracy for nodal and skeletal recurrence prostate cancer [8]. Imaging protocols for cancer staging are now well established. Increasing cancer survivorship has created a need to develop equivalent protocols for the diagnosis and assessment of tumour recurrence.

American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects

To review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors. An American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006. Few studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans. An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.

Cognitive functions of adolescent childhood cancer survivors assessed by event-related potentials.

Neurophysiological methods were applied to examine subtle central nervous system (CNS) adverse effects for adolescent childhood cancer survivors. We analyzed auditory event-related potentials (ERPs)-P300 and MMN/P3a complex-to find out whether there was impaired attention orientation in asymptomatic cancer survivors, and whether these ERP methods could be used as more objective tools in detecting those survivors who might need academic testing. Previous clinical studies of P300 have focused on leukemia survivors. MMN for cancer survivors has not been reported. The subjects were survivors of childhood leukemia (n=11) and solid tumors (n=8), as well as healthy controls (n=10). The mean age was 15.5 years for survivors and 15.9 years for controls. Pure sine-wave tones (500 and 553 Hz, 100 ms) were used as stimuli in an oddball paradigm. The ERPs to frequency change were measured. MMN recordings were performed in a passive non-attended situation where the subject was watching a voiceless video cartoon. P300 was produced thereafter, but in an active attend situation, by the same auditory oddball paradigm as MMN. A significant difference was detected between the groups for the latency of P300 at electrodes Cz (P = 0.03) and C4 (P = 0.05). The cancer survivors had prolonged P300 latencies as an indication of prolonged short-term memory processing. The area and latency parameters of MMN did not differ significantly between the study groups, but in cancer survivors, the area and the mean amplitude of the subsequent P3a wave were diminished. The results indicate that the discrimination process was not as easy for the survivors as for the controls. However, it seems that in cancer survivors the basic mechanism starting attention shift to novel stimuli is not impaired. These results indicate that it is important to carefully evaluate the proper methods for the teaching of children who are survivors of malignancies. The auditory information may not always lead to the best possible learning results.