Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy that is characterized by microangiopathic haemolytic anaemia, consumption thrombocytopenia and organ injury. It is caused by a severe deficiency of ADAMTS13, which can be either congenital or acquired. There is a plethora of things that can cause the acquired form, including medications and infections. Vaccines have also been shown to cause TTP. In the midst of the COVID-19 pandemic, with multiple new vaccines being developed and distributed to the masses, the medical community needs to be aware of adverse events associated with these new vaccines. We present a case of TTP following administration of the Moderna booster vaccine.
e16508 Background: Circulating tumor DNA (ctDNA) are short DNA sequences shed by tumor cells into systemic circulation. The sensitivity and specificity of single ctDNA test to predict relapse or recurrence in solid tumor vary widely and the utility of monitoring serial ctDNA trends has not been well-described in genitourinary cancers. Methods: We conducted a retrospective study including adult patients with genitourinary cancers at the hematology-oncology clinic at William Beaumont - Royal Oak and Troy Hospitals, Michigan from, August 2021 to May 2022, who had ctDNA testing done with imaging available for comparison. We evaluated the correlation between ctDNA test, both single test as well as dynamic trends in value over time, with imaging findings. We also calculated lead time for uptrending ctDNA to detect disease progression compared to imaging. Results: 21 total ctDNA test results from eight patient were included in the study; five had renal cell cancer, two had urothelial cancer and one had prostate cancer. The median age at diagnosis was 62 years (Range: 45-82); 90% were Caucasian and 50% were female. Majority (87.5%) had Stage III or IV disease. Out of the 21 total ctDNA samples, all 16 positive ctDNA results had evidence of disease on corresponding imaging: 13 showed progression while 3 showed regression with residual disease compared to prior imaging. Of the 5 negative ctDNA test results, 2 showed no evidence of disease and 3 showed regression with residual disease on corresponding imaging. Sensitivity and specificity of a single positive ctDNA test to detect evidence of disease on imaging was 84.2% and 100%, respectively. Six patients had multiple ctDNA test results with 12 pairs of serial ctDNA values, of which 9 were up-trending, and 3 were down-trending. Both sensitivity and specificity of up-trending ctDNA values to detect progression and down-trending ctDNA values to detect regression on imaging were 100%. Uptrending ctDNA values predicted disease progression with a median lead time of 55.5 days compared to imaging. Conclusions: Given the high sensitivity and specificity of serial ctDNA monitoring to detect disease progression and regression in our study, we conclude that this may be a valid way to reliably monitor for changes in disease status in genitourinary cancers before they become evident on imaging studies. Further clinical studies are needed to prove its utility in detecting immediate changes in disease status and guide therapeutic intervention in genitourinary cancers. [Table: see text] [Table: see text]
Circulating tumour DNA (ctDNA) is defined as short DNA sequences shed by tumour cells into the systemic circulation. A promising use of ctDNA includes the detection of minimal residual disease (MRD) and is currently being studied in multiple types of solid tumours. Literature for the use of individualised ctDNA in nasopharyngeal carcinoma (NPC) is not available, although circulating Epstein-Barr virus DNA level is validated as a prognostic factor. We present a man in his 40s diagnosed with stage IV NPC who was started on chemotherapy with cis-platinum and gemcitabine. Serial monitoring of ctDNA completed to aid in detecting MRD after treatment demonstrated initial up-trending values correlating with subsequent imaging findings showing progression. Reinitiation of a different chemotherapy regimen significantly improved the ctDNA level, with corresponding imaging exhibiting a similar response. This case provides insight into the potential use of ctDNA in NPC and the benefit of serial ctDNA monitoring during treatment.
Introduction: Circulating tumor DNA are short DNA sequences of tumor cells shed into the systemic circulation. Post-operative ctDNA positivity has been studied as a potential marker for disease recurrence, however, dynamic changes in its level and immediate correlation with imaging have not been well described. Methods: We conducted a retrospective study including adult patients with non-colorectal gastrointestinal (GI) cancer. We evaluated the correlation of ctDNA with imaging studies to detect disease progression or regression. Eighteen patients, with 33 ctDNA samples were included. Results: Out of the 18 patients, five had pancreatic, three each had hepatocellular and cholangiocarcinoma, two each had anal cancer and neuroendocrine tumor, and one each had gastric, small bowel, and GI malignancy of unknown primary. Among the patients, 50% were male, and the median age at diagnosis was 64 years. 72.2% of the patients had advanced disease (stage III/IV), and only 22.2% had a predisposing condition leading to malignancy. Our primary endpoint, the correlation of single positive ctDNA results with imaging showing either progression or residual disease, showed a sensitivity of 60% and specificity of 100%. Secondarily, serial ctDNA was analyzed in ten patients with at least two ctDNA test results. This revealed a sensitivity of 80% and specificity of 100% for up-trending ctDNA values to detect progression, down-trending to detect regression, and persistent negative results to detect the absence of disease. This calculated sensitivity was lower than our separate analysis of colorectal cancer, where the sensitivity of single and serial ctDNA was 84.8% and 92.9%, respectively. The specificity, however, was 100% in both cancer groups. The positive ctDNA results detected disease progression with a median lead-time of 44 days compared to imaging. Conclusion: Colorectal cancer is the most studied malignancy in regards to the use of circulating tumor DNA as a marker of tumor recurrence. Similar studies in non-colorectal GI cancers are lacking. However, limited studies have shown some promising results for the use of post-operative ctDNA. The test’s sensitivity in our study was inferior compared to colorectal cancer, but given high specificity and improvement in sensitivity with serial analysis, ctDNA can be a valid way to monitor disease progression or regression in non-colorectal GI cancers. Further clinical studies are required to prove its utility in the reliable detection of immediate changes in disease status.
The use of post-operative circulating tumor DNA (ctDNA) to detect cancer recurrence has been reported in various studies but the literature describing variable changes in ctDNA is limited. The objective of this study is to describe the utility of single and serial ctDNA values in detecting the progression or regression of gynecological cancers.
Methods
This is a retrospective observational study including nineteen patients, aged >=18 years who had the ctDNA test completed at hematology/oncology clinic of William Beaumont – Royal Oak and Troy Hospitals, Michigan, USA.
Results
Among the nineteen patients, fifteen had breast, three had ovarian, and one had endometrial cancer. The median age at diagnosis was 57 years, and 73.7% of patients had either stage III or IV disease. Our primary endpoint, the correlation of single ctDNA results with imaging showing either progression or residual disease, showed a sensitivity and specificity of 100% and 93.3%, respectively. Secondarily, serial ctDNA analysis in ten patients revealed both sensitivity and specificity of 100% for up-trending ctDNA to detect progression, down-trending to detect regression, and negative results to detect the absence of disease. The positive ctDNA results detected disease progression with a median lead-time of 36.5 days compared to imaging.
Conclusions
Given the high sensitivity and specificity to detect disease progression and regression in gynecologic cancer by single and serial values in our study, we conclude that ctDNA can be a valid way to monitor for changes in disease status. Further clinical studies are required to prove the utility of ctDNA in detecting changes in disease status
Background and aimsOrganized screening programs reduce colorectal cancer (CRC)-related mortality. The multitarget stool DNA (MT-sDNA) test is approved by the United States Food and Drug Administration as a screening modality with good compliance and follow-up. In cases of positive MT-sDNA test results and negative colonoscopy results, experts recommend a 10-year follow-up interval. Concern about interval CRC has led to varying opinions and practices among endoscopists. The goal of our study was to determine how often endoscopists give 10-year follow-up recommendations in the setting of positive MT-sDNA test results and negative colonoscopy results.MethodsWe retrospectively identified patients who underwent an average-risk colonoscopy after a positive MT-sDNA test result. Data were collected from 4 hospitals in Southeast Michigan from August 2014 to February 2021. We excluded patients with previous colonoscopies, polyps, personal or family history of CRC, inflammatory bowel disease, and history of familial polyposis. Before analysis, we further excluded patients with procedure extent reached to less than the cecum, those whose bowel preparation was less than “excellent” or “good” according to the modified Aronchick scale, and any patient with missing or unavailable data necessary for analysis. For our secondary outcomes, we assessed predictors that may influence an endoscopist’s recommendation to give a 10-year follow-up, including physician factors (ie, perceived adenoma detection rate [ADR]), years of experience, and estimated procedure volume), patient factors (ie, age, gender, comorbidities according to the Charlson index, and presence of diverticulosis), and procedural variables (ie, timing of procedure and withdrawal time). We used Fisher exact tests and multivariate logistic regression to compare recommendations to the variables collected.ResultsWe identified 689 patients who underwent a diagnostic colonoscopy after a positive MT-sDNA test result. After initial exclusion, we were left with 515 patients for analysis. Of those patients, 333 had a positive finding on colonoscopy (adenocarcinoma, advanced adenoma, or nonadvanced adenoma), and 182 patients had presumed negative colonoscopy results. After further exclusions (114 additional patients), we had 68 patients who met our strict criteria. We observed a 13% false positive rate for the MT-sDNA stool test. For the 68 patients, a 10-year follow-up interval was recommended 51% of the time and ≤5 years 21% of the time. In logistic regression analysis, older patients and patients with multiple comorbidities were more likely to receive shorter screening intervals than the standard 10 years.ConclusionOnly 51% of endoscopists give 10-year follow-up recommendations in the setting of a positive MT-sDNA test result and negative colonoscopy result. Despite fewer benefits from further screening, older patients and patients with multiple comorbidities were more likely to be given shorter screening intervals after a false positive MT-sDNA result. Organized screening programs reduce colorectal cancer (CRC)-related mortality. The multitarget stool DNA (MT-sDNA) test is approved by the United States Food and Drug Administration as a screening modality with good compliance and follow-up. In cases of positive MT-sDNA test results and negative colonoscopy results, experts recommend a 10-year follow-up interval. Concern about interval CRC has led to varying opinions and practices among endoscopists. The goal of our study was to determine how often endoscopists give 10-year follow-up recommendations in the setting of positive MT-sDNA test results and negative colonoscopy results. We retrospectively identified patients who underwent an average-risk colonoscopy after a positive MT-sDNA test result. Data were collected from 4 hospitals in Southeast Michigan from August 2014 to February 2021. We excluded patients with previous colonoscopies, polyps, personal or family history of CRC, inflammatory bowel disease, and history of familial polyposis. Before analysis, we further excluded patients with procedure extent reached to less than the cecum, those whose bowel preparation was less than “excellent” or “good” according to the modified Aronchick scale, and any patient with missing or unavailable data necessary for analysis. For our secondary outcomes, we assessed predictors that may influence an endoscopist’s recommendation to give a 10-year follow-up, including physician factors (ie, perceived adenoma detection rate [ADR]), years of experience, and estimated procedure volume), patient factors (ie, age, gender, comorbidities according to the Charlson index, and presence of diverticulosis), and procedural variables (ie, timing of procedure and withdrawal time). We used Fisher exact tests and multivariate logistic regression to compare recommendations to the variables collected. We identified 689 patients who underwent a diagnostic colonoscopy after a positive MT-sDNA test result. After initial exclusion, we were left with 515 patients for analysis. Of those patients, 333 had a positive finding on colonoscopy (adenocarcinoma, advanced adenoma, or nonadvanced adenoma), and 182 patients had presumed negative colonoscopy results. After further exclusions (114 additional patients), we had 68 patients who met our strict criteria. We observed a 13% false positive rate for the MT-sDNA stool test. For the 68 patients, a 10-year follow-up interval was recommended 51% of the time and ≤5 years 21% of the time. In logistic regression analysis, older patients and patients with multiple comorbidities were more likely to receive shorter screening intervals than the standard 10 years. Only 51% of endoscopists give 10-year follow-up recommendations in the setting of a positive MT-sDNA test result and negative colonoscopy result. Despite fewer benefits from further screening, older patients and patients with multiple comorbidities were more likely to be given shorter screening intervals after a false positive MT-sDNA result.
Immune thrombocytopenia (ITP) has been associated with immunizations with various proposed mechanisms, including overactivation of the immune system and production of antibodies against circulating platelets. ITP has also been associated with several viral infections, including HCV, HIV, and most recently, active SARS-CoV-2 infection. Here, we present a case of a 52-year-old male with no past medical history who sought evaluation with his primary care physician for upper and lower extremity ecchymosis of one week duration. Outpatient laboratory studies were notable for severe isolated thrombocytopenia with platelet count of 8 × 10^9/L. Interestingly, he received the Johnson and Johnson COVID-19 vaccine 16 days prior to his presentation. Clinical work up and laboratory investigations led to the diagnosis of ITP.
