Prior History Of Malignancy Research Articles

8078 TERT Positive Thyroid Nodule in the Setting of Metastatic Melanoma

Abstract Disclosure: E. Langnas: None. S. Chao: None. K.M. Gomes: None. A. Bhan: None. Metastatic disease to the thyroid gland is uncommon with a reported incidence of up to 4% in post-surgical specimens. Lung cancer is the most common primary tumor site in autopsy series. Clinically, renal cell carcinoma is the most common primary tumor site. Metastatic melanoma to the thyroid gland is clinically rare, however, in autopsy series, it has been reported with incidence of up to 39%. A 61-year-old man presented to the endocrinology clinic for an incidentally detected thyroid nodule. He had recently presented with a chronic cough, prompting a chest x-ray that revealed pulmonary nodules. Subsequent computed tomography (CT) showed numerous bilateral lung nodules measuring up to 2.5 cm and an incidental thyroid nodule. Ultrasound of the thyroid identified a 2.7 cm mixed cystic-solid right thyroid nodule. No risk factors for thyroid cancer were identified. His TSH was 3.51uIU (0.45 - 5.33 uIU/mL). The thyroid nodule was biopsied, and pathology revealed atypical spindle cells with irregular nuclear membranes and scattered histiocytes. A further review with cytopathology suggested non-thyroidal origin of the cells. Molecular testing with AFIRMA reported a telomerase reverse transcriptase (TERT) promoter mutation at C228T. The sequencing was negative for TERT C250T, BRAF, RET, PETC1, PTC3 and MTC. Due to concerns about metastatic disease, a positron-emission tomography (PET)-CT was conducted, revealing hypermetabolic lesions in numerous bilateral lung nodules, right thyroid nodule, porta hepatis lymph node, and a soft tissue nodule within the greater curvature of the gastric body. Subsequent biopsies of the right lung and gastric body confirmed the diagnosis of metastatic melanoma. On further questioning, it was found that the patient had a history of a skin lesion on his back that was excised several years ago with pathology reporting tumoral melanosis. Malignant melanoma has a poor prognosis due to high recurrence and metastatic rates. In melanoma, TERT promoter mutations are the most common mutations in noncoding regulatory regions. TERT C228T mutations and C250T mutations are seen in malignant melanoma and studies have shown that TERT promoter mutations are associated with aggressive clinical behavior. These TERT promoter mutations can also be seen in various other cancers including primary thyroid cancers with a similar association with more aggressive thyroid tumor characteristics. Our case describes a patient with a thyroid nodule and molecular testing noting a TERT promoter mutation. Both primary thyroid cancer and metastatic disease to the thyroid should be considered in these cases. This case also highlights the importance of obtaining a thorough history of prior malignancy in patients with thyroid nodules to assess the risk of metastatic disease. Presentation: 6/1/2024

Wedge Resection versus Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors ≤8 mm.

The objective of this study was to evaluate the overall survival of patients with ≤8 mm non-small cell lung cancer (NSCLC) who undergo wedge resection versus stereotactic body radiation therapy (SBRT). Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score-matched analysis were performed to evaluate the overall survival of patients with ≤8 mm NSCLC in the National Cancer Database (NCDB) from 2004 to 2017 who underwent wedge resection versus patients who underwent SBRT. The above-mentioned matched analyses were repeated for patients with no comorbidities. Patients who were coded in the NCDB as having undergone radiation because surgery was contraindicated due to patient risk factors (e.g., comorbid conditions, advance age, etc.) and those with a history of prior malignancy were excluded from analysis. Of the 1505 patients who had NSCLC ≤8 mm during the study period, 1339 (89%) patients underwent wedge resection, and 166 (11%) patients underwent SBRT. In the unadjusted analysis, multivariable Cox modeling and propensity score-matched analysis, wedge resection was associated with improved survival when compared to SBRT. These results were consistent in a sensitivity analysis limited to patients with no comorbidities.

The Clinical Value of Pre-Diagnostic Thrombocytosis for the Detection of Lung Cancer in Primary Care.

Thrombocytosis is a risk marker for lung cancer in primary care. We investigated whether thrombocytosis presents pre-diagnostically for all the histological subtypes of lung cancer and its association with the stage at diagnosis. A matched cohort study used English electronic primary care data linked to the national cancer registry. Patients diagnosed with lung cancer aged ≥40 years with no prior history of malignancy were matched by age, sex, and general practice to five controls without lung cancer. Multivariable logistic regression models quantified the incidence of pre-diagnostic thrombocytosis and advanced-stage diagnoses, adjusting for COPD diagnosis, smoking status, and anti-platelet drug prescriptions. A total of 9504 cases were matched to 45,647 controls, consisting of 3260 (34%) adenocarcinomas (ADC), 2020 (21%) squamous cell carcinomas (SCC), 70 (<1%) large-cell carcinomas (LCC), and 1089 (12%) small-cell lung cancers (SCLC). The patients with lung cancer were 8.9 (95% CI 8.0-9.9) times more likely to exhibit pre-diagnostic thrombocytosis than the controls. The odds ratios were highest for the comparison between SCC and ADC (1.8, 95% CI 1.5-2.1). Thrombocytosis is associated with advanced-stage ADC and SCC but presented equally for early- and advanced-stage SCLC. Pre-diagnostic thrombocytosis may aid in the detection of all the histological subtypes in primary care.

Safety and Diagnostic Efficacy of Image-Guided Biopsy of Small Renal Masses.

Image-guided renal mass biopsy is gaining increased diagnostic acceptance, but there are limited data concerning the safety and diagnostic yield of biopsy for small renal masses (≤4 cm). This study evaluated the safety, diagnostic yield, and management after image-guided percutaneous biopsy for small renal masses. A retrospective IRB-approved study was conducted on patients who underwent renal mass biopsy for histopathologic diagnosis at a single center from 2015 to 2021. Patients with a prior history of malignancy or a renal mass >4 cm were excluded. Descriptive statistics were used to summarize patient demographics, tumor size, the imaging modality used for biopsy, procedure details, complications, pathological diagnosis, and post-biopsy management. A biopsy was considered successful when the specimen was sufficient for diagnosis without need for a repeat biopsy. Complications were graded according to the SIR classification of adverse events. A chi-squared test (significance level set at p ≤ 0.05) was used to compare the success rate of biopsies in different lesion size groups. A total of 167 patients met the inclusion criteria. The median age was 65 years (range: 26-87) and 51% were male. The median renal mass size was 2.6 cm (range: one-four). Ultrasound was solely employed in 60% of procedures, CT in 33%, a combination of US/CT in 6%, and MRI in one case. With on-site cytopathology, the median number of specimens obtained per procedure was four (range: one-nine). The overall complication rate was 5%. Grade A complications were seen in 4% (n = 7), consisting of perinephric hematoma (n = 6) and retroperitoneal hematoma (n = 1). There was one grade B complication (0.5%; pain) and one grade D complication (0.5%; pyelonephritis). There was no patient mortality within 30 days post-biopsy. Biopsy was successful in 88% of cases. A sub-group analysis showed a success rate of 85% in tumors <3 cm and 93% in tumors ≥3 cm (p = 0.01). Pathological diagnoses included renal cell carcinoma (65%), oncocytoma (18%), clear cell papillary renal cell tumors (9%), angiomyolipoma (4%), xanthogranulomatous pyelonephritis (1%), lymphoma (1%), high-grade papillary urothelial carcinoma (1%), and metanephric adenoma (1%), revealing benign diagnosis in 30% of cases. The most common treatment was surgery (40%), followed by percutaneous cryoablation (22%). In total, 37% of patients were managed conservatively, and one patient received chemotherapy. This study demonstrates the safety and diagnostic efficacy of image-guided biopsy of small renal masses. The diagnostic yield was significantly higher for masses 3-4 cm in size compared to those <3 cm. The biopsy results showed a high percentage of benign diagnoses and informed treatment decisions in most patients.

Determinants of survival following heart transplantation in adults with congenital heart disease

BackgroundAdult patients surviving with congenital heart disease (ACHD) is growing. We examine the factors associated with heart transplant outcomes in this challenging population with complex anatomy requiring redo-surgeries.MethodsWe reviewed the United Network for Organ Sharing-Standard Transplant Analysis and Research database and analyzed 35,952 heart transplants from January 1st, 2000, to September 30th, 2018. We compared transplant characteristics for ischemic cardiomyopathy (ICM) (n = 14,236), nonischemic cardiomyopathy (NICM) (n = 20,676), and ACHD (n = 1040). Mean follow-up was 6.20 ± 4.84 years. Kaplan–Meier survival curves and Cox-proportional hazards analysis were used to analyze survival data.ResultsMultivariable analysis confirmed that ACHD was associated greater in-hospital death compared to ICM (HR = 0.54, P < 0.001) and NICM (HR = 0.46, P < 0.001). Notable factors associated with increased mortality were history of cerebrovascular disease (HR = 1.11, P = 0.026), prior history of malignancy (HR = 1.12, P = 0.006), pre-transplant biventricular support (HR = 1.12, P = 0.069), postoperative stroke (HR = 1.47, P < 0.001) and postoperative dialysis (HR = 1.71, P < 0.001). ACHD transplants had a longer donor heart ischemic time (P < 0.001) and trend towards more deaths from primary graft dysfunction (P = 0.07). In-hospital deaths were more likely with ACHD and use of mechanical support such as use of right ventricular assist device (HR = 2.20, P = 0.049), biventricular support (HR = 1.62, P < 0.001) and extracorporeal membrane oxygenation (HR = 2.36, P < 0.001). Conditional survival after censoring hospital deaths was significantly higher in ACHD (P < 0.001).ConclusionHeart transplant in ACHD is associated with a higher post-operative mortality given anatomical complexity but a better long-term conditional survival. Normothermic donor heart perfusion may improve outcomes in the ACHD population by reducing the impact of longer ischemic times.

Major Stressful Life Events and the Risk of Pancreatic, Head and Neck Cancers: A Case-Control Study.

Major stressful life events have been shown to be associated with an increased risk of lung cancer, breast cancer and the development of various chronic illnesses. The stress response generated by our body results in a variety of physiological and metabolic changes which can affect the immune system and have been shown to be associated with tumor progression. In this study, we aim to determine if major stressful life events are associated with the incidence of head and neck or pancreatic cancer (HNPC). This is a matched case-control study. Cases (CAs) were HNPC patients diagnosed within the previous 12 months. Controls (COs) were patients without a prior history of malignancy. Basic demographic data information on major stressful life events was collected using the modified Holmes-Rahe stress scale. A total sample of 280 was needed (79 cases, 201 controls) to achieve at least 80% power to detect odds ratios (ORs) of 2.00 or higher at the 5% level of significance. From 1 January 2018 to 31 August 2021, 280 patients were enrolled (CA = 79, CO = 201) in this study. In a multivariable logistic regression analysis after controlling for potential confounding variables (including sex, age, race, education, marital status, smoking history), there was no difference between the lifetime prevalence of major stressful event in cases and controls. However, patients with HNPC were significantly more likely to report a major stressful life event within the preceding 5 years when compared to COs (p = 0.01, OR = 2.32, 95% CI, 1.18-4.54). Patients with head, neck and pancreatic cancers are significantly associated with having a major stressful life event within 5 years of their diagnosis. This study highlights the potential need to recognize stressful life events as risk factors for developing malignancies.

Late Presentation of a Primary Spinal Epidural Non-Hodgkin Lymphoma

Primary spinal epidural lymphomas (PSELs) constitute a unique subset of epidural tumors characterized by the exclusive presence of lymphoma within the epidural space at initial presentation, with no concurrent lymphoma in other sites. We aim to present a unique of PSEL and compare it with the present literature This case report presents a 65-year-old female with delayed-onset primary spinal epidural non-Hodgkin lymphoma (NHL). The patient exhibited paraplegia and walking difficulties, following a year of lower-extremity weakness and tingling sensations. Magnetic resonance imaging revealed a mass in the L1 through L3. Surgical decompression, stabilization, and tumor resection were performed. Microscopic examination confirmed NHL. Chemotherapy with the CHOP regimen was administered postsurgery. Subsequent follow-up revealed motoric and sensory improvements. PSEL primarily affects the thoracic spine and is more common in males. Patient age and gender impact prognosis. PSEL typically exhibits two phases – prodromal and rapid neurological deterioration. Surgical intervention coupled with chemotherapy is recommended, but the optimal surgical approach varies. Combined therapy could lead to improved disease-free survival. Cases of PSEL have shown potential for local and systemic relapse. Late presentation can still yield improvements with surgical and prompt chemotherapeutic intervention. Even without a prior history of malignancy or significant disease, PSEL should still be considered in patients presenting with spinal compression symptoms. Cases of delayed presentation, like the one presented here, can still benefit from surgical and prompt chemotherapeutic intervention.

Metastatic Mullerian adenocarcinoma involving the pancreas initially misdiagnosed as an intraductal papillary mucinous neoplasm (IPMN): A case report, and lessons learned

Abstract Introduction/Objective Metastases to the pancreas from Mullerian primaries are rare and can be confused with primary pancreatic malignancies. Methods/Case Report A 49-year-old woman presented with right lower abdominal pain. She denied any prior history of malignancy but had undergone hysterectomy and bilateral salpingo-oophorectomy for unknown reasons. CT scan revealed an 8.9 cm predominantly cystic mass in the pancreas, highly suspicious of an invasive mucinous neoplasm. EUS-guided FNA of the pancreas showed large, complex papillary fronds of mucinous epithelial cells in a background of abundant extracellular mucin, findings that were interpreted as an intraductal papillary mucinous neoplasm (IPMN) with foci of high-grade dysplasia and possible adenocarcinoma. A subsequent PET/CT scan demonstrated a 3.9 cm hepatic mass and a 3.8 cm perihepatic lesion. FNA of the liver was interpreted as metastatic pancreatic adenocarcinoma. Despite aggressive treatment, her disease progressed. Molecular profiling of her liver tumor demonstrated a pathogenic KRAS G12D mutation and a PDGFRA variant of uncertain significance. Genomic (DNA) and transcriptomic (RNA) analysis indicated a 96% probability that the patient had ovarian or fallopian tube adenocarcinoma and a 4% probability of uterine endometrial adenocarcinoma rather than metastatic pancreatic adenocarcinoma. A panel of immunocytochemical stains was performed on the pancreas and liver FNAs. The tumor cells were strongly positive for CK7, CK19, ER, and WT1, focally positive for PAX8 (nuclear) and P53 (wild-type), and negative for CK20, CDX2, and SATB2. Results (if a Case Study enter NA) NA Conclusion These findings corroborated the molecular analysis suggesting that the patient had metastatic Mullerian adenocarcinoma rather than metastatic pancreatic adenocarcinoma. Her oncologic treatment was adjusted accordingly.

The spectrum of malignant diagnoses in cerebrospinal fluid cytology from an adult population: a multi-institutional retrospective review

IntroductionLimited updated literature exists about the prevalence and spectrum of malignancies involving cerebrospinal fluid (CSF). In this multi-institutional study, we review our experience with focus on first time malignancy diagnosis in CSF samples of adults. Materials and MethodsInstitutional databases at 4 academic centers were queried retrospectively for CSFs over a 10-year period. The following data elements were collected: total # of CSFs, total # of CSFs with a malignant diagnosis; for each patient with a first time CSF diagnosis of malignancy: age, gender, diagnosis, prior history of malignancy and ancillary studies. Results24142 CSFs were collected with a positive for malignancy rate of 2.3% (n=551). Out of 347 (1.4%) adults with a first-time diagnosis of CSF malignancy 182 (52%) were female (age range: 19-89/mean: 57) and 165 (48%) were male (age range: 20-95/mean: 60). Hematolymphoid malignancies (48%, n=168) were overall the most common neoplasm. In women, metastatic carcinomas (63%, n=114) were the leading malignancy, of which the majority were breast primaries. In men, lymphomas/leukemias (64%, n=106) were the leading malignancy, of which the majority were B-cell lymphomas. Ancillary studies aided the final diagnosis in 110 (32%) cases. For 286 (82%) cases, a prior history of malignancy was available to correlate CSF findings. ConclusionsA malignancy diagnosis in the CSF of adults is rare. The most common malignancies in females and males are metastatic breast carcinoma and hematolymphoid malignancies, respectively. Metastatic neoplasms account for the majority, with primary CNS neoplasms being quite uncommon. History of malignancy and ancillary tests can be helpful.

SAT543 A Case of Non-iodine-Avid Papillary Thyroid Cancer With a Rare Distant Metastasis to the Pancreas

Abstract Disclosure: A.H. Alcain: None. M.C. Isidro: None. Papillary Thyroid Carcinoma is the most common type of differentiated thyroid cancer. Distant metastasis is rare occurring only in 5% of patients and typically involves the lungs and bones. Metastasis to the pancreas is extremely rare with few cases reported over the years. We present a case of a 65-year-old female, who presented with sudden onset of abdominal pain. A review of the patient’s medical history revealed a history of a non-iodine avid Papillary Thyroid Carcinoma in 2015. The patient underwent Radioactive Iodine (RAI) ablation therapy twice due to elevated Thyroglobulin (Tg) levels. Despite RAI, Tg levels were still elevated with no recurrence nor metastasis noted on scan. Chemotherapy was offered but the patient opted for Tomotherapy. The patient completed Tomotherapy in 2017 but afterward was lost to follow-up. A CT scan of the abdomen showed findings of a pancreatic tail and body mass (10 x 7 cm) with an invasion of the mid-descending colon with pulmonary nodules which are possibly metastatic. The patient underwent an endoscopic ultrasound-guided biopsy, and pathology showed findings of a pancreatic papillary neoplasm (CK and beta-catenin positive, synaptophysin negative). Chemotherapy was given (FOLFOX) and a PET scan was requested to monitor the response to treatment. However, PET-scan showed FDG-avid (SUV 32.1) mass in the pancreatic tail (7.2 x 7.8 x 13.3 cm), FDG-avid (SUV 17.61) nodules in the lungs, and an ill-defined heterogeneous mass in the left surgical site (2.2 x 2.6 x 5.3 cm). Given that patient had a thyroidectomy in 2015, recurrence was considered. The possibility of probable metastasis to the pancreas was entertained hence re-biopsy was done. Serum Tg levels were elevated (4,115 ng/ml NV: 1.59-50.0) and negative for Anti-Tg. Biopsy showed high-grade neoplasm with papillary features. IHC staining showed positive for CK7, Tg, and TTF-1, and negative for CK20 which was consistent with metastatic papillary thyroid carcinoma. The patient was given Lenvatinib and is at present tolerating the treatment well with evidence of decreasing Tg levels suggesting a response to treatment. This is a case of a rare site of distant metastasis of a non-iodine avid papillary thyroid carcinoma. Targeted therapy such as Tyrosine kinase inhibitors can improve the survival rate of patients with Radioiodine Refractory Thyroid cancers. Metastasis should be considered especially in patients with a history of prior malignancy. Presentation Date: Saturday, June 17, 2023

Development of a Screening Nomogram for Regional Lymph Node Metastasis Development in Muscle Invasive Bladder Cancer after Multiagent Systemic Therapy

A reliable method of identifying clinically node negative bladder cancer patients at greater risk of developing lymph node metastasis and may require intensified therapy is needed. The purpose of this study was to create a nomogram to quantify the risk for regional lymphatic involvement in non-metastatic muscle invasive bladder cancer. Usingthe National Cancer Database, patients with clinical T2-4N0M0 urothelial carcinoma of the bladder between the years of 2004 - 2020 were selected. All patients completed multiagent chemotherapy followed by surgery for pathologic nodal staging to determine presence or absence of nodal disease. No neoadjuvant radiation therapy was allowed and patients with history of prior malignancies were excluded. Following a 70:30 training to testing data split, baseline variables were assessed using univariate logistic regression. Variables were selected for inclusion in the multivariate logistic regression model using a combination of previously reported findings in the literature and/or if found to have a p-value < 0.05 on univariate analysis. A nomogram was constructed using this final model with assessment using calibration plots and the area under the receiver operating characteristics curve (AUC), respectively. An empiric cut point was chosen at 95% sensitivity to identify patients at "high" and "low" risk for pathologic nodal disease with overall assessment in both cohorts using chi-square. A total of 6194patients were identified for study with a median age of 65 years (IQR = 58 - 71 years). Most patients were male (68.0%) with T2 disease (81.2%). The final multivariate model included age at time of diagnosis (OR = 0.99; 95% CI = 0.99 - 1.00; p = 0.172), time from diagnosis to initiation of chemotherapy (OR = 1.00; 95% CI = 1.00 - 1.01; p = 0.005), papillary histology (OR = 0.85; 95% CI = 0.72 - 1.01; p = 0.068), and clinical T stage (Table 1). Model calibration demonstrated excellent goodness-of-fit with good discrimination (AUC = 0.644). Within the training data, high risk patients were seen to have a twofold increase in pathologic nodal disease (N = 835/3924, 21.2%) when compared to those identified as low risk (N = 38/347, 9.9%) (p < 0.001). Validation within the testing data set demonstrated similar results with pathologic node rates of 22.8% and 7.8% for high- and low-risk patients, respectively (AUC = 0.645, p < 0.001). This study demonstrates a clinically applicable risk stratification tool for identifying patients at risk for developing lymphadenopathy in T2-4 bladder cancer and may help guide future research in selecting patients eligible for escalation of therapy. Future studies should aim to externally validate this tool within prospective cohorts, and seek to determine if this nomogram may provide further prognostic utility.

LDL-C: An Important Independent Risk Factor for New-Onset Heart Block in Patients with Severe Aortic Stenosis and Heart Failure after TAVR.

Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR ( = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), HR, QRS interval, QT interval, and QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and QRS interval remained significant independent risk factors after adjusting for potential confounds. Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and QRS interval.

Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review.

Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.

Biochemical recurrence (BCR) among patients (pts) with prostate cancer (PC) after radiation therapy (RT).

e17111 Background: RT is a frequent primary treatment for pts with clinically localized PC. Despite its frequent success, 30-50% of pts eventually present with BCR, defined as rising prostate-specific antigen (PSA). BCR is associated with a higher risk of developing distant metastasis and ultimately death from PC. Understanding BCR occurrence and its impact on clinical outcomes is important for optimizing diagnostic and therapeutic strategies for recurrent disease. Methods: This is a retrospective cohort study using nationally representative Electronic Medical Records (EMR) data from Optum© from 1/2010-9/2021. Eligible pts were adults who underwent RT after PC diagnosis, had ≥ 3 available PSA values after initiating RT, and had EMR activity for at least 6 mo before and 12 mo after RT. Pts with a history of prior malignancy except nonmelanoma skin cancers and pts with metastatic PC (mPC) at baseline (BL) or within 3 months after RT were excluded. The BL period was 6 mo before RT initiation. Primary outcome was frequency of BCR, defined as rising PSA (PSA ≥ nadir + 2 ng/mL); secondary analyses included % of pts who progressed to mPC, castration-resistant PC (CRPC), and death after BCR and factors impacting time to BCR. Results: 9,292 RT pts were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 69.0 (40-88) y, 83.2% of pts were White, and 13.4% were Black. Median PSA nadir was 0.11 ng/mL, 32.5% of pts had received androgen deprivation therapy (ADT) during BL period, and median (Q1-Q3) follow-up from RT initiation was 3.8 (2.4-5.7) y. Overall, 10.2% of pts developed BCR. Among BCR pts (n = 949), 51.2% had a PSA doubling time (PSADT) &lt; 6 mo and 16.9% had a PSADT between 6-10 mo; 35.0% developed mPC, 30.2% developed CRPC, and 23.4% died. In multivariate Cox regression models, the BL factor associated with the highest risk of developing BCR was PSA ≥ 20 ng/mL. Conversely, the risk of developing BCR was lower for pts who received ADT during BL. Conclusions: This real-world (RW) study evaluates BCR occurrence in pts who underwent RT with a curative intent from a large US database. The study confirms BL PSA as an important prognostic marker for BCR, while use of ADT before RT is associated with a lower risk of BCR. A considerable % of pts with BCR developed mPC (35%) or died (23%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC in pts with high-risk localized disease. [Table: see text]

Prognostic value of prior malignancy history in stage I differentiated thyroid cancer: a SEER-based study.

Thyroid cancer is the most common endocrine cancer today. Differentiated thyroid cancer (DTC) comprises more than 95% of all thyroid cancers. With the increasing incidence of tumors and development of screening, more patients suffer from multiple cancers. The purpose of this study was to explore the prognostic value of a history of prior malignancy for stage I DTC. Stage I DTC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and Cox proportional hazards regression method were used to determine the risk factors for overall survival (OS) and disease-specific survival (DSS). A competing risk model was also used to determine the risk factors for DTC-related death after considering the competitive risks. In addition, conditional survival analysis in patients with stage I DTC was performed. A total of 49,723 patients with stage I DTC were enrolled in the study, and 4,982 (10.0%) had prior malignancy history. Prior malignancy history was a factor affecting OS (P<0.001) and DSS (P<0.001) in the Kaplan-Meier analysis and an independent risk factor for OS [hazard ratio (HR) =3.6, 95% confidence interval (CI): 3.17-4.088, P<0.001] and DSS (HR =4.521, 95% CI: 2.224-9.192, P<0.001) in the multivariate Cox proportional hazards regression analysis. In the competing risk model, in the multivariate analysis, prior malignancy history was a risk factor for the DTC-related deaths [subdistribution HR (SHR) =4.32, 95% CI: 2.233-8.3593, P<0.001] after considering the competitive risks. Conditional survival showed that the probability of achieving 5-year DSS was not changed in either the two groups with or without prior malignancy history. For the patients with prior malignancy history, the probability of achieving 5-year OS increased with each additional year survived, but for the patients without prior malignancy history, the improvement of conditional OS only appeared with 2 years already prior survived. Prior malignancy history has an adverse impact on the survival of patients with stage I DTC. The probability of achieving 5-year OS for stage I DTC patients with prior malignancy history increases with each additional year survived. The inconsistent survival effects of prior malignancy history should be considered in clinical trial design and recruitment.

Metastatic solid tumours to the penis: a clinicopathologic evaluation of 109 cases from an international collaboration.

To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.

Looking Beyond Toxicities: Other Health-related Morbidities Noted in Childhood Solid Tumor Survivors.

In addition to the well-known toxicities of treatment, survivors of pediatric solid tumors can also develop other health-related conditions. They may either be an indirect consequence of therapy or could be unrelated to their prior history of malignancy. We aim to evaluate the nontoxicity related health conditions in survivors of pediatric solid tumors. The study included a cohort of hepatoblastoma (HB), Wilm's tumor (WT), and malignant germ cell tumors (MGCT) survivors registered at pediatric surgical-oncology clinic from 1994 to 2016. Follow-up was done according to standard protocols and children were evaluated at each visit for any health-related conditions. Of the survivors, 318 survivors, comprising of 48, 81, and 189 survivors of HB, MGCT, and WT, respectively, were included in the analysis. We found 20.8% of patients with HB, 11.1% of patients with MGCT, and 16.4% of patients with WT to report nontoxicity-related health issues. A high prevalence of surgical conditions (3.4%), secondary malignancies (1.2%), gynecological conditions in girls (16.9%), tuberculosis (1.2%), gallstone disease (0.9%), pelvi-ureteral junction obstruction (0.9%), and neurological issues (0.9%) was noted. Two presumed survivors had died, one due to a late recurrence and the other due to a secondary malignancy. A high prevalence of medically or surgically manageable conditions makes it imperative to keep these children under follow-up to address any health-related conditions they may subsequently develop.

Second Malignancies Among Older Patients with Classical Myeloproliferative Neoplasms Treated with Ruxolitinib

Introduction: Myeloproliferative neoplasms (MPN) are associated with an increased risk of clonal evolution to more aggressive myeloid disorders and the development of second malignancies (SM) including lymphoproliferative and solid tumors. The reasons for SM are unclear, but a therapy-related effect has been invoked. Ruxolitinib (RUX) is a guideline-recommended cytoreductive agent used in the US for myelofibrosis (MF) and polycythemia vera (PV) since 2011 and 2014, respectively. RUX has been linked to an increased risk of non-melanoma skin cancers (NMSC), but its influence on the development of other SM is debated. We aimed to evaluate the effect of RUX on the development of solid and lymphoid SM in a large, population-based cohort of patients (pts) with MPN. Methods: We conducted a retrospective cohort study of older adults with MPN including PV, essential thrombocythemia (ET) and MF in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Pts were required to 1) be diagnosed in 2012-2017, 2) be 66-99 years of age at diagnosis, 3) have continuous enrollment in Medicare Parts A and B from one year before MPN diagnosis through end of follow-up, and 4) have continuous Part D coverage from diagnosis to the end of follow-up. We excluded pts who were health maintenance organizations members, or treated with chlorambucil, busulfan or allogeneic stem cell transplant. We followed pts from MPN diagnosis to 12/31/2019, SM diagnosis, death or change of insurance status, whichever came first. RUX proportion of days covered (PDC) was calculated as the ratio of the number of days the patient was covered by RUX to the number of days from RUX initiation to 6 months before end of follow-up. Our outcome of interest was first SM, i.e., any new malignancy other than new myeloid malignancy and NMSC, diagnosed at least 6 months after cohort entry. We identified SM using SEER data for the years 2012-2017 and Medicare claims for the years 2018-2019. We categorized SM as solid or lymphoid. The cumulative incidence function (CIF) of SM was computed via a competing risk model. Death and development of a SM other than malignancy of interest (solid or lymphoid) were considered as competing events. Gray's test was utilized to assess difference across strata. The impact of RUX on the development of SM was assessed by multivariable competing risks models. The models adjusted for age at MPN diagnosis, sex, race, marital status, SEER region, Elixhauser comorbidity score, history of prior malignancy, disability status, state buy-in, census tract Yost index and hydroxyurea exposure. All statistical tests were two-sided and performed with SAS Version 9.4. Results: The study included 4019 pts (1556 PV, 1896 ET, 567 MF) with a median age at diagnosis of 77 (interquartile range [IQR]: 71-83) years. The median follow-up was 3.5 (IQR: 2.23- 4.98) years and 3.18 (IQR: 2.17- 4.75) years for 408 RUX users and 3611 non-users, respectively. Among RUX users, RUX was initiated after a median of 0.66 years since diagnosis. Pts received RUX for a median of 1.15 (IQR: 0.42-2.12) years with a median PDC of 94.6% (IQR: 71.3- 99.7%). Compared with those who did not receive RUX, RUX users were more likely to be younger, have MF and a history of prior malignancy. A total of 396 pts developed a SM including 306 solid SMs and 90 lymphoid SM. About 9% RUX users and 10% non-users developed a SM, resulting in a CIF of 17.8% (95% confidence interval [CI]: 10.1-27.4%) and 16.3% (95% CI: 13.9-18.9%), respectively (Gray's test, p=0.17; (Figure 1). The CIF of solid SM among RUX users was 11.8% (95% CI: 5.4-21.1%), and 13.0% among non-users (95% CI: 10.7-15.5%, p= 0.06); in lymphoid SM, CIF was 6.0 % (95% CI: 2.64-11.3%) among RUX users, and 3.3% (95% CI: 2.6- 4.2%) among non-users (p=0.52). In the multivariable model, the risk of any SM (hazard ratio [HR]=1.07, 95% CI: 0.73-1.58, p=0.72), solid (HR=0.97, 95% CI: 0.62-1.51, p=0.89) and lymphoid SM (HR=1.45, 95% CI: 0.66-3.20, p=0.35) did not differ by RUX use status. No difference in the risk of any SM was observed when evaluating the influence of RUX PDC (Figure 2) Similar findings were seen in MPN subgroups. Conclusions: In this large population-based study of older pts with MPN, the risk of solid and lymphoid SM was similar among RUX users and non-users. Our results suggest that the use of RUX does not increase the risk of SM in older pts with MPN. Acknowledgments: The study was supported by Frederick A. Deluca Foundation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Subgroup Analysis of Adverse Events Following Rusfertide Dosing in Revive: A Phase 2 Study of Patients with Polycythemia Vera

Background Rusfertide (PTG-300) is a potent mimetic of hepcidin that binds to ferroportin causing it to be internalized and degraded, thereby decreasing iron availability in bone marrow and reducing aberrant erythrocytosis. In the phase 2 REVIVE study (PTG-300-004; NCT04057040) of patients with polycythemia vera (PV), rusfertide treatment resulted in sustained control of hematocrit (HCT) at <45% and eliminated the requirement for therapeutic phlebotomy (TP) in 84% of patients. Rusfertide was well tolerated, with limited grade 3 treatment-emergent adverse events (TEAEs) and no grade 4 or 5 TEAEs [Hoffman, ASH 2021]. We present an analysis of the rusfertide TEAE profile in clinically relevant subgroups. Methods Patients with TP-dependent (i.e., ≥3 phlebotomies within a 6-month period) PV were eligible for REVIVE, which was comprised of 3 parts: a 28-week open-label, dose-finding stage; a 12-week double-blind randomized withdrawal stage; and a long-term extension. In the dose-finding stage, subcutaneous rusfertide doses (10-120 mg) were administered with TP or with TP plus prior cytoreductive agents (CYR-T), with individualized dose titration to maintain HCT at <45%. This analysis focuses on the 70 patients enrolled in the study with ≥8 weeks of exposure to study treatment. Results Forty-one patients (59%) were considered to be high-risk for thrombotic events because of age ≥60 years (n=26, 37%) or because of a prior thrombotic event (n=15, 21%). The TEAE profile was similiar in high-risk and low-risk patients. The TEAEs with the greatest difference in incidence between high-risk and low-risk patients, respectively, were fatigue (34% vs 21%), hyperuricemia (5% vs 17%), rash (12% vs 0), and paresthesia (15% vs 3%). The incidence of grade 3 TEAEs (11% vs 15%) was similiar in patients receiving rusfertide with TP (n=36) compared to those receiving rusfertide with TP plus CYR-T (n=34). The incidence of all-grade TEAEs was also similar except for a greater incidence of contusions (14% vs 0), and fatigue (33% vs 24%) in the rusfertide with TP group, and a greater incidence of dyspnea in the rusfertide with TP plus CYR-T group (18% vs 8%). There were no notable differences in injection site reactions in any of the subgroups or in any TEAEs by rusfertide dose. Rusfertide controlled HCT and decreased red blood cell counts. This was often accompanied by small (<20%) and clinically insignificant changes in platelet (PLT) counts that returned to baseline when rusfertide was stopped (Figure 1). However, 6 (9%) patients (3 male, 3 female) reported a PLT count >106/µL and a >20% increase from baseline on ≥1 consecutive assessment with most (n=5) being in the rusfertide with TP group. Of these 6 patients, 4 were categorized as high-risk and 2 as low-risk. In most cases, the PLT elevations occurred by week 4 and stabilized over the course of treatment. The PLT elevations were not associated with increasing rusfertide dose or duration, or with clinical sequelae such as bleeding, thrombosis, or disease progression. Across all rusfertide phase 2 PV trials (N= 90), 18 patients had a history of pre-existing cancers at baseline, of which 9 had a history of non-melanomatous skin cancers (NMSC). After beginning treatment with rusfertide, secondary malignancies were identified in 5 patients (5.5% of patients) (Figure 2). All 5 patients had prior concomitant cytoreductive therapy with HU or Rux, each of which is associated with an increased risk of NMSC [Verner, Leuk Lymph 2014; Lin, J Am Acad Dermatol 2022]. One had a pre-existing lesion confirmed as an in situ NMSC upon protocol mandated biopsy. Conclusions The TEAE profile of rusfertide is consistent across subgroups defined by thrombotic risk and concomitant CYR-T, with no clear differences in TEAE profile. While a small proportion of patients developed thrombocytosis, it was asymptomatic, stabilized over the course of treatment, and did not increase with higher rusfertide dose and treatment duration. Reactive thrombocytosis may have resulted from localized iron deficiency [Kasper, JAMA 1965]. Importantly, it was not associated with clinical sequelae. Consistent with previous reports [Pemmaraju, Blood 2019], secondary malignancies (6 early-stage skin cancers and 1 AML) were observed in 5 patients, all with prior history of malignancy or cytoreductive therapy. These data suggest that the rusfertide TEAE profile is manageable across the range of PV patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Concurrent JAK2 V617F Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL): Case study

Abstract Introduction/Objective We report a unique case of concurrently occurring Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL) in an 86-year-old male. To the best of our knowledge, this is the first report of AML occurring in the background of LN-MCL, with no known history of any malignancy or chemotherapy. Methods/Case Report An 86-year old Caucasian male with unremarkable past medical history presented with pancytopenia, fatigue and generalized weakness. Abdominal CT scan was negative for lymphadenopathy or hepatosplenomegaly. Peripheral blood showed 2% blasts with atypical lymphocytes 89%. Bone marrow aspirate showed 30% myeloblasts expressing CD34, CD117, CD13, CD33, HLA-DR and CD56 (dim) by flow cytometry (FC). Lymphocytes accounted for 40% of bone marrow cellularity. FC identified a population of CD5+ kappa restricted clonal B cells 2%, consistent with a concurrent CD5+ B-lymphoproliferative disorder/lymphoma. The bone marrow biopsy was inadequate for further evaluation of the B- cell lymphoma. Chromosomal analysis revealed a normal male karyotype. FISH analysis was positive for t(11:14) CCND1::IGH rearrangement (in 3.5% of interphase cells) supporting involvement by MCL. Myeloid panel next generation sequencing (51 genes) was positive for JAK2 V617F (VAF, 38%) and ASXL1 P920Tfs*4 (VAF, 22%) variants Results (if a Case Study enter NA) NA Conclusion Concurrent presence of LN-MCL and AML as seen in our patient in the absence of prior history of malignancy or chemotherapy is rare. Presence of JAK2V617F mutation in de-novo AML is extremely rare (&amp;lt;5%). There is no prior history of myeloproliferative neoplasm (MPN) or CBC data to suggest that this may have progressed from an MPN. While the absence of lymphadenopathy suggests that the CD5+ B-LPD likely represents LN-MCL, it is also likely that the CD5+, IgH/CCND1 rearranged B-cells may represent prior undetected circulating cells without overt LN-MCL development, similar to those reported in otherwise healthy individuals. It is unclear but tempting to speculate that the two co-occurring hematologic malignancies may have a common cell of origin