Routine Surveillance Imaging Research Articles

Relapse after non-metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post-relapse survival.

Patients with rhabdomyosarcoma (RMS) whose disease relapses have little chance of being cured, so front-line treatments are usually followed up with surveillance imaging in an effort to detect any recurrences as early as possible, and thereby improve post-relapse outcomes. The real benefit of such routine surveillance imaging in RMS remains to be demonstrated, however. This retrospective, single-center study examines how well surveillance imaging identifies recurrent tumors and its impact on post-relapse survival. The analysis concerned 79 patients <21years old treated between 1985 and 2020 whose initially localized RMS relapsed. Clinical findings, treatment modalities, and survival were analyzed, comparing patients whose relapse was first suspected from symptoms they developed (clinical symptoms group) with those whose relapse was identified by radiological surveillance (routine imaging group). Tumor relapses came to light because of clinical symptoms in 42 cases, and on routine imaging in 37. The time to relapse was much the same in the two groups. The median overall survival (OS) and 5-year OS rate were, respectively, 10months and 12.6% in the clinical symptoms group, and 11months and 27.5% in the routine imaging group (p-value .327). Among patients with favorable prognostic scores, survival was better for those in the routine imaging group (5-year OS 75.0% vs. 33.0%, p-value .047). It remains doubtful whether surveillance imaging has any real impact on RMS relapse detection and patients' post-relapse survival. Further studies are needed to establish the most appropriate follow-up recommendations, taking the potentially negative effects of regular radiological exams into account.

Is Regular Radiographic Upper Urinary Tract Imaging for Surveillance of Non-Muscle Invasive Bladder Cancer Justified?

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.

PSUN279 Refractory Hypoglycemia in the Setting of Incidental Urothelial Carcinoma

Abstract Introduction Hypoglycemia is uncommon in individuals who do not have drug-treated diabetes mellitus. In such patients, differentials include cortisol deficiency, insulinomas or autoantibodies against insulin/ insulin receptor. Malignancy related causes include non-islet cell tumors and extensive liver infiltration. This case highlights the workup of hypoglycemia in a patient with an incidental diagnosis of urothelial cancer. Clinical Case We present a 62 year old male who was assessed by the EMS at home for difficulty in arousal and facial drooling. Initial assessment found him to have a random glucose of 26mg/dL. His glucose was corrected with dextrose and the EMS left. Nine hours later the EMS was called again strange behavior, where he was found again to be hypoglycemic (19mg/dL). Glucagon and dextrose was administered and he was transported to the ED. His finger stick glucose on arrival was 26mg/dL. Endocrine history is primary hypothyroidism only. Other significant past medical history was a retroperitoneal mass seen on routine surveillance imaging one month ago, after being treated for renal cell carcinoma with right partial nephrectomy 10 years ago. On physical exam, vitals were stable, he was alert and oriented. Other physical examination findings were normal. His BMI was 35.23 kg/m2. Relevant initial labs were venous blood glucose 43 mg/dL, TSH 11.4 uU/mL and T4 was 1.1 ng/dL. Blood ethanol level was undetectable. Despite receiving multiple ampules of 50% dextrose and continuous 10-20% dextrose IV infusion he continued to be hypoglycemic and therefore was admitted to the ICU. The initial management course was as follows: He was started on octreotide infusion and given scheduled diazoxide for persistent hypoglycemia with no improvement. For suspected non-islet cell tumor, he was started on glucagon infusion, however there was no significant correction. Calorie intake was monitored and increased by nutrition and was subsequently given enteral/ parenteral nutrition. He was also started on hydrocortisone 50mg every 8 hours. Endocrine investigations were as follows: Insulin, C-peptide, urine sulfonylureas and ß-hydroxybutyrate were undetectable, proinsulin 2.9 pmol/L (ref &amp;lt;= 8.0 pmol/L), Insulin antibody negative, IGF-1 44 ng/mL (ref 49-214 ng/mL), IGF-2 129 ng/dL (IGF-II/IGF-I &amp;lt; 10). Random cortisol was 26 µg/dL. Investigations for the retroperitoneal mass were as follows: a biopsy showed high grade invasive urothelial carcinoma. MRI abdomen showed extensive and diffuse infiltrative metastatic liver disease without evidence of pancreatic endocrine tumor. The final diagnosis was determined to be due to extensive tumor infiltration in the liver. His condition deteriorated during ICU stay and comfort measures were initiated; subsequently he deceased. Conclusion The causes of hypoglycemia in patients with known tumors include extensive tumor infiltration and nonislet cell tumors, two uncommon causes of hypoglycemia. Differentiating between nonislet tumor secretion and direct tumor infiltration is based on IGF-2 level and the IGF-2/IGF-1 ratio. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Innovative IntraValvular Impedance Sensing Applied to Biological Heart Valve Prostheses: Design and In Vitro Evaluation.

Subclinical valve thrombosis in heart valve prostheses is characterized by the progressive reduction in leaflet motion detectable with advanced imaging diagnostics. However, without routine imaging surveillance, this subclinical thrombosis may be underdiagnosed. We recently proposed the novel concept of a sensorized heart valve prosthesis based on electrical impedance measurement (IntraValvular Impedance, IVI) using miniaturized electrodes embedded in the valve structure to generate a local electric field that is altered by the cyclic movement of the leaflets. In this study, we investigated the feasibility of the novel IVI-sensing concept applied to biological heart valves (BHVs). Three proof-of-concept prototypes of sensorized BHVs were assembled with different size, geometry and positioning of the electrodes to identify the optimal IVI-measurement configuration. Each prototype was tested in vitro on a hydrodynamic heart valve assessment platform. IVI signal was closely related to the electrodes' positioning in the valve structure and showed greater sensitivity in the prototype with small electrodes embedded in the valve commissures. The novel concept of IVI sensing is feasible on BHVs and has great potential for monitoring the valve condition after implant, allowing for early detection of subclinical valve thrombosis and timely selection of an appropriate anticoagulation therapy.

Impact of Routine Surveillance Imaging on Recurrence in Sinonasal Malignancies.

There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examined the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies. We performed a retrospective review on an IRB-approved dataset of patients with sinonasal malignancies treated at a single institution between 2005 to 2021. Patients were categorized into groups based on the frequency of annual imaging and total number of imaging studies. We compared time-to-recurrence between the groups using log-rank test. A two-sided p-value of <0.05 was considered as the threshold for significance. A total of 93 patients were eligible for this study with a median follow up of 42.3 months and 25.8% (n=24) of patients had documented recurrence. Sensitivity and specificity for recurrence based on computed tomography (CT) scans within one year of treatment completion were 50.0% and 19.5%; positron emission tomography/CT was 90.0% and 19.5%; and magnetic resonance imaging was 60.0% and 61.0%, respectively. Regardless of the type of imaging, symptomatic presentation after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95%CI=1.06-8.22). The frequency of scans was not associated with the risk of recurrence (HR=0.55; 95%CI=0.23-1.29, p=0.17). Similarly, no association was noted between the total number of scans and risk of recurrence (HR=0.64; 95%CI=0.27-1.51, p=0.31). The total number of frequency of scans within the first year after treatment had no association with time to recurrence of sinonasal malignancies. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.

Impact of Routine Surveillance Imaging with Recurrence in Sinonasal Malignancies

<h3>Purpose/Objective(s)</h3> There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examines the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies. <h3>Materials/Methods</h3> Of an available 267 patients (pts), we performed a retrospective review on an IRB approved dataset of 89 consecutive pts with sinonasal malignancies treated at a single institution between 2005 to 2021. Pts with incomplete surveillance imaging or histologic sarcomas, lymphomas, and melanoma were excluded from the study. Information regarding tumor location, staging, pathology, treatment modalities, and surveillance imaging including type, frequency, concern for and actual recurrence were collected. Pts were categorized into groups based on the annual frequency and total number of imaging studies done. We compared recurrence-free survival between the groups using log-rank test. A two-sided p-value of < 0.05 was considered the threshold for significance. <h3>Results</h3> Median follow up was 42.3 months. Overall, 60.7% (n=54) pts had primary nasal cavity malignancies and 39.3% (n=35) had paranasal sinus disease. 43.8% of pts (n = 35) had squamous cell carcinoma, 25.0% (n=20) had esthesioneuroblastoma, 11.2% (n=9) had sinonasal undifferentiated carcinomas, and 6.2% (n=5) had adenocarcinoma. Most pts had locally advanced disease at diagnosis (AJCC 7^th edition). 78.7% (n=70) pts underwent surgical resection, 88.8% (n=79) received radiotherapy, and 52.9% (n=46) received chemotherapy. Approximately 25% (n=23) of pts had recurrence. 21.3% (n=19) had locoregional recurrence and 4.5% (n=4) had distant recurrence. CT surveillance scans within one year of treatment completion had a sensitivity of 74.7%, but specificity of 20.0%. Similarly, PET/CT had a sensitivity of 82.3%, while the specificity was 20.0%. Surveillance MRI had a sensitivity of 43.0%, but a specificity of 60.0%. Regardless of imaging, symptomatic presentation of a pt after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95% CI: 1.06-8.22). However, the sensitivity was 27%. There was no association of frequency (0-2 vs. >2) of surveillance scans within the first year with risk of recurrence (HR: 0.55; 95% CI: 0.23-1.29, P=0.17). Similarly, no association was noted with total number of scans (0-3 vs >3) with risk of recurrence (HR: 0.64; 95% CI: 0.27-1.51, P=0.31). Recurrence-free survival at 2-year was 41% and 36% in pts with 0-3 scans/year and >3 scans/year, respectively. <h3>Conclusion</h3> In our study, with a median follow-up just short of 4 years, approximately 1/4^th patients recurred. Total number or frequency of scans in the first year after treatment was not associated with time to recurrence. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.

Relapsing pediatric non-rhabdomyosarcoma soft tissue sarcomas: The impact of routine imaging surveillance on early detection and post-relapse survival

PurposeThe chances of patients with relapsing pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) being cured are limited. This retrospective single-institutional study examines the potential role of routine surveillance imaging for detecting recurrent tumor, and its impact on post-relapse survival. MethodsThe analysis concerned 86 patients < 21 years old with relapsing NRSTS treated from 1985 to 2020. Clinical findings, treatment modalities and survival were analyzed, comparing patients whose relapse was first suspected from symptoms (symptomatic group) with those whose relapse was detected by radiological surveillance (imaging group). ResultsTumor relapses were identified from clinical symptoms in 49 cases and on routine imaging in 37. Time to relapse was similar in the two groups. Routine imaging detected 6/32 local relapses and 31/48 distant relapses (and 79% of the cases of lung metastases). Overall survival (OS) at 5 years was 34.3% for the symptomatic group, and 24.0% for the imaging group (p-value 0.270). In patients with lung metastases at relapse, the 5-year OS was statistically better for the imaging group, that is, 25.8% versus 0% for the symptomatic group (p-value 0.044). ConclusionThis is the first study to explore the role of surveillance imaging in pediatric NRSTS. Judging from our findings, the value of routine scanning of primary sites seems limited, while radiological surveillance may help to detect lung metastases, improving survival for this patient category. The potentially negative effects of periodic radiological exams should be considered in deciding the optimal follow-up for patients off therapy.

245P Impact of regular intensive imaging surveillance on survival after recurrence in patients with early breast cancer; a propensity score matching study

Current major guidelines recommend only mammography as routine imaging surveillance for asymptomatic breast cancer survivors after curative treatment. However, as improving of the treatment for patients with metastatic disease, we assume that the detection of metastases in an asymptomatic status may improve the survival. Therefore, we investigated impact of intensive imaging surveillance on survival in breast cancer patients who developed distant metastasis as a first event.

Imaging Features of Hepatocellular Carcinoma in Children With and Without Underlying Risk Factors.

BACKGROUND. Pediatric hepatocellular carcinoma (HCC) is an aggressive malignancy for which imaging findings remain poorly described. In comparison with adult HCC, pediatric HCC more commonly occurs without underlying risk factors, and standardized surveillance guidelines for those with predispositions are lacking. OBJECTIVE. The purpose of this article was to evaluate imaging findings of nonfibrolamellar pediatric HCC and to identify associations between these imaging findings and the presence of predisposing factors. METHODS. This retrospective study included children (≤ 18 years) with histologically confirmed nonfibrolamellar HCC who underwent multiphase CT or MRI at one of four academic children's hospitals between July 2009 and April 2019. Surveillance regimens in children with predispositions were at the discretion of treating physicians. Clinical characteristics were recorded. Scan indications were classified as surveillance versus clinical signs and symptoms. Images from all sites were submitted to a cloud-based server. Two radiologists independently assessed imaging features of HCC, including tumor size, tumor in vein, Pre-Treatment Extent of Tumor (PRETEXT) stage, and LI-RADS major features of adult HCC. Imaging findings were compared between patients with and without predispositions. RESULTS. The study included 39 patients: 17 with predispositions (mean age, 10.5 ± 4.5 years; nine boys, eight girls) and 22 without predispositions (mean age, 11.3 ± 5.1 years; 12 boys, 10 girls). Scan indication was surveillance in 14/17 patients with predispositions versus 0/22 patients without predispositions (p < .001). Patients with versus those without predispositions had smaller tumor size (reader 1: 6.0 vs 11.9 cm [p = .003]; reader 2: 6.0 vs 12.9 cm [p < .001]) and less frequent tumor in vein (reader 1: 0% vs 41% [p = .002]; reader 2: 0% vs 36% [p = .006]). PRETEXT stage IV disease was observed in 18% (both readers) of patients with predispositions versus 50-55% of patients without predispositions. No LI-RADS major feature of adult HCC showed a significant difference in frequency between patients with and without predispositions for either reader (all p > .05). CONCLUSION. Among children with HCC, those with predispositions exhibited smaller and lower-stage tumors and less frequent tumor in vein, likely because of surveillance imaging. CLINICAL IMPACT. The study supports the role of routine surveillance imaging in children with HCC predispositions to facilitate earlier detection. Standardization of surveillance guidelines remains needed.

A dissection … of the Dacron?

A dissection … of the Dacron?

Impact of Routine Surveillance Imaging on Detecting Recurrence in Sinonasal Malignancies

<h3>Purpose/Objective(s)</h3> Surveillance imaging guidelines for sinonasal malignancies are varied and lack scientific data supporting the basis of these recommendations. This study wishes to examine the utility of surveillance imaging in detecting local, regional, and distant failures as well as second primary tumors in patients with sinonasal malignancies treated with surgical resection followed by adjuvant radiation. <h3>Materials/Methods</h3> Using an IRB-approved institutional database of head and neck cancer patients, we performed a retrospective review of 41 patients with sinonasal malignancies treated at a single institution between the years 2005 to 2021. Patient information regarding tumor location, staging, pathology, smoking status, alcohol use, chemotherapy, radiation treatment plan, and data surrounding surveillance imaging including type, frequency, and concern for recurrence were collected. Patients were divided into two groups comparing the frequency and type of imaging ordered: patients with <4 scans/year Group 1 and ≥ 4 scans/year Group 2. We compared the time to recurrence between the two groups using log-rank test and Cox proportional hazard ratio. A p-value of < 0.05 was considered the threshold for significance. <h3>Results</h3> Median follow up was 37.5 months (14.4-68.9 months). Overall 80% (n=32) patients had primary nasal cavity malignancies and 20% (n=8) had paranasal sinus disease. Thirteen (32.5%) patients had a squamous cell carcinoma (32.5%), twelve (30.0%) patients had an esthesioneuroblastoma, 5 (12.5%) patients had an adenocarcinoma and 3 (7.5%) patients had sinonasal undifferentiated carcinomas. The remaining few patients had sarcomatoid squamous cell carcinoma, adenoid cystic carcinoma, large cell neuroendocrine, and small cell neuroendocrine tumors – with a majority of patients having advanced disease (AJCC 7^th edition). In 27.5% (n=11) patients there was a recurrence: 4 had local failures, 4 had regional failures, and 3 had distant failures. The type of imaging (CT vs. PET/CT vs. MRI) ordered had a non-significant association with recurrence (p=0.802). There was no association with the frequency (HR: 1.13, 95% CI: 0.73-1.74) and total number of scans (HR: 1.24 [0.93-1.66]) with time to recurrence. Rate of recurrence-free survival at 2-years was 86% and 80% in patients with <4 scans/year and ≥ 4 scans/year, respectively. <h3>Conclusion</h3> In our study, the recurrence rates were limited for patients with sinonasal malignancies treated with definitive intent. Increasing the total number or frequency of scans in the first year after treatment was not associated with time to recurrence. These findings suggest a judicious approach in using post-treatment surveillance imaging.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Cost Evaluation Study of Management and Surveillance, and Review of the Recent USA and UK Guidelines

IntroductionBreast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell lymphoma associated with textured breast implants, recently recognized by the revised WHO Classification. Recommended management for BIA-ALCL involves a multidisciplinary team (MDT) approach with breast surgery, haemato-oncology, pathology, radiology and oncoplastic input. Definitive management for the 'effusion-only' subset is surgical implant and capsule removal; systemic therapy is reserved for 'mass-forming' and 'advanced-disease' cohorts. Overall prognosis is excellent with the vast majority achieving remission.Although the diagnostic and treatment paradigm is established, post treatment surveillance and follow-up guidance varies widely (globally); over-utilisation of imaging tests compromises the patient pathway, impacts limited health-care resources and is associated financial burdens on patients and providers. Recently, newly published consensus guidelines (UK MHRA and USA NCCN clarify follow-up and surveillance imaging (Table 1).The aim of this study was to review our BIA-ALCL specialist centre institutional practise; to quantify the direct economic cost (EC) of imaging surveillance and indirect EC of outpatient clinic (OPC) assessment compared EC if recent guidelines were followed. The secondary aim is to highlight and raise awareness of the latest international guidance to promote the standardisation of practise.MethodsA retrospective analysis of a prospectively maintained patient database between July 2015 to October 2019 was conducted, with Institutional Review Board Approval. Data collection included patient demographics, tumour subset, treatment, clinical and imaging surveillance. Follow-up and imaging undertaken for symptomatic concerns / non-BIA-ALCL related pathology was excluded. Imaging costs were calculated using UK NHS tariffs.ResultsEleven patients were treated for BIA-ALCL during the study period, with a median age of 49 at diagnosis (range 30-82years). Patients were diagnosed with: effusion-only (n=7), effusion and mass (n=2), mass-only (n=2) subtypes, at a median time of eleven years from implant insertion (IQR 8-12). All patients underwent explantation and en-bloc capsulectomy, with 1 patient required neo-adjuvant (CHOP, Brentuximab) and 1 adjuvant (CHOP) therapy (CHOP. Surveillance with imaging and OPC detected no disease recurrence to date (overall median follow-up 38 months, IQR 12-47). Post treatment episodes of surveillance imaging or follow-up related to patient symptoms were excluded.8 patients underwent surveillance imaging at our institute (Table 2). Total cost of imaging was £10,396 ($14,396) with a median cost of £1,953 ($2,705) per patient [IQR £526-2029 ($728-2,810)].7 patients had completed at least 24 months follow-up since surgery during the study period (Table 3), with 3 patients having not yet completed their follow-up period of two years. Of those with completed follow-up, the median OPC follow-up per patient was 48 months (IQR 38-52), median number of OPC was 7 (IQR 6-11) and the median cost of clinic review was £982 (IQR 804-1395). The surplus cost per patient compared with recommended follow-up was £118 ($164) [IQR £0-531 ($0-738)].ConclusionsOur data shows the variable BIA-ALCL surveillance practise pattern and the associated additional direct and indirect EC of unnecessary asymptomatic surveillance imaging, with an excessive number of follow-up OPC and period of clinical follow-up after complete remission. With no recurrence detected in our patient cohort to date, this data supports the new UK and updated USA NCCN Guidelines (extrapolated from data in other NHLs, and analogous to principles of the ASH Choosing Wisely Campaign) that routine post-treatment surveillance imaging should not be performed in BIA-ALCL patients. Routine asymptomatic post-treatment surveillance imaging is clinically unnecessary and potentially leads to a 'Cascade Effect' of further tests, with increased radiation exposure, excess costs and impact on limited health-care resources. We also support open-access follow-up for patients in remission, to reduce unnecessary follow up appointments. With UK and USA guidelines now available for BIA-ALCL, we support training and education of health-care professionals, global consensus guidelines and a registry, for this rare however increasingly recognised new entity. [Display omitted] DisclosuresIyengar: Takeda: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: conference support; Janssen: Other: conference support, Speakers Bureau. Nicholson: Pfizer: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; BMS/Celgene: Consultancy; Novartis: Consultancy, Other: Conference fees. El-Sharkawi: Kyowa Kirin: Other: Ad boards; Beigene: Other: Ad boards; ASTEX: Other: Ad boards; Novartis: Other: Travel Support; Takeda: Honoraria; Roche: Honoraria; Janssen: Honoraria, Other: Ad boards; AstraZeneca: Honoraria, Other: Ad boards; AbbVie: Honoraria, Other: Travel Support, Ad boards. Tasoulis: BMJ: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cunningham: Roche: Research Funding; Clovis Oncology: Research Funding; Celgene: Research Funding; Eli Lilly: Research Funding; Bayer: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; 4SC: Research Funding; AstraZeneca: Research Funding; MedImmune: Research Funding.

18F]FDG-PET Evaluation of Spinal Pathology in Patients in Oncology: Pearls and Pitfalls for the Neuroradiologist.

[18F]FDG-PET is a widely used technique for specific evaluation of disease and treatment response in oncology. However, the principles behind [18F]FDG-PET imaging allow a wide-ranging array of benign and malignant pathologies to be identified on both initial and routine surveillance imaging. This is important for clinicians and radiologists, alike, in that effective and accurate evaluation of malignancy and metastatic disease, specifically involving the spine and central nervous system, is crucial. In this article, we review the normal and posttherapy appearance of the spine on [18F]FDG-PET, the various types and patterns of metastatic disease that involve the spine and spinal cord, and, finally, important spinal pathologies that may mimic malignancy on [18F]FDG-PET.

Renal Neoplasia in Hyperparathyroidism–Jaw Tumor Syndrome

A male patient in his late teens presented with primary hyperparathyroidism and underwent a parathyroidectomy. Germline testing revealed a pathogenic truncating alteration of the CDC73 gene (c.25C>T; p.Arg9Ter). On the basis of these findings, he was diagnosed with hyperparathyroidism–jaw tumor syndrome. In addition, multiple first-degree family members including his father and brother were found to have this syndrome. Approximately 2 decades later, he was found to have a 1.1-cm left renal mass on routine surveillance imaging. This was treated with a partial nephrectomy, and representative images of the renal tumor (hematoxylin and eosin stain, magnification ×100) are shown in Figure 1. This tumor showed a combination of papillary and nested architecture and exhibited inconspicuous nucleoli (World Health Organization grade 1). No recurrences or metastases were identified at 154 months of follow-up. What immunohistochemistry-based marker can be used to screen for tumors arising secondary to hyperparathyroidism–jaw tumor syndrome and what is the expected pattern of expression?a.Calcitonin, loss of stainingb.Parathormone, loss of stainingc.Parafibromin, loss of stainingd.Parafibromin, diffuse overexpression Answer: c Hyperparathyroidism–jaw tumor syndrome is inherited in an autosomal dominant manner secondary to pathogenic mutations of the CDC73 gene.1Carpten J.D. Robbins C.M. Villablanca A. et al.HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome.Nat Genet. 2002; 32: 676-680Crossref PubMed Scopus (553) Google Scholar Specifically, the pathogenic CDC73 c.25C>T, p.Arg9Ter alteration has been reported in both the somatic and germline setting.1Carpten J.D. Robbins C.M. Villablanca A. et al.HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome.Nat Genet. 2002; 32: 676-680Crossref PubMed Scopus (553) Google Scholar,2Cetani F. Pardi E. Borsari S. et al.Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors.J Clin Endocrinol Metab. 2004; 89: 5583-5591Crossref PubMed Scopus (189) Google Scholar These patients typically present with primary hyperparathyroidism secondary to parathyroid tumors, and in a subset of these patients, ossifying fibromas of the maxilla and mandible develop.1Carpten J.D. Robbins C.M. Villablanca A. et al.HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome.Nat Genet. 2002; 32: 676-680Crossref PubMed Scopus (553) Google Scholar Renal manifestations in this syndrome include cysts, hamartomas, metanephric adenoma, and Wilms tumor.1Carpten J.D. Robbins C.M. Villablanca A. et al.HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome.Nat Genet. 2002; 32: 676-680Crossref PubMed Scopus (553) Google Scholar,3Carlo M.I. Hakimi A.A. Stewart G.D. et al.Familial kidney cancer: implications of new syndromes and molecular insights.Eur Urol. 2019; 76: 754-764Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar,4Gupta S. Vanderbilt C.M. Leibovich B.C. et al.Secondary renal neoplasia following chemotherapy or radiation in pediatric patients.Hum Pathol. 2020; 103: 1-13Crossref PubMed Scopus (5) Google Scholar The spectrum of renal neoplasia in hyperparathyroidism–jaw tumor syndrome is poorly defined because of the rarity of these tumors and limited reports of detailed histopathologic findings.3Carlo M.I. Hakimi A.A. Stewart G.D. et al.Familial kidney cancer: implications of new syndromes and molecular insights.Eur Urol. 2019; 76: 754-764Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar,4Gupta S. Vanderbilt C.M. Leibovich B.C. et al.Secondary renal neoplasia following chemotherapy or radiation in pediatric patients.Hum Pathol. 2020; 103: 1-13Crossref PubMed Scopus (5) Google Scholar As the CDC73 gene encodes the parafibromin protein, immunohistochemistry for parafibromin has been proposed as a screening tool for tumors occurring in the context of hyperparathyroidism–jaw tumor syndrome.5Andrici J. Gill A.J. Hornick J.L. Next generation immunohistochemistry: emerging substitutes to genetic testing?.Semin Diagn Pathol. 2018; 35: 161-169Crossref PubMed Scopus (17) Google Scholar Loss of nuclear expression of parafibromin is thought to correlate with pathogenic loss of function alterations of CDC73 and has been proposed as an immunohistochemistry-based screening tool.5Andrici J. Gill A.J. Hornick J.L. Next generation immunohistochemistry: emerging substitutes to genetic testing?.Semin Diagn Pathol. 2018; 35: 161-169Crossref PubMed Scopus (17) Google Scholar This renal tumor exhibited papillary and nested architecture and a cytokeratin 7–positive immunophenotype (Figure 2A-C). Immunohistochemistry for parafibromin showed loss of nuclear expression in tumor cells, in contrast to retained expression in non-neoplastic vascular elements (Figure 2D). In addition to the patient described herein, loss of parafibromin expression has been reported in metachronous renal tumors (metanephric adenomas) for at least 1 other patient with this syndrome.4Gupta S. Vanderbilt C.M. Leibovich B.C. et al.Secondary renal neoplasia following chemotherapy or radiation in pediatric patients.Hum Pathol. 2020; 103: 1-13Crossref PubMed Scopus (5) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Derivation of a Clinical Score for Prediction of Recurrence Following Evacuation of Chronic Subdural Hematoma: A Retrospective Cohort Study at a National Referral Centre

Chronic subdural hematoma (cSDH) is a common pathology, and recurrence is a common complication, which may be predicted by certain patient and radiologic factors. Empiric radiologic surveillance has been shown to convey no benefit. A retrospective review of a prospectively collated database was performed. Preoperative and postoperative noncontrast computed tomography scans were reviewed. Radiologic appearance, preoperative hematoma volume, patient age, presence of bilateral hematomas, maximal hematoma thickness, and therapeutic coagulopathy were assessed as predictors. Receiver operating characteristic curve analysis, logistic regression, and LASSO regression were used to select potential predictors. A multivariate model was then fitted, and a score was derived. A total of 142 patients were included. Maximal hematoma thickness >12 mm (P= 0.02) and age >65 years (P= 0.01) were found to correlate with the likelihood of recurrence. Bilateral hematomas and a hyperdense or mixed density appearance were also identified on LASSO regression. Bilateral hematomas (P= 0.19), hyperdense or mixed density (P= 0.66), maximum thickness >12 mm (P= 0.01), and age >65 years (P= 0.02) were included in the multivariate model. A 6-point score was derived. A score of>3 had a sensitivity of 89% (95% confidence interval [CI] 78%-97%) and specificity of 26% (95% CI, 17%-34%) for predicting recurrence, with recurrence significantly more likely in patients with a score of 4-6 versus those with a score of 0-3 (P= 0.02). Certain radiologic findings may predict the recurrence of cSDH following evacuation. The score derived may be useful in identifying patients who might benefit from routine postoperative surveillance imaging.

Utility Of Non-Invasive Monitoring Of Circulating Tumor DNA At Diagnosis, Interim Therapy, and Relapse Of DLBCL Using High-Throughput Sequencing Of Immunoglobulin Genes

BackgroundRecent studies have shown limited utility of routine surveillance imaging for patients with diffuse large B-cell lymphoma achieving remission after R-CHOP (Thompson et al, ASCO 2013 #8503; Ghesquieres et al, ICML 2013 #226). Separately, response assessment using early interim PET-CT during R-CHOP has suboptimal accuracy. We hypothesized that non-invasive tumor burden monitoring using peripheral blood could have utility for diagnosis and monitoring of DLBCL. MethodsWe prospectively profiled two cohorts of patients with DLBCL at various stages in their disease, including at diagnosis, during various therapies, after achieving remission, and upon relapse or progression. Cohort1 patients were treated with curative intent at Stanford University with blood collected at multiple time points during follow-up. Cohort2 patients participated in a multi-center Austrialian Phase 2 study (ALLG NHL21), where patients with poor risk DLBCL as identified by residual disease on interim PET/CT after 4 R-CHOP cycles received early treatment intensification using R-ICE/ASCT; blood samples were collected before the 1st and after the 4thR-CHOP cycles. Tumor-derived clonotypic IgH and IgK sequences were defined in diagnostic tissues grossly involved with DLBCL, and then tracked using high-throughput sequencing of immunoglobulin genes (Faham et al 2012 Blood). ResultsWe successfully defined for 77% (30/39) of patients the tumor-specific immunoglobulin sequences required for non-invasive surveillance, with calibration success correlating with input tissue mass. Using 194 assays on 79 blood specimens from these patients, we detected disease in 75% of patients at diagnosis of DLBCL, in 18% at interim time-points during therapy, 0% during radiographic/clinical remissions, and 80% at relapse or disease progression. When considering radiographic/clinical follow-up, noninvasive monitoring had 0% false positive rate but 26% false negative rate, with the latter likely due to low tumor burden at time of phlebotomy. Disease burden detectable in the blood was significantly correlated between IgH and IgK assays, and between the cellular (leukocyte) and acellular (plasma) fractions (r=0.77, p=0.004). Strikingly, clonotypic IgH/IgK sequences were significantly more abundant in plasma than in circulating leukocytes, and identified exclusively in plasma in 5% of blood samples with available paired cellular/acellular fractions. This allowed more accurate disease detection and monitoring using plasma circulating tumor DNA than blood leukocytes, including in cases of radiographically defined isolated CNS involvement, and in histological transformation of FL. Within the limitations of this small study employing frequent surveillance imaging, we observed no significant lead time between detection of disease in the plasma and radiographic/clinical evidence of progression. ConclusionsNon-invasive surveillance of circulating tumor DNA has utility for tumor burden at diagnosis and relapse of DLBCL using high-throughput sequencing of immunoglobulin genes, with superior detection in blood plasma. The current assay has limited sensitivity at early interim time points during therapy. Disclosures:Kong:Sequenta Inc.: Employment. Faham:Sequenta, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Chest CT Has Higher Yield for Infection than CT Sinus in Febrile Neutropenic Patients

ObjectiveChest and sinus CT imaging among cancer patients undergoing chemotherapy and bone marrow transplant in the setting of neutropenic fever is not uncommon, yet the utility of routine imaging surveillance remains unclear. We aim to compare the rates of acute infection detected on CT chest and CT sinus exams performed in this clinical setting. MethodsReports of 1059 consecutive CT chest and sinus examinations for the clinical indication of neutropenic fever on 262 patients performed between January through June 2017 were retrospectively reviewed. Infection as reported was characterized as acute or worsening, improving, stable, indeterminate or negative. Results were tabulated and Pearson's chi-square test was used for comparison analysis. ResultsAbsence of infection on CT sinus was significantly higher than CT chest (86.1% vs. 58.5%; P<0.001). Conversely, CT chest had significantly higher incidence of acute or worsening infection than CT sinus (28.7% vs. 11.6%; P<0.001). CT chest also showed significantly higher incidence of improving infection compared to CT sinus (6.2% vs. 1.1%; P<0.001). There was no significant difference between incidence of stable infection on CT chest and CT sinus (1.1% vs. 0.2%; P=0.059). Infection was indeterminate in 5.5% of CT chest vs. 1% on CT sinus (P<0.001). ConclusionsCT chest showed significantly higher diagnostic yield for acute infection than CT sinus, suggesting that sinusitis is less likely to be the source of fever than chest infections in febrile neutropenic patients. The majority of CT studies showed absence of infection, raising the question of the overall utility of routine surveillance CT imaging among this subset of patients.

Early-Onset Spinal Deformity in Neurofibromatosis Type 1: Natural History, Treatment, and Imaging Surveillance.

Early-onset scoliosis (EOS) or kyphosis is common in patients with neurofibromatosis (NF) and is characterized by rapid progression of deformity. Traditional growing rods provide good functional and deformity outcomes in patients with NF and EOS; magnetically controlled growing rods (MCGRs) also provide good deformity correction, although high rates of revision have been reported after their use. Among patients with NF type 1 (NF1), morphologic characteristics of the spinal deformity are different in those with paraspinal neurofibromas than in those without paraspinal tumors. Patients with NF1 are at low risk for developing malignant peripheral nerve sheath tumors during childhood (<1%) and their lifetime (8% to 12%), and routine imaging surveillance for malignancy in the absence of symptoms should be clinically directed. Further investigation is needed to standardize screening for EOS in children with NF1 and to develop guidelines for ideal imaging modalities, including their frequency and a timeline.

Surveillance Imaging during First-Remission in Follicular Lymphoma Does Not Impact Overall Survival

Surveillance Imaging during First-Remission in Follicular Lymphoma Does Not Impact Overall Survival

Surveillance imaging during first remission in follicular lymphoma does not impact overall survival.

Although many patients with follicular lymphoma (FL) undergo routine radiographic surveillance during their first remission, no consensus exists on the modality, duration, frequency, or need for routine imaging studies. The authors retrospectively examined the effect of surveillance imaging on relapse detection and overall survival (OS) in patients with FL. Patients with newly diagnosed FL who had a response to induction therapy were identified from the Lymphoid Malignancies Enterprise Architecture Database (LEAD) at Emory University and from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic. Patients were evaluated for both relapse and method of relapse detection (ie, clinical concerns vs radiologic detection through surveillance imaging in an asymptomatic patient). Of 148 patients in the LEAD cohort, 55 (37%) relapsed, and the majority (n = 35; 64%) of relapses were detected clinically. In the MER cohort, 63 of 177 relapses (54%) were detected clinically. There was no significant difference in OS from the date of diagnosis between the 2 methods of relapse detection in the LEAD (hazard ratio [HR], 0.61; 95% CI, 0.13-2.94; P = .54) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts. Similarly, there was no significant difference in OS from the date of relapse between the 2 methods of relapse detection in the LEAD (HR, 0.47; 95% CI, 0.10-2.27; P = .35) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts. These findings suggest a limited role for routine surveillance imaging in patients with FL who complete front-line therapy. Future studies should evaluate which patients may benefit from a more aggressive surveillance approach and should explore novel methods of relapse detection.