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An accurate and non-invasive histologic assessment of renal masses remains elusive, as approximately 15% of resected renal masses prove benign upon resection. Oncocytomas and hybrid oncocytoma/chromophobe tumors (HOCTs) are the most commonly-resected oncologically low-risk masses and are not reliably distinguished from malignant lesions with standard cross-sectional imaging. Histologically, these tumors are notable for densely-packed mitochondria. Technetium-99m-sestamibi single-photon emission CT/ x-ray CT is a nuclear imaging modality that utilizes a mitochondria-targeting tracer. Early series using 99mTc-sestamibi SPECT/CT showed promise in differentiating renal cell carcinoma (RCC) from oncocytomas and HOCTs, but recently published data from our institution found that oncocytomas still accounted for 20% of lesions with low 99mTc-sestamibi tracer uptake, as qualitatively interpreted by a senior nuclear radiologist. Here, we asses performance of 99mTc-sestamibi scans utilizing quantitative assessment thresholds, hypothesizing that this may improve test characteristics over qualitative assessments. Patients undergoing 99mTc-sestamibi SPECT/CT for evaluation of renal masses between February 2020 and December 2021 were included in our analysis. A mass was labeled as "hot" by the radiologist if its 99mTc-sestamibi uptake was qualitatively equivalent or higher than that of the ipsilateral renal parenchyma; otherwise it was labeled as "cold". Using nuclear medicine image processing software, TBRs were calculated by comparing signal counts of the masses to those of the normal ipsilateral renal parenchyma using manually generated regions of interest. Quantitative "hot"/"cold" determinations for each mass were then re-evaluated using previously published TBR cutoffs of 0.46 and 0.6. Masses for which TBRs could not be calculated were assumed to have unchanged classifications on quantitative analysis. Qualitative and quantitative 99mTc-sestamibi SPECT/CT findings were then correlated to histology for masses that underwent pathologic confirmation via biopsy or surgical excision. 78 patients underwent 99mTc-sestamibi SPECT/CT for 98 renal masses. 52 masses had diagnostic pathology available from biopsy or surgical excision. Of these, 7 were "hot" (1 RCC, 6 oncocytomas) and 45 were "cold" (34 RCC, 2 non-RCC malignancies, 9 oncocytomas). The negative predictive value of qualitatively-interpreted "cold" 99mTc-sestamibi scans for ruling out oncocytoma was 80%. 1/52 (1.9%) malignant masses were interpreted as "hot" and;likely benign. When a TBR cutoff of 0.46 was applied, 17/45 "cold" masses were reclassified as "hot" (13 RCC, 1 non-RCC malignancy, 6 oncocytomas). For a TBR cutoff of 0.6, 6/45 "cold" masses were reclassified as "hot" (1 RCC, 1 non-RCC malignancy, 4 oncocytomas) while 1 "hot" RCC was reclassified as "cold" (Figure 1).; TBR cutoffs of 0.46 and 0.6 improved the NPV;of 99mTc-sestamibi SPECT/CT to 89% and 88% but increased the rate of "hot" malignant tumors to 23.1% and 3.8%, respectively. When assessing histology of renal masses, applying previously-published quantitative TBR cutoffs to 99mTc-sestamibi SPECT/CT provides <10% improvement in the negative predictive value for ruling out oncocytomas compared to previously published qualitative interpretations of these scans. Conversely, the use of these thresholds in place of qualitative assessments tends to categorize more RCCs as "hot," thereby erroneously mimicking oncocytomas. Further work is needed to determine whether 99mTc-sestamibi SPECT/CT has a role in routine clinical practice. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) occur in various regions of the body and present with complex clinical and biochemical phenotypes. The molecular underpinnings that give rise to such varied manifestations have not been completely deciphered. The management of neuroendocrine tumors (NETs) involves surgery, locoregional therapy, and/or systemic therapy. Several forms of systemic therapy, including platinum-based chemotherapy, temozolomide/capecitabine, tyrosine kinase inhibitors, mTOR inhibitors, and peptide receptor radionuclide therapy have been extensively studied and implemented in the treatment of NETs. However, the potential of immune checkpoint inhibitor (ICI) therapy as an option in the management of NETs has only recently garnered attention. Till date, it is not clear whether ICI therapy holds any distinctive advantage in terms of efficacy or safety when compared to other available systemic therapies for NETs. Identifying the characteristics of NETs that would make them (better) respond to ICIs has been challenging. This review provides a summary of the current evidence on the value of ICI therapy in the management of ICIs and discusses the potential areas for future research. [ABSTRACT FROM AUTHOR]

A modified version of the PGDx elioTM Plasma Resolve assay was validated as a laboratory-developed test (LDT) for clinical use in the Molecular Diagnostics Laboratory at Fox Chase Cancer Center. The test detects single nucleotide variants (SNVs) and small insertions and deletions (indels) in 33 target genes using fragmented genomic DNA extracted from plasma. The analytical performance of this assay was assessed with reference standard DNA and 29 samples from cancer patients and detected 66 SNVs and 23 indels. Using 50 ng of input DNA, the sensitivity was 95.5% to detect SNVs at 0.5% allele frequency, and the specificity was 92.3%. The sensitivity to detect indels at 1% allele frequency was 70.4%. A cutoff of 0.25% variant allele frequency (VAF) was set up for diagnostic reporting. An inter-laboratory study of concordance with an orthologous test resulted in a positive percent agreement (PPA) of 91.7%. [ABSTRACT FROM AUTHOR]

A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathologic complete response (pCR) following chemoradiation. We evaluated pre- and post-CRT PET-CT imaging to predict pCR and prognosis in this set of patients undergoing resection after neoadjuvant therapy. We retrospectively identified patients from 2002 to 2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET-CT imaging, and resection. Univariate and multivariate analysis was performed and receiver operating characteristic (ROC) curves were generated to evaluate the association of PET-CT characteristics with pCR and survival. ROC curves were generated to define optimal cutoff points for predictive PET-CT characteristics. 125 patients were included. pCR rate was 28%, and follow-up was 48 mo. On multivariable analysis, patients who had a pCR had lower median post-CRT maximal standardized uptake value (SUV max) (3.2 versus 5.2, P = 0.009) and higher median %SUV decrease (72 versus 58%, P = 0.009). ROC curves were generated for %SUV max decrease (AUC = 0.70) and post-CRT SUV (AUC = 0.69). Post-CRT SUV max <4.3 and %SUV max decrease of >66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-y overall and relapse-free survival were improved for patients with post-CRT SUV <4.3 (OS: 86 versus 66%, P = 0.01; RFS: 75 versus 52%, P = 0.01) or %SUV decrease of >66% (OS, 82 versus 66%, P = 0.05; RFS, 75 versus 54%, P = 0.01). PET/CT may be useful in identifying patients who did not achieve pCR, as well as overall survival in patients undergoing CRT for rectal cancer. Patients with a post-CRT SUV of >4.3 should be considered for operative management, as an estimated 86% of these patients will not have a pCR. [ABSTRACT FROM AUTHOR]

Purpose: [(18) F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [(18) F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.Procedures: Successive whole-body PET/CT scans were performed after intravenous injection of [(18) F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software.Results: High uptake of [(18) F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28 ± 1 μSv/MBq and the absorbed doses for the kidneys and liver were 273 ± 31 and 240 ± 68 μGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10 ± 0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101 ± 11 and 89 ± 25 mGy, respectively.Conclusions: [(18) F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [(18) F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region. [ABSTRACT FROM AUTHOR]

Background: The impact of extranodal extension (ENE) of metastatic papillary thyroid carcinoma (PTC) on short- and long-term clinical outcomes, including biochemical testing, has not been reported. Methods: This single-institution National Cancer Institute-designated Comprehensive Cancer Center cohort study included patients with macroscopic metastases and excluded patients with gross residual disease after surgery, distant disease, or poorly differentiated papillary carcinoma. A suppressed or stimulated thyroglobulin (Tg) <1 ng/mL, without suspicious imaging or anti-thyroglobulin antibodies, after radioactive iodine (RAI) treatment was termed an excellent or 'complete biochemical response' (CR). Results: Of 89 subjects included, 60 previously untreated patients underwent total thyroidectomy and therapeutic neck dissection; 29 additional patients underwent a neck dissection for persistence or recurrence after prior surgery and RAI administration. ENE, identified in 29 patients (33%), was associated with T4 classification ( p=0.02) and involvement of a greater number of nodes (median 11 vs. 5, p=0.03). ENE was associated with a 20% increased risk of nodal persistence necessitating additional surgery ( p=0.02). In a multivariable analysis, ENE, T4 classification, and recurrence/persistence proved to be independent predictors of systemic disease progression (ENE: hazard ratio [HR] 4.3 [95% confidence interval (CI) 1.2-15], p=0.02; T4 classification: HR 4.2 [CI 1.3-14], p=0.01; recurrent/persistent status: HR 3.6 [CI 1.1-12], p=0.035). Nodal or systemic disease progression was rare after a biochemical CR; in contrast, in previously untreated patients, stimulated Tg levels (sTg) >50 ng/mL prior to initial RAI administration, heralded the progression of nodal disease, and also predicted the eventual development of systemic disease ( p=0.0001). Of those with a sTg >50 ng/mL, over 70% underwent surgery for nodal persistence within five years. The presence of ENE diminished the odds of a biochemical CR (odds ratio 3.5% [CI 1.3-10], p=0.02), and increased the probability that the sTg levels after surgery will exceed 50 ng/mL (odds ratio 5 [CI 1.2-21], p=0.03). Following surgery for tumor persistence, 25% of those with ENE were rendered biochemically free of disease. Conclusions: ENE diminishes the probability of a biochemical CR after treatment for regional metastatic PTC, and increases the probability of tumor persistence after initial resection, likely from abundant metastasis. ENE and nodal persistence independently predict eventual systemic disease progression. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine factors associated with symptomatic cardiac toxicity in patients with esophageal cancer treated with chemoradiotherapy. Material and methods: We retrospectively evaluated 102 patients treated with chemoradiotherapy for locally advanced esophageal cancer. Our primary endpoint was symptomatic cardiac toxicity. Radiation dosimetry, patient demographic factors, and myocardial changes seen on 18F-FDG PET were correlated with subsequent cardiac toxicity. Cardiac toxicity measured by RTOG and CTCAE v3.0 criteria was identified by chart review. Results: During the follow up period, 12 patients were identified with treatment related cardiac toxicity, 6 of which were symptomatic. The mean heart V20 (79.7% vs. 67.2%, p =0.05), V30 (75.8% vs. 61.9%, p =0.04), and V40 (69.2% vs. 53.8%, p =0.03) were significantly higher in patients with symptomatic cardiac toxicity than those without. We found the threshold for symptomatic cardiac toxicity to be a V20, V30 and V40 above 70%, 65% and 60%, respectively. There was no correlation between change myocardial SUV on PET and cardiac toxicity, however, a greater proportion of women suffered symptomatic cardiac toxicity compared to men (p =0.005). Conclusions: A correlation did not exist between percent change in myocardial SUV and cardiac toxicity. Patients with symptomatic cardiac toxicity received significantly greater mean V20, 30 and 40 values to the heart compared to asymptomatic patients. These data need validation in a larger independent data set. [Copyright &y& Elsevier]

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3-deoxy-3[18F]f luorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respec tively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUVmax), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1 + months), with 1 complete and 2 partial responses (18% objective response rate 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≤ 87.5% reductions in summed FLT SUVmax and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. [ABSTRACT FROM AUTHOR]

Purpose: To correlate changes in 2-deoxy-2-[18F]fluoro-d-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer. Methods and Materials: Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival. Results: A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival. Conclusions: A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer. [Copyright &y& Elsevier]

Purpose: To determine whether 18-fluorodeoxyglucose positron emission tomography (PET) computed tomography scans predict the pathologic complete response and disease-free and overall survival in patients with esophageal carcinoma undergoing definitive or preoperative chemoradiotherapy.Methods and Materials: The records of patients with esophageal carcinoma presenting for definitive or preoperative treatment and undergoing pre- and post-treatment 18-fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed. The histologic type, T stage, and nodal status were the variables investigated to determine a relationship with the baseline standardized uptake value (SUV) of the primary tumor at diagnosis. We also attempted to determine whether a relationship exists between the percent decrease in SUV and a pathologic complete response, overall and disease-free survival.Results: A total of 81 patients, 14 women and 67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before treatment and 63 also had post-treatment scans. T stage and tumor location predicted in univariate, but not multivariate, analysis for the initial SUV. Of the patients with a postchemoradiotherapy SUV of <2.5, 66% had tumor in the surgical specimen and 64% of patients had positive lymph nodes at surgery that were not imaged on the postchemoradiotherapy PET scan. A trend existed for post-treatment SUV and the days from radiotherapy to surgery to predict for a pathologic complete response (p = 0.09 and p = 0.08, respectively). The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group (p = 0.01).Conclusions: A correlation was found between the depth of tumor invasion and the baseline SUV. The post-treatment SUV predicted for disease-free survival in the definitive chemoradiotherapy group. Caution should be exercised in using post-treatment PET scans to determine the necessity for surgical resection. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that F-18 FDG-PET could be a useful, functional imaging modality for assessing the initial staging, response to therapy and follow-up of children diagnosed with lymphoma.Objective: To assess the role of whole-body F-18 FDG-PET imaging in patients with lymphoma as an initial staging modality and to measure its predictive value for monitoring the response to therapy and disease recurrence compared to CT and clinical follow-up studies.Materials and Methods: As part of their routine clinical care, 24 patients with histologically proven lymphoma (18 Hodgkin disease and 6 non-Hodgkin lymphoma) underwent an F-18 FDG-PET and a CT scan. A total of 28 studies were performed and the entire set of scans retrospectively reviewed. Seven studies were performed for initial staging, 12 for monitoring therapy response and 9 for detecting recurrence. Initial diagnosis was confirmed by histopathology while the gold standard at follow-up was established by clinical follow-up, additional imaging modalities and/or biopsy. F-18 FDG-PET was visually compared to CT on a lesion-by-lesion basis. Fifteen anatomic regions (seven nodal and eight extranodal) were analyzed.Results: Of the 414 regions analyzed, PET and CT were concordant in 366 (positive in 16 and negative in 350). Discordance was found in 48 regions. Overall sensitivities, specificities, and positive and negative predictive values were 78%, 98%, 94% and 90% for F-18 FDG-PET and 79%, 88%, 90% and 46% for CT, respectively.Conclusion: F-18 FDG-PET imaging is a useful technique for the staging and follow-up of pediatric patients with lymphoma. [ABSTRACT FROM AUTHOR]