Outcomes and technical modifications of vascularized lymph node transplantation from the lateral thoracic region for treatment of lymphedema.

BACKGROUND AND OBJECTIVES: This study evaluates clinical outcomes of vascularized lymph node transplantation (VLNT) from the lateral thoracic region and technical modifications. METHODS: Consecutive patients that underwent lateral thoracic VLNT to treat extremity lymphedema were included. Demographic and treatment data were recorded, and outcomes data including limb volume, LDex score, and Lymphedema Life Impact Scale (LLIS), QuickDASH, and LEFS questionnaires, were collected prospectively. Consecutive patients that underwent single-photon emission computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (RLM) were analyzed to characterize the physiological drainage of the normal upper extremity. RESULTS: A consecutive series of 32 flaps were included. At 24 months postoperatively mean reduction in limb volume excess was 47.2% (±11.6; p = 0.0085), LDex score was 63.1% (±8.5; p < 0.001), and LLIS score was 65.1% (±7.4; p < 0.001). Preoperatively 14/31 patients (45.2%) reported cellulitis, and postoperatively there were no episodes at up to 24 months (p < 0.001). No patient developed donor extremity lymphedema at mean 18.6 (±8.3) months follow-up. SPECT/CT-RLM of 182 normal axillae demonstrated that the sentinel lymph node(s) of the upper extremity was consistently anatomically located in the upper outer quadrant of the axilla (97%). CONCLUSIONS: VLNT from the lateral thoracic region is effective and versatile for the treatment of lymphedema with a low donor site complication rate.

Anatomy and physiology of the sentinel lymph nodes of the upper extremity: Implications for axillary reverse mapping in breast cancer.

BACKGROUND: This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). METHODS: A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. RESULTS: A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). CONCLUSIONS: The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Preoperative PET/CT does not accurately detect extrauterine disease in patients with newly diagnosed high-risk endometrial cancer: A prospective study.

BACKGROUND: The identification of extrauterine disease is critical to the management of patients with high-risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease. METHODS: Women with high-risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy. Primary tumor factors on PET/CT were correlated with lymph node pathology. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the detection of lymphadenopathy and peritoneal disease by PET/CT. RESULTS: A total of 112 patients were enrolled and underwent PET/CT between April 2013 and May 2016, 108 of whom were evaluable. On PET/CT, 21 patients (19.4%) were found to have extrauterine disease, 18 (17%) had positive lymph nodes, and 8 (7%) had peritoneal disease. A total of 108 patients underwent surgery, 103 of whom (95%) underwent lymphadenectomy. The sensitivity of PET/CT to detect positive lymph nodes was 45.8%, with a specificity of 91.1%, positive predictive value of 61.1%, and negative predictive value of 84.7%. The false-negative rate was 54.2%. There was no difference in primary tumor characteristics on imaging noted between patients with positive and negative lymph nodes. The sensitivity of PET/CT to detect peritoneal disease was 37.5%, with a specificity of 97.8%, positive predictive value of 75%, and negative predictive value of 90.0%. The false-negative rate was 62.5%. CONCLUSIONS: Preoperative PET/CT did not reliably predict the presence of extrauterine disease in women with high-risk endometrial cancer. Given the high false-negative rates, PET/CT should not be used in the preoperative treatment planning of these patients.

Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy.

BACKGROUND: This study aims to investigate the prognostic role of complete metabolic response (CMR) on interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with breast cancer (BC) receiving neoadjuvant chemotherapy (NAC) according to tumor subtypes and PET timing. PATIENTS AND METHODS: Eighty-six consecutive patients with stage II/III BC who received PET/CT during or following NAC were included. Time-dependent receiver operating characteristic analysis and Kaplan-Meier analysis were used to determine correlation between metabolic parameters and survival outcomes. RESULTS: The median follow-up duration was 71 months. Maximum standardized uptake value (SUVmax) on an interim PET/CT independently correlated with survival by multivariate analysis (overall survival [OS]: hazard ratio: 1.139, 95% confidence interval: 1.058-1.226, p = .001). By taking PET timing into account, best association of SUVmax with survival was obtained on PET after two to three cycles of NAC (area under the curve [AUC]: 0.941 at 1 year after initiation of NAC) and PET after four to five (AUC: 0.871 at 4 years), while PET after six to eight cycles of NAC had less prognostic value. CMR was obtained in 62% of patients (23/37) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) BC, in 48% (12/25) triple-negative BC (TNBC), and in 75% (18/24) HER2-positive (HER2+) tumors. Patients with CMR on an early-mid PET had 5-year OS rates of 92% for ER+/HER2- tumors and 80% for TNBC, respectively. Among HER2+ subtype, 89% patients (16/18) with CMR had no relapse. CONCLUSION: CMR indicated a significantly better outcome in BC and may serve as a favorable imaging prognosticator. The Oncologist 2017;22:526-534 IMPLICATIONS FOR PRACTICE: This study shows a significantly better outcome for breast cancer (BC) patients who achieved complete metabolic response (CMR) on 18F-fluorodeoxyglucose emission tomography/computed tomography (PET/CT) during neoadjuvant chemotherapy, especially for hormone receptor-positive tumors and triple negative BC. Moreover, PET/CT performed during an early- or mid-course neoadjuvant therapy is more predictive for long-term survival outcome than a late PET/CT. These findings support that CMR may serve as a favorable imaging prognosticator for BC and has potential for application to daily clinical practice.

Long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema.

BACKGROUND: The free vascularized omental lymphatic flap provides an option without the risk for iatrogenic donor site lymphedema that plagues alternative lymph node transfer donor sites. The omental flap has been associated with significant morbidity in the past; however, with modern techniques and advanced in technology, a minimally invasive approach to flap harvest is feasible. We present the long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema. METHODS: All consecutive patients with advanced lymphedema undergoing minimally invasive free vascularized omental lymphatic flap transfer were included. Perioperative evaluation included qualitative assessments, lymphoscintigraphy, and volumetric measurements. RESULTS: Overall, 42 patients underwent a free omental lymphatic flap and had a mean follow-up of 14 (3-32) months. Subjective improvements were noted in 83% of patients. Mean volumetric improvement was 22%. Complications occurred in 16% (n = 7) of patients; this included one episode of pancreatitis and one flap loss. Postoperative imaging revealed viable lymphatic transfers. Cellulitis history was present in 74% (n = 31) patients with post-operative cellulitis occurring in 5% (n = 2) patients. CONCLUSIONS: The minimally invasive free vascularized omental lymphatic flap provides a safe donor site, a durable and versatile flap, and an efficacious therapy against lymphedema and lymphedema-related cellulitis. J. Surg. Oncol. 2017;115:84-89. © 2016 Wiley Periodicals, Inc.

Risk stratification in patients with advanced-stage breast cancer by pretreatment [(18) F]FDG PET/CT.

BACKGROUND: The objective of the current study was to investigate the prognostic value of pretreatment [(18) F] fluorodeoxyglucose position emission tomography/computed tomography ([(18) F]FDG PET/CT) in patients with advanced-stage breast cancer. METHODS: Pretreatment PET/CT scans from 240 consecutive patients with American Joint Committee on Cancer stage III or stage IV BC were analyzed retrospectively. Clinicopathological factors and metabolic parameters of the primary tumor including maximum standardized uptake value (SUVmax ), metabolic tumor volume, and total lesion glycolysis (TLG) with a range of thresholds were compared to predict progression-free survival (PFS) and overall survival (OS) using a time-dependent receiver operating characteristic curve and Cox proportional hazards regression analyses. RESULTS: SUVmax with a cutoff value of 6.0, TLG30% with a cutoff value of 158 g, and phenotype associated with PFS and OS were analyzed using multivariate analysis. The mean TLG30% of primary tumors for patients with stage III and stage IV disease was 405 g and 750 g (P = .010), respectively. Patients with triple-negative breast cancer or a TLG30% >158 g or with both were categorized as being at high risk, and those with non-triple-negative breast cancer and a primary tumor with a TLG30% ≤158 g were defined as low risk. The 5-year PFS rates for stage III disease among patients with low-risk versus high-risk BC were 85% and 67.5%, respectively. For patients with stage IV disease, the 5-year PFS rates were 45% and 9%, respectively, for patients with low-risk versus high-risk disease. Patients with stage III and high-risk BC had OS rates that were similar to those for patients with stage IV and low-risk BC (P = .552). CONCLUSIONS: The TLG30% from pretreatment PET/CT was found to independently correlate with survival outcomes and appears to be able to effectively stratify both patients with stage III and those with stage IV BC.

Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer.

BACKGROUND: Radiopharmaceutical use may improve the survival time of patients with castrate-resistant prostate cancer and bone metastases. Whether androgen-deprivation therapy (ADT) combined with bone-targeted therapy provides a clinical benefit to patients with advanced castrate-sensitive prostate cancer has not been investigated. METHODS: Eighty male patients were enrolled, and 79 were randomized: 40 to the control arm and 39 to the strontium-89 (Sr-89) arm. After randomization, patients in both study arms received ADT, doxorubicin, and zoledronic acid. Kaplan-Meier methodology was used to evaluate the progression-free survival (PFS) time. Multivariate Cox proportional hazards regression was used to evaluate the effects of Sr-89 after controlling for the number of bone metastases. RESULTS: The median follow-up time for the 29 patients alive at the last follow-up was 76.9 months (range, 0.07-103.4 months). The median PFS time was 18.5 months (95% confidence interval, 9.7-49.4 months) for the control arm and 12.9 months (95% confidence interval, 8.9-72.5 months) for the Sr-89 arm (P = .86). No patient developed myelodysplastic syndrome or a hematologic malignancy. An unplanned subgroup analysis suggested increased efficacy of bone-targeted therapy with a greater extent of bone involvement (ie, >6 bone metastases vs ≤6 bone metastases on the bone scan). CONCLUSIONS: The data showed that bone-targeted therapy using 1 dose of Sr-89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate-sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone-targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation.

Parathyroid carcinoma: Imaging features of initial presentation and recurrence. A single center experience.

BACKGROUND AND PURPOSE: Parathyroid carcinoma is the rarest endocrine neoplasm with very few published data discussing its imaging appearance with primary focus on ultrasound imaging features. We present our 23 years institutional experience to highlight multimodality imaging evaluation at presentation and at recurrence. MATERIAL AND METHODS: Retrospective chart review of clinical and pathological diagnosis of parathyroid carcinoma patients presented for initial or recurrent disease management at M.D. Anderson Cancer Center between the period of January 2000 and February 2023 was performed. Imaging findings on US, CT, PET/CT, and technetium-99m sestamibi were analyzed for initial and local recurrent parathyroid carcinoma. We further assess patterns of distant recurrence and its location. RESULTS: Twenty three patients with pathological and clinical diagnosis of initial (14 patients) or recurrent parathyroid carcinoma (14 patients) were included in this study. US findings of parathyroid carcinoma were larger lesions, increased/irregular vascularity, and non-circumscribed margins. Multiphasic CT findings of parathyroid carcinoma included an arterially enhancing lesion that is hypoenhancing relative to the thyroid and demonstrates no washout on delayed imaging. Highly suggestive findings for recurrent disease included a hypoechoic solid nodule (91.67%) with increased vascularity on ultrasound (81.8%) with corresponding enhancement on CT. CONCLUSION: Parathyroid carcinoma is a rare malignancy often diagnosed after surgical resection. We provided CT and US imaging features that are helpful in suggesting the diagnosis of parathyroid carcinoma and detection of early local recurrence.

Phase I trial of single-photon emission computed tomography-guided liver-directed radiotherapy for patients with low functional liver volume.

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.

Supraclavicular and Axillary Lymphadenopathy Induced by COVID-19 Vaccination on 18F-Fluorthanatrace, 68Ga-DOTATATE, and 18F-Fluciclovine PET/CT.

ABSTRACT: COVID-19 vaccination has started in most countries, and postvaccination imaging is inevitable in the oncologic population. The immune response to the vaccination in the form of reactive lymphadenopathy has been well documented on 18F-FDG PET/CT. We present the imaging findings of 3 patients who have undergone non-FDG PET/CT imaging including 18F-fluorthanatrace, 68Ga-DOTATATE, and 18F-fluciclovine PET/CT. It is crucial to recognize the timing and laterality of immunization to avoid false-positive findings.

18F-Fluciclovine-Avid Reactive Axillary Lymph Nodes After COVID-19 Vaccination.

ABSTRACT: A 74-year-old man presenting with biochemical recurrent prostate cancer 9 months after robotic-assisted radical prostatectomy and pelvic lymphadenectomy underwent 18F-fluciclovine PET/CT for restaging to determine subsequent treatment strategy. Serum prostate-specific antigen was 0.7 ng/mL at the time of imaging. Images demonstrated foci of abnormal increased 18F-fluciclovine uptake corresponding to prominent round lymph nodes in the left axilla, some of which with fatty hila. Due to recent mRNA COVID-19 vaccination in the ipsilateral arm and the low likelihood of nodal metastases to the axilla from prostate cancer in this patient, the lymph nodes were considered to be benign, reactive to the vaccine.

Single-Photon Emission Computed Tomographic Reverse Lymphatic Mapping for Groin Vascularized Lymph Node Transplant Planning.

BACKGROUND: Superficial inguinal (groin) vascularized lymph node transplantation is the most common option for the treatment of lymphedema, particularly in combination with free abdominal flap breast reconstruction. This study examines the utility of single-photon emission computed tomographic (SPECT/CT) lymphoscintigraphy for lower extremity reverse lymphatic mapping in presurgical planning for groin vascularized lymph node transplantation and appraises the physiologic lymphatic drainage to the superficial inguinal lymph nodes. METHODS: All patients who underwent bilateral lower extremity SPECT/CT reverse lymphatic mapping over a 5-year period were included. Retrospective case note analysis was performed to collect demographic, surgical, and outcomes data. RESULTS: The study included 84 patients; 56 of these subsequently underwent groin vascularized lymph node transplantation (58 flaps). Fifty-four of these flaps were combined with free abdominal flaps for breast reconstruction (55 flaps). Using SPECT/CT reverse lymphatic mapping investigation of 168 inguinal regions, drainage to at least one superficial inguinal region was visualized in 38.1 percent of patients; in 13.1 percent, drainage was visualized to both superficial inguinal regions. Using this information for presurgical planning, groin vascularized lymph node flap harvest was performed from the contralateral side in 57 of 58 cases (98.3 percent) using intraoperative gamma probe guidance, and no patient developed donor lower extremity lymphedema during follow-up (mean ± SD, 34.5 ± 15.4 months). CONCLUSIONS: The authors' use of presurgical SPECT/CT reverse lymphatic mapping together with limited flap dissection and intraoperative gamma probe guidance resulted in no clinical cases of iatrogenic donor lower extremity lymphedema. The high incidence of drainage from the lower extremity to the superficial inguinal region mandates the use of reverse lymphatic mapping when performing groin vascularized lymph node transplantation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A CT acquisition technique to generate images at various dose levels for prospective dose reduction studies.

OBJECTIVE: The purpose of this article is to determine whether the average of N CT images acquired at a particular dose (D) has image noise equivalent to that of a single image acquired at a dose of N × D. MATERIALS AND METHODS: An electron density phantom, an image quality phantom, and an adult anthropomorphic phantom were scanned multiple times on a 16-MDCT scanner at five effective tube current-rotation time product (mAs) settings (130 kVp; 12, 24, 48, 72, and 144 mAs). Lower-mAs images were averaged to simulate higher-mAs images. Differences in CT number and image noise between simulated and acquired images were quantified using the electron density phantom. Image quality phantom images were scored by three physicists to investigate differences in low- and high-contrast resolution. A forced-choice observer study was performed with three radiologists using anthropomorphic phantom images to evaluate differences in overall image quality. RESULTS: The CT number was, on average, reproduced to within 1 HU, and image noise was reproduced to within 4%, which is below the threshold for visibly perceptible differences in noise. Low- and high-contrast resolution were not degraded, and simulated images were visually indistinguishable from acquired images. CONCLUSION: For the dose range studied, it was concluded that the image quality of a CT image produced by averaging multiple low-mAs CT images is identical to that of a high-mAs image acquired at equivalent effective dose, when all other acquisition and reconstruction parameters are held constant. Prospective CT dose-reduction studies may be feasible by acquiring multiple low-dose scans instead of a single high-dose scan. Simulated high-dose images could be interpreted clinically, whereas lower-dose images would be available for an observer study.

A Comparison of the Diagnostic Value of Positron Emission Tomography/Computed Tomography and Ultrasound for the Detection of Metastatic Axillary Nodal Disease in Treatment-Naive Breast Cancer.

ABSTRACT: The objective of this study was to describe the diagnostic value of positron emission tomography/computed tomography (PET/CT) and ultrasound (US) for identifying metastatic axillary disease in primary breast cancer. This is a retrospective review of 240 patients with treatment-naive unilateral primary breast cancer of at least stage T2. Eighty-five patients met our inclusion criteria. Initial whole-body PET/CT and axillary US examinations were reviewed and compared with the criterion standard of fine-needle aspiration cytology. Sensitivity, accuracy, and positive predictive value (PPV) for each modality were computed. Because of all positive US cases, specificity and negative predictive value of US were not determined. Sensitivity and accuracy between modalities were compared using McNemar test. The majority of the patients were White women with clinical inflammatory breast cancer and with histologically invasive ductal carcinoma. The most common tumor and nodal stage was T4N3. The tumors were predominantly estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 negative. The sensitivities of PET/CT and US were 96.2% and 100%, respectively. The accuracies for PET/CT and US were 91.8% and 94.1%, respectively. The PPV for PET/CT was 95.1%, and for US, the PPV was 94.1%. No significant difference in sensitivity or accuracy was shown between PET/CT and US for the diagnosis of metastatic axillary nodal disease. Three of 85 cases showed discordance between negative PET/CT and positive US and fine-needle aspiration cytology.

An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advanced pancreatic cancer (OncoPaC-1): Technical details and study protocol.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed. Currently, there is no brachytherapy device approved for pancreatic cancer treatment. Hereby, we present the protocol of a prospective, multicenter, interventional, open-label, single-arm pilot study (OncoPac-1, Clinicaltrial.gov-NCT03076216) aiming to determine the safety and efficacy of Phosphorus-32 when implanted directly into pancreatic tumors using EUS guidance, for patients with unresectable LAPC undergoing chemotherapy (gemcitabine ± nab-paclitaxel).

18F-FDG PET/CT in the Evaluation of Bing-Neel Syndrome.

Waldenström macroglobulinemia is an indolent B-cell lymphoproliferative disorder. When there is involvement of the central nervous system, Waldenström macroglobulinemia is known as Bing-Neel syndrome. We present a case of Bing-Neel syndrome in a patient who presented with confusion and left orbital pain. 18F-FDG PET/CT was utilized in making the diagnosis.

Correlation of L-Dex Bioimpedance Spectroscopy with Limb Volume and Lymphatic Function in Lymphedema.

Background: Bioimpedance spectroscopy (BIS) is an established tool for the measurement of extracellular fluid in lymphedema. This study assesses the validity of BIS measurements using the l-Dex® for evaluating the effectiveness of interventions to treat lymphedema. Measurements are correlated with limb volume, assessment of pitting edema, physiologic measures of lymphatic function, and response to surgical intervention. Three l-Dex BIS metrics are compared. Methods and Results: This retrospective study of prospectively collected data identified consecutive patients with lymphedema. l-Dex BIS measurements, limb volume measurements using perometry, transport index (TI) evaluation using radioisotope lymphoscintigraphy, staging using indocyanine green (ICG) fluorescent lymphography, and clinical evaluation of degree of pitting edema were compared to examine correlations. l-Dex BIS metrics included the l-Dex ratio, absolute difference between the affected and unaffected extremities, and their unadjusted ratio. The study included 26 patients with 70 sets of evaluations. There were significant correlations between the l-Dex ratio and limb volume ratio (LVR) using perometry, the degree of pitting edema, TI evaluation using lymphoscintigraphy, and staging using ICG lymphography. Of the l-Dex BIS metrics, the l-Dex ratio correlated most closely with all measures (ρ = 0.71-0.94, p < 0.0001). Following complete decongestive therapy, the mean decrease in the l-Dex ratio was 48.3% whereas the corresponding mean reduction in limb volume was 13.8% (ρ = 0.19; p = 0.65); subsequent physiological surgery including lymphovenous bypass and vascularized lymph node transfer resulted in an average reduction in l-Dex ratio of 36.1% and mean limb volume reduction of 25.2% (ρ = 0.38; p = 0.27). Conclusions: L-Dex BIS measurements demonstrate face, construct, and criterion validity, and correlate with clinical assessment, LVR, physiologic measures of lymphatic function, and response to conservative and surgical intervention. The L-Dex ratio correlates most closely with all measures and is the recommended metric when using BIS.

Mechanism-Specific Pharmacodynamics of a Novel Complex-I Inhibitor Quantified by Imaging Reversal of Consumptive Hypoxia with [18F]FAZA PET In Vivo.

Tumors lack a well-regulated vascular supply of O2 and often fail to balance O2 supply and demand. Net O2 tension within many tumors may not only depend on O2 delivery but also depend strongly on O2 demand. Thus, tumor O2 consumption rates may influence tumor hypoxia up to true anoxia. Recent reports have shown that many human tumors in vivo depend primarily on oxidative phosphorylation (OxPhos), not glycolysis, for energy generation, providing a driver for consumptive hypoxia and an exploitable vulnerability. In this regard, IACS-010759 is a novel high affinity inhibitor of OxPhos targeting mitochondrial complex-I that has recently completed a Phase-I clinical trial in leukemia. However, in solid tumors, the effective translation of OxPhos inhibitors requires methods to monitor pharmacodynamics in vivo. Herein, 18F-fluoroazomycin arabinoside ([18F]FAZA), a 2-nitroimidazole-based hypoxia PET imaging agent, was combined with a rigorous test-retest imaging method for non-invasive quantification of the reversal of consumptive hypoxia in vivo as a mechanism-specific pharmacodynamic (PD) biomarker of target engagement for IACS-010759. Neither cell death nor loss of perfusion could account for the IACS-010759-induced decrease in [18F]FAZA retention. Notably, in an OxPhos-reliant melanoma tumor, a titration curve using [18F]FAZA PET retention in vivo yielded an IC50 for IACS-010759 (1.4 mg/kg) equivalent to analysis ex vivo. Pilot [18F]FAZA PET scans of a patient with grade IV glioblastoma yielded highly reproducible, high-contrast images of hypoxia in vivo as validated by CA-IX and GLUT-1 IHC ex vivo. Thus, [18F]FAZA PET imaging provided direct evidence for the presence of consumptive hypoxia in vivo, the capacity for targeted reversal of consumptive hypoxia through the inhibition of OxPhos, and a highly-coupled mechanism-specific PD biomarker ready for translation.

Correlation of chromogranin A levels and somatostatin receptor scintigraphy findings in the evaluation of metastases in carcinoid tumors.

OBJECTIVE: Chromogranin A (CgA) has been gaining acceptance as a helpful tumor marker in patients with neuroendocrine tumors, with respect to both diagnosis and prognosis. The objective of this study was to correlate serum CgA levels and somatostatin receptor scintigraphy (SRS) findings in the evaluation of metastases in carcinoid tumors. MATERIALS AND METHODS: A total of 125 patients(61 men and 64 women, aged from 23 to 84 years) with histologically diagnosed carcinoid tumor underwent serum CgA assay and SRS for detecting metastasis or disease recurrence. The quantitative determination of CgA was performed in serum using an enzyme immunoassay with a cut-off value fixed at 39 U/l. Scintigraphies were performed with 200-220 MBq of In-111-DTPA-Phel-octreotide including whole-body images as well as single-photon emission computed tomography and computed tomography scans of the chest and abdomen. RESULTS: The primary tumors originated from the gastrointestinal tract in 115 of 125 patients (92.0%), the lung in 7 of 125 patients (5.6%), the kidney in 2 of 125 patients (1.6%), and the breast in 1 of 125 patients (0.8%). The primary tumors originated from the foregut, midgut, and hindgut in 13.6%, 71.2%, and 12.8%, respectively. Correlation of SRS with other imaging modalities and clinical follow-up findings revealed a sensitivity, a specificity, and an accuracy of 82.9%, 97.7%, and 88.0%, respectively, and for CgA 62.2%, 83.7%, and 69.6%, respectively. There was 1 false-positive and 14 false-negative SRS results and 7 false-positive and 31 false-negative CgA analyses. SRS demonstrated higher sensitivity, specificity, and accuracy than CgA for the evaluation of metastatic carcinoid tumors. The concordance between SRS and CgA results was 67.2%. Discrepancies, such as positive SRS with normal CgA levels, were noted in 26 (20.8%) cases, whereas negative SRS with high CgA levels was seen in 15 (12.0%) cases. Combining the results of CgA and SRS increased the sensitivity (92.7%) but decreased the specificity (81.4%) of tumor detection. CONCLUSIONS: In our study, SRS proved to be more sensitive, more specific, and more accurate than CgA for metastatic evaluation of carcinoid tumors. Positive SRS correlated with elevation of serum CgA levels. Serum CgA might have some diagnostic utility in patients with negative SRS studies. Nevertheless, both SRS and CgA should be considered useful tools in the evaluation of metastases in carcinoid patients.

Diagnostic impact of SPECT image display on assessment of obstructive coronary artery disease.

BACKGROUND: Diagnostic assessment of myocardial perfusion impacts the management of patients with suspected coronary artery disease (CAD). Although various image displays are available for single photon emission computed tomography (SPECT) interpretation, the effects of display differences on SPECT interpretation remain undetermined. METHODS AND RESULTS: We studied 183 patients undergoing SPECT, including 131 consecutive patients referred for angiography and 52 at low CAD risk. Studies were visually interpreted by use of color and gray images, with readers blinded to the results of the other display. In accordance with established criteria, a summed stress score (SSS) of 4 or greater was considered abnormal. The prevalence of abnormal SPECT findings was higher with gray images than with color images (54% vs 48%, P < .001) based on a uniform criterion (SSS > or =4). However, color images yielded equivalent sensitivity (79% vs 82%, P = .7) and improved specificity for global (50% vs 33%, P = .02) and vessel-specific CAD involving the right coronary artery (P < .01) and left anterior descending artery (P < .05). When the criterion for gray images was adjusted upward (SSS > or =5) to reflect increased mean defect severity (SSS of 5.1 vs 4.4, P = .01), gray and color images provided equivalent sensitivity and specificity for global and vessel-specific CAD. CONCLUSIONS: SPECT interpretation can vary according to image display as a result of differences in perfusion defect severity. Adjustment of abnormality criteria for gray images to reflect minor increases in defect severity provides equivalent diagnostic performance of gray and color displays for CAD assessment.