Effect of Ibuprofen as an Albumin Binder on Melanoma-Targeting Properties of 177Lu-Labeled Ibuprofen-Conjugated Alpha-Melanocyte-Stimulating Hormone Peptides.

The purpose of this study was to examine how the introduction of ibuprofen (IBU) affected tumor-targeting and biodistribution properties of 177Lu-labeled IBU-conjugated alpha-melanocyte-stimulating hormone peptides. The IBU was used as an albumin binder and conjugated to the DOTA-Lys moiety without or with a linker to yield DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex peptides. Their melanocortin-receptor 1 (MC1R) binding affinities were determined on B16/F10 melanoma cells first. Then the biodistribution of 177Lu-labeled peptides was determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to choose the lead peptide for further examination. The full biodistribution and melanoma imaging properties of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex were further evaluated using B16/F10 melanoma-bearing C57 mice. DOTA-Lys(IBU)-GG-Nle-CycMSHhex, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex displayed the IC50 values of 1.41 ± 0.37, 1.52 ± 0.08, 0.03 ± 0.01, and 0.58 ± 0.06 nM on B16/F10 melanoma cells, respectively. 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex exhibited the lowest liver and kidney uptake among all four designed 177Lu peptides. Therefore, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was further evaluated for its full biodistribution and melanoma imaging properties. The B16/F10 melanoma uptake of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was 19.5 ± 3.12, 24.12 ± 3.35, 23.85 ± 2.08, and 10.80 ± 2.89% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Moreover, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex could clearly visualize the B16/F10 melanoma lesions at 2 h postinjection. The conjugation of IBU with or without a linker to GGNle-CycMSHhex affected the MC1R binding affinities of the designed peptides. The charge of the linker played a key role in the liver and kidney uptake of 177Lu-Asp-IBU, 177Lu-Asn-IBU, and 177Lu-Dab-IBU. 177Lu-Asp-IBU exhibited higher tumor/liver and tumor/kidney uptake ratios than those of 177Lu-Asn-IBU and 177Lu-Dab-IBU, underscoring its potential evaluation for melanoma therapy in the future.

FDG PET in Evaluation of Patients With Fever of Unknown Origin: AJR Expert Panel Narrative Review.

Fever of unknown origin (FUO) is a diagnostic challenge, with its cause remaining undiagnosed in approximately half of patients. Nuclear medicine tests typically are performed after a negative or inconclusive initial workup. Gallium-67 citrate and labeled leukocytes were previous mainstays of radionuclide imaging for FUO, although they had limited diagnostic performance. FDG PET/CT has subsequently emerged as the nuclear medicine imaging test of choice, supported by a growing volume of evidence. A positive FDG PET/CT result contributes useful information by identifying potential causes of fever, localizing sites for further evaluation, and guiding further management; a negative result contributes useful information by excluding focal disease as the cause of fever and predicts a favorable prognosis. In 2021, CMS rescinded a prior national noncoverage determination for FDG PET for infection and inflammation, leading to increasing national utilization of FDG PET/CT for FUO workup. This article reviews the current status of the role of FDG PET/CT in the evaluation of patients with FUO. The literature reporting the diagnostic performance and yield of FDG PET/CT in FUO workup is summarized, with comparison with historically used nuclear medicine tests included. Attention is also given to the test's clinical impact; protocol, cost, and radiation considerations; and application in children.

Death attitudes among older Asian and Pacific Islander Americans: The role of religiosity, spirituality, and psychosocial health factors.

With the growth of older minorities in the United States, more attention is needed on what the experience of dying means in this population. Previous research has overlooked older Asians and Pacific Islanders. This study examined death attitudes among 69 diverse nursing home residents in Hawai'i. Results from correlational and regression analyses showed religiosity and spirituality had significantly distinct impacts on death attitudes and psychosocial health. Ethnicity and religious/spiritual affiliation had significant effects on study outcomes, even between minority subgroups. These findings highlight the importance of exploring the differential impact of religious/spiritual and cultural factors on death attitudes among older minorities.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole.

OBJECTIVE: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment. METHODS: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure. RESULTS: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002). CONCLUSION: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

Postbiopsy Pigmentation is Prognostic in Head and Neck Melanoma.

PURPOSE: To assess postbiopsy pigmentation (PBP) as a prognostic feature in patients with cutaneous head and neck (H&N) melanoma. METHODS: Retrospective review of patients undergoing sentinel lymph node biopsy (SLNB) for H&N melanoma (1998-2018). PBP was defined as visible remaining pigment at the scar or biopsy site that was documented on physical exam by both a medical oncologist and a surgeon at initial consultation. Variables associated with disease-free survival (DFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. RESULTS: Among 300 patients, 34.3% (n = 103) had PBP and 44.7% (n = 134) had microscopic residual disease on final pathology after wide local excision. Prognostic factors associated with DFS included advanced age, tumor depth, ulceration, PBP, and positive SLNB (p < 0.05). Patients with PBP fared worse than their counterparts without PBP in 5-year DFS [44.1% (31.1-56.3%) vs. 73.0% (64.1-80.0%); p < 0.001] and 5-year OS [65.0% (50.0-76.6%) vs. 83.6% (75.7-89.2%); p = 0.005]. After multivariable adjustment, PBP remained associated with shorter DFS [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.01-2.93; p = 0.047], but was not prognostic of OS. CONCLUSIONS: In patients with H&N melanoma, PBP is associated with significantly shorter DFS. Patients with PBP may warrant greater consideration for SLNB and closer postoperative surveillance.

EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy.

INTRODUCTION: Scintigraphic evaluation of the thyroid gland enables determination of the iodine-123 iodide or the 99mTc-pertechnetate uptake and distribution and remains the most accurate method for the diagnosis and quantification of thyroid autonomy and the detection of ectopic thyroid tissue. In addition, thyroid scintigraphy and radioiodine uptake test are useful to discriminate hyperthyroidism from destructive thyrotoxicosis and iodine-induced hyperthyroidism, respectively. METHODS: Several radiopharmaceuticals are available to help in differentiating benign from malignant cytologically indeterminate thyroid nodules and for supporting clinical decision-making. This joint practice guideline/procedure standard from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides recommendations based on the available evidence in the literature. CONCLUSION: The purpose of this practice guideline/procedure standard is to assist imaging specialists and clinicians in recommending, performing, and interpreting the results of thyroid scintigraphy (including positron emission tomography) with various radiopharmaceuticals and radioiodine uptake test in patients with different thyroid diseases.

Frequency and implications of occipital and posterior auricular sentinel lymph nodes in scalp melanoma.

BACKGROUND: Patients with scalp melanoma have poor oncologic outcomes compared with those with other cutaneous sites. Sentinel lymph node (SLN) biopsy provides prognostic information but is challenging in the head and neck. We explore the anatomic distribution of scalp melanoma and describe the most common sites of SLN drainage and of SLN metastatic disease. METHODS: Retrospective review of scalp melanoma patients who underwent SLN biopsy. Melanoma location was classified as frontal, coronal apex, coronal temporal, or posterior scalp. SLN location was classified by lymph node level and region. RESULTS: We identified 128 patients with scalp melanoma. The most common primary tumor location was the posterior scalp (43%) and the most frequent SLN drainage site was the level 2 lymph node basin (48%). Total 31 patients (24%) had metastatic disease in an SLN. Scalp SLNs, classified as being in the posterior auricular or occipital region, were localized in 26% of patients. For patients in which a scalp SLN was identified, 30% had a positive scalp SLN (n = 10). CONCLUSIONS: Scalp SLNs are frequent drainage sites for scalp melanoma and, when found, have a 30% chance of harboring metastatic disease. Surgeons, radiologists, and pathologists should be vigilant in identifying, removing, and analyzing scalp SLNs.

SPECT/CT Adds Distinct Lymph Node Basins and Influences Radiologic Findings and Surgical Approach for Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

BACKGROUND: Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel lymph nodes (SLNs) in head and neck melanoma compared with other sites. We assessed situations when single-photon emission computed tomography/computed tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the impact of SPECT/CT on surgical approach and oncologic outcomes. METHODS: Patients who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT between November 2011 and December 2016 were included. Surgeons and radiologists completed a real-time survey inquiring about the utility of SPECT/CT. Patients were divided into two groups: patients with nodal basins identified by both PL and SPECT/CT ('PL + SPECT/CT'), and patients in whom SPECT/CT identified additional nodal basins not seen on PL ('SPECT/CT only'). Patient demographics and long-term outcomes including follow-up duration, recurrence, and survival are described. RESULTS: In the PL + SPECT/CT group, 73 (61.9%) patients were included and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added 51 basins to those seen on PL, primarily in the supraclavicular region (43.1%). Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time, SPECT/CT influenced the location of incision for SLNB. CONCLUSIONS: SPECT/CT influences the location of incision and contributes most to identification of nodes in the supraclavicular region. It also detects additional SLN basins when compared with PL. Further studies are necessary to determine when these additional basins require sampling.

Implications of Sentinel Lymph Node Drainage to Multiple Basins in Head and Neck Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for head and neck melanoma is challenging due to unpredictable drainage. We sought to determine the frequency of drainage to multiple lymphatic basins and asked if this was associated with prognosis in a large, single-center cohort. METHODS: We queried patients diagnosed with head and neck melanomas who had a SLNB performed from January 1998 to April 2016. Demographic and clinical characteristics were compared using Student's t test, Pearson chi-square analysis, log-rank test, Wilcoxon-Mann-Whitney test, and Kaplan-Meier curves. RESULTS: We identified 269 patients with head and neck melanoma that had SLNBs performed in the following locations: 223 neck, 92 parotid/preauricular, 29 occipital/posterior auricular, 1 axilla. There were 68 (25%) patients who had drainage to multiple basins. These patients were similar to those with single basin drainage in age, gender distribution, Breslow depth, and percent with a positive SLNB (all p > 0.05). Fewer patients with drainage to multiple basins had a completion lymph node dissection (CLND, p = 0.03). A trend toward increased 3-year locoregional recurrence was seen for patients with drainage to multiple basins in univariate analysis (27% vs. 18%, p = 0.10) but was lost in multivariate analysis (p = 0.49), possibly because of higher recurrence rates in patients with positive nodes but no CLND (p = 0.02). No difference was detected for distant recurrence or overall survival based on SLN drainage. CONCLUSIONS: Head and neck melanoma SLNB drainage to multiple basins is common. Drainage to multiple basins does not seem to be associated with increased sentinel lymph node positivity, locoregional recurrence, distant recurrence, or survival.

Ethical Concerns and Procedural Pathways for Patients Who are Incapacitated and Alone: Implications from a Qualitative Study for Advancing Ethical Practice.

Adults who are incapacitated and alone, having no surrogates, may be known as "unbefriended." Decision-making for these particularly vulnerable patients is a common and vexing concern for healthcare providers and hospital ethics committees. When all other avenues for resolving the need for surrogate decision-making fail, patients who are incapacitated and alone may be referred for "public guardianship" or guardianship of last resort. While an appropriate mechanism in theory, these programs are often under-staffed and under-funded, laying the consequences of inadequacies on the healthcare system and the patient him or herself. We describe a qualitative study of professionals spanning clinical, court, and agency settings about the mechanisms for resolving surrogate consent for these patients and problems therein within the state of Massachusetts. Interviews found that all participants encountered adults who are incapacitated and without surrogates. Four approaches for addressing surrogate needs were: (1) work to restore capacity; (2) find previously unknown surrogates; (3) work with agencies to obtain surrogates; and (4) access the guardianship system. The use of guardianship was associated with procedural challenges and ethical concerns including delays in care, short term gains for long term costs, inabilities to meet a patient's values and preferences, conflicts of interest, and ethical discomfort among interviewees. Findings are discussed in the context of resources to restore capacity, identify previously unknown surrogates, and establish improved surrogate mechanisms for this vulnerable population.

Validation of Software Gating: A Practical Technology for Respiratory Motion Correction in PET.

Purpose To assess the performance of hardware- and software-gating technologies in terms of qualitative and quantitative characteristics of respiratory motion in positron emission tomography (PET) imaging. Materials and Methods Between 2010 and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in 116 patients for assessment of pulmonary nodules. All patients provided informed consent in this institutional review board-approved study. Acquisitions were reconstructed as respiratory-gated images by using hardware-derived respiratory triggers and software-derived signal (via an automated postprocessing method). Asymmetry was evaluated in the joint distribution of reader preference, and linear mixed models were used to evaluate differences in outcomes according to gating type. Results In blind reviews of reconstructed gated images, software was selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of 657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion quality. Quantitative analysis demonstrated that the two gating strategies exhibited similar performance, and the performance of both was significantly different from that of nongated images. The mean increase ± standard deviation in lesion maximum standardized uptake value was 42.2% ± 38.9 between nongated and software-gated images, and lesion full width at half maximum values decreased by 9.9% ± 9.6. Conclusion Compared with vendor-supplied respiratory-gating hardware methods, software gating performed favorably, both qualitatively and quantitatively. Fully automated gating is a feasible approach to motion correction of PET images. (©) RSNA, 2016 Online supplemental material is available for this article.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy.

AIMS: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). METHODS: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. RESULTS: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. CONCLUSION: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis.

PURPOSE: This study was performed to evaluate the efficacy of (177)Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). METHODS: Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of "neuroendocrine", "(177)Lu" and "prognosis". All published studies of neuroendocrine tumours treated with (177)Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. RESULTS: Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8% with a pooled effect of 29% [95% confidence interval (CI) 24-34%]. Disease control rates ranged from 71.8 to 100%. The random-effects model showed an average disease control rate of 81% (95% CI 71-91%). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5% with a pooled effect of 23% (95% CI 11-38%). Disease control rates ranged from 73.9 to 89.1%. The random-effects model showed an average disease control rate of 82% (95% CI 71-91%). CONCLUSION: (177)Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.

Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events.

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.

Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET.

Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PET on the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.

Novel Functional Radiomics for Prediction of Cardiac Positron Emission Tomography Avidity in Lung Cancer Radiotherapy.

PURPOSE: Traditional methods of evaluating cardiotoxicity focus on radiation doses to the heart. Functional imaging has the potential to provide improved prediction for cardiotoxicity for patients with lung cancer. Fluorine-18 (18F) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging is routinely obtained in a standard cancer staging workup. This work aimed to develop a radiomics model predicting clinical cardiac assessment using 18F-FDG PET/CT scans before thoracic radiation therapy. METHODS: Pretreatment 18F-FDG PET/CT scans from three study populations (N = 100, N = 39, N = 70) were used, comprising two single-institutional protocols and one publicly available data set. A clinician (V.J.) classified the PET/CT scans per clinical cardiac guidelines as no uptake, diffuse uptake, or focal uptake. The heart was delineated, and 210 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. Training data were divided into training (80%)/validation (20%) sets. Feature reduction was performed using the Wilcoxon test, hierarchical clustering, and recursive feature elimination. Ten-fold cross-validation was carried out for training, and the accuracy of the models to predict clinical cardiac assessment was reported. RESULTS: From 202 of 209 scans, cardiac FDG uptake was scored as no uptake (39.6%), diffuse uptake (25.3%), and focal uptake (35.1%), respectively. Sixty-two independent radiomics features were reduced to nine clinically pertinent features. The best model showed 93% predictive accuracy in the training data set and 80% and 92% predictive accuracy in two external validation data sets. CONCLUSION: This work used an extensive patient data set to develop a functional cardiac radiomic model from standard-of-care 18F-FDG PET/CT scans, showing good predictive accuracy. The radiomics model has the potential to provide an automated method to predict existing cardiac conditions and provide an early functional biomarker to identify patients at risk of developing cardiac complications after radiotherapy.

Lack of Adherence to Guideline-Based Imaging Before Subsequent Radiation in Patients with Non-Small Cell Lung Cancer: Impact on Patient Outcomes.

Lung cancer is the leading cause of cancer death within the United States, yet prior studies have shown a lack of adherence to imaging and treatment guidelines in patients with lung cancer. This study evaluated the use of 18F-FDG PET/CT imaging before subsequent radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC), as recommended by National Comprehensive Cancer Network guidelines, and whether the use of this imaging modality impacts cancer-specific survival. Methods: This was a retrospective study of the National Cancer Institute's Surveillance, Epidemiology, and End Results program of Medicare-linked data in patients with NSCLC. Hazard ratios and 95% CIs for overall and cancer-specific survival were estimated for patients diagnosed between 2006 and 2015 who underwent either 18F-FDG PET/CT-based or CT-based imaging before subsequent RT. Results: Significant improvement in cancer-specific survival was found in patients who underwent 18F-FDG PET/CT imaging before subsequent RT, compared with those who underwent CT (hazard ratio, 1.43 [95% CI, 1.32-1.55; P < 0.0001]). Although the National Comprehensive Cancer Network recommends 18F-FDG PET/CT before subsequent RT, 43.6% of patients were imaged with CT alone. Conclusion: Many patients with NSCLC are not being imaged according to national guidelines before subsequent RT, and this omission is associated with a lower cancer-specific survival.