Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment 'high' vs. 'low' C11-AMT SUVmax of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.

The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer - defining a new treatment option for older vulnerable patients.

INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no treatment guidelines for OA with metastatic pancreatic cancer (mPCA) and selecting a chemotherapy regimen for these patients is subjective, based largely on chronologic age and performance status (PS). Geriatric screening tools provide a more objective and accurate evaluation of a patient's overall health but have not yet been validated in patient selection for mPCA treatment. This study aims to elucidate the optimal chemotherapy treatment of vulnerable OA with mPCA and understand the geriatric factors that affect outcomes in this population. METHODS/DESIGN: The GIANT (ECOG-ACRIN EA2186) study is multicenter, randomized phase II trial enrolling patients over age 70 with newly diagnosed mPCA. This study utilizes a screening geriatric assessment (GA) which characterizes patients as fit, vulnerable, or frail. Patients with mild abnormalities in functional status and/or cognition, moderate comorbidities, or over age 80 are considered vulnerable. Enrolled patients are randomized to one of two dose-reduced treatment regimens (gemcitabine/nab-paclitaxel every other week, or dose-reduced 5-fluoruracil (5FU)/ liposomal irinotecan (nal-IRI) every other week). GA and quality of life (QoL) evaluations are completed prior to treatment initiation and at each disease evaluation. Overall survival (OS) is the primary endpoint, with secondary endpoints including progression free survival (PFS) and objective response rate (ORR). Enrolled patients will be stratified by age (70-74 vs ≥75) and ECOG PS (0-1 vs 2). Additional endpoints of interest for OA include evaluation of risk factors identified through GA, QoL evaluation, and toxicities of interest for older adults. Correlative studies include assessment of pro-inflammatory biomarkers of aging in the blood (IL-6, CRP) and imaging evaluation of sarcopenia as predictors of treatment tolerance. DISCUSSION: The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population. TRIAL REGISTRATION: This trial is registered with ClinicalTrial.gov Identifier NCT04233866.

18F-FDG-PET/CT Imaging for Gastrointestinal Malignancies.

Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.

Tumor protein p53 mutation in archived tumor samples from a 12-year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long-term survival with DeltaRex-G: A case report and literature review.

DeltaRex-G is a replication-incompetent amphotropic murine leukemia virus-based retroviral vector that displays a collagen-matrix-targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal 'dominant negative', i.e. a truncated construct of the executive cyclin G1 (CCNG1) oncogene. DeltaRex-G inhibits the CCNG1 function of promoting cell competence and survival through the commanding CCNG1/cyclin-dependent kinase (CDK)/Myc/mouse double minute 2 homolog (Mdm2)/p53 axis. In 2009, DeltaRex-G was granted Fast Track designation from the US Food and Drug Administration for the treatment of pancreatic cancer. In 2019, the results of a phase 1/2 study that used DeltaRex-G as monotherapy for stage 4 chemotherapy-resistant pancreatic ductal adenocarcinoma (PDAC) were published. A unique participant of the aforementioned phase 1/2 study is now an 84-year-old Caucasian woman with chemoresistant PDAC who was treated with DeltaRex-G, 3x1011 colony forming units (cfu)/dose, 3 times/week for 4 weeks with a 2-week rest period, for 1.5 years. During the treatment period, the patient's tumors in the liver, lymph node and peritoneum exhibited progressive decreases in size, which were accompanied by a reduction and normalization of serum carbohydrate antigen 19-9 levels, and the patient achieved complete remission after 8 months of DeltaRex-G therapy with minimal side effects (grade 2 fatigue). Henceforth, the patient has been in remission for 12 years with no evidence of disease, no late therapy-related adverse events, and no further cancer therapy following DeltaRex-G treatment. The present study reports a mutation of tumor protein p53 (TP53) (G199V) found retrospectively in the patient's archived tumor samples. TP53 is a well-characterized tumor suppressor gene, and a critical regulatory component of the executive CCNG1/CDK/Myc/Mdm2/p53 axis, which regulates proliferative cell competence, DNA fidelity and survival. Studies are underway to determine whether TP53 mutations in pancreatic cancer can help identify a subset of patients with advanced metastatic cancer with an otherwise poor prognosis who would respond favorably to DeltaRex-G, which would broaden the treatment options for patients with otherwise lethal PDAC.

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series.

ABSTRACT: Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are ß-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary ß-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.

Implementation of a Hepatic Artery Infusion Program: Initial Patient Selection and Perioperative Outcomes of Concurrent Hepatic Artery Infusion and Systemic Chemotherapy for Colorectal Liver Metastases.

BACKGROUND: Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program. METHODS: The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%. CONCLUSION: Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.

PURPOSE: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. METHODS AND MATERIALS: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). RESULTS: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. CONCLUSIONS: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.

Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC).

INTRODUCTION: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. PATIENTS AND METHODS: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). RESULTS: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. CONCLUSIONS: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.

Molecular Imaging and Therapy for Neuroendocrine Tumors.

OPINION STATEMENT: Neuroendocrine tumors (NETs) are relatively rare, with 12,000-15,000 new cases diagnosed annually in the USA. Although NETs are a diverse group of neoplasms, they share common molecular targets that can be exploited using nuclear medicine techniques for both imaging and therapy. NETs have traditionally been imaged with SPECT imaging using 111In-labeled octreotide analogs to detect neoplasms with somatostatin receptors. In addition, certain NETs (pheochromocytomas, paragangliomas, and neuroblastomas) are also effectively imaged using 123I- or 131I-labeled metaiodobenzylguanidine (MIBG), an analog of guanethidine. More recently, PET imaging with 68Ga-labeled somatostatin receptor (SSR) analogs allows neuroendocrine tumors to be imaged with much higher sensitivity. 68Ga-DOTATATE was approved as a PET tracer by the FDA in June 2016. In addition to imaging, both MIBG and DOTATATE can be labeled with therapeutic radionuclides to deliver targeted radiation selectively to macroscopic and microscopic tumor sites. The incorporation of the same molecular probe for imaging and therapy provides a radio-theranostic approach to identifying, targeting, and treating tumors. Over the years, several centers have experience treating NETs with high-dose 131I-MIBG. 177Lu-DOTATATE was approved by the FDA in 2018 for treatment of gastroenteropancreatic NETs and constitutes a major advancement in the treatment of these diseases. In this paper, we provide an overview of imaging and treating neuroendocrine tumors using MIBG and SSR probes. Although uncommon, neuroendocrine tumors have provided the largest experience for targeted radionuclide imaging and therapy (with the exception of radioiodine treatment for thyroid disease). In addition to benefitting patients with these rare tumors, the knowledge gained provides a blueprint for the development of future paired diagnostic/therapeutic probes for treating other diseases, such as prostate cancer.

Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates at Multiple Centers.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A "design, measure, analyze, improve, and control" quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers' aggregated baseline infiltration rate was 6.2% (range, 2%-16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% (P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates (P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important.

Changes on Midchemoradiation Therapy Fluorodeoxyglucose Positron Emission Tomography for Cervical Cancer Are Associated with Prognosis.

PURPOSE: To assess whether radiographic and metabolic changes on midchemoradiation therapy (CRT) fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for cervical cancer predict outcome. METHODS AND MATERIALS: Women with International Federation of Gynecology and Obstetrics stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy were enrolled on a single-institution prospective clinical trial; FDG-PET/CT was obtained before CRT and at 30 to 36 Gy. Max and mean standard uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling and competing risk analysis. RESULTS: Thirty women were enrolled from 2012 to 2016. After a median follow-up of 24 months, 2-year rates of OS, DFS, DM, NR, and CR were 68% (95% confidence interval [CI], 51%-85%), 44% (95% CI, 26%-63%), 42% (95% CI, 23%-59%), 14% (95% CI, 4%-30%), and 10% (95% CI, 2%-24%), respectively. Intra-PET metrics and TLG across all PET scans were most consistently associated with OS, DFS, DM, and NR on univariate analysis. Intra-CRT TLG was associated with OS (hazard ratio [HR] 1.35; 95% CI, 1.15-1.55; P = .001), DFS (HR 1.19; 95% CI, 1.04-1.34; P = .018), and NR (HR 1.25; 95% CI, 1.10-1.40; P = .002). No absolute or relative changes between parameters of baseline and mid-CRT FDG-PET/CT were associated with disease outcomes on univariate analysis, with the exception of relative change in mean standard uptake values and CR (P = .004). CONCLUSIONS: In this group of patients with high-risk cervical cancer treated with CRT and brachytherapy, TLG and metabolic tumor volume on intra-CRT FDG-PET/CT was associated with OS. These metrics may provide an early signal for selective treatment intensification with either dose escalation or adjuvant chemotherapy.

Visual and semiquantitative analysis of 82Rb uptake in malignant tumors on PET/CT: first systematic analysis.

OBJECTIVE: The objective of this study was to analyze the uptake of rubidium in malignant tumors. PARTICIPANTS AND METHODS: Sixteen malignant lesions were included. Two radiologists compared each lesion to four references (subcutaneous fat, lung, mediastinal blood pool, and liver) at rest and stress and scored as 1-4. Maximum standardized uptake value (SUV) in each lesion and four references, as well as ratios of lesion SUV to SUV of each of the references, were calculated at rest and stress. We assessed an agreement for scores of reader 1 versus reader 2 (inter-reader) at rest and stress, scores at rest versus stress (intrapatient) for reader 1 and reader 2, and lesion SUV and respective ratios at rest and stress using paired t-test and Bland-Altman analyses. RESULTS: Fifteen (94%) out of 16 lesions had a score of 3 or 4 at rest or stress or both by at least one reviewer. We did not find evidence of inter-reader bias at rest or stress or intrapatient (rest vs. stress) bias for either reader. SUV ranged from 1.0 to 8.1 at rest and from 0.7 to 6.7 at stress. There was an excellent agreement between ratios of lesion SUV to lung SUV at rest versus stress. On the extreme, there was a poor agreement between ratios of lesion SUV to liver SUV at rest versus stress. Otherwise, the agreement was good for the majority of the results, and moderate for a few others. CONCLUSION: Malignant tumors can be readily depicted and quantified on rubidium PET/CT. Further research is needed.

Predictors of Survival in 211 Patients with Stage IV Pulmonary and Gastroenteropancreatic MIBG-Positive Neuroendocrine Tumors Treated with 131I-MIBG.

This retrospective analysis identifies predictors of survival in a cohort of patients with meta-iodobenzylguanidine (MIBG)-positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with 131I-MIBG therapy, to inform treatment selection and posttreatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from 211 P/GEP-NET patients treated with 131I-MIBG between 1991 and 2014. For patients with CT follow-up (n = 125), imaging response was assessed by RECIST 1.1 if images were available (n = 76) or by chart review of the radiology report if images could not be reviewed (n = 49). Kaplan-Meier analysis and Cox multivariate regression estimated survival and progression-free survival benefits predicted by initial imaging, biochemical response, and symptomatic response. Results: All patients had stage IV disease at the time of treatment. Median survival was 29 mo from the time of treatment. Symptomatic response was seen in 71% of patients, with the median duration of symptomatic relief being 12 mo. Symptomatic response at the first follow-up predicted a survival benefit of 30 mo (P < 0.001). Biochemical response at the first clinical follow-up was seen in 34% of patients, with stability of laboratory values in 48%; response/stability versus progression extended survival by 40 mo (P < 0.03). Imaging response (20% of patients) or stability (60%) at the initial 3-mo follow-up imaging extended survival by 32 mo (P < 0.001). Additionally, multiple 131I-MIBG treatments were associated with 24 mo of additional survival (P < 0.05). Conclusion: Therapeutic 131I-MIBG for metastatic P/GEP-NETs appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up help prognosticate expected survival after 131I-MIBG therapy. Multiple rounds of 131I-MIBG are associated with prolonged survival.

Pitfalls of post-treatment PET after de-intensified chemoradiotherapy for HPV-associated oropharynx cancer: Secondary analysis of a phase 2 trial.

OBJECTIVES: We evaluated patterns of nodal response and positive predictive value (PPV) of 3 month post-treatment PET in patients with HPV-associated oropharyngeal cancer treated on a multi-institutional de-intensification trial. MATERIALS AND METHODS: Eligibility criteria included: (1) T0-3, N0-2c, M0, (2) HPV+/p16+ oropharyngeal squamous cell carcinoma, and (3) ≤10 pack-years smoking or ≤30 pack-years and abstinent ≥5 years. Patients received 60 Gy radiation alone (T0-2, N0-1) or with concurrent weekly cisplatin 30 mg/m2 and surveillance PET three months post-radiation. Nodal responses were categorized as complete (CR), equivocal (ER), or incomplete (IR) using both local and central radiographic review. A "true positive" was ER/IR with clinical/radiographic progression or positive pathology. RESULTS: 79 node-positive pts (84% N2) were analyzed. Distribution of nodal CR, ER, and IR was 44 (56%), 27 (34%), and 8 (10%), respectively. 29 (37%) had ER/IR in pre-treatment node-positive neck levels, whereas 14 (18%) had ER/IR in pre-treatment node-negative levels. Of patients with ER/IR, 5 were observed clinically, 19 received repeat imaging, and 11 received either biopsy (1) or neck dissection (10). The PPV was 9% for ER/IR and 13% for IR, with 3 patients found to have persistent disease on neck dissection. There was no difference in nodal relapse rate in patients with nodal CR vs. nodal ER/IR. CONCLUSION: Post-treatment PET may not accurately predict the presence of persistent disease in patients with favorable-risk oropharynx cancer. These results support close surveillance rather than surgical evaluation in most favorable-risk patients.

Early cardiac perfusion defects after left-sided radiation therapy for breast cancer: is there a volume response?

PURPOSE: Cardiac single-photon emission computed tomography (SPECT) is often used to identify defects in myocardial perfusion due to atherosclerotic coronary artery disease. It was also used in studies to evaluate radiation therapy (RT)-associated cardiac abnormalities. In the current review, we aim to evaluate the rates of post-RT cardiac SPECT early perfusion abnormalities and relate this to the irradiated left ventricular volume. METHODS: The studies cited in this systematic review were identified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: Six studies between 1996 and 2016 fulfilled the inclusion criteria. The reported perfusion defects in these studies were seen in the apical and anterolateral aspects of the left ventricle. Three studies show correlation between the percent of the left ventricle within the RT-field and percent of patients with early perfusion defects on cardiac SPECT. In two studies that used cardiac sparing techniques (such as deep inspiration), that resulted in a low mean heart dose, no perfusion defects were noted. CONCLUSIONS: Data suggest that incidental irradiation of the heart in cases of left breast/chest wall RT can result in early post-RT perfusion defects on cardiac SPECT. There appears to be strong dose/volume dependence to the risk, and hence techniques to reduce cardiac exposure are recommended.

Integration of PET/MR Hybrid Imaging into Radiation Therapy Treatment.

Hybrid PET/MR imaging is in early development for treatment planning. This article briefly reviews research and clinical applications of PET/MR imaging in radiation oncology. With improvements in workflow, more specific tracers, and fast and robust acquisition protocols, PET/MR imaging will play an increasingly important role in better target delineation for treatment planning and have clear advantages in the evaluation of tumor response and in a better understanding of tumor heterogeneity. With advances in treatment delivery and the potential of integrating PET/MR imaging with research on radiomics for radiation oncology, quantitative and physiologic information could lead to more precise and personalized RT.

Utility of Deep Inspiration Breath Hold for Left-Sided Breast Radiation Therapy in Preventing Early Cardiac Perfusion Defects: A Prospective Study.

PURPOSE: To evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH). METHODS AND MATERIALS: We performed a prospective single-institution single-arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (± internal mammary nodes). The DIBH was done by use of a controlled surface monitoring technique (AlignRT, Vision RT Ltd, London, UK). The RT was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall motion changes were assessed by pre-RT and 6-month post-RT SPECT scans. A cumulative SPECT summed-rest score was used to quantify perfusion in predefined left ventricle segments. The incidence of wall motion abnormalities was assessed in each of these same segments. RESULTS: A total of 20 patients with normal pre-RT scans were studied; their median age was 56 years (range, 39-72 years). Seven (35%) patients also received irradiation to the left internal mammary chain, and 5 (25%) received an additional RT field to supraclavicular nodes. The median heart dose was 94 cGy (range, 56-200 cGy), and the median V25Gy was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities. CONCLUSIONS: Our results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.