DMSA-SPECT: A Novel Approach to Nephron Sparing SBRT for Renal Cell Carcinoma.

PURPOSE: Stereotactic body radiation therapy (SBRT) treatment planning for renal cell carcinoma requires accurate delineation of tumor from normal tissue due to the radiosensitivity of normal renal cortical tissue. Tc-99m dimercapto succinic acid (DMSA) renal imaging is a functional imaging technique that precisely differentiates normal renal cortical tissue from tumor. There are no prior publications reporting using this imaging modality for SBRT treatment planning. METHODS AND MATERIALS: A 59-year-old female with stage IV renal cell carcinoma progressed on systemic therapy and was dispositioned to primary cytoreduction with SBRT. She had baseline renal dysfunction and her tumor was 9 cm without clear delineation from normal tissue on conventional imaging. DMSA-single-photon emission computerized tomography (SPECT)/computed tomography (CT) was used for treatment planning. RESULTS: DMSA-SPECT/CT precisely delineated normal renal cortical tissue from tumor. Three months after treatment, labs were stable and DMSA-SPECT/CT was unchanged. The treated lesion had markedly decreased positron emission tomography avidity. CONCLUSIONS: DMSA-SPECT or SPECT/CT can be incorporated into radiation therapy planning for renal lesions to improve target delineation and better preserve renal function.

Electrical Impedance Characterization of in Vivo Porcine Tissue Using Machine Learning.

The incorporation of sensors onto the stapling platform has been investigated to overcome the disconnect in our understanding of tissue handling by surgical staplers. The goal of this study was to explore the feasibility of in vivo porcine tissue differentiation using bioimpedance data and machine learning methods. In vivo electrical impedance measurements were obtained in 7 young domestic pigs, using a logarithmic sweep of 50 points over a frequency range of 100 Hz to 1 MHz. Tissues studied included lung, liver, small bowel, colon, and stomach, which was further segmented into fundus, body, and antrum. The data was then parsed through MATLAB's classification learner to identify the best algorithm for tissue type differentiation. The most effective classification scheme was found to be cubic support vector machines with 86.96% accuracy. When fundus, body and antrum were aggregated together as stomach, the accuracy improved to 88.03%. The combination of stomach, small bowel, and colon together as GI tract improved accuracy to 99.79% using fine k nearest neighbors. The results suggest that bioimpedance data can be effectively used to differentiate tissue types in vivo. This study is one of the first that combines in vivo bioimpedance tissue data across multiple tissue types with machine learning methods.

Controversies in Tracheostomy for Patients With COVID-19: The When, Where, and How.

COVID-19 has impacted how we deliver care to patients, and much remains unknown regarding optimal management of respiratory failure in this patient population. There are significant controversies regarding tracheostomy in patients with COVID-19 related to timing, location of procedure, and technique. In this narrative review, we explore the recent literature, publicly available guidelines, protocols from different institutions, and clinical reports to provide critical insights on how to deliver the most benefit to our patients while safeguarding the health care force. Consensus can be reached that patients with COVID-19 should be managed in a negative-pressure environment with proper personal protective equipment, and that performing tracheostomy is a complex decision that should be made through multidisciplinary discussions considering patient prognosis, institutional resources, staff experience, and risks to essential health care workers. A broad range of practices exist because there is no conclusive guidance regarding the optimal timing or technique for tracheostomy.

T-cell lymphoma secondary to checkpoint inhibitor therapy.

BACKGROUND: Murine model suggests programmed cell death-1 (PD-1), an immune checkpoint not only plays role in tumor escape but is also a tumor suppressor for T-cells. But until, no reports of secondary T-cell lymphoma postuse of immune checkpoint inhibitors (ICIs) has been reported. Herein, we present a hitherto unreported phenomenon of secondary T-cell lymphoma when PD-1 inhibitor was used in a patient diagnosed with a tumor of epithelial origin. CASE REPORT: A man in mid-70s presented with biopsy-proven metastatic tumor of epithelial origin. Patient received carboplatin in combination with paclitaxel for four cycles leading to partial remission. The patient was subsequently switched to pembrolizumab due to persistent disease in the mediastinum. After four cycles of PD-1 inhibitor, patient presented with progression of disease and was diagnosed with biopsy-proven peripheral T-cell lymphoma-not otherwise specified. Based on the reported tumor suppressor function of PD-1 in murine models, we hypothesized that the use of PD-1 inhibitor caused clonal proliferation of abnormal T-cell clone leading to T-cell lymphoma. T-cell receptor (TCR) sequencing was performed by TCRß sequencing and T-cell clones from pre-ICI treatment specimen were compared with post-ICI treatment specimens. We show that one of the T-cell clones present in pre-ICI treatment specimen at a low frequency of had massive expansion to become most dominant clone in post-ICI treatment specimens leading to lymphoma. Moreover, targeted exome sequencing revealed a new TET2 mutation in the clone representing the lymphoma.Next, we retrospectively reviewed the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), the pharmacovigilance database from 2012 to 2018 to find the reported incidence of this phenomenon and calculated the reporting OR (ROR) for disproportionality analysis for risk of T-cell lymphoma due to checkpoint inhibitors compared with other drugs. In FAERS, the incidence of T-cell lymphoma post-ICIs (pembrolizumab, nivolumab and ipilimumab) was found to be 0.02% with 17% mortality. The ROR probability of risk of T-cell lymphoma compared with other drugs in pharmacovigilance database was increased at 1.91. CONCLUSIONS: T-cell lymphoma is a rare sequela of ICIs with high mortality. Larger studies with long-term follow-up of patients receiving ICIs is needed.

The utility of positron emission tomography/computed tomography in target delineation for stereotactic body radiotherapy for liver metastasis from primary gastric cancer: an illustrative case report and literature review.

The liver is a common site for metastatic disease for many cancers. Radiation therapy is one means of treatment for liver metastases, especially for patients unable to undergo surgery or ineligible for systemic chemotherapy. In particular, stereotactic body radiotherapy (SBRT) has become an important option in the treatment of metastatic disease in the liver. SBRT delivers ablative doses of radiation in relatively few fractions. As such, precise and clear imaging plays an important role in maximizing disease control while minimizing normal tissue toxicity. We present a case that highlights the importance of using multiple imaging modalities for target volume delineation in stereotactic radiation treatment of liver metastases.

Overcoming the challenges of characterizing normal urodynamic parameters in middle-aged and older women.

INTRODUCTION: To describe urodynamic study (UDS) findings in middle-aged and older women with various lower urinary tract symptoms (LUTS) who were found to have a normal study interpretation. MATERIALS AND METHODS: Following institutional review board approval, UDS tracings of non-neurogenic women who were tested for various LUTS and whose study was interpreted as normal were reviewed. Demographic data, indications for UDS, and UDS parameter findings were extracted. UDS was conducted according to an established protocol using a 6F dual-lumen catheter (ICS guidelines) with a Laborie system and interpreted with a pre-existing template to standardize each reading. The fill-void study was frequently repeated during the same UDS session to confirm normal findings. Study interpretation was done by a neutral reviewer with UDS expertise. RESULTS: From 2000-2012, 42 middle-aged women, who had been coded as having a normal study, were retrospectively reviewed from a database of over 2200 studies. The majority were Caucasian, with mean age 63 (range 42-85), mean body mass index 24.5 (20-37), mean parity 2 (0-4), and 67% were post-menopausal. Of the 42 patients, 28 underwent a second fill-void study. UDS findings were reported based on clinical indication for UDS: 1) incontinence, 2) pelvic organ prolapse, or 3) other LUTS symptoms. UDS findings were consistent between first and second studies. CONCLUSIONS: UDS parameters from a cohort of middle-aged and older women with normal findings could serve as reference values when interpreting urodynamic studies or for designing an age-comparable nomogram.

Impact of PET-CT on involved field radiotherapy design for pediatric Hodgkin lymphoma.

PURPOSE: To determine how the incorporation of PET-CT changes radiotherapy treatment in pediatric Hodgkin lymphoma. PROCEDURE: Fifty-three Hodgkin lymphoma patients with a median age of 14 years (6-21 years) underwent multiagent chemotherapy followed by involved field radiotherapy (IFRT) to initial sites of disease. All patients had conventional staging which included CT scan of the neck, chest, abdomen and pelvis, bone marrow biopsy ± MRI, Gallium scan and bone scan. All had an initial 18-F-fluoro-deoxy-D-glucose (FDG) PET-CT. When there was discordance between conventional staging and PET-CT staging, true sites of disease were determined either by biopsy or response to multiagent chemotherapy. RESULTS: In 19 of 53 (35.8%) patients, there was discordance between conventional staging and PET-CT findings. The most common location for the 23 sites of discordance were the spleen in 6 (26.1%), neck in 3 (13%), inguinal nodes in 3 (13%) and mediastinum in 3 (13%). A change in stage occurred in 5 (9.4%) as a result of PET-CT imaging. A change in IFRT fields occurred in 9 (17%); eight were more extensive while one was less extensive. For PET-CT, the specificity, sensitivity, positive predictive value and accuracy were 99.5%, 96.3%, 97.9%, and 98.9%. CONCLUSION: Incorporation of PET-CT information was found to influence IFRT design in 17% of patients, with most having more extensive radiotherapy fields.

Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study.

PURPOSE: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). MATERIALS AND METHODS: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 microg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. RESULTS: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 microg. When indocyanine green dosages were 10 microg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 microg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. CONCLUSION: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

Versatility of the Novalis system to deliver image-guided stereotactic body radiation therapy (SBRT) for various anatomical sites.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) programs to treat brain tumors were implemented when we first acquired the Brainlab Novalis system in 2003. Two years later, we started an extra-cranial stereotactic radio-ablation or more appropriately a stereotactic body radiation therapy (SBRT) program using the Brainlab Novalis image-guided system at The Methodist Hospital in Houston, Texas. We hereby summarize our initial experience with this system in delivering image-guided SBRT to a total of 80 patients during our first year of clinical implementation, from February 2005 to January 2006. Over 100 lesions in more than 20 distinct anatomical sites were treated. These include all levels of spine from cervical, thoracic, lumbar, and sacral lesions. Spinal lesions encompass intramedullary, intradural, extradural, or osseous compartments. Also treated were lesions in other bony sites including orbit, clavicle, scapula, humerus, sternum, rib, femur, and pelvis (ilium, ischium, and pubis). Primary or metastatic lesions located in the head and neck, supraclavicular region, axilla, mediastinum, lung (both central and peripheral), abdominal wall, liver, kidney, para-aortic lymph nodes, prostate, and pelvis were also treated. In addition to primary radiotherapy, SBRT program using the Brainlab Novalis system allows re-irradiation for recurrence and "boost" after conventional treatment to various anatomical sites. Treating these sites safely and efficaciously requires knowledge in radiation tolerance, fraction size, total dose, biologically equivalent dose (BED), prior radiotherapy, detailed dose volume histograms (DVH) of normal tissues, and the radiosensitive/radioresistant nature of the tumor. Placement of radio-opaque markers (Visicoil, Radiomed) in anatomical sites not in close proximity to bony landmarks (e.g., kidney and liver) helps in measuring motion and providing image guidance during each treatment fraction. Tumor/organ motion data obtained using 4D-CT while the patient is immobilized in the body cast aids in planning treatment margin and determining the need for respiratory motion control, e.g., abdominal compressor, gating, or active breathing control. The inclusion of PET/CT to the Brainlab treatment planning system further refines the target delineation and possibly guides differential fraction size prescription and delivery. The majority of the patients tolerated the SBRT treatment well despite the longer daily treatment time when compared to that of conventional treatment. All patients achieved good pain relief after SBRT. Compared to conventional standard radiotherapy of lower daily fraction size, we observed that the patients achieved faster pain relief and possibly more durable symptom control. Very high local control with stable disease on imaging was observed post SBRT. Our initial experience shows that the Brainlab Novalis system is very versatile in delivering image-guided SBRT to various anatomical sites. This SBRT approach can be applied to either primary or metastatic lesions in the primary, "boost," or re-irradiation settings. The understanding of fraction size, total dose, BED, and DVH of normal tissues is very important in the treatment planning. Appropriate use of immobilization devices, radio-opaque markers for image-guidance, 4D-CT for tumor/organ motion estimates, and fusion of planning CT scans with biological/functional imaging will further improve the planning and delivery of SBRT, hopefully leading to better treatment outcome.

Can [18F]fluorodeoxyglucose positron emission tomography imaging complement biopsy results from the iliac crest for the detection of bone marrow involvement in patients with malignant lymphoma?

OBJECTIVES: To assess the usefulness of [18F]fluorodeoxyglucose positron emission tomography in the detection of bone marrow involvement in malignant lymphoma, and its impact in clinical management. METHODS: One hundred and six consecutive patients with a confirmed diagnosis of lymphoma, referred for staging or restaging of Hodgkin's lymphoma (n=18) or non-Hodgkin's lymphoma (n=88), were reviewed retrospectively. A positron emission tomography scan and bone marrow biopsy of the iliac crest were performed in all patients. The assessment of bone marrow involvement by lymphoma was confirmed by histology and/or progression of bone marrow lesions in clinical follow-up. RESULTS: In 28 of 106 patients, bone marrow involvement was found. Positron emission tomography was more sensitive (86%) than bone marrow biopsy (57%). Positron emission tomography and bone marrow biopsy were concordant by positive correlation in 12 of 28 cases (43%) and by negative correlation in 77 of 78 cases (99%). Ten cases of non-Hodgkin's lymphoma and two cases of Hodgkin's lymphoma with positive positron emission tomography results and an initial negative bone marrow biopsy showed clinical progression of the bone marrow lesions and/or subsequent positive histology. These were considered as false-negative results for bone marrow biopsy. In seven of the 12 positive cases with negative bone marrow biopsy, positron emission tomography uptake distant from the site of the biopsy was seen. In four cases of follicular lymphoma, the bone marrow biopsy was positive and the positron emission tomography scan was normal. CONCLUSIONS: Positron emission tomography and bone marrow biopsy are complementary in assessing the presence of bone marrow involvement in patients with malignant lymphoma. In our series, positron emission tomography was more sensitive than bone marrow biopsy in Hodgkin's and non-Hodgkin's lymphoma, except in follicular lymphoma.

Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner.

INTRODUCTION: Fully three-dimensional (3-D) reconstruction algorithms have the potential to better utilize PET data acquired in true 3-D acquisition modes, as compared to 2-D approaches involving data reduction through rebinning procedures followed by a 2-D or 2.5-D reconstruction. Our previous studies, involving simulated and real phantom data from PET scanners working purely in 3-D acquisition mode, showed that the fully 3-D reconstruction approaches bring appreciable improvement on physical measures and visual image quality as well. Reconstruction procedures utilized in those studies were based upon the row action maximum likelihood algorithm (RAMLA) implemented on our clinical scanners. The purpose of this study was to investigate if the fully 3-D RAMLA reconstruction software brings an appreciable improvement in clinical image quality and reader confidence. MATERIALS AND METHODS: Ninety patient scans acquired on the Philips CPET scanner at our institution were reconstructed using 2.5-D RAMLA and 3-D RAMLA with differing reconstruction parameters. These scans were blindly presented to four experienced PET scan readers who graded various aspects of image quality. RESULTS: Our study concluded that 3-D RAMLA on the CPET scanner reduces artifacts and image noise and improves clinical confidence in interpreting PET images. CONCLUSION: This study led to the routine use of 3-D RAMLA reconstruction on the CPET scanner at our institution.

Is 18F-FDG PET more accurate than standard diagnostic procedures in the detection of suspected recurrent melanoma?

UNLABELLED: The aim of this study was to determine the accuracy of (18)F-FDG PET in detecting recurrent melanoma. METHODS: PET findings were compared with those obtained by standard diagnostic clinical procedures (CP) to establish the role of PET in the management of patients with melanoma. From 156 patients with confirmed melanoma and recurrence suspected by clinical examination, 184 PET scans were retrospectively reviewed. Histology or clinical follow-up was used for final diagnosis. RESULTS: The sensitivity and specificity of PET for detecting lesions on an individual-patient basis were 74% and 86%, respectively, compared with respective values of 58% and 45% for CP alone. The overall accuracy for PET was 81%, compared with 52% for other methods. PET was more accurate (91% vs. 67%) than CP in detecting locoregional disease and distant metastases (85% vs. 55%), and PET results led to a change in the planned clinical management of 36% of patients included in this study. PET was more accurate than CT in detecting skin lesions, malignant lymph nodes, and metastases to the abdomen, liver, and bone. In the assessment of pulmonary disease, PET showed higher specificity (92% vs. 70%) than CT for the detection of lung parenchyma lesions; however, the sensitivity was better for CT (93%) than for PET (57%). CONCLUSION: PET is better than CP in detecting locoregional disease and distant metastases in all sites except the lung, where it appears to be a useful adjunct to CT. The use of PET as a routine clinical tool can lead to a substantial change in the clinical management of suspected recurrent melanoma.

Roles of positron emission tomography with fluorine-18-deoxyglucose in the detection of local recurrent and distant metastatic sarcoma.

Sarcomas are a heterogeneous group of tumors comprising approximately 1% of all malignancies. Definitive treatment of sarcoma is surgical resection. However, after surgical removal, 40% to 60% of the patients will develop local or distant recurrence. Therefore, the early detection and treatment of recurrence is an important part of modern sarcoma therapy. Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) has been highly successful in detecting and staging a variety of malignancies. However, its use in the management of patients with sarcoma is less defined. The purpose of our study was to assess the potential roles of FDG-PET in the detection of local recurrence and distant metastases. In this retrospective study, the images of 33 FDG-PET scans, reports of 29 computed tomography (CT) scans, and 8 magnetic resonance imaging (MRI) scans from 28 patients were compared with surgical pathology or clinical follow up for at least 6 months. FDG-PET detected all 25 cases of local and distant recurrences with 100% sensitivity. CT was able to detect 18 of the 22 possible cases of recurrent disease, whereas MRI was able to detect 5 of 7 cases of recurrent disease. PET was particularly useful in patients with extensive histories of surgery and radiation therapy, precisely the setting in which CT and MRI have the lowest specificity and sensitivity. In conclusion, FDG-PET was a sensitive test to detect local and distant recurrences of sarcoma and this warrants further investigation.

Potential false-positive FDG PET imaging caused by subcutaneous radiotracer infiltration.

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been useful in the management of a variety of malignancies with high accuracy. However, numerous nonmalignant lesions can also result in increased FDG accumulation and consequently may cause potential false-positive interpretation if the causes are not recognized. A single focus of FDG accumulation in the axilla can often easily be attributed to tracer infiltration when the injection was on the same side. However, multiple foci of FDG uptake can be similar to malignant lesions. A case is presented in which the follow-up study clarified the nature of multifocal increased FDG uptake in the axilla.