Shyam Srinivas

Comparative Analysis of the Safety and Efficacy of Transcatheter Arterial Chemoembolization and Yttrium-90 Radioembolization in Patients with Unresectable Hepatocellular Carcinoma

PURPOSE To compare retrospectively the safety and efficacy of yttrium-90 ((90)Y) radioembolization with the safety and efficacy of chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Survival and complication rates were evaluated for patients with HCC who underwent chemoembolization or radioembolization at a single institution between August 2007 and April 2010. Complications were graded according to a standardized grading system for embolization procedures. Survival was determined via the Kaplan-Meier method, and multivariable analysis for factors affecting survival was performed. RESULTS This study included 73 patients with HCC who underwent index embolization with radioembolization (n = 38; 52.1%) or chemoembolization (n = 35; 47.9%). The two patient populations were similar in terms of demographics, etiology of cirrhosis, functional status, tumor characteristics, Child-Pugh class, previous liver-directed therapy, and number of patients with bilirubin > 2.0 mg/dL. There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (P = .33). Postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates in these patients. The rates of other complications and rehospitalization were similar between groups. Increased age, Child-Pugh class B, hepatitis seropositivity, bilobar tumor distribution, tumor vascular invasion, and presence of extrahepatic metastases were associated with reduced patient survival. CONCLUSIONS Patients treated with radioembolization did not show a survival advantage over patients treated with chemoembolization. However, patients who underwent chemoembolization had significantly higher rates of hospitalization as a result of postembolization syndrome.

MAXIMUM STANDARDIZED UPTAKE VALUE FROM STAGING FDG-PET/CT DOES NOT PREDICT TREATMENT OUTCOME FOR EARLY-STAGE NON-SMALL-CELL LUNG CANCER TREATED WITH STEREOTACTIC BODY RADIOTHERAPY

PURPOSE To perform a retrospective review to determine whether maximum standardized uptake values (SUV(max)) from staging 2-deoxy-2- [(18)F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) studies are associated with outcomes for early-stage non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Seventy-two medically inoperable patients were treated between October 17, 2003 and August 17, 2007 with SBRT for T1-2N0M0 NSCLC. SBRT was administered as 60 Gy in 3 fractions, 50 Gy in 5 fractions, or 50 Gy in 10 fractions using abdominal compression and image-guided SBRT. Cox proportional hazards regression was performed to determine whether PET SUV(max) and other variables influenced outcomes: mediastinal failure (MF), distant metastases (DM), and overall survival (OS). RESULTS Biopsy was feasible in 49 patients (68.1%). Forty-nine patients had T1N0 disease, and 23 had T2N0 disease. Median SUV(max) was 6.55 (range, 1.5-21). Median follow-up was 16.9 months (range, 0.1-37.9 months). There were 3 local failures, 8 MF, 19 DM, and 30 deaths. Two-year local control, MF, DM, and OS rates were 94.0%, 10.4%, 30.1%, and 61.3%, respectively. In univariate analysis, PET/CT SUV(max), defined either as a continuous or dichotomous variable, did not predict for MF, DM, or OS. On multivariable analysis, the only predictors for overall survival were T1 stage (hazard ratio = 0.331 [95% confidence interval, 0.156-0.701], p = 0.0039) and smoking pack-year history (hazard ratio = 1.015 [95% confidence interval, 1.004-1.026], p = 0.0084). CONCLUSIONS Pretreatment PET SUV(max) did not predict for MF, DM, or OS in patients treated with SBRT for early-stage NSCLC.

Determination of whole-body metabolic burden as a quantitative measure of disease activity in lymphoma: a novel approach with fluorodeoxyglucose-PET.

Background and objectivesCurrently, there is no definite consensus regarding the best index to assess disease activity with fluorodeoxyglucose-PET imaging. Maximum standardized uptake value (SUVmax) is most frequently used in day-to-day practice for this purpose. This approach very often reflects the metabolic activity of only a small sample of the total ongoing process in the entire body. Here we introduce a new concept called metabolic burden (MB) to measure disease activity in cancer patients. Materials and methodsMB was calculated by measuring the volume (VCT) around a lesion that appeared on computed tomography (CT), the mean SUV that appeared on PET of the CT volume (SUVmean CT), and the recovery coefficient (RC) using the following formula:If CT was unavailable, a region of interest (ROI) around the lesion was defined by a 40% SUVmax threshold and the volume and SUVmean were determined for that ROI. The whole-body metabolic burden (WBMB) was calculated as the sum of the individual MBs of all the lesions identified. We retrospectively reviewed 19 patients with non-Hodgkins lymphoma who were treated with commercially available anti-CD20 radioimmunotherapy agents or conventional chemotherapy. All had a pretreatment and posttreatment fluorodeoxyglucose-PET and CT scan within 1–3 months of receiving systemic therapy. Either abnormal areas appearing on PET alone or corresponding lesions on CT were used to calculate the tumor volume (TV). Nodes of less than 2 cm occurring in clusters were grouped together into a single ROI. Thirty-eight regional collections in 14 patients were found in combined pretreatment and posttreatment studies and were assessed. The TVs varied in pretreatment size from 5.8 to 857 cm3 and posttreatment from 0 to 81 cm3. Pretreatment WBMB varied from 27 to 10 218 cm3 and posttreatment from 0 to 279 cm3. We then compared the standard indices of SUVmean and SUVmax with those of WBMB to determine which of the indices would have the best sensitivity as a predictor of therapeutic response. ResultsFive of the 19 patients had a complete response. In 14 patients with partial response, the average change in WBMB was 80%, the TV decreased by 76%, the SUVmax decreased by 42%, and the SUVmean decreased by 38.5%. ConclusionThe results of this analysis demonstrate that measurement of WBMB may prove to be superior to the existing methods in assessing and managing patients with non-Hodgkins lymphoma. This index may be the best way to monitor the changes in WBMB as a patient is undergoing treatment.

Comparison of diffuse optical tomography of human breast with whole‐body and breast‐only positron emission tomography

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization 90Y PET

Background: Radioembolization with Yttrium-90 (90 Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment 90 Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of 90 Y delivered to liver and treated tumors. Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres®) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). 90 Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90–120 Gy; range 0–570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60–70 Gy; range 10–120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). Conclusion: Our cohort of patients showed a possible dose–response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose that the tumor or normal liver received.

Role of positron emission tomography in management of sinonasal neoplasms—a single institution's experience

OBJECTIVE The objective of the study is to examine the utility of positron emission tomography (PET) for staging and restaging after treatment of paranasal sinus carcinomas. STUDY DESIGN Retrospective data review was done. SUBJECTS AND METHODS Patients selected underwent PET for sinonasal neoplasms from 2003 to 2008 at a tertiary care referral center. RESULTS Seventy-seven scans were reviewed from 31 patients. The pathologies included olfactory neuroblastoma (n = 9), squamous cell carcinoma (n = 6), sinonasal undifferentiated carcinoma (n = 6), sinonasal melanoma (n = 6), and minor salivary gland carcinomas (n = 4). The positive predictive value of studies performed for restaging at the primary, neck, and distant sites were 56%, 54%, and 63%; negative predictive values were 93%, 100%, and 98%, respectively. During restaging, 32% of patients were accurately upstaged secondary to neck or distant site involvement. CONCLUSION Positron emission tomography serves as a useful adjunct to conventional imaging in the management of sinonasal malignancies. Negative studies are effective in predicting absence of disease as seen in the consistently high-negative predictive values. Positive studies need to be viewed cautiously given the high rate of false-positive studies. When viewed in conjunction with clinical examination, endoscopic assessment, and focused biopsies, they may effectively result in a more accurate assessment of the extent of disease.

Nontargeted Y-90 microsphere radioembolization to duodenum visualized on Y-90 PET/CT and Bremsstrahlung SPECT/CT.

Yttrium-90 (Y-90) radioembolization has emerged as a new method for treatment of unresectable hepatic tumors. We present interesting imaging findings of extrahepatic Y-90 activity in the duodenum on Y-90 PET/CT and Bremsstrahlung SPECT/CT, after injection of radiomicrospheres into the right hepatic artery. This is the first reported case of nontargeted embolization of Y-90 microspheres to duodenum visualized post-therapy on both Y-90 PET/CT and Bremsstrahlung SPECT/CT.

Use of lymphoscintigraphy in radiation treatment of primary breast cancer in the context of lymphedema risk reduction

PURPOSE The goal of this study was to determine the feasibility of SPECT/CT scintigraphic method for mapping lymphatic drainage for radiation therapy of breast cancer. MATERIALS AND METHODS Thirty-six patients were enrolled in a SPECT/CT lymphoscintigraphy study. (99m)Tc sulfur colloid (1mCi) was injected intradermally in the ipsilateral arm. After 5-8h post-injection, the SPECT/CT scans were taken and analyzed on a GE eNTRGRA system. The SPECT/CT images were co-registered in the treatment planning system (TPS). The original treatment plan was recreated for nodal dosimetry. Intensity modulated radiation therapy (IMRT) planning was performed for reducing lymph node dose for reducing arm lymphedema. RESULTS The number of lymph nodes varied from 0 to 10 with a mean value of 3.4±5.4 nodes. The location of nodes varied in the axillary, supraclavicular, and breast regions depending upon the surgical procedure and the extent of the disease. The prescribed radiation dose to the breast varied from 45 to 50.4Gy depending on the disease pattern in 32 evaluated patients having CT data. The dose to lymph nodes varied from 0 to 61.8Gy depending upon the location and the radiation technique used. SPECT/CT study in conjunction with IMRT plan showed that it is possible to decrease nodal dose and thereby potentially reduce the risk of developing arm lymphedema. CONCLUSIONS The SPECT/CT device provides a novel method to map the lymph nodes in the radiation treatment fields that could be used to tailor the radiation dose.

Administered activity and outcomes of glass versus resin 90 Y microsphere radioembolization in patients with colorectal liver metastases

BACKGROUND Given the differences in size, specific activity, and dosing methods for glass yttrium-90 microspheres ((90)Y-glass) and resin (90)Y microspheres ((90)Y-resin), these therapies may expose the liver to different amounts of radiation, thereby affecting their efficacy and tolerability. We aimed to compare the prescribed activity of (90)Y-glass and (90)Y-resin for real-world patients undergoing selective internal radiation therapy (SIRT) for liver-dominant metastatic colorectal cancer (mCRC) and to assess efficacy and safety outcomes in these patients. METHODS We examined the records of 28 consecutive patients with unresectable colorectal liver metastases treated with SIRT between June 2008 and May 2011 at our institution. Using baseline CT and MR images, we calculated a projected activity as if we had used the other product and compared it to the actual prescribed activity of (90)Y-glass and (90)Y-resin for each SIRT treatment per manufacturer guidelines. Progression and adverse events were evaluated at follow up visits. Survival was analyzed by the Kaplan-Meier method. RESULTS For (90)Y-glass treatments with a mean prescribed (90)Y activity of 1.77 GBq, the mean projected (90)Y-resin activity was 0.84 GBq. For (90)Y-resin treatments with a mean prescribed (90)Y activity of 1.05 GBq, the mean projected (90)Y-glass activity was 2.48 GBq. The median survival was 9.3 months versus 18.2 months for (90)Y-glass and (90)Y-resin, respectively (P=0.292). During the second year after SIRT, the hazard ratio of death for patients treated with (90)Y-glass versus (90)Y-resin was 4.0 (95% CI: 1.3, 12.3; P=0.017). No significant difference in progression, adverse events or liver toxicity was observed. CONCLUSIONS Using manufacturer recommended guidelines, (90)Y-resin delivers significantly less activity than (90)Y-glass to patients with liver-dominant mCRC undergoing SIRT with no significant difference in adverse events and a trend toward improved survival.

Diffuse Optical Tomography and Positron Emission Tomography of Human Breast

We have acquired images of the breasts of four females with suspicious masses using Diffuse Optical Tomography and Positron Emission Tomography. The images are compared, and new types of contrast for cancer imaging are proposed.