Sanjana Ballal

SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone

ObjectiveTo assess the patient radiation dose during routine clinical single-photon emission computed tomography-computed tomography (SPECT-CT) and measure the increase as compared with SPECT alone. Materials and methodsData pertaining to 357 consecutive patients who had undergone radioisotope imaging along with SPECT-CT of a selected volume were retrospectively evaluated. Dose of the injected radiopharmaceutical (MBq) was noted, and the effective dose (mSv) was calculated as per International Commission on Radiological Protection (ICRP) guidelines. The volume-weighted computed tomography dose index (CTDIvol) and dose length product of the CT were also assessed using standard phantoms. The effective dose (mSv) due to CT was calculated as the product of dose length product and a conversion factor depending on the region of investigation, using ICRP guidelines. The dose due to CT was compared among different investigations. The increase in effective dose was calculated as CT dose expressed as a percentage of radiopharmaceutical dose. ResultsThe per-patient CT effective dose for different studies varied between 0.06 and 11.9 mSv. The mean CT effective dose was lowest for 99mTc-ethylene cysteine dimer brain SPECT-CT (0.9±0.7) and highest for 99mTc-methylene diphosphonate bone SPECT-CT (4.2±2.8). The increase in radiation dose (SPECT-CT vs. SPECT) varied widely (2.3–666.4% for 99mTc-tracers and 0.02–96.2% for 131I-tracers). However, the effective dose of CT in SPECT-CT was less than the values reported for conventional CT examinations of the same regions. ConclusionAddition of CT to nuclear medicine imaging in the form of SPECT-CT increases the radiation dose to the patient, with the effective dose due to CT exceeding the effective dose of RP in many instances. Hence, appropriate utilization and optimization of the protocols of SPECT-CT is needed to maximize benefit to patients.

Lung metastases from differentiated thyroid carcinoma: prognostic factors related to remission and disease-free survival.

Distant metastases, although rare, account for maximum disease‐related mortality in differentiated thyroid cancer (DTC). Lungs and bones are the most frequent sites of metastases. We sought to identify the prognostic factors in adult DTC patients presenting with pulmonary metastases at initial diagnosis.

Can 18F-FDOPA PET/CT predict survival in patients with suspected recurrent glioma? A prospective study

UNLABELLED Purpose of the present study was to evaluate the role of (18)F-FDOPA PET/CT for predicting survival in patients with suspected recurrent glioma. METHODS A total of 33 previously treated, histopathologically proven glioma patients with clinical and contrast enhanced MRI findings suspicious for recurrence were enrolled in this prospective study. All patients underwent (18)F-FDOPA PET/CT. Ratios of tumor uptake to normal tissue uptake were generated by dividing the tumor SUVmax with SUVmax of the contralateral normal brain tissue (T/N), normal striatum (T/S), normal white matter (T/W) and normal cerebellum (T/C). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was performed for the distributions of each variable and by multivariate analysis. RESULTS (18)F-FDOPA PET/CT was positive for recurrence in 25 patients and negative in 8. Death occurred in nineteen patients. Median follow up period was 20.2 months. Median survival in this study was 39.2 months. In univariate analysis significant association of survival was noted with results of (18)F-FDOPA PET/CT (P=0.007) and (18)F-FDOPA PET/CT quantitative parameters namely SUVmax (P=0.001), T/S (P=0.005), T/W (P=0.0004), T/N (P=0.001) and T/C (P=0.003) were found to be significant. On multivariate analysis, only MRI size of the recurrent tumor (P=0.002) and T/N ratio of (18)F-FDOPA PET/CT (P=0.005) were found to be independent predictors of survival. CONCLUSION T/N ratio on (18)F-FDOPA PET/CT is an independent predictor of survival in patients with suspected recurrent glioma, along with size of recurrent tumor on MRI.

Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases.

Abstract Aim: This study was aimed at identifying the prognostic factors predicting remission in pediatric differentiated thyroid cancer (DTC) patients presenting with pulmonary metastases. Little is known about the prognostic factors in reference to pediatric DTC patients presenting with pulmonary metastases. Methods: Fifty-three DTC patients aged ≤21 years were diagnosed with pulmonary metastases at initial presentation. The demographic and disease characteristics were compared between the patients who achieved remission and those who did not. Results: During the median follow-up of 72 months, 38 patients became disease free, 14 patients had biochemically and/or structurally persistent disease, and one patient died due to disease progression. Patient age >15 years, presence of macronodular pulmonary metastases, and surgical methods lesser than total/near-total thyroidectomy were identified as factors associated with reduced odds of remission. Conclusion: This study describes the disease course and depicts the disease related prognostic factors in pediatric DTC patients with pulmonary metastases.

Intermediate-risk differentiated thyroid carcinoma patients who were surgically ablated do not need adjuvant radioiodine therapy: long-term outcome study

The mute question is whether patients with DTC of intermediate risk of recurrence, second most common presentation, who were surgically ablated in the first place, ever needed adjuvant RAI therapy? This study exclusively evaluated the long‐term outcome in intermediate‐risk patients with DTC.

Differentiated thyroid cancer in patients over 60 years of age at presentation: A retrospective study of 438 patients

OBJECTIVES The aim of this study is to identify the prognostic factors predicting remission and subsequent disease relapse in patients with differentiated thyroid cancer (DTC) greater than 60years of age. MATERIALS AND METHODS The institute thyroid cancer database had 4370 patients with DTC, of which 447 (10%) were aged>60. However, 9 patients were excluded due to follow-up less than 1year. The prognostic factors in the remaining 438 patients were studied. RESULTS Among the 438 patients, 311 (71%) had only loco-regional disease (M0) and 127 (29%) had distant metastases (M1) at the time of initial presentation. The host factors predictive of distant metastases at presentation were female gender, primary tumor size (>4cm), follicular histology, and extra-thyroidal extension. Among Mo patients, 195 (63%) achieved complete remission while only 12 (9%) M1 patients did so. Average number of radioactive iodine ((131)I) doses administered to achieve complete remission was 2.3 (range, 1-6) and the mean cumulative dose was 3404MBq (range, 925-46,250MBq). In multivariate logistic regression among M0 patients, follicular histology, nodal metastases, and surgical treatment lesser than total/near-total thyroidectomy and among M1 patients, site of distant metastases (skeletal and multiple sites) were independent factors predicting non-remission. Among the patients (both M0 and M1) who achieved remission, factors associated with disease recurrence were primary tumor size (>4cm), nodal metastases, pulmonary metastases, and non-remission after first dose of radioactive iodine and were associated with greater chances of disease relapse. CONCLUSION This study highlights that DTC in older patients behaves more aggressively than in adults age<60years, and identifies several prognostic factors for remission and subsequent relapse.

Comparison of software programs for the assessment of left ventricular ejection fraction using 99mTc-tetrofosmin-gated SPECT/CT: correlation with equilibrium radionuclide ventriculography in the Indian population.

ObjectiveThe goal of this study was to compare Emory Cardiac Toolbox (ECTb), quantitative gated SPECT (QGS), four-dimensional single photon emission computed tomography (4D-MSPECT) and Myometrix cardiac software programs for the assessment of left ventricular ejection fraction (LVEF) using 99mTc-tetrofosmin-gated SPECT/CT [myocardial perfusion SPECT (MPS)] and correlate them with the LVEF values derived from equilibrium radionuclide ventriculography (ERNV) in patients with known/suspected coronary artery disease (CAD). Materials and methodsA total of 109 patients (80 men, 29 women) were recruited into the study. Fifty-five patients had known CAD and 54 were referred with suspicion of CAD. All the patients underwent ERNV and MPS as per the standard protocol. ERNV was processed using the vendor-provided ‘EF analysis’ and gated MPS was processed using individual software programs. ResultsThe mean LVEF on ERNV was 47.9±15.5%. The mean LVEF values for ECTb, QGS, 4D-MSPECT and Myometrix were 51.5±19.6, 51.0±18.6, 57.1±19.3 and 49.7±19%, respectively. On correlation analysis, a very strong positive correlation was observed between LVEF values derived by ERNV and those derived by the MPS software programs: ECTb (r=0.842, P<0.0001), QGS (r=0.835, P<0.0001), 4D-MSPECT (r=0.830, P<0.0001) and Myometrix (r=0.875, P<0.0001). Significant correlation was also seen for LVEFs among the four software programs. Normal cutoff values for ejection fraction on ECTb, QGS, 4D-MSPECT and Myometrix were 56, 52, 54 and 51%, respectively, using a 50% or more cutoff value on ERNV. ConclusionA strong correlation was observed among ECTb, QGS, 4D-MSPECT and Myometrix software programs when compared with ERNV and also between them for assessment of LVEF. However, there are subtle differences in the objective values of ejection fraction generated by individual software, which must be taken into account for clinical studies.

Is There Any True Association Between BRAF V600E Mutation and Recurrence, Particularly in Low-Risk, Papillary Thyroid Cancer?

TO THE EDITOR: Your esteemed journal recently published an article by Xing et al, entitled, “Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer,” which we read with great interest. This article reports the largest multicenter study to demonstrate the association of BRAF V600E mutation with recurrence of papillary thyroid cancer (PTC). In view of the fairly large sample size of patients with PTC, the authors were able to stratify the effect of BRAF V600E mutation in classic PTC and its variants. However, two pertinent questions need to be addressed. First, the main objective of the study was to investigate the association of BRAF V600E mutation with recurrence of PTC. In this article, the term recurrence was defined as “recurrent or persistent disease per authoritative histologic, cytologic, radiographic, or biochemical criteria.” The American Cancer Society defines recurrence as “the return of cancer after treatment, and after a period of time during which cancer can’t be detected.” The definition of recurrence, as proposed by Elisei et al, was “the reappearance of tumor (either locally in thyroid bed, in neck nodes, or as distant metastatic disease) after a well-documented disease-free period.” Persistent disease was defined as “suppressed thyroglobulin values (Tg) values 1 ng/mL and/or stimulated Tg 2 ng/mL, or any evidence of disease on cross-sectional imaging (ultrasonography, computed tomography, or magnetic resonance imaging), functional imaging (RAI [XXXX] scan or 18-FDG-PET [fluorodeoxyglucose–positron emission tomography] scan) or biopsy proven disease” by Tuttle et al. Interestingly, both of the principal authors of these articles, Elisei and Tuttle, are also coauthors of this latest publication. The very definition of recurrence (recurrent and persistent) used in the article by Xing et al creates great confusion among readers; thus, the association of BRAF V600E mutation with recurrence needs to be critically appraised. Interestingly, with a median follow-up of only 36 months, the overall recurrence rate reported in the article by Xing et al was 16% (338 of 2,099 patients). On subgroup analysis, the recurrence rate reported in patients who were positive for BRAF V600E mutations was 20.9% (213 of 1,017), and in patients negative for this mutation was 11.6% (125 of 1,082; P .001), which is fairly high. Moreover, in the low-risk group, the recurrence rates were 12.1% (stage I), 20.6% (stage II), and 17.8% (tumor 1 cm) in patients positive for BRAF mutations, and 7.3% (stage I), 9.2% (stage II), and 5.7% (tumor 1 cm) in patients negative for BRAF mutations. Contrary to these results, many studies with fairly longer median follow-up periods have shown a comparatively lower recurrence rate in low-risk patients with differentiated thyroid cancer, irrespective of whether the BRAF V600E mutation was present or not. Schvartz et al showed a recurrence rate of 1.5% (19 of 1,298) with a median follow-up of 10.3 years, and Tuttle et al observed a recurrence rate of 0.7% (one of 136) with a median follow-up of 7 years. Interestingly, Elisei et al and Vianello et al, with median follow-up periods of 3.7 years and 4 years, respectively, observed no recurrences in patients with low-risk differentiated thyroid carcinoma. This discordance of results in comparison with previous literature needs explanation. We strongly presume that the high rate of recurrence could be a result of persistent disease, rather than true recurrence, as per the definition of recurrence adopted in the study by Xing et al. The great effort made by Xing et al to determine whether there is an association between BRAF V600E mutation and PTC recurrence, in a study involving such a large number of patients recruited from multinational institutions, deserves our appreciation. So far, only single-center studies with small numbers of patients have been published. However, certain important issues, which are mentioned here, need to be clarified so that the role of BRAF V600E mutation in predicting recurrence in various subtypes of PTC, particularly in lowrisk patients, can be elucidated in such a way as to influence future patient management.

Radioiodine remnant ablation in low-risk differentiated thyroid cancer patients who had R0 dissection is an over treatment

Low‐risk (LR) differentiated thyroid cancer (DTC) patients should be ablated or not, albeit, with small dose of radioiodine is highly controversial. We hypothesized that those LR DTC patients who were surgically ablated need no radioiodine remnant ablation (RRA). This study aims to evaluate the long‐term outcome in these two groups of patients. Retrospective cohort study conducted from January 1991 to December 2012. Based on extent of surgical resection and histopathology, LR DTC patients were classified as Gr‐1: 169 patients, who were surgically ablated; Gr‐2: 153 patients, who had significant remnant in thyroid bed. Basal parameters were comparable between two groups except pretherapy 24 h radioiodine uptake (0.16 ± 0.01% vs. 5.64 ± 0.46%; P < 0.001). No patient received RRA in Gr‐1; Gr‐2 patients were administered 30 mCi 131I. Total number of events (recurrence, persistent, and progression of disease), with median follow up of 10.3 years, was observed in 10/322 (3.1%) of LR DTC patients. Only one patient had disease recurrence from Gr‐1, who became disease‐free after radioiodine therapy. Similarly, one patient from 126, who was ablated with single dose of RRA, had recurrence from Gr‐2. However, 8/27 (29.7%) patients from Gr‐2 had persistent disease; even two of them subsequently developed disease progression, who failed first‐dose of RRA. The event‐free survival rates were 99.4% and 94.1% (P = 0.006) in Gr‐1 and Gr‐2, respectively. RRA is an overtreatment in surgically ablated LR DTC patients. Successfully ablated RRA patients also had similar long‐term outcome, however, those who failed, should be re‐stratified as intermediate‐risk category, and managed aggressively.

Concomitant 177lu-dotatate and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-outcome, Toxicity, Survival, and Quality-of-life Study

Purpose The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. Methods One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline 68Ga-DOTANOC PET/CT scans. 177Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with 177Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. Results There was no significant difference in the hemoglobin levels after 177Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/&mgr;L with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. Conclusions Addition of capecitabine therapy with 177Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.