Molecular Response Assessment with Immune Adaptive PERCIST in Lung Cancer Patients Treated with Nivolumab: Is It Better Than iRECIST?

Aims We compared the immune response evaluation criteria in solid tumors (iRECIST) with immune adaptive positron emission tomography response criteria in solid tumors (imPERCIST) in lung cancer patients treated with nivolumab. Materials and Methods Twenty lung cancer patients underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan at baseline (PET-0), after four cycles (PET-1) and six to eight cycles (PET-2) of nivolumab were included. Kappa coefficient ( k ) was derived to see the level of agreement in two response criteria. Progression-free survival (PFS) curves were computed by the Kaplan-Meier method and compared with the Log Rank test. Univariate and multivariate regression for the percentage change in the sum of diameters (SoD), standard uptake value maximum (SUVmax), sum of metabolic tumor volume (SoMTV), and sum of total lesion glycolysis (SoTLG) was computed. A p -value less than 0.05 was considered significant. Results Kappa coefficient showed a substantial level of agreement (k 0.769) in two response criteria. Mean PFS in partial response, stable disease, and progressive disease (PD) patients in iRECIST and imPERCIST was 27.3, 17.7, 4.2, and 23.3, 18.8, 3.8 months, respectively. The Kaplan-Meier method with the log rank test showed a significant difference in PFS on intracomparison within both criteria; however, it was not significant on intercomparison. On univariate analysis, the percentage change in SoD, SoMTV, SoTLG was significant. However, on multivariate analysis, only percentage change in SoD was a significant predictor. Conclusions We concluded that imPERCIST was equally effective as currently recommended criteria iRECIST for response evaluation of nivolumab in lung cancer patients.

Impact of COVID-19 on Nuclear Medicine in Asia.

Coronavirus disease 2019 (COVID-19) was first detected in China in late 2019 and rapidly spread to nearby Asian countries in early 2020. Outbreaks occurred differently in each country and affected nuclear medicine (NM) practice significantly even before the COVID-19 pandemic. The Asian NM community has worked together from the beginning of the pandemic. Fortunately, the Asian Regional Cooperative Council for Nuclear Medicine annual general meeting and Asia Nuclear Medicine Board examination was held in Manila from January 28 to February 2, 2020; these were the last face-to-face events of these organizations to date. Members shared information about COVID-19 at the conference, and through online means afterwards. Web-based surveys performed from March to April 2020 for the Asian Regional Cooperative Council for Nuclear Medicine and Asia Nuclear Medicine Board communities showed a significant reduction of NM practice and supply of radioisotopes (RI) at the beginning of the COVID-19 pandemic. A follow-up survey in March to April 2021 clearly showed the recovery of both NM practice and RI supplies. The pattern of recovery is variable according to institutions and countries. Herein, we have reported the case-in-point operational histories of four representative institutions in the East, Southeast, South, and West Asia. The second outbreak in India is ongoing on a worrisome scale. Various communications and educational sessions were actively performed online in the Asian NM community during the pandemic.

Changes in the global impact of COVID-19 on nuclear medicine departments during 2020: an international follow-up survey.

AIM: As a follow-up to the international survey conducted by the International Atomic Energy Agency (IAEA) in April 2020, this survey aims to provide a situational snapshot of the COVID-19 impact on nuclear medicine services worldwide, 1 year later. The survey was designed to determine the impact of the pandemic at two specific time points: June and October 2020, and compare them to the previously collected data. MATERIALS AND METHODS: A web-based questionnaire, in the same format as the April 2020 survey was disseminated to nuclear medicine facilities worldwide. Survey data was collected using a secure software platform hosted by the IAEA; it was made available for 6 weeks, from November 23 to December 31, 2020. RESULTS: From 505 replies received from 96 countries, data was extracted from 355 questionnaires (of which 338 were fully completed). The responses came from centres across varying regions of the world and with heterogeneous income distributions. Regional differences and challenges across the world were identified and analysed. Globally, the volume of nuclear medicine procedures decreased by 73.3% in June 2020 and 56.9% in October 2020. Among the nuclear medicine procedures, oncological PET studies showed less of a decline in utilization compared to conventional nuclear medicine, particularly nuclear cardiology. The negative impact was also significantly less pronounced in high-income countries. A trend towards a gradual return to the pre-COVID-19 situation of the supply chains of radioisotopes, generators, and other essential materials was evident. CONCLUSION: The year 2020 has a significant decrease in nuclear medicine diagnostic and therapeutic procedures as a result of the pandemic-related challenges. In June, the global decline recorded in the survey was greater than in October when the situation began to show improvement. However, the total number of procedures remained below those recorded in April 2020 and fell to less than half of the volumes normally carried out pre-pandemic.

Theranostics in India: a Particularly Exquisite Concept or an Experimental Tool.

The term theranostics is a combination of a diagnostic tool that helps to define a right therapeutic tool for specific disease and paves the approach towards personalized or precision medicine. In Nuclear Medicine, a diagnostic radionuclide is labeled with the target and once expression is documented, the same target is labeled with a therapeutic radionuclide and treatment is executed. The theranostic concept was applied first time in 1964 in the treatment of thyroid cancer with I-131 (RAI). Over the years, other theranostic radiotracers became available indigenously from the Bhabha Atomic Research Centre (BARC) in the country. Currently Lu-177 is produced in India and peptides like DOTATATE and PSMA are available in a kit form indigenously. At the present time, the radionuclide therapies of oncological disorders which are being performed in India are mainly for neuroendocrine tumors (NET) and metastatic castration resistant prostate cancer (mCRPC). The main constraints pertaining to this concept is the cost of treatment and awareness among the clinicians which are gradually being taken care of by the private health insurance and our participation in disease management group meetings respectively. The theranostic concept has become popular over the years and has the potential for sustained growth.

Differentiated thyroid cancer theranostics: radioiodine and beyond.

The term theranostics is the combination of a diagnostic tool that helps to define the right therapeutic tool for specific disease. It signifies the "we know which sites require treatment (diagnostic scan) and confirm that those sites have been treated (post-therapy scan)" demonstrating the achievable tumor dose concept. This term was first used by John Funkhouser at the beginning of the 90s, at the same time the concept of personalized medicine appeared. In nuclear medicine, theranostics is easy to apply and understand because of an easy switch from diagnosis to therapy with the same vector. It helps in maximizing tumor dose and sparing normal tissue with high specific and rapid uptake in metastasis. The oldest application of this concept is radioactive iodine I-131 (RAI). The first treatment based on the theranostic concept was performed on thyroid cancer patients with RAI in 1946. From then on management of differentiated thyroid cancer (DTC) has evolved on the multimodality concept. We now use the term "our" patient instead of "my" patient to signify this. However, the initial surgical management followed by RAI as per the theranostics has remained the mainstay in achieving a cure in most of DTC patients. The normal thyroid cells metabolise iodine, the principle of which is utilized in imaging of the thyroid gland with isotopes of iodine. RAI treatment of DTC is based on the principle of sodium iodide symporter (NIS) expressing thyroid cells with DTC cells having the ability of trapping circulating RAI successfully helping in treatment of residual and metastatic disease. NIS is usually negative in poorly differentiated cells and is inversely proportional to Glucose transporter receptor Type 1 expression. Both positive and negative NIS are the key components of the theranostic approach in treatment of DTC. Presence or absence of NIS is documented by either whole body iodine scintigraphy (WBS) or 2-deoxy-2(18F) fludeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT). Currently, single photon emission CT and CT (SPECT-CT) has significantly improved the precision and sensitivity of whole body iodine scintigraphy with its capability of accurate localization of disease foci whether iodine avid or non-avid. This has helped in a more personalized approach in treatment. This review will give an overview of the role of NIS in the theranostic approach to management with RAI, its current status and also the molecular approach to treatment in RAI refractory disease.

A Comparative Study of 68Gallium-Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography and Magnetic Resonance Imaging for Lymph Node Staging in High Risk Prostate Cancer Patients: An Initial Experience.

Lymph node staging plays an important role in planning initial management in nonmetastatic prostate cancer. This article compares the role of 68Gallium (68Ga)-prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) with magnetic resonance imaging (MRI), which is considered the standard staging modality. Out of 39 high-risk prostate cancer patients who underwent 68Ga-PSMA PET-CT for staging (December 2014-December 2015), 12 patients underwent radical prostatectomy along with ePLND and were included in the analysis. Findings of the PSMA PET and MRI were compared with final histopathology. Sensitivity, specificity, positive predicative value (PPV), negative predicative value (NPV), and accuracy of 68Ga-PSMA PET-CT and MRI were calculated for numbers of patients and pelvic lymph node metastasis. Chi-square test, McNemar's test, and receiver operating characteristic (ROC) analysis were also done. 68Ga-PSMA PET-CT and MRI sensitivity, specificity, PPV, NPV, and accuracy for number of patients detection were 100%, 80%, 87.5%, 100%, 91.67%, and 57.14%, 80%, 80%, 57.4%, 66.67%, respectively. For detection of metastatic lymph node, it was 66.67%, 98.61%, 85.71%, 95.95%, 95.06% and 25.93%, 98.61%, 70%, 91.42%, 90.53%, respectively. Difference of lymph nodal detectability was statistically significant on Chi-square test. On McNemar's test, P value was statistically insignificant for number of patient detection (P = 0.250) but statistically significant for lymph nodal detection (P = 0.001) for 68Ga-PSMA PET-CT. In ROC analysis, area under the curve was also significantly high for lymph node detectability by 68Ga-PSMA PET-CT. Our initial experience shows that 68GaPSMA PET-CT is a very promising tracer for N staging in the initial workup of prostate cancer. It has the potential to impact patient's initial management and can up- and down-stage effectively.

Can 18F-Fluoroestradiol Positron Emission Tomography Become a New Imaging Standard in the Estrogen Receptor-positive Breast Cancer Patient: A Prospective Comparative Study with 18F-Fluorodeoxyglucose Positron Emission Tomography?

Correct staging is the most crucial for the treatment outcome in cancer management. Molecular imaging with 18F-fluoroestradiol (FES) positron emission tomography-computed tomography (PET-CT) targets estrogen receptor (ER) and may have a higher incremental value in diagnosis by aiding specificity. We enrolled 12 female breast cancer patients prospectively and did 18F-FES PET-CT and 18F-fluorodeoxyglucose (FDG) PET-CT within 1 week interval time. Lesion detection sensitivity was compared for a total number of lesions and for nonhepatic lesions only by McNemar test. 18F-FES PET-CT was taken as reference in case of indeterminate lesions. The incremental value reported by identifying 18F-FES exclusive lesions and by characterization of 18F-FDG indeterminate lesions. Spearman rank test was used to correlate ER expression and maximum standardized uptake value (SUVmax). Two ER-negative patients with no 18F-FES uptake were excluded. Ten ER-positive patients with 154 disease lesions were finally analyzed. 18F-FDG picked-up 142 lesions (sensitivity 92.21%), whereas 18F-FES picked-up 116 lesions (sensitivity 75.32%) and this difference was statistically significant. For nonhepatic lesions (n = 136) detectability, 18F-FDG picked-up 124 (sensitivity 91.18%), whereas 18F-FES picked-up 116 (sensitivity 85.29%) lesions and this difference was not statistically significant. Beside 12 exclusive lesions, 18F-FES characterized 41 (27.5%) 18F-FDG indeterminate lesions. Overall 18F-FES impacted 20% patient management. The positive trend was also seen with 18F-FES SUVmax with ER expression and negative with 18F-FDG SUVmax. We conclude, 18F-FDG has overall better sensitivity than 18F-FES PET-CT, however for nonhepatic metastasis difference was not significant. 18F-FES PET-CT better-characterized lesions and impacted 20% patient management. Therefore, 18F-FES PET-CT should be used with 18F-FDG PET-CT in strongly ER expressing patients for better specificity.

Stimulated high serum thyroglobulin with negative whole body imaging do not warrant an aggressive diagnostic and therapeutic approach in differentiated thyroid cancer patients: A follow-up of 5 years or till recurrence.

OBJECTIVE: To study the clinical significance of stimulated high serum thyroglobulin (sTg) and of normal whole body imaging (WBI) in differentiated thyroid cancer (DTC) patients during their first follow-up and in a 5 years follow-up or till recurrence. SUBJECTS AND METHODS: Sixty four DTC patients were retrospectively studied and were divided into two groups. Group 1, of 35 patients with disease free status on their first follow-up and group 2, of 29 patients with high sTg (>2 µg/mL), but with normal WBI, iodine-131 (¹³¹I) findings. Patients were categorized into low, intermediate and high risk patients based on the ¹³¹I WBS findings. Histology, stage and risk-categories of both groups were statistically correlated. Best sTg cut-off for predicting recurrence was generated by receiver operating characteristic (ROC). Odd ratio for sTg trend was also analyzed for risk of recurrence in group 2. Independent t test was used for progression free survival (PFS) comparison of the two groups. RESULTS: No statistical differences were seen in histology, stage and risk category distributions between the groups. Group 2 patients with high sTg (range 2.5-81 µg/L, mean 20.5 µg/L) on their first follow-up had higher risk of recurrence (odd ratio 4.304) but P value was insignificant (P:0.090). Eighty six per cent of group 2 patients showed decreasing trends and in 62% of group 2 patients, high serum sTg fell to normal. Indeed, decreasing trends of sTg reduced the risk of recurrence (odd ratio 1.3939, P:0.79). Analysis by ROC showed that sTg>11 µg/L was the best cut-off in predicting recurrence with sensitivity 100% and specificity 56%. High sTg was not associated with low PFS, (P:0.232), however patients with increasing sTg had significantly shorter PFS (P<0.005). CONCLUSION: High sTg with negative ¹³¹I WBS did not warrant an aggressive DTC disease. These patients in their 5 years or till recurrence follow-up showed downward trends of serum sTg, no higher risk or recurrence and no shorter PFS.

(99m)Tc glucarate as a potential radiopharmaceutical agent for assessment of tumor viability: from bench to the bed side.

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. (99m)Tc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with (18)F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent (99m)Tc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent (99m)Tc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. (99m)Tc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy.