Tata Memorial Centre Evidence Based Use of Nuclear medicine diagnostic and treatment modalities in cancer.

ABSTRACT: PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring disease-specific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Objective: Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Methods: Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Results: Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. Conclusion: The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Evaluation of post-chemotherapy residual seminomatous masses by 18F-fluorodeoxyglucose PET/CT using tumor-to-liver ratio - conundrum or solution?

OBJECTIVE: Assessment of diagnostic accuracy of FDG-PET/CT in the detection of viable disease in post-chemotherapy seminomatous residual masses using visual interpretation, SUVmax, and T/L ratio. METHODS: This is a retrospective study assessing the post-chemotherapy seminomatous residual masses of size >3 cm. The PET/CT scan findings were interpreted visually for presence of residual disease which were validated from histopathology reports or imaging follow-up for a maximum of 3 years. SUVmax and T/L ratios were also determined for all the residual lesions. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value NPV were calculated and compared for all three parameters along with ROC analysis to obtain an optimal cutoff value for SUVmax and T/L ratio, respectively. RESULTS: Sample size was 49. Out of these 49 patients, 8 had validation of PET results with histopathology. Rest was validated with imaging follow-up. FDG-PET was positive in 30 patients and negative in 19 patients by visual interpretation. The sensitivity, specificity, PPV, and NPV by this method were 100%, 62.5%, 73%, and 100%, respectively. The SUVmax and T/L ratios were also calculated for these lesions. The cutoff for these two variables was 4.56 and 1.21, respectively. The sensitivity, specificity, PPV, and NPV at these cutoffs were 76%, 87.5%, 86%, 77.7%, and 92%, 87.5%, 88%, 91%, respectively. CONCLUSION: FDG-PET has a favorable diagnostic value in predicting viable disease in post-chemotherapy seminomatous residual masses and using T/L ratio cutoff of 1.21 will increase the specificity of the test.

Primary Neuroendocrine Tumor of Prostate in a Case of Metastatic Adenocarcinoma of Lung: Rare Entity with Histopathological and Gallium 68 DOTANOC Positron Emission Tomography Correlation.

Neuroendocrine tumor (NET) of the prostate is an extremely rare entity which represents <1% of the prostatic cancers, but with increasing incidence. Its spectrum encompasses several histological variants ranging from well-differentiated tumor which are often indolent in nature; to aggressive neuroendocrine carcinoma which portends aggressive management. Hence, such rare entities are to be characterized and treated accordingly. We report an unusual case of well-differentiated NET of prostate which was flagged on fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) performed for other indication and confirmed on Gallium-68 DOTANOC PET/CT. Histopathology and immunohistochemistry confirmed the findings subsequently.

Surgical templates for inguinal lymph node dissection in cN0 penile cancer: A comparative study.

PURPOSE: Modified and superficial inguinal lymph node dissection (MILD and SILD) are the 2 widely used templates for surgical staging of clinically node negative (cN0) penile cancer (PeCa); however, no previous reports have compared their outcomes. We compared these 2 surgical templates for oncological outcomes and complications. MATERIALS AND METHODS: We retrospectively reviewed records of cN0 PeCa patients who underwent MILD/SILD at our cancer care center from January 2013 to December 2019. Patients who developed a penile recurrence during follow up were excluded from analysis of oncological outcomes. The 2 groups (MILD and SILD) were compared for baseline clinico-pathological characteristics. The primary outcome was the groin recurrence free survival (gRFS). Secondary outcomes included the false negative rate (FNR) and disease free survival (DFS) for both templates and also the post-operative wound related complication. RESULTS: Of the 146 patients with intermediate and high risk N0 PeCa, 74 (50.7%) and 72 (49.3%) underwent MILD and SILD respectively. The 2 groups were comparable with regards to the distribution of T stage, tumor grade and the proportion of intermediate and high-risk patients. At a median follow up of 34 months (47 for SILD and 23 for MILD), a total of 5 groin recurrences were encountered; all of them occurred in the MILD group. The gRFS and DFS for the MILD group was 93.2% and 91.8% respectively; while that for the SILD group was 100% and 94.4% respectively. Too few events had occurred to determine any statistically significant difference. The FNR for MILD and SILD was 26.3% and 0% respectively. The overall complication rate was significantly higher in the SILD group (46% vs 20.3%, p=0.001), especially for Clavien Dindo 3A complications. CONCLUSION: MILD can fail to pick up micro-metastatic disease in a small proportion of cN0 PeCa patients, while SILD provides better oncological clearance with no groin recurrences. This oncological superiority comes at the cost of a higher incidence of wound-related complications.

Metabolic tumor parameters complement clinicopathological factors in prognosticating advanced stage Hodgkin Lymphoma.

Objectives: Advanced Hodgkin Lymphoma has a higher probability of relapse and recurrence. Classical clinicopathological parameters including the International Prognostic Score (IPS) have not been reliable in predicting prognosis or tailoring treatment. Since FDG PET/CT is the standard of care in staging Hodgkin Lymphoma, this study attempted to evaluate the clinical utility of baseline metabolic tumor parameters in a cohort of advanced Hodgkin lymphoma (stage III and IV). Methods: Histology-proven advanced Hodgkin Patients presenting to our institute between 2012-2016 and treated with chemo-radiotherapy (ABVD / AEVD) were followed up till 2019. Quantitative PET/CT and clinicopathological parameters were used to estimate the Event Free Survival (EFS) in 100 patients. Kaplan-Meier method with log-rank test was used to compare the survival times of prognostic factors. Results: At a median follow-up of 48.83 months (IQR:33.31-63.05 months), the five-year-EFS was 81%. Of the 100 patients, 16 had relapsed (16%) and none died at the last follow-up. On Univariate analysis, among non-PET parameters bulky disease (P=0.03) and B-symptoms (P=0.04) were significant while among PET/CT parameters SUVmax (p=0.001), SUVmean (P=0.002), WBMTV2.5 (P<0.001), WBMTV41% (P<0.001), WBTLG2.5 (P<0.001) and WBTLG41% (P <0.001) predicted poorer EFS. 5-year EFS for patients with low WBMTV2.5 [<1038.3 cm3] was 89% and 35% for patients with high WBMTV2.5 [≥1038.3 cm3] (p <0.001). In a multivariate model, only WBMTV2.5 (P=0.03) independently predicted poorer EFS. Conclusion: PET-based metabolic parameter (WBMTV2.5) was able to prognosticate and complement the classical clinical prognostic factors in advanced Hodgkin Lymphoma. This parameter could have a surrogate value for prognosticating advanced Hodgkin lymphoma. Better prognostication at baseline translates to tailored or risk-modified treatment and hence higher survival.

A Rare Case of Plasmablastic Lymphoma of the Ovary with Synchronous Lung Malignancy.

Primary ovarian lymphoma is a rare malignancy with <1% incidence. Plasmablastic lymphoma usually associated with immunocompromised diseases such as HIV rarely involves the ovary; only two case studies are reported in the literature - plasmablastic lymphomatous involvement of an ovarian teratoma and another of plasmablastic variant of B-cell lymphoma involving bilateral ovaries. There are reported case series of synchronous presentation of carcinomas usually including lung, stomach, and colon and nonaggressive lymphomas. Here, we report a rare case of synchronous aggressive primary plasmablastic ovarian lymphoma with adenocarcinoma of the lung, both of which are associated with immune-compromised conditions.

Demonstration of Multiple Metastatic Sites by Positron Emission Tomography/Computed Tomography in a Rare Case of Epithelioid Angiosarcoma of the Scalp.

Epithelioid angiosarcoma is a rare subtype of angiosarcoma, with metastases occurring in more than 50% of cases and the lung is the most organ which is involved. Whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has demonstrated its clinical utility in the early detection of metastases in angiosarcoma. It is helpful to differentiate between benign lesions with low FDG uptake as compared to malignancies with high FDG avidity. Here, we present a rare case of a young man with epithelioid angiosarcoma, in which FDG PET/CT has demonstrated metastatic sites (especially lung metastases).

FAPI PET Positivity in Fibrolamellar Hepatocellular Carcinoma.

ABSTRACT: Fibrolamellar hepatocellular carcinoma (HCC) is a variant of HCC. It is a malignant tumor, but its imaging features often overlap focal nodular hyperplasia, which is a benign entity. FDG PET/CT is also not much help in these cases because both lesions do not concentrate FDG. We present one such case of fibrolamellar HCC with FAPI PET/CT positivity.

Diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder and its impact on post-recurrence survival.

PURPOSE: To analyze diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder (GBC) and to establish its possible impact on post-recurrence survival. METHOD: FDG PET/CT studies of suspected recurrent GBC were retrospectively analyzed alongside tumor markers serum CEA and CA 19-9. Abnormal FDG-avid lesions and abnormal morphological lesions were considered positive for recurrence, and were categorized as isolated abdominal wall recurrence, loco-regional recurrence, and distant metastatic disease. Histopathology, definite progression on imaging and positive response to treatment was considered as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used as diagnostic performance parameters. Post-recurrence survival was calculated whenever appropriate follow-up was available, based on the abovementioned categories of sites of recurrence using survival curves and log-rank test. RESULTS: Out of 117 PET/CT studies, 93 (79.5%) were positive and 24 (20.5%) were negative for recurrence. 86 out of 93 were true positive and 23 of 24 were true negative. PET/CT demonstrated sensitivity, specificity, PPV, NPV and accuracy of 98.8%, 76.7%, 92.5%, 95.8% and 93.1%, respectively. Diagnostic performance of PET/CT was significantly better than combination tumor markers. Of 66 cases with available follow-up, isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence demonstrated significantly higher post-recurrence survival as compared to distant metastasis; median survival being 39, 25 and 12 months, respectively. CONCLUSION: F-18 FDG PET/CT has better diagnostic performance than tumor markers combination. Isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence on PET/CT demonstrated better survival than non-regional metastatic disease. These results suggest a possible role of PET/CT as a surveillance modality, as well as a guide to therapeutic decision-making in cases of recurrent GBC.

Sporadic Cerebellar Hemangioblastoma With Strong SSTR Expression on 68 Ga-DOTANOC PET/CT.

ABSTRACT: Sporadic cerebellar hemangioblastomas are rare with majority of these tumors presenting as a part of von Hippel-Lindau syndrome. We demonstrate an unusual case of a symptomatic sporadic cerebellar hemangioblastoma mimicking a meningioma on MRI and 68 Ga-DOTANOC PET imaging.

Multimodal Management of Testicular Mesothelioma - A Retrospective Analysis From a Tertiary Cancer Care Centre.

The main modality of management of paratesticular mesothelioma remains orchiectomy while the use of adjuvant chemotherapy has not yet been explored. We aim to analyse the outcome of the multimodal management protocol in testicular mesothelioma We conducted a retrospective analysis of patients registered and treated for testicular mesothelioma between 2009 and 2019 in an oncology tertiary care hospital. Patients presenting with nodal, metastatic disease were treated with adjuvant, palliative chemotherapy respectively and their response to treatment was periodically monitored. Eight patients (3 early, 1 nodal, 4 metastatic) with median age of 58 years was included in the study. Patients who had limited (early, nodal) disease (n = 4) had overall survival ranging from 20 to 140 months while metastatic disease (n = 4) had poor outcomes with overall survival ranging from 2 to 13 months. Surgery remains to be an important modality of therapy that improves the local control and overall outcomes and the quality of life even in patients with metastatic disease at the time of diagnosis. Adjuvant chemotherapy might play a role in effective management of locoregional disease. The performance status, the extent of disease at the time of presentation are the important prognostic factors in deciding the outcome of the disease management.

Bone metastases in prostate cancer - Gallium-68-labeled prostate-specific membrane antigen or Fluorine 18 sodium fluoride PET/computed tomography - the better tracer?

OBJECTIVE: The objective was to assess the roles of 68Ga-PSMA PET/CT and 18F-NaF PET/CT in evaluation of skeletal metastatic lesions in prostate cancer. METHODS: Two hundred consecutive prostate cancer patients who had undergone 68Ga-PSMA PET/CT and 18F-NaF PET/CT at baseline evaluation (n = 80) and following suspected recurrence or disease progression (restaging) (n = 120) were analyzed retrospectively. RESULTS: PSMA and NAF scans were positive for skeletal metastatic lesions in 67% (134 patients) and negative in 33% (66 patients). The scans were concordant in 80% (160 patients: 66 negative and 94 positive) and discordant in 20% (40 patients). Among 40 discordant results, 14 were baseline and 26 were restaging studies. PSMA detected more number of lesions in 11 (nine baseline and two restaging). These were true positive marrow or lytic metastatic lesions. NaF revealed more number of lesions in 29 (5 initial and 24 restaging). These were false positive on follow-up imaging. No statistical difference (P value = 0.7 by McNemar test) between the two scans for identifying absence or presence of at least one skeletal lesion was noted at baseline staging. CONCLUSION: Though, both 18F-NaF and 68Ga-PSMA are excellent tracers for evaluation of skeletal metastases in prostate cancer, there is a distinct advantage of 68Ga-PSMA PET/CT due to detection of additional skeletal lesions and absence of false positive lesions. In addition, absence of PSMA avidity in healed metastases in the restaging setting opens up new avenue for assessment of response of skeletal metastases.

Impact of FDG PET/CT Scan in Changing Management of Well-Differentiated Neuroendocrine Tumors With Ki67 Index Less Than or Equal to 5.

OBJECTIVES: This study aimed to see the impact of FDG PET/CT with somatostatin receptor PET (SSTR PET) in directing the treatment plan in lower-grade well-differentiated neuroendocrine tumors (NETs) with Ki67 index ≤5%. METHODS: Sixty-three NET cases with Ki67 index ≤5% with both FDG PET and SSTR PET ( 68 Ga-DOTANOC PET) were included for this retrospective observational study. FDG PET findings were classified into positive, weakly positive, and negative based on a visual scale. Clinical factors considered while referring for FDG PET scan were audited from electronic medical records. The addition of chemotherapy was considered as FDG-directed change in treatment. RESULTS: Sixty patients showed intense SSTR expression in the primary and metastatic sites (if present). Three patients showed no evidence of SSTR expression, in whom the scans were done after resection of the primary tumor. The FDG PET was positive in 25 (39.6%), weakly positive in 11 (17.4%), and negative in 27 (42.8%). Specific clinical reason for doing FDG PET was found in 34 patients, and in the remaining 29, there was no justification or specific indication for doing the FDG study; 73.5% of patients from the former group was either FDG positive or weakly positive, and 26.5% were negative; in the other group, 62.1% were FDG-negative, and 37.9% were positive ( P = 0.004). Treatment-naive patients with symptom duration of ≤5 months were associated with more FDG positivity than patients with >5 months' symptom duration ( P = 0.006). FDG PET/CT led to change in management in 17.4% of all the patients, 9.6% of grade 1, and 25% of grade 2 patients. CONCLUSIONS: In lower-grade NET, FDG positivity was seen in a sizable number of the cases, and this led to change in management in 17.4% of the cases. Specific clinical features could be utilized to successfully discriminate between FDG-avid and non-FDG-avid disease in lower-grade NETs, and this had impact in management change as well.

Second-line therapy in testicular germ cell tumours: results from a tertiary cancer care centre in India.

Background: Malignant testicular neoplasms constitute about 1% of all cancers in males. This is one of the most common tumours in adolescents and young adult males. After the introduction of cisplatin-based chemotherapy, the survival of germ cell tumour patients, even those with poor prognostic risk factors, has significantly improved over the years. Second-line chemotherapy in patients who have progressed over the first-line cisplatin-based chemotherapy has shown convincing 5 years of overall survival (OS). Methodology: This study is a retrospective analysis of testicular cancer patients from 2014 to 2020 who have received salvage chemotherapy treatment at Tata Memorial Centre. Patient demographics, tumour characteristics and treatment details were recorded in a specific format, and progression-free survival and OS were analysed along with response to therapy. Results: A total of 46 testicular cancer patients from 2014 to 2020, who received second-line chemotherapy, were analysed from the database maintained at our hospital. The median age at diagnosis was 29.5 (18-60) years. Most of the patients (30, 65.2%) presented with lung metastasis and 11 (23.9%) patients with liver metastasis. Most of the patients (21, 45.6%) received vinblastine, ifosfamide and cisplatin, whereas 13 (28.2%) patients received paclitaxel, ifosfamide and cisplatin regimen and 7 (15.2%) patients received GemOx regimen as the second-line chemotherapy. Median OS was observed to be 33.97 months and median progression-free survival was 29.01 months. Conclusion: Second-line chemotherapy in testicular germ cell tumours can result in long-term disease control and all patients who are fit to tolerate second-line therapy should be offered it. Patients with relapsed seminoma did better than relapsed non-seminomatous germ cell tumours.

Sentinel node biopsy in node negative early oral cancers: Solution to the conundrum!

Ideal management of the node-negative neck in early oral cancers is a debated issue. Elective neck dissection (END) is recommended in these patients as it offers a survival benefit. However, about 50-70% of patients who do not harbor occult metastasis are overtreated with this approach. Surgery is associated with morbidity, predominantly shoulder dysfunction. Numerous attempts have been made to identify true node-negative patients through imaging and prediction models but none have high diagnostic accuracy to safely spare the neck dissection. The recent publications of 2 large randomized controlled trials comparing the outcomes of sentinel node biopsy (SNB) and END have spurred interest in SNB. Both the trials reported SNB to be an oncologically safe procedure and spared unnecessary neck dissections. The functional outcomes of the trials showed that SNB limits the morbidity compared to END, which albeit evens out at the end of one-year post-surgery. Despite its benefits, SNB has failed to gain widespread acceptability due to various limitations including the need for infrastructure, equipment costs, staff, and multidisciplinary collaboration of nuclear medicine, surgical, and pathology fraternity. The labor-intensive pathology protocol with serial step sectioning and immunohistochemistry poses a challenge to the feasibility at a high-volume center. This perspective discusses these limitations and propose plausible solutions to the conundrum. To make it widely applicable and feasible across the globe efforts should be directed to understand biology better, find novel solutions, and implement the lessons learned over decades from other sites.