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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 13  |  Issue : 2  |  Page : 81-84

High-grade esophageal neuroendocrine neoplasm with waxing and waning disease course and differential response to chemotherapy: Dual tracer positron emission tomography-computed tomography (18F-flurodeoxyglucose and 68Ga-DOTATATE) features and disease monitoring with functional molecular imaging


Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe; Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission10-Nov-2021
Date of Decision06-Dec-2021
Date of Acceptance07-Dec-2021
Date of Web Publication09-Feb-2022

Correspondence Address:
Prof. Sandip Basu
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe; Homi Bhabha National Institute, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_51_21

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  Abstract 

Esophageal neuroendocrine neoplasms (NENs) are uncommon type of esophageal malignancies. We describe the clinical course and molecular imaging features of the relatively rare esophageal malignancy (an aggressive poorly differentiated NEN) that was widely metastatic at the initial presentation. The patient underwent multiple cycles of chemotherapeutic regimens, employing cisplatin-etoposide and nanopaclitaxel-carboplatin and later on rechallenge with cisplatin-etoposide. There was observation of fluctuating disease course and differential characteristics of tumor lesions in terms of treatment response and recurrences with multiple cycles of chemotherapy. In view of the histopathology of high Mib-1 labeling index and dual tracer positron emission tomography-computed tomography (PET-CT) (flurodeoxyglucose [FDG] and 68Ga-DOTATATE) features, the patient was not a suitable candidate for 177Lu-DOTATATE PRRT and FDG PET-CT was the preferred imaging modality for both treatment response assessment and disease monitoring in this patient. The varying response among metastatic lesions in the same individual (with one lesion showing partial response and the other one demonstrating disease progression) was an additional noteworthy feature of the case.

Keywords: Neuroendocrine neoplasm, esophagus, neuroendocrine tumors, 68Ga-DOTATATE, flurodeoxyglucose, positron emission tomography-computed tomography, dual tracer positron emission tomography-computed tomography, 177Lu-DOTATATE PRRT


How to cite this article:
Sitani K, Basu S. High-grade esophageal neuroendocrine neoplasm with waxing and waning disease course and differential response to chemotherapy: Dual tracer positron emission tomography-computed tomography (18F-flurodeoxyglucose and 68Ga-DOTATATE) features and disease monitoring with functional molecular imaging. J Radiat Cancer Res 2022;13:81-4

How to cite this URL:
Sitani K, Basu S. High-grade esophageal neuroendocrine neoplasm with waxing and waning disease course and differential response to chemotherapy: Dual tracer positron emission tomography-computed tomography (18F-flurodeoxyglucose and 68Ga-DOTATATE) features and disease monitoring with functional molecular imaging. J Radiat Cancer Res [serial online] 2022 [cited 2022 Aug 16];13:81-4. Available from: https://www.journalrcr.org/text.asp?2022/13/2/81/337484


  Introduction Top


Esophageal neuroendocrine tumors (NETs) are relatively uncommon esophageal tumors. The reported incidence and prevalence of NETs have increased since the 1970s due to improved diagnostic techniques, yet these NETs are still rare, comprising around 1.4% of all gastroenteropancreatic NETs and 0.15%−2.80% of esophageal carcinomas. The most common reported symptom of esophageal NET is dysphagia and abdominal discomfort.[1] While esophageal NETs have the potential for distant metastasis, they commonly metastasize to lymph nodes, lung, liver, bone, and brain originating from an esophageal NET. Based on the clinical and histopathological similarity between NEC and small cell lung cancer (SCLC), the chemotherapeutic regimens for gastrointestinal NEC are generally the same as those for extensive SCLC, with one widely used option being etoposide (VP-16) plus cisplatin.[2]


  Case Report Top


A 36-years-old male, presented with chief complaints of dysphagia, gastrointestinal reflux disease, and burning sensation in the throat and weight loss in 2016. The baseline computed tomography (CT) of the thorax and abdomen demonstrated asymmetrical circumferential wall thickening involving the mid and lower end of the esophagus measuring 7.4 cm in length and 1.2 cm in maximal thickness causing luminal narrowing with proximal esophageal dilatation approximately 4.9 cm proximal to gastroesophageal junction. Enlarged gastrohepatic lymph node (largest measuring 2.3 cm × 2.8 cm) and multiple hepatic metastasis were noted in both the lobes of the liver (largest measuring 2.6 cm × 2.1 cm in segment V and 1.65 cm × 1.55 cm in segment III). The esophagogastroduodenoscopy showed a growth 33 cm from the incisor, the histopathology diagnosing it to be Grade III neuroendocrine carcinoma with Mib-1 labeling index (LI) of 70%, positive for synaptophysin and weakly positive for Chromogranin A. He received six cycles chemotherapy of cisplatin and etoposide during 2016–2017. Flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT post six cycles of chemotherapy revealed good partial response and post nine cycles of chemotherapy showed complete resolution of the celiac lymph nodes noted previously with the esophageal lesion seen on the previous scan showed no significant interval change. With further three more cycles of cisplatin-etoposide followed by a PET/CT was suggestive of stable disease. The patient was put off all chemotherapeutic drugs for 3 months following which a PET/CT was done which showed increase in size and metabolic activity of the esophageal lesion and the gastroesophageal lymph node as compared to the previous scan suggestive of disease progression. Following this, the patient was started on nanopaclitaxel-carboplatin underwent (nine cycles) and 10 fractions/30 Gy of external-beam radiation therapy till August 2018. The FDG-PET/CT (August 2018) showed complete resolution of the esophageal and the liver lesions are noted suggesting a complete response to therapy. The patient was observed for 3 months, with FDG-PET/CT for follow-up showed moderate to intense FDG avidity noted in the transmural thickening in the esophagus, FDG avid hypodense liver lesions noted in the segment V of the liver suggestive of disease recurrence. A repeat biopsy of the esophageal lesion confirmed the neuroendocrine nature of the cancer with poor differentiation. He was administered three more cycles of nanopaclitaxel-carboplatin following which a PET/CT documented decrease in size and metabolic activity of the esophageal and the liver lesion suggestive of partial response and was considered for five more cycles of nanopaclitaxel-carboplatin. A follow-up at FDG-PET/CT in August 2019 demonstrated the esophageal lesion to be stable as compared to previous scan, while there was the appearance of new FDG avid liver lesions suggestive of significant disease progression.

Following this patient was administered six cycles of nanopaclitaxel-carboplatin till February 2020, a FDG-PET/CT showed progression of the esophageal lesion and liver lesions both in terms of size and metabolic activity on FDG-PET CT [Figure 1]a, [Figure 1]b, [Figure 1]c. A 68Ga-DOTATATE PET-CT done earlier to assess the somatostatin receptor (SSTR) expression which showed a very low SSTR expression commensurate with the high grade of the tumor [Figure 2], hence not considered for therapy monitoring in this particular case. The high grade and low SSTR expression in this case also prevent the use of any receptor-directed therapy, such as 177Lu-DOTATATE PRRT. Following this, the patient was started on cisplatin-etoposide June − August 2020. A treatment response FDG-PET/CT for in September 2020 showed reduction in the FDG avidity of the liver lesions with ensuing central necrosis suggestive of partial response in this lesion, the esophageal lesion was stable in size and metabolic activity and increase in gastrohepatic and left paraaortic lymph nodes [Figure 1]a, [Figure 1]b, [Figure 1]c.
Figure 1: (a) (upper row). This figure gives a comparison of the MIP images of the 18 flurodeoxyglucose-positron emission tomography-computed tomography between September and March 2020 (left and right panel, respectively), showing the liver lesions which have partially responded and the lymph nodal lesions (gastrohepatic and paraaortic lymph nodes), which have seemed to progress. (a) (middle row). Computed tomography transaxial slices showing the size of the liver lesions reduced (right panel) on anatomical imaging, compared to the previous scan (right panel). (a) (lower row). Flurodeoxyglucose-positron emission tomography-computed tomography fused transaxial slices demonstrating flurodeoxyglucose avidity or the tumor metabolic activity of the liver lesions, to be stable between both the scans. (b) CT and FDG-PET/CT transaxial slices of the gastrohepatic lymph node which has progressed in size (left panel) compared to the previous scan (right panel) but stable in metabolic acitivity. (c) CT and FDG-PET/CT transaxial slices showing the left paraaortic lymph node which has increased in size increase in the metabolic activity as compared to the previous scan

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Figure 2: Baseline 68Ga-DOTATATE positron emission tomography-computed tomography undertaken earlier had shown low grade somatostatin receptor expression on the liver lesions and no somatostatin receptor expression in the lymph node lesions, which were flurodeoxyglucose avid, a feature commensurate with Mib-1 labeling index and high grade of the primary

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  Discussion Top


A retrospective multicenter study done by Lee et al.,[3] where out of 2037 cases of esophageal cancers 26 were proven to be esophageal NEC (1.3%), this study showed an overall survival of esophageal NEC to be 27.04 months (1–59 months), the prognosis depending on tumor size, this study concluded that although GEP-NET is seen to have a good survival and less aggressive potential, esophageal NET has a more aggressive course and they do behave differently. In the case study by Chin et al.,[1] unusual sites of metastasis of esophageal NET to the cervical lymph nodes, bone, and liver were observed, associated with death of the patient 10 days after the diagnosis of the tumor suggesting the aggressive nature of the tumor. In a series of 14 patients of esophageal NEC,[4] Egashira et al. gave some insight into the biology and treatment modalities for this tumor, showing that the median survival for disease limited to the esophagus was 17.5 months and for extensive disease was 8.5 months; limited disease was treated with surgery while extensive disease was treated with concurrent chemotherapy and radiotherapy along with surgery when feasible. They subdivided esophageal NECs into two categories based on immunohistochemistry: (i) Those that were positive for C-KIT and (ii) those that were positive for p53.

In a large retrospective study[5] including 80 patients of NEC of esophagus and cardia, 59 patients were of esophageal NEC, the conclusion formed by this study group was as follows: (a) Tumors are predominantly located in the center of the esophagus, (b) the small cell type comprises the main histological classification, (c) gross appearance is mainly of the ulcerative type, (d) around half of the patients have lymph node metastasis and the juxta-esophageal lymph node is the most frequently affected, and (e) patients who have distal metastasis or lymph node metastasis have a worse clinical outcome.

The esophageal neuroendocrine neoplasm (NEN) in the presented case was diagnosed to be a Grade III poorly differentiated NEN, not amenable to surgery in view of systemic metastatic disease at presentation. As described, the patient was administered on multiple cycles of cisplatin-etoposide and nanopaclitaxel (an albumin-based preparation of paclitaxel for enhancing solubility)-carboplatin for varying periods with disease response and recurrence and progression at various time points. The dual tracer PET-CT showed high uptake of FDG and minimal uptake of 68Ga-DOTATATE scan (reflecting the SSTR expression in the tumor) consistent with the high grade of the tumor and aggressive biology. In view of this feature, FDG PET-CT was utilized and the preferred PET tracer for both treatment response assessment and disease monitoring in this patient. Furthermore, noteworthy was the varying response among metastatic lesions, with one lesion showing partial response and the other disease progression, in the same individual.


  Conclusion Top


In summary, we described a relatively rare variety of esophageal malignancy (an aggressive poorly differentiated NEN), widely metastatic at the initial presentation, who underwent multiple cycles of chemotherapeutic regimens using cisplatin-etoposide and nanopaclitaxel-carboplatin and then cisplatin-etoposide again, with documentation of fluctuating and differential nature of the tumor in terms of treatment response and recurrences following the multiple cycles of chemotherapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Chin YP, Lai WF, Chiang MT, Chang SC. Esophageal neuroendocrine tumor with initial presentation as painless forehead and neck masses: A case report. Medicine (Baltimore) 2017;96:e9282.  Back to cited text no. 1
    
2.
Tomiyama T, Orino M, Nakamaru K, Tanaka T, Suzuki R, Okazaki T, et al. Esophageal large-cell neuroendocrine carcinoma with inconsistent response to treatment in the primary and metastatic lesions. Case Rep Gastroenterol 2018;12:234-9.  Back to cited text no. 2
    
3.
Lee CG, Lim YJ, Park SJ, Jang BI, Choi SR, Kim JK, et al. The clinical features and treatment modality of esophageal neuroendocrine tumors: A multicenter study in Korea. BMC Cancer 2014;14:569.  Back to cited text no. 3
    
4.
Egashira A, Morita M, Kumagai R, Taguchi KI, Ueda M, Yamaguchi S, et al. Neuroendocrine carcinoma of the esophagus: Clinicopathological and immunohistochemical features of 14 cases. PLoS One 2017;12:e0173501.  Back to cited text no. 4
    
5.
Hong L, Zhang Y, Liu Z. Neuroendocrine carcinoma of esophageal and gastric cardia: Clinicopathologic and immunohistochemistry study of 80 cases. Oncotarget 2018;9:10754-64.  Back to cited text no. 5
    


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