Preface
In mainland China, the incidence and mortality of esophageal cancer rank 7th and 5th among all malignant tumors, respectively1, and the main histopathological types are squamous cell carcinoma and adenocarcinoma. Primary small cell esophageal carcinoma (PSCCE) is a rare type of esophageal cancer with a specific pathology. It has the characteristics of high malignancy, easy recurrence and metastasis, and poor prognosis. There is a lack of prospective randomized controlled trials, and there is no standard standard protocol for treatment. The treatment is mainly based on the diagnosis and treatment protocol of small cell lung cancer. The existing chemotherapy, radiotherapy and other treatments have limited effects and cannot meet the clinical needs. Effective treatments are needed to further improve long-term survival and quality of life. Based on the results of the CAPSTONE-1 study, adebelimab in combination with chemotherapy was included in the 2023 CSCO guidelines for the diagnosis and treatment of small cell lung cancer as first-line treatment and grade I preferred recommendation2. At the same time, breakthroughs have also been made in the neoadjuvant therapy of esophageal cancer, which is expected to bring new options and hope to patients with small cell esophageal cancer.
In order to strengthen the academic exchange of such rare diseases and strengthen the dissemination of the concept of tumor immunotherapy, Professor Li Changying from Dalian Port Hospital is invited to share the diagnosis and treatment of a patient with advanced small cell esophageal cancer with multiple metastases and make comments, aiming to provide ideas and references for the selection and management of clinical treatment options for small cell esophageal cancer.
Expert Profile
Prof. Changying Li
Chief Physician of the Department of Medical Oncology of Dalian Port Hospital
Member of the Oncology Branch of Dalian Medical Association
Member of the first Oncology Branch of Dalian Medical Doctor Association
Member of the Tumor Rare Mutation Group of the Lung Cancer Prevention and Control Professional Committee of Liaoning Preventive Medicine Association
He is a member of the Cancer Nutrition Committee of the Chinese Anti-Aging Promotion Association
He is a member of the Gastrointestinal Oncology Professional Committee of the Chinese Geriatric Health Care Association
Case sharing
Basic information
● The patient is a 65-year-old male.
● He was admitted to our hospital for diagnosis and treatment due to "hoarseness, difficulty swallowing, choking on water, and weight loss for more than 1 month". ECOG score: 1 point.
● Past medical history & personal history & family history: There is a history of type 2 diabetes and hypertension in the past, all of which are well controlled. He has been a smoker for 20 years, smokes 20 cigarettes a day, and occasionally drinks alcohol. Denial of a history of hereditary diseases, tumors, and similar conditions in families.
INVESTIGATIONS
● Chest CT (2023.9.7): mass lesions in the middle and lower esophagus, clumpy soft tissue density shadows can be seen in the right parathyroid and right upper mediastinum, and cervical and mediastinal lymph node metastasis is considered.
Fig.1 Chest CT scan (2023.9.7)
● CT with full abdominal contrast (2023.9.7): multiple metastatic intrahepatic cancers, the largest one is 2.3×4.4cm, bilateral adrenal metastases, retroperitoneal and multiple lymph node metastases in the hilar area.
Fig.2 CT examination of the whole abdomen with contrast (2023.9.7)
● Gastroscopy (2023.9.8): 21-28cm from the incisors, the right posterior wall of the esophagus can be seen to be raised, the center is uneven with white lichen, and the anterior and posterior walls of the right esophageal wall are mainly 30-39cm away from the incisors. Microscopic diagnosis: esophageal cancer, chronic atrophic gastritis with multiple erosions.
Fig.3 Gastroscopy (2023.9.8)
●Neck ultrasound: multiple hypoechoic sensations in the right neck, the larger one is 42.7×27.6 cm, the internal echo is uneven, and blood flow signals are seen peripherially.
● Esophageal histopathology: low-grade malignant tumors, immunohistochemical testing is recommended to assist in diagnosis.
Clinical diagnosis
Esophageal cancer stage IV with multiple liver metastases, bilateral adrenal metastases, and multiple lymph node metastases (right neck, mediastinum, retroperitoneal, hilar area).
Diagnosis and treatment: first-line treatment
The first cycle of chemotherapy was nab-paclitaxel 470 mg d1 + cisplatin 30 mg d1-4, and the patient had second-degree alopecia and no gastrointestinal reaction. 2023.9.22Immunohistochemical detection and pathological consultation showed small cell esophageal cancer. At the beginning of the second cycle, adebelimab 1200mg + nab-paclitaxel 470mg d1 + cisplatin 30mg d1-4 regimen was given for a total of 5 cycles, and the patient only experienced second-degree gastrointestinal reactions and slight numbness of the hands and feet. The efficacy evaluation reached partial remission (PR), and the imaging disappearance of esophageal lesions, liver metastases, and cervical and mediastinal lymph nodes were significantly smaller than baseline
Fig.4 The efficacy of abdominal contrast-enhanced CT liver metastasis was assessed as PR
baseline
2 cycles
4 cycles
6 cycles
Fig.5 The efficacy of lymph node metastasis in the right neck of chest CT was assessed as PR
baseline
2 cycles
4 cycles
6 cycles
Fig.6 The efficacy of mediastinal lymph node metastasis in chest CT was assessed as PR
baseline
2 cycles
4 cycles
6 cycles
Fig.7 Efficacy evaluation of esophageal cancer lesions by chest CT is CR (further confirmation by gastroscopy)
Diagnosis and treatment: second-line treatment
The patient presented with stage IV esophageal cancer with multiple distant metastases. After receiving first-line treatment, the primary lesion disappeared, and the efficacy evaluation of multiple metastases reached PR, but due to the severity of the patient's condition at the time of presentation, the patient developed bone metastases while obtaining the curative effect. Therefore, from February 1, 2024, the original chemotherapy regimen of "nab-paclitaxel 470mg d1 + cisplatin 30mg d1-4" will be adjusted to "etoposide 150mg d1-3 + carboplatin 400mg d1 chemotherapy", and the combination of adebelimab 1200mg will continue for 3 cycles of treatment so far. The patient tolerated well, with a marked reduction in hoarseness, disappearance of dysphagia symptoms, weight gain, and good quality of life scores.
Case summary
In this case, a 65-year-old man was diagnosed with esophageal small cell carcinoma with multiple metastases, stage IV. After 9 cycles of adebelimab combined with chemotherapy, PR was achieved, clinical symptoms were reduced, and the safety profile was good.
Expert commentary
Professor Li Changying
In patients with advanced esophageal cancer with multiple metastases in the distance, surgical resection of the lesion is no longer feasible, which poses a huge treatment challenge for our oncologists. How to make patients live better and longer? Immunotherapy has taken on an important role and has become one of the basic treatments for esophageal cancer. Immunotherapy not only shows excellent efficacy in the first-line treatment of advanced esophageal cancer, but also shows good potential in neoadjuvant therapy and adjuvant therapy, and the number of treatment lines is gradually moving forward. In 2023, the NAITON-1907 study, a phase Ib trial of adebelimab monotherapy for the neoadjuvant treatment of locally advanced resectable esophageal squamous cell carcinoma, initiated by Professor Tan Lijie of Zhongshan Hospital of Fudan University, was released in Nature Medicine3, confirming that it has great potential for application in the field of esophageal cancer. In the future, clinicians need to continue to explore how to further screen the dominant population of immunotherapy, and there is still a lack of specific biomarkers as a guide.
Primary small cell esophageal carcinoma (PSCCE) is the most common extrapulmonary small cell carcinoma with a low incidence. It is characterized by high aggressiveness and high metastasis rate, and its biological behavior and treatment mode are different from those of squamous cell carcinoma and adenocarcinoma, and the prognosis is poor. At present, there is a lack of prospective studies in clinical treatment, and there are no relevant guidelines. Small cell esophageal cancer and small cell lung cancer are similar in many ways. From the perspective of biological characteristics, there was no significant difference in the positive distribution of anti-apoptotic proteins Survivin, caspase-3, BCL-2 and MTP53 in the apoptotic pathway of the two types of cancers4. There are also some similarities in genetic variants that may affect tumor development and patient survival5. Therefore, for the treatment of PSCCE, the treatment strategy that refers to the small cell lung cancer guidelines may be effective. The CAPSTONE-1 study, the first of its kind in China, showed that patients with extensive-stage small cell lung cancer achieved a 3-year OS rate of 21.1% with a good safety profile6. Considering the similarity of the two types of cancer at the molecular biological level and the clinical study data, adebelimab in combination with chemotherapy may have potential anti-tumor activity in the treatment of extensive-stage small cell esophageal cancer.
The patient in this case was a patient with advanced small cell esophageal cancer with multiple metastases. At the time of diagnosis, the tumor burden was heavy, and there were already feeding problems, and the subsequent risks such as nutrition and obstruction were exposed, and it was easy to lose the opportunity for treatment. Therefore, the choice of first-line treatment is particularly important, which is related to the patient's compliance and confidence in subsequent treatment. In view of the fact that immunotherapy combined with chemotherapy has become the first-line standard treatment for advanced esophageal cancer, individualized treatment is selected based on the basic condition and pathological type of patients. In this case, the first-line and second-line chemotherapy regimens were exchanged, and the initial treatment of adebelimab combined with nab-paclitaxel + cisplatin achieved significant efficacy (PR), and the tolerability was good, and the quality of life was significantly improved, which enhanced the patient's confidence in treatment. The efficacy of second-line therapy is stable (SD), and the patients are still in a state of sustained clinical benefit. Considering that this patient does not exclude the possibility of other pathological types at the same time, many scholars at home and abroad also agree with the pluripotent stem cell theory of PSCCE, and the tumor immune microenvironment of PSCCE may improve the immune response rate. The specific mechanism is expected to be further studied. In summary, the application of PD-L1 combined chemotherapy (adebelimab plus nab-paclitaxel + cisplatin in the first line and etoposide + carboplatin in the second line) showed long-lasting and deep benefits and a controllable safety profile in this advanced small cell esophageal cancer case. It provides another potential option for the treatment of patients with small cell esophageal cancer, and looks forward to further clinical studies to confirm.
Bibliography:
1. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024. Volume 4, Issue 1, Pages 47-53.
2. 2023 CSCO guidelines for the diagnosis and treatment of small cell lung cancer
3. Yin J, Yuan J, Li Y, et al. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023; 29(8):2068-2078.
4. Wang Yan, Song Ying, Xu Linping, et al.Study on the biological characteristics of apoptosis of esophageal small cell carcinoma and small cell lung cancer[J].China Oncology, 2008, 17(12):3.
5. Dong Li.Association between genetic variation and survival of esophageal cancer and small cell lung cancer[D].Peking Union Medical College,2013.
6. Ying C, Wang J, Zhou C, et al. ESMO IO, 2023: 84P
编辑：Julius
审校：Dreams
Typesetting: KIKI
Execution: Uni
This platform aims to deliver more medical information to healthcare professionals. The content published on this platform should not be used as a substitute for professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice. If such information is used for purposes other than understanding medical information, the platform does not assume relevant responsibilities. This platform does not mean that it agrees with its descriptions and views on the published content. If copyright issues are involved, please contact us, and we will deal with it as soon as possible.