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Overview of the condition
In April 2020, Mr. Dong had an irritating dry cough of unknown cause, but it did not attract attention. Until the re-examination after 3 months, a class of round soft tissue masses were found in the upper lobe of the right lung during chest CT examination, and lung cancer was considered. Surgery was followed by postoperative pathology: (upper lobe of the right lung) hypodifferentiated carcinoma, immunohistochemistry: CgA+, Ki-67 +60%. Conjugated immunohistochemistry: consistent with neuroendocrine carcinoma, consider large cell neuroendocrine carcinoma, pT2aN0M0 IB stage.
Popular science trivia
1. Neuroendocrine tumors
Neuroendocrine tumors, as the name suggests, are tumors that originate from neuroendocrine cells, which are a large class of cells in the body that can produce a variety of hormones. Neuroendocrine tumors are also divided into functional and non-functional, non-functional most of them do not secrete hormones, nor will they have obvious symptoms, functional neuroendocrine tumors can secrete various hormones to produce corresponding clinical manifestations, such as gastrinoma can secrete a large amount of gastrin and cause duodenal ulcers; insulinomas can secrete a large amount of insulin leading to hypoglycemia. Neuroendocrine tumors are mostly benign, malignant neuroendocrine tumors are called neuroendocrine carcinoma, and common neuroendocrine cancers are large cell neuroendocrine carcinoma, carcinoid carcinoma, and small cell carcinoma. Among them, small cell carcinoma has a poor prognosis, such as small cell lung cancer.
2. Ki-67 in immunohistochemistry
Ki-67 is used to check the proliferation rate of cells, Ki-67 +60% refers to the fact that 60% of the cells in the sample are in the process of dividing and proliferating, and the higher the value, the worse the prognosis.
Mr. Dong did not implement chemotherapy as adjuvant due to the early clinical stage. But he understood that despite radical surgery, the "low differentiation", "neuroendocrine cancer" and "Ki-67 index" of pathological results still meant that the risk of recurrence and metastasis was high. It is obviously uneasy not to intervene by any means.
So Mr. Dong contacted the team of Professor Zhang Minghui of Tsinghua University School of Medicine to learn more about the principles and demonstration cases of NKT cell therapy, and especially hoped to try to reduce the risk of tumor recurrence and delay the time of recurrence/metastasis.
After reading Mr. Dong's medical records, Professor Zhang Minghui made the following analysis and judgment:
1. The patient's neuroendocrine tumor was treated with radical resection, and although the prognosis of large cell carcinoma was relatively good, the pathological results suggested low differentiation and there was still a great risk of metastasis.
2. The patient did not undergo other adjuvant therapy after surgery, which increased the risk of metastasis recurrence.
3. NKT treatment is the use of immune cells NKT to kill those tumor cells that may remain but are not easy to find, and basically no side effects are very friendly to patients. Systematic long-term stabilization can be achieved with NKT cell therapy after completion of conventional surgical treatment.
Therefore, Mr. Dong underwent NKT cell immunotherapy in September 2020, and the program was 1 course/month.
Interestingly, three months after Mr. Dong entered the NKT treatment, a re-examination found that there was a brain metastase! Is this NKT treatment not working?
With this question in mind, our medical team conducted a careful traceability and efficacy analysis:
1. By reviewing in detail the imaging and medical records of Mr. Dong in the three months before and after the baseline period (that is, the time when he began to enter NKT treatment), we found that before the operation, Mr. Dong had suspected signs of brain metastases, but the report did not show it. So much so that everyone ignores this important information! Mr. Dong performed the operation according to the established plan.
2. The slow onset time of cellular immunotherapy is its characteristic. Chemoradiation or other drug therapy, like sprinters, is explosive and can see results in a short time, but not for a long time. NKT cell therapy is just like a long-distance runner, usually in the second half of the force, can maintain stability for a longer time. This is also the best time to intervene in NKT cell therapy when the tumor burden is at its lowest after the end of pre-treatment.
3. It is true that some patients will still have new metastases or recurrences in the early stage of cellular immunotherapy, but they cannot rudely use the time standard for judging radiotherapy/chemotherapy to conclude that cellular immunotherapy is "ineffective". Only by stretching the patient's timeline can we observe the effectiveness of NKT in "suppressing" tumor activity after long-term treatment.
It is also because our team has many cases of more than 5 years to verify this view, so it is recommended that the efficacy evaluation time node of cellular immunotherapy be "6 months for preliminary evaluation and 12 months for annual evaluation".
Subsequently, Mr. Dong accepted Professor Zhang's suggestion and used the radiation knife to treat the brain metastases and then continue to follow up on NKT treatment. As of December 2021, a total of 15 months and 13 courses of re-infusion have been completed. In subsequent treatment, there was no progress in the repeated re-examination of the brain metastases, and the mental and physical state was very good.
Imagery
2020.12 Cranial magnetic resonance shows an abnormal signal foci of the right occipital lobe, combined with the medical history, considering metastatic foci. Although the disease progressed, considering that the evaluation time was only 3 months, it could not be judged that treatment was ineffective, and it was recommended to continue treatment and follow up closely. 2021.7 and 2021.11 Review the right occipital lobe metastases significantly reduced, considering changes after treatment. 2021.7 and 2021.11 Review chest CT showed that the right upper lobectomy was changed after resection, and no obvious signs of recurrence or metastasis were seen. 2021.7 Review of neck and abdomen ultrasound showed no obvious signs of metastases.
Swelling aspect
From 2020.10 to 2021.11, no abnormalities were found in the tumor markers.
quality of life
Mr. Dong's quality of life has been greatly improved. Appetite has improved significantly compared with before treatment, and the improvement of sleep quality has made the mental state very good, returning to the state before illness and not being affected by the disease.
Conclusion
Mr. Dong's case illustrates that NKT cell therapy plays an important role in combating neuroendocrine tumors with a high degree of malignancy, even if metastases appear early in the treatment, but with the advancement of further treatment, NKT cell therapy can provide long-term stability for patients. In the subsequent review, Mr. Dong evaluated the stability, and the overall mental and physical level was systematically improved.
Popular science knowledge, for reference only, individual patients are subject to clinical treatment.