Tongxin Association Case No. 5 | Multidisciplinary collaboration to help high-risk god mothers survive long-term-high-risk neuroblastoma long-term survival case sharing

Written by: Zhu Jia, Sun Yat-sen University Cancer Center, Child Oncology Department Case Brief 1.
Basic information Li, female, 2 years old.

Neuroblastoma was admitted to our hospital 3 weeks after a course of chemotherapy outside the hospital.

2.
There was no obvious cause of bilateral hip pain and claudication in the patient with current medical history from 2013 to December.
CT of the abdomen of the local hospital: space-occupying lesion in the left adrenal area, about 7.
7cm*6.
5cm, considering neuroblastoma.

Bone scan: The bone metabolism of the left frontal parietal bone and occipital bone is abnormal.
Considering bone metastasis, the sternum bone metabolism is increased.

Head MRI: multiple meningeal lesions, metastases? Bone marrow smear: small round cells, arranged in nests or chrysanthemum clusters, suggesting neuroblastoma bone marrow metastasis.

N-myc(-).

According to the neuroblastoma stage IV high-risk group, the outer hospital underwent a course of CAV (cyclophosphamide, pirarubicin, vincristine) chemotherapy on December 27, 2013, and the symptoms of bone pain disappeared after chemotherapy.

2014-1-16 Referred to our hospital for increased neuron-specific enolase (NSE), increased VMA (vanillin mandelic acid)/Cr (creatinine) and HVA (homvanillic acid)/Cr (creatinine) , Bone marrow smear suggests neuroblastoma bone marrow metastasis.

Color Doppler ultrasound: a solid mass in the left adrenal area, about 54*53mm in size.

The chest radiograph showed no abnormalities.

3.
On physical examination, there is no obvious swelling of the superficial lymph nodes, a nodule about 2.
0cm*1.
5cm in size can be palpable on the left forehead, and there is no ecchymosis around the orbit.

The heart and lungs are nothing special.

The abdomen was flat and soft, no tenderness and rebound pain, no masses were palpated, and no swelling of the liver and spleen.

4.
Auxiliary examination 2013-12-24 outside hospital CT: space-occupying lesions in the left adrenal gland area, about 7.
7cm*6.
5cm, consider neuroblastoma. 2013-12-27 Brain MRI in the outside hospital: multiple meningeal lesions, possible metastasis.

2013-12-30 Outer Hospital ECT: Abnormal bone metabolism of the left frontal parietal bone and occipital bone.
Consider bone metastasis.

2014-1-14 Our hospital consults the external hospital bone marrow film: see scattered and clustered malignant tumor cells, these cells are large in size, round or round, with a lot of cytoplasm, light blue, with a feeling of shedding, cells There are fibrils connected between them, the nucleus is round, oval, and occasionally sunken, the nuclear chromatin is relatively thick, and most of the nucleoli are seen in different numbers.

2014-1-14 My hospital bone marrow film: malignant tumor cells are occasionally seen at the end of the film.
These cells are large in size, round or round, with a large amount of cytoplasm, light blue, with a feeling of shedding, and there are fibrous phases between the cells The nucleus is round and elliptical, and occasionally sunken, with thick nuclear chromatin.

2014-1-16 our hospital NSE 87.
56ng/ml, VMA/Cr 51.
8mmol/mmol, HVA/Cr 95.
7mmol/mmol.

5.
Admission to diagnosis of left adrenal neuroblastoma stage IV high-risk group 6.
Treatment and outcome 2014-1-18 to 2014-3-26 continue VIP (etoposide, ifosfamide, cisplatin) in our hospital /CAV chemotherapy for 3 courses.

Bone marrow after 3 cycles: complete remission (CR).

Re-examination of CT after 4 courses: a mass of about 6cm*6cm*5.
8cm in left adrenal gland with retroperitoneal lymph node metastasis.
Left pelvic lymph node metastasis was not excluded.
Curative effect: stable primary and frontal metastatic disease (SD), bone marrow metastasis Stove CR.

2014-4-17 Complete resection of left adrenal tumor + retroperitoneal lymph node dissection in Zhongshan First Hospital.

Postoperative pathology showed: ganglion cell neuroblastoma, metastasis to the iliac vessels behind the pelvic bladder (2/2), no tumors in the abdominal lymph nodes (0/14), and no residual tumors on the abdominal CT after operation.

On April 20, 2014, a course of chemotherapy with nedaplatin + VP16 regimen was performed in an outside hospital.

Considering the poor effect of the original program, our hospital changed to 2 courses of VIT (vincristine, temozolomide, irinotecan) chemotherapy on May 13, 2014 and June 4, 2014.

Re-examination of the brain MRI: the left frontal mass, roughly the same as before.

After the children's tumor MDT consultation in our hospital, it is recommended that the frontal metastases be surgically removed and the primary abdominal tumor and craniocerebral metastases should be treated with radiotherapy after the operation.

2014-7-7 in our hospital neurosurgery department underwent left frontal lesion microresection and left frontal mass resection, the affected skull was completely resected and the skull was repaired with titanium mesh.

Pathology: Ganglion cell neuroblastoma (differentiated), involving the skull.

There was no residual tumor on brain MRI in our hospital after operation.

Four courses of VIT chemotherapy were continued after the operation.

From August 29, 2014, craniocerebral radiotherapy (conformal intensity modulation) was started, the first segment of whole brain radiotherapy, the dose was 20.
8Gy/13F, and the second segment of meningeal metastases was locally pushed 14.
4Gy/9F.

2014-10-23 Started radiotherapy in the abdominal area and lymphatic drainage area (three-dimensional conformal), the dose was 20Gy.

After radiotherapy, the chest, abdomen and pelvis CT, craniocerebral MRI, ECT, bone marrow and other examinations were rechecked, and no tumor was found.
The curative effect: CR.

From December 2014 to June 2015, oral CTX+NVB maintenance chemotherapy.

7.
Follow-up The child has stopped treatment for 5 years, followed up until March 22, 2021, and continued complete remission.

Comment: Neuroblastoma is the most common extracranial solid tumor in children.
Two-thirds of patients are in advanced stage when they are first diagnosed.
The primary site is more common in the adrenal gland and retroperitoneum.
Distant metastasis often involves bone and bone marrow.

The primary site of this patient is the left adrenal gland.

Metastasis to the retroperitoneal lymph nodes, bone marrow, forehead and frontal parietal bone, stage IV.

The patient's age is more than 1.
5 years old, and the risk is high.

Neuroblastoma can secrete catecholamines, which are metabolized into VMA and HVA in the body, and then excreted in the urine.

Therefore, urine VMA and HVA are correspondingly increased, which has higher sensitivity and specificity for neuroblastoma.

In the absence of tumor pathology, according to the patient’s bone marrow puncture smear, characteristic neuroblasts (small round cells, arranged in nests or chrysanthemum clusters) accompanied by elevated urine catecholamine metabolites can be clinically diagnosed as neuroblasts tumor.

The initial diagnosis of this case met the clinical diagnostic criteria.
After chemotherapy and surgery, the pathology of the tumor was removed, and the final diagnosis was confirmed.

The high-risk group of neuroblastoma has a poor prognosis.
At present, under the comprehensive treatment model of chemotherapy + surgery + radiotherapy ± autologous hematopoietic stem cell transplantation + immunotherapy, the 5-year overall survival rate is about 50% to 60%.

However, for most children in China, GD2 monoclonal antibody is still out of reach.
The treatment of children with neuroblastoma in China is mainly a comprehensive treatment model of chemotherapy + surgery + radiotherapy + transplantation + maintenance treatment.

This patient is a successful case of neuroblastoma treatment in the high-risk group.
The patient achieved complete remission after multidisciplinary treatment with chemotherapy, surgery, and radiotherapy, and has survived 69 months without recurrence so far.

The reasons are as follows: First, the long-term survival of this patient benefits from multidisciplinary comprehensive treatment.

After chemotherapy, the tumor pathologically changed into a componentized type, the primary tumor was completely removed, and the metastatic frontal bone tumor was also completely removed by surgery, supplemented by radiotherapy.

Complete resection and radiotherapy of metastases can improve the local control rate of neuroblastoma.

From this case, it is also one of the reasons for long-term recurrence-free survival.

Secondly, this patient was given oral cyclophosphamide and vinorelbine maintenance therapy, and maintenance therapy also played a role in removing minimal residual disease and long-term recurrence-free survival.

It should also be noted that high-risk neuroblastoma also has biological heterogeneity.

N-myc amplification, ALK mutation, and abnormalities of segmental chromosomes 1p, 1q, 3p, 11q, 14q and 17p are all poor prognostic factors.

This patient had no N-myc amplification, and was sensitive to chemotherapy at the first diagnosis, plus a series of standard treatments such as chemotherapy under the guidance of stratification, complete resection of primary and metastatic lesions, and primary, cranial, and local radiotherapy.
The patient finally achieved complete remission and survived for a long time. With the deepening of research, risk stratification needs to be further subdivided in combination with biological examination.

High-risk neuroblastoma needs to rely on multidisciplinary comprehensive treatment.
With the introduction of GD2 monoclonal antibody, it is expected to further improve the survival of high-risk neuroblastoma patients in China.

In the past, it is recommended to hit the target and turn the danger to safety-Inflammatory myofibroblastoma case sharing | Tongxin Association Case Study Professor Zhang Yizhuo comments | Nature Medicine blockbuster article: Whole genome, transcriptome and methylated genome analysis improves the risk of high-risk childhood tumors Target Discovery Tongxin Association Case Sharing | Multidisciplinary Comprehensive Treatment to Cure Hepatoblastoma Lung Metastasis Children with "Tong" Heart Association Cases | Declare War on Sarcoma! HER2 CAR T cell treatment of HER2-positive children with metastatic rhabdomyosarcoma can be expected to be effective [Tongxin Association Case] ​​Column Introduction The prognosis of childhood tumors in my country is far behind that of developed countries.
The fundamental reason lies in the imbalance of regional development in my country and the insufficient level of average standardized diagnosis and treatment.
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In order to promote the development of standardized treatment of children's tumors in my country, Yimaitong and the Department of Children's Oncology, Sun Yat-sen University Cancer Center, set up a column of "Children's Association Cases", aiming to share standardized diagnosis and treatment cases of children's tumors and help pediatric oncologists in primary hospitals to enrich their diagnosis and treatment experience .

Sun Yat-sen University Cancer Center is the first cancer hospital in China to set up the specialty of pediatric cancer chemotherapy.

The Pediatric Oncology Department of the center focuses on chemotherapy and combines with the departments of surgery, radiotherapy and other disciplines to conduct multidisciplinary comprehensive diagnosis and treatment of pediatric oncology patients.
It has strong technical force, rich experience, standardized treatment, and the treatment plan is in line with foreign developed countries.

He led the formulation of guidelines for diagnosis and treatment of CSCO lymphoma, and guidelines for diagnosis and treatment of medulloblastoma.