In recent years, gastrointestinal stromal tumors (GIST) have progressed rapidly in diagnosis, treatment and research. In order to promote the standardized diagnosis and treatment of GIST and establish a multidisciplinary cooperation model including pathology, imaging, surgery and internal medicine, it is necessary to develop expert consensus or clinical practice guidelines as an important reference. The previous Chinese consensus on the diagnosis and treatment of gastrointestinal mesenchymal tumors (2011 version) used to play an active role.
In the following years, the expert committee on gastrointestinal mesenchymal tumor consulted widely on the consensus, organized several expert discussions, and revised and updated the 2011 version according to the latest information. In December 2012, the 2012 version of the Chinese consensus on the diagnosis and treatment of gastrointestinal mesenchymal tumor was formed and is now published.
I. Principles of pathological diagnosis
Definition of GIST
GIST is the most common mesenchymal-derived tumor of the gastrointestinal tract, which can range from benign to malignant on the clinical spectrum. Immunohistochemical detection usually expresses CD117, shows Cajal cell (Cajal cell) differentiation, and most cases contain c-kit or PDGFRA activating mutations [1].
By current diagnostic criteria, most smooth muscle tumors previously diagnosed (including smooth muscle blastoma) are actually GIST. tumors once defined as gastrointestinal autonomic neuroma (GANT) have the same clinical presentation, histologic morphology, immunophenotype, and molecular pathology as GIST and are classified as GIST, and no longer as a separate lesion type.
(II) Requirements for specimens
Post-surgical specimens need to be fixed in a timely manner. Specimens should be sent to the pathology department within 30 minutes after isolation and fixed by complete immersion in sufficient neutral 10% formalin solution (at least 3 times the volume of the specimen). For tumor tissues ≥2 cm in diameter, they must be cut at 1 cm intervals to achieve full fixation. The fixation time should be 12~48h to ensure the feasibility and accuracy of subsequent immunohistochemistry and molecular biology detection. If available, fresh tissues should be properly frozen for future genetic testing.
(C) The pathological diagnosis of GIST based on
1, basic diagnosis.
(1) Histologically, GIST can be divided into 3 major categories based on the morphology of tumor cells: spindle cell type (70%), epithelioid cell type (20%) and mixed spindle cell-epithelioid cell type (10%). A few cases may contain pleomorphic cells, commonly found within epithelioid GIST. The interstitium may be sclerotic, especially in small tumors with calcification, and may occasionally be mucinous;
(2) The immunohistochemical detection rate is about 94%-98% for CD117 and 94%-96% for DOG1 [3-5], where CD117 and DOG1 have a high concordance. Most spindle cell GISTs (especially gastric GISTs) express CD34, but the expression is inconsistent in epithelioid GISTs, and CD34 can be negative in small intestinal GISTs.
The combined use of these 3 markers is recommended in routine workup. It should also be noted that some non-GIST tumors can also express CD117 and or DOG1, such as pancreatic smooth muscle tumors, retroperitoneal smooth muscle tumors, intrapelvic smooth muscle tumor disease, malignant melanoma of the rectum and anal canal, and uterine smooth muscle sarcoma [4,7-9], which should be identified in combination with other markers (e.g., desmin and HMB45).
In addition, immunohistochemical detection of succinate dehydrogenase B (SDHB) is helpful to help identify succinate dehydrogenase-deficient GIST (SDH-deficient GIST). This type of GIST does not express SDHB and is often clinically associated with the Carney triad (GIST, paraganglioma and pulmonary chondrosarcoma) or CarneyCStratakis syndrome (familial GIST and paraganglioma).
2. Diagnostic ideas and criteria.
(1) For cases with histological patterns consistent with typical GIST and diffuse positive for CD117 and DOG1, the diagnosis of GIST can be made;
(2) For cases with histological pattern considered as GIST, but CD117+, DOG1- or CD117-, DOG1+, the diagnosis of GIST can be made after excluding other types of tumors, and if necessary, further molecular pathology testing can be performed to determine the presence of c-kit or PDGFRA gene mutation. If there is no c-kit or PDGFRA mutation even after molecular pathology, it is recommended to ask the pathologist to make the final diagnosis;
(3) For cases with histological patterns consistent with typical GIST but negative for both CD117 and DOG1, further testing for c-kit gene and or PDGFRA gene is required after excluding other types of tumors (e.g. smooth muscle tumors, nerve sheath tumors and fibromatosis). If there is a mutation of c-kit gene or PDGFRA gene, the diagnosis of GIST can be made, and if there is no mutation of c-kit gene or PDGFRA gene, the diagnosis of wild-type GIST can also be made, see Figure 1.
Figure 1 GIST pathology diagnosis idea
3, genetic testing: Genetic testing should be performed in a qualified laboratory, and the polymerase chain reaction (PCR) amplification-direct sequencing method is recommended to ensure the accuracy and consistency of the test results. Gene mutation testing is important to help diagnose some difficult cases, predict the efficacy of molecularly targeted therapeutic agents and guide clinical treatment.
The expert committee recommends that genetic analysis should be performed when the following conditions exist.
(1) c-kit or PDGFRA mutation analysis should be performed for difficult cases to clarify the diagnosis of GIST;
(2) Those who intend to use targeted therapy preoperatively;
(3) All first diagnosed recurrent and metastatic GIST, proposed to be treated with molecular targeted therapy;
(4) Those at moderate-to-high risk of recurrence after primary resectable GIST surgery, to be treated with adjuvant imatinib;
(5) Identification of NF1 type GIST, complete or incomplete Carney’s triad, familial GIST, and pediatric GIST;
(6) Identification of concurrent and heterochronous multiple primary GISTs [12]; (7) Secondary drug resistance requiring retesting.
Loci for detection of mutations should include at least exons 9, 11, 13 and 17 of the c-kit gene and exons 12 and 18 of the PDGFRA gene. Since the majority of GISTs (65%-85%) have mutations in exon 11 or exon 9 of the c-kit gene [13], priority can be given to testing these two exons. For patients with secondary drug resistance, additional testing of exons 13, 14, 17 and 18 of the c-kit gene is advisable.
4, The concept of micro GIST: GISTs ≤1 cm in diameter are defined as micro GISTs.
5, Risk assessment of primary completely resected GIST: The biological behavior of GIST varies from case to case, and the 2013 edition of WHO Soft Tissue Tumor Classification classifies it into benign, undetermined malignant potential and malignant types.
The assessment of the risk level for limited GIST should include the site of the primary tumor, the size of the tumor, the nuclear split image, and whether rupture occurs. The National Institutes of Health (NIH) risk classification, which includes tumor size and the number of nuclear divisions per 50 high-powered views, has been used (data in Table 1 are based on a 0.65 microscope lens; emphasis must be placed on the 50 high-powered views where nuclear divisions are more abundant).
Several retrospective studies have confirmed the clear correlation between these two indicators and the prognosis of GIST, and have also found that relying on them alone to predict the prognosis of GIST patients is not sufficient. Therefore, in 2008, Joensuu revised the NIH risk classification system to include primary tumor site (non-gastric GIST has a worse prognosis than gastric GIST) and tumor rupture as basic indicators of prognosis in the new risk classification, as shown in Table 1.
Table 1 Risk grading after primary GIST resection
Risk level Tumor size Nuclear schwannoma number Primary tumor site
Grading (cm) (/50HPF)
Very low <2 ≤5 Any site
Low >2 ≤5 ≤5 Any site
Moderate ≤2 >5 Non-gastric primary
>2 ≤5 >5 Stomach
>5≤10 ≤5 Stomach
High Any Any Tumor rupture
>10 Any Any site
Any >10 Any site
>5 >5 Any site
>2≤5 >5 Non-gastric primary
>5≤10 ≤5 Non-gastric primary
Both the 2010 WHO Gastrointestinal Tract Tumor Classification and the 2013 WHO Soft Tissue Tumor Classification adopted the 6-category, 8-grade criteria reported by Miettinen et al [1,17] and classified GIST into benign, undetermined malignant potential, and malignant categories based on prognostic subgroups, see Tables 2 and 3.
Table 2 Prognosis of GIST patients (based on long-term follow-up data)
Tumor parameters Disease progression (% of patients)a
Prognostic grouping Tumor size Nuclear schistogram (50 high-powered field of view) Gastric GIST Small intestine GIST
1 ≤2 ≤5 0 0
2 >2 ≤5 ≤5 1.9 4.3
3a >5≤10 ≤5 3.6 24
3b >10 ≤5 12 52
4 ≤2 >5 0b 50b
5 >2 ≤5 >5 16 73
6a >5 ≤10 >5 55 85
6b >10 >5 86 90
aStudy based on AFIP of 1784 patients
bLower number of cases. Data based on literature18.
Table 3 Benign and malignant nature of GIST and their corresponding ICD-O codes
Benign GIST Prognostic grouping 1, 2, 3a 8936/0
GIST of undetermined malignant potential Prognostic subgroup 4 8936/1
Malignant GIST Prognostic subgroup 3b, 5, 6a, 6b 8936/3
6. GIST after targeted therapy: After targeted therapy, GIST may undergo necrosis and or cystic transformation. In some cases, the cell density is significantly reduced, the tumor cell component is sparse, and the interstitium is accompanied by extensive collagenization, which may be accompanied by more or less inflammatory cell infiltration and histiocytic reaction. In a few cases, rhabdomyosarcoma-like differentiation [19], or dedifferentiation [20] may occur.
(iv) Standardization of GIST pathological diagnosis report
The pathology report should be standardized and must accurately indicate the primary site, tumor size, nuclear splitting image and tumor rupture. Immunohistochemical test results should be attached to the report, and molecular pathology test results can be attached separately. See annex.
II. Principles of surgical treatment
(A) Principles of biopsy
If it is estimated that the surgery can be completely resected and does not seriously affect the function of related organs, surgery can be performed directly. Recent NCCN guidelines [13] have clarified that biopsy is required if neoadjuvant therapy is needed. It should be noted that inappropriate biopsy may cause tumor rupture, bleeding and increase the risk of tumor dissemination, and caution is needed.
1. Principles of pre-surgical biopsy.
①For most GISTs that can be completely resected, routine biopsy or puncture before surgery is not recommended.
②For those who need combined multi-vessel resection, or those who may affect the function of related organs after surgery, preoperative biopsy can be considered to clarify the pathological diagnosis and help to decide whether to operate directly or to treat with preoperative drugs first;
③ For lesions that cannot be resected or are estimated to be difficult to obtain R0 resection and are to be treated with preoperative medication, biopsy should be performed first.
2, hollow core needle aspiration biopsy tissue examination: it is recommended to perform hollow core needle aspiration (CNB) under ultrasound or CT guidance, and the consistency of immunohistochemical staining expression of surgical specimens can reach more than 90%, and the diagnostic accuracy also reaches more than 90%. Note that immunohistochemical labeling of CNB specimens must be combined with CD117, DOG1 and CD34 labeling. The use of FNB (fine needle biopsy) for biopsy is not recommended.
3.Endoscopic biopsy: It is often difficult to make a clear pathological diagnosis by endoscopic biopsy, because tumor tissue can only be obtained when GIST involves mucosa, and it may occasionally lead to serious bleeding of the tumor, which needs to be performed with caution.
4.Intraoperative frozen biopsy: Intraoperative frozen biopsy is not recommended. Unless lymph node metastasis around GIST is suspected during surgery or other malignant tumors cannot be excluded.
(II). Indications for surgery of GIST
①Limited GIST, in principle, can be surgically resected; for unresectable limited GIST, or those who can be resected at the borderline, but the risk of resection is high or the function of the organs is seriously affected, preoperative drug therapy is recommended first, and surgery will be performed after the tumor shrinks.
②Asymptomatic proposed GIST located in the stomach with a maximum diameter ≤2 cm, once diagnosed, ultrasound endoscopic risk classification should be determined according to its presentation (adverse factors are irregular border, ulceration, strong echogenicity and heterogeneity). If combined with adverse factors, resection should be considered; if no adverse factors are present, ultrasound endoscopy can be reviewed periodically. For GIST located in rectum, surgical resection is preferred because of the higher malignancy and the corresponding increase in difficulty of surgery to preserve anal function once the tumor increases.
③ Recurrent or metastatic GIST is treated differently in the following cases.
Without molecular targeted drug treatment, but it is estimated that complete resection can be achieved and the risk of surgery is not significant, surgical resection combined with drug treatment can be considered.
For recurrent or metastatic GIST with effective drug therapy and stable tumor maintenance, surgical resection of all recurrent metastatic lesions is recommended if all of them are estimated to be resectable.
For locally progressive recurrent metastatic GIST, given that the overall control is satisfactory after molecular targeted drug therapy and only a single or a few lesions progress, surgical resection may be considered in carefully selected patients in good systemic condition. Intraoperatively, the progressive lesions are removed and as many metastases as possible are removed to complete a more satisfactory tumor reduction surgery.
Recurrent metastatic GIST with extensive progression under molecular targeted drug therapy is in principle not considered for surgical treatment.
Palliative tumor reduction surgery is limited to cases where the patient can tolerate the surgery and where the surgery is expected to improve the patient’s quality of life.
(iv) Indications for emergency surgery: Emergency surgery is required when GIST causes complete intestinal obstruction, gastrointestinal perforation, gastrointestinal hemorrhage where conservative treatment is ineffective, and abdominal hemorrhage caused by spontaneous rupture of the tumor.
(C) Surgical principles of GIST
3.1 Surgical principles
①The goal of surgery is to try to achieve R0 resection. If the initial surgery is only for R1 resection, a second surgery can be considered if the difficulty of re-operation is expected to be low and the risk can be controlled without causing damage to the major functional organs. GIST rarely has lymph node metastasis, and routine debulking is usually not necessary unless there are clear signs of lymph node metastasis.
②Tumor rupture and bleeding: one of the reasons is spontaneous bleeding which rarely occurs, another reason is improper touching of the tumor during surgery, which causes rupture and bleeding; therefore, intraoperative probing should be careful and gentle.
③Postoperative positive incision margin: At present, domestic and foreign scholars tend to carry out molecular targeting drug therapy.
3.2 Laparoscopic surgery
Laparoscopic surgery is easy to cause tumor rupture and lead to abdominal implantation, so it is not recommended for routine application. It is mostly used for gastric GIST treatment and is not advocated for the treatment of GIST in other sites. Experienced centers may consider laparoscopic resection depending on the site and size. Intraoperative “retrieval pouch” must be used, with special attention to avoid tumor rupture and dissemination.
3.6 Extra-gastrointestinal GIST surgery (Slides17)
Surgery is still the preferred treatment modality. The thoroughness of surgical treatment is closely related to the prognosis of the disease, and complete resection of the whole lesion is recommended. In some patients, the tumor may adhere extensively to surrounding tissues or spread, and sometimes biopsy or palliative surgery may be used to achieve a definitive diagnosis or symptomatic relief by tumor reduction .
3.7 Principles of endoscopic treatment of GIST
Since GIST originates from the submucosa and has various growth patterns, it is difficult to perform radical resection under endoscopy, and the complications are high, so it is not routinely recommended.
III. Principles of molecular targeted drug therapy
1.Preoperative treatment of GIST
1.1 The significance of preoperative treatment
The main significance of preoperative treatment [13,17,18]: reduce the tumor volume and clinical stage; reduce the scope of surgery, avoid unnecessary combined organ resection, reduce the risk of surgery, and increase the chance of radical resection; for tumors in special sites, the structure and function of important organs can be protected; for patients with huge tumors and high risk of intraoperative rupture and bleeding, the possibility of medical dissemination can be reduced. For patients with huge tumors and high risk of intraoperative rupture and bleeding, it can reduce the possibility of medical dissemination.
1.2 Indications for preoperative treatment [13,17,18]
(i) Preoperative estimation is difficult to achieve R0 resection;
②Tumor size is huge (>10 cm), which is prone to bleeding and rupture during surgery and may cause medical dissemination;
③Tumors in special sites (e.g., gastroesophageal junction, duodenum, low rectum, etc.), surgery may easily damage the function of important organs;
④ Although the tumor can be resected, it is estimated that the surgical risk is high, and the postoperative recurrence rate and mortality rate are high;
⑤ It is estimated that a combined multi-organ resection is needed.
1.3 Preoperative treatment time, treatment dose and surgery timing selection
During drug treatment, the treatment effect should be evaluated periodically (every 3 months), and it is recommended to use the Choi criteria [19] or refer to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. For the duration of preoperative treatment, it is generally considered appropriate to give imatinib preoperative treatment for about 6 months to perform surgery. Excessive prolongation of preoperative treatment may lead to secondary drug resistance.
For preoperative treatment, genetic testing is recommended and the initial dose of imatinib should be determined based on the genetic test results. For patients with tumor progression, the condition should be comprehensively evaluated. Those who are still operable (with the possibility of complete resection of the lesion) should discontinue the drug in time for early surgical intervention; those who cannot be operated, second-line therapy can be used according to patients with recurrence/metastasis.
1.4 Preoperative drug discontinuation time and postoperative treatment time
It is recommended to discontinue drugs for about 1 week before surgery, and surgery can be considered when the patient’s basic condition meets the requirements. After surgery, in principle, postoperative drug therapy should be performed as soon as the patient recovers gastrointestinal function and can tolerate drug therapy. For those with R0 resection, the duration of post-operative drug maintenance can refer to the criteria of adjuvant therapy, and the time of adjuvant therapy can be decided by the grading of recurrence risk before drug therapy; for patients with palliative resection or metastasis or recurrence (whether or not R0 resection is achieved), post-operative therapy is similar to that for patients with recurrent/metastatic unoperated GIST.
2.Adjuvant therapy after GIST surgery
2.1 Indications for adjuvant therapy
Patients with medium to high risk of recurrence are currently recommended as the indication population for adjuvant therapy. The benefit of adjuvant therapy varies among patients with different mutation types. c-kit exon 11 mutation and PDGFRA non-D842V patients can benefit from adjuvant therapy; meanwhile, whether c-kit exon 9 mutation and wild-type GIST can benefit from adjuvant therapy needs further study. In contrast, patients with PDGFRA D842V mutated GIST did not benefit from adjuvant therapy.
2.2 Dose and duration of adjuvant therapy
The recommended dose of imatinib adjuvant therapy is 400 mg/d; treatment time frame: for intermediate risk patients, imatinib should be given adjuvant therapy for at least 1 year; for high risk patients, the duration of adjuvant therapy should be at least 3 years; for patients with tumor rupture, extended adjuvant therapy can be considered.
3.Treatment of metastatic recurrent/unresectable GIST
3.1 Imatinib first-line treatment
Imatinib is the first-line treatment for metastatic recurrent/unresectable GIST, and the recommended initial dose is 400 mg/d [25]. c-kit exon 9 mutation patients have a recommended initial treatment dose of imatinib of 600 mg/d -800 mg/d. Given that most patients cannot tolerate imatinib 800 mg/d treatment in domestic clinical practice, the recommended initial treatment dose of imatinib for c-kit exon 9 mutation patients is 600 mg/d -800 mg/d. If imatinib treatment is effective, it should be continued until disease progression or intolerable toxicity occurs.
Common adverse reactions to imatinib include edema, gastrointestinal reactions, leukopenia, anemia, rash, muscle cramps, and diarrhea [25,27]; most adverse reactions are mild to moderate and improve with symptomatic supportive therapy.
3.2 Treatment options after failure of standard doses of imatinib
If tumor progression occurs during imatinib treatment, first confirm whether the patient should comply with medical advice, i.e., adhere to the drug at the correct dose; after excluding patient compliance factors, it should be treated according to the following principles.
3.2.1 Limited progression
Limited progression is manifested by the progression of some lesions during imatinib treatment, while others remain stable or even partially remitted.
In the case of GIST with limited progression, if surgery can completely remove the focal progressive lesions, it is recommended to perform surgery, and after surgery, the original dose of imatinib can be continued or the dose can be increased; if complete resection cannot be obtained, the subsequent treatment should follow the principles for the management of GIST with extensive progression; in the case of GIST with extensive progression, surgery is not recommended.
For some patients with GIST liver metastases who cannot undergo surgery, arterial embolization with radiofrequency ablation therapy can also be considered as an adjuvant treatment modality [28, 29]; and patients with focal progression who are not suitable for local treatment can be treated with an increased dose of imatinib or given sunitinib.
3.2.2 Widespread progression
For those who develop extensive progression after standard dose of imatinib treatment, it is recommended to give an increased dose of imatinib or switch to sunitinib treatment.
Imatinib increase dose: Considering the tolerability issue, the priority incremental dose of 600 mg/d is recommended for national GIST patients.
Sunitinib treatment: 37.5 mg/d continuous vs. 50 mg/d (4/2) regimen are both options. Despite the lack of randomized controls, studies confirm that sunitinib 37.5 mg/d may have better efficacy and better tolerability. Common adverse effects of sunitinib are anemia, granulocytopenia, thrombocytopenia, hand-foot syndrome, hypertension, oral mucositis, and hypothyroidism, all of which can be resolved with symptomatic treatment.
3.3 Treatment after failure of imatinib and sunitinib therapy
GIST patients who have progressed on both imatinib and sunitinib therapy are recommended to participate in clinical studies with new drugs or consider giving maintenance therapy with drugs that are effective and well tolerated by previous treatment; regorafenib for GIST that has failed on imatinib and sunitinib has shown further antitumor activity and can be selected as a third-line treatment drug, but regorafenib in China still lacks sufficient application experience.
4. Correlation between c-kit/PDGFRA gene mutation and efficacy of molecular targeted therapy
It is generally believed that the type of c-kit/PDGFRA mutation can predict the efficacy of imatinib, with the best efficacy in those with c-kit exon 11 mutation; PDGFRA D842V and D846V mutations may be primary resistant to imatinib and sunitinib treatment. The survival benefit of sunitinib in second-line treatment of patients with primary c-kit exon 9 mutations and wild-type GIST was better than that of patients with c-kit exon 11 mutations; the efficacy of treating patients with secondary c-kit exon 13 and 14 mutations was better than that of secondary c-kit exon 17 and 18 mutations.
5. Blood concentration monitoring
If available, imatinib blood concentration testing is recommended for the following patients.
①Patients progressing on first-line treatment with imatinib 400 mg;
②Patients with more severe adverse drug reactions;
③Patients who do not follow the medical advice to take regular doses of the drug.
GIST patients with plasma imatinib concentration below 1100ng/ml, clinical efficacy is reduced and the disease progresses quickly.
6. Judgment of drug efficacy
6.1 Definition of primary drug resistance and secondary drug resistance
Primary resistance is defined as tumor progression within 6 months of first-line treatment with imatinib.
Secondary resistance is defined as tumor progression that occurs again with the extension of treatment after initial treatment with imatinib or sunitinib has achieved tumor remission or stabilization.
6.2 Modified Choi efficacy assessment criteria
The RECIST criterion, the previously adopted standard for evaluating the efficacy of cytotoxic drugs, only considers the factor of volume change and has obvious shortcomings.Choi et al. proposed a new criterion (Table 2) by combining the Hu value of long diameter and CT [19], and some studies showed that its efficacy evaluation ability is better than the RECIST criterion. This consensus suggests that for tumors with insignificant or even increasing volume reduction in the early stage of treatment, the Hu value of CT should be measured additionally and evaluated by referring to the Choi criteria.
Table 2 Evaluation criteria of Choi efficacy of GIST-targeted therapy
Efficacy
Definition
CR
All lesions disappeared, no new lesions
PR
≥10% reduction in tumor length and diameter and/or ≥15% reduction in tumor density (Hu) as measured by CT;
No new lesions; no significant progression of non-measurable lesions
SD
No CR, PR or PD criteria; no worsening of symptoms due to tumor progression
PD
Increase in tumor length ≥10% and density change not meeting PR criteria;
New lesions; new intratumoral nodules or increased volume of existing intratumoral nodules
6.3 CT scan and measurement specifications
The scanning range should include the whole abdominal and pelvic area; the layer thickness should be ≤5mm; the maximum diameter of the tumor should be measured in the axial image; the overall CT value of the tumor (Hu) should be obtained by using the curve edge tracing method at the maximum level of the tumor during the enhanced venous phase; the average CT value of the lesion should be reported if the conditions allow.
6.4 Application of PET-CT
PET-CT scan is currently a sensitive means to assess the efficacy of molecularly targeted drugs in the treatment of GIST, but the machine is not popular enough and expensive, and it has not been clearly written in the guidelines, so it is not routinely recommended for the time being.
6.5 Application of MRI
Magnetic resonance diffusion-weighted imaging (DW-MRI) may become another imaging tool besides PET-CT that can provide quantitative indicators of function, but its exact clinical significance needs to be further confirmed.
7.Follow-up principles
7.1 Patients with postoperative follow-up
The most common sites of metastasis after GIST surgery are the peritoneum and liver, therefore, abdominal and pelvic enhanced CT or MRI scans are recommended as routine follow-up items.
① For intermediate and high-risk patients, CT or MRI should be performed every 3 months for 3 years, and then every 6 months until 5 years;
②Low-risk patients should have CT or MRI every 6 months for 5 years;
(iii) Due to the relatively low incidence of pulmonary and skeletal metastases, at least 1 chest X-ray per year is recommended, and ECT bone scan is recommended in the presence of associated symptoms.
7.2 Patients with recurrent metastases/unresectable or preoperative treatment
①Enhanced CT or MRI must be performed before treatment as a basis for baseline and efficacy assessment;
②After starting treatment, follow-up visits should be performed at least every 3 months to review the enhanced CT or MRI; if treatment decisions are involved, the number of follow-up visits can be increased appropriately;
③Close monitoring at the beginning of treatment (the first 3 months) is very important, and PET-CT scan can be done to confirm the tumor response to treatment if necessary.