September 28, 2022

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What have new treatments of gastric cancer been added into ESMO guidelines?

What have new treatments of gastric cancer been added into ESMO guidelines?



 

What have new treatments of gastric cancer been added into ESMO guidelines?

The heterogeneity of gastric cancer is very large. Each guideline update will determine the existing diagnosis and treatment standards, and supplement new therapies and drugs in the diagnosis and treatment.

 

This article summarizes the 2022 ESMO clinical practice guidelines for the diagnosis, treatment and follow-up of gastric cancer, with a view to It is helpful for clinical diagnosis and treatment.

 

What have new treatments of gastric cancer been added into ESMO guidelines?
What have new treatments of gastric cancer been added into ESMO guidelines?

 

 


Prevent diseases

In 2020, the number of new gastric cancer cases worldwide exceeded  1  million (1,089,103), with 768,793 deaths.

 The burden of disease will continue to grow as the population ages and the number of high-risk groups increases.

 

About  10%  of gastric cancers show familial aggregation, and up to  3%  of cases have a genetic predisposition.

 Regarding the prevention of gastric cancer, the guidelines recommend the following:

  1. If a familial cancer syndrome is suspected , evaluation by a geneticist is recommended  [V, A] .

  2. Population-based asymptomatic individual endoscopic screening is only suitable for use in areas with a very high incidence of gastric cancer  [V, B] .

 


Diagnosis, Pathology and Molecular Biology

Early gastric cancer is usually asymptomatic.

Common signs and symptoms of advanced disease include dysphagia, fatigue, indigestion, vomiting, weight loss, early satiety, and/or iron deficiency anemia. 

In many cases, however, these nonspecific symptoms go unnoticed.

 In conclusion, about  60%  of gastric cancer patients lose the chance of curative treatment due to late detection or comorbidity.

 

Endoscopy and biopsy are the gold standard for the diagnosis of gastric cancer . 

About  90%  of gastric cancers are adenocarcinomas . In addition to pathological typing, molecular profiling of gastric cancer can provide a better understanding of gastric cancer subtypes and may also help identify clinically relevant biomarkers and therapeutic targets.

 

Intratumoral and intertumoral heterogeneity is a feature of gastric cancer that can make diagnosis and treatment challenging. In terms of diagnosis, pathology and molecular biology, the guidelines recommend the following:

  1. Endoscopic biopsies should be obtained from multiple sites (5-8) to ensure adequate tumor coverage  [IV, B] .

  2. Pathology should be reported according to  WHO standards  [V, B] .

  3. Immunohistochemistry (IHC) and/or in situ hybridization amplification can be used to detect HER2 expression  [I, A; ESCAT score: IA] , IHC to detect PD-L1 expression CPS score  [I, A]  and  MSI-H/dMMR  [ II, A; ESCAT score: IB] , these are predictive markers of effective drug therapy.

 


Staging and Risk Assessment


Fine staging
 is the basis on which patients can receive appropriate treatment. 

The sensitivity of CT  for lymph node staging varies (62.5%-91.9%), and there is currently no global consensus standard. EUS was more sensitive for lymph node staging (91% vs 77%).

 

The clinical staging of gastric cancer should follow the AJCC/UICC 8th edition TNM staging. The relevant recommendations are as follows:

  1. Initial staging and risk assessment should include physical examination, blood count and classification, liver and kidney function, endoscopy, and contrast-enhanced CT scan of chest, abdomen ± pelvis  [V, A] .

  2. FDG-PET-CT is not routinely recommended  [III, C] .

  3. Diagnostic laparoscopy and peritoneal lavage cytology are recommended in operable patients who are also candidates for perioperative chemotherapy  [III, B] . Surgical resection is uncertain for patients with positive lavage cytology.

  4. TNM staging should refer to the 8th edition of the AJCC/UICC Grading Manual  [IV, A] .


Treatment of gastric cancer

Treatment of local disease: Multidisciplinary diagnosis and treatment (MDT) is required before any treatment decision  [IV, B] .

 

Resections:

  1. Pure endoscopic or surgical resection is only suitable for very early stage disease (stage IA) [III, B] .

  2. Perioperative treatment and radical surgical resection are recommended for patients with  stage IB-III gastric cancer [I, A] . 

  3. D2 radical mastectomy can be performed in patients with larger surgical volumes   [II, B] .

 

Perioperative chemotherapy:

  1. Perioperative chemotherapy (preoperative and postoperative) is recommended for  patients with resectable gastric cancer of stage IB or higher [I, A] .

  2. A 3-drug combination regimen  containing fluorouracil , platinum compounds , and docetaxel is recommended when possible [I, A] .

  3. The FLOT regimen is the standard treatment regimen for perioperative chemotherapy, provided that chemotherapy toxicity can be tolerated [I, A; ESMO-MCBS version 1.1 score: A] . 

  4. For patients who are not suitable for 3-drug chemotherapy, fluorouracil combined with cisplatin or oxaliplatin is recommended as a perioperative chemotherapy regimen  [II, B] .

 

Adjuvant therapy:

  1. Adjuvant chemotherapy is strongly recommended for patients with stage IB and above if they have not received preoperative chemotherapy before surgery  [I, A] .

  2. In patients with negative margins (R0 resection), postoperative radiotherapy has shown no additional benefit and is not recommended  [I, D] .

  3. In patients who have received preoperative or postoperative chemotherapy, postoperative radiotherapy has shown no benefit and is not recommended  [I, E] .

  4. Adjuvant chemoradiation should be considered in patients not receiving perioperative chemotherapy and without D2 lymph node dissection [I, C] .   

  5. For patients with positive margins (R1 resection), adjuvant radiotherapy or chemoradiation may be performed on an individual basis, but is not recommended as standard treatment [IV, C] . 

  6. Postoperative adjuvant chemotherapy is not recommended for patients with MSI-H after radical gastrectomy  [IV, D] . However, if the tumor needs to be downstaged before surgery,  FLOT chemotherapy is recommended.

     

Treatment of locally advanced and metastatic patients: Treatment modalities include chemotherapy, targeted therapy, and immunotherapy .

 

First-line treatment   :

  1. The platinum-based combination with fluorouracil is recommended as the first-line regimen. Oxaliplatin is preferred, especially in elderly patients  [I, A] . S-1 is only recommended for Asian patients  [I, A] .

  2. Considering the high toxicity and uncertainty of efficacy, paclitaxel -based three-drug chemotherapy regimen is not recommended as standard in first-line therapy  [I, C] .

  3. Irinotecan + 5-FU  regimen can be used as a first-line alternative for  patients with platinum complex toxicity intolerance  [II, B] .

  4. Trastuzumab combined with chemotherapy is recommended for  patients with HER2-positive gastric cancer  [I, A; ESMO-MCBS v1.1 score: 3; ESCAT score: IA] .

  5. Nivolumab combined with chemotherapy is recommended for advanced, untreated, PD-L1 expression CPS ≥ 5 patients with esophagogastric junction and esophageal cancer   [I, A; ESMO-MCBS v1.1 score: 4] .

  6. Pembrolizumab is approved for patients with esophageal or gastroesophageal junction adenocarcinoma with PD-L1 expression CPS ≥ 10  [II, C; ESMO-MCBS v1.1 score: 4] .

 

 

Second-line and later-line treatments:

  1. Ramucirumab combined with paclitaxel is the standard second-line treatment regimen for  gastric cancer  [I, A; ESMO-MCBS v1.1 score: 2] . Ramucirumab monotherapy is also an option  [I, B; ESMO-MCBS v1.1 score: 1] .

  2. In areas where ramucirumab is not available, single-agent paclitaxel , docetaxel  [I, A],  or  OLFIRI chemotherapy   [I, B]  is the recommended second-line regimen . 

  3. After progression on first-line trastuzumab in HER2-positive patients, continuation of second-line trastuzumab is not recommended   [I, D] , but desiccated trastuzumab (DS8201) may be considered [II, B; ESMO-MCBS v1.1 Score: 4; FDA approved, EMA not approved] .

  4. Pembrolizumab is recommended for second-line treatment of MSI-H/dMMR patients  II, A; ESMO-MCBS v1.1 score: 3; ESCAT score: IB] . 

  5. Trifluridine /tipiramidine (TAS-102) is recommended for patients who have failed second-line therapy  [I, A; ESMO-MCBS v1.1 score: 3] . Taxanes or irinotecan are also available as alternatives   [II, B] .

  • Surgical treatment of metastatic gastric cancer:

  1. Surgery is not recommended for patients with metastatic gastric cancer unless surgery is required for symptomatic relief  [I, D] .

  2. In general, resection of metastatic tumors is not recommended , but it can be used as a treatment for some patients with highly selective oligometastases and effective chemotherapy  [V, C] .

     

In addition, the guidelines also recommend that the treatment of gastric cancer patients should include early palliative care and nutritional support   [I, A] . In addition to diagnosis and treatment, follow-up questions are suggested as follows:

  1. Regular follow-up is recommended to detect and treat symptoms, psychological support, and early detection of relapse  [III, B] .

  2. The follow-up plan should be based on the individual patient and disease stage  [V, B] .

  3. Vitamin and mineral deficiencies should be noted in the diet  [V, B] .

  4. For follow-up of patients with advanced disease, the primary goal is to detect progression of disease symptoms before clinically apparent disease progression [IV, B] . 

  5. For patients on further antitumor therapy,  follow-up imaging, especially chest and abdominal CT  , every 6-12 weeks is recommended [IV, B] .

✩ This article is for reference only by professionals such as medical and health care professionals, please check with ESMO for details

 

 

 

 

Reference:

1 Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Annals of Oncology (2022)

What have new treatments of gastric cancer been added into ESMO guidelines?

(source:internet, reference only)


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