gastric%20cancer
GASTRIC CANCER
Treatment Guideline Chart
Gastric cancer is the cancer originating in the esophagus, esophagogastric junction and stomach.
Most of gastric cancers are adenocarcinomas, subdivided according to histological appearances into diffuse (undifferentiated) and intestinal (well differentiated) types.
It is the 4th most common cancer and the 2nd most common cause of cancer-related deaths worldwide.
Most common sites of gastric cancer are the proximal lesser curvature, cardia and esophagogastric junction.

Gastric%20cancer Treatment

Supportive Therapy

  • Should be considered in patients with stage IV disease that can improve survival compared with best supportive care alone
    • Co-morbidities, organ function and performance status must always be taken into consideration
  • Decision to offer palliative or best supportive care alone or in combination with systemic therapy is based on the patient's performance status

Chemoradiation

  • May be an option for medically fit patients with locally unresectable tumors and have no previous therapy
  • Preferred regimens include:
    • Cisplatin and Fluorouracil
    • Cisplatin and Capecitabine
    • FOLFOX
    • CAPOX
  • Other recommended regimens include: Fluoropyrimidine (Fluorouracil or Capecitabine) and Paclitaxel
Systemic Therapy
  • Provides palliation of symptoms, enhances quality of life and improves survival of patients with locally advanced or metastatic gastric cancer

First-line Therapy

  • Two-drug cytotoxic combination regimens are preferred due to lower toxicity
  • Three-drug cytotoxic combination regimens are reserved for medically fit patients with good performance status
  • Oxaliplatin is preferred over Cisplatin due to lower toxicity
  • Preferred regimens for HER2 overexpression-positive adenocarcinoma include:
    • Fluoropyrimidine (5-FU or Capecitabine) and Cisplatin and Trastuzumab
    • Fluoropyrimidine (5-FU or Capecitabine) and Oxaliplatin and Trastuzumab
  • Preferred regimens for HER2 overexpression-negative adenocarcinoma include:
    • Fluoropyrimidine (5-FU or Capecitabine) and Cisplatin
    • Fluoropyrimidine (5-FU or Capecitabine) and Oxaliplatin
    • Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Nivolumab for tumors with PD-L1 expression levels by CPS1 ≥5
  • Other recommended regimens include:
    • Docetaxel
    • Docetaxel and Cisplatin
    • Docetaxel, Cisplatin and Fluorouracil (DCF)
      • Has been recommended as alternative treatment option for the treatment of patients with advanced gastric cancer, including EGJ cancers, in patients who have not received prior chemotherapy
      • However, it was associated with increased myelosuppression and infectious complications
    • Docetaxel, Carboplatin and Fluorouracil
    • Docetaxel, Oxaliplatin and Fluorouracil
    • Fluoropyrimidine (Fluorouracil or Capecitabine)
    • Fluoropyrimidine (5-FU or Capecitabine) + Cisplatin + Trastuzumab + Pembrolizumab
      • For HER2 overexpression-positive adenocarcinoma
    • Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Trastuzumab + Pembrolizumab
      • For HER2 overexpression-positive adenocarcinoma
    • Fluorouracil and Irinotecan (FOLFIRI)
    • Paclitaxel
    • Paclitaxel and Cisplatin or Carboplatin
  • Fluoropyrimidine (5-FU or Capecitabine) + Oxaliplatin + Nivolumab may be useful in HER2 overexpression-negative adenocarcinoma with PD-L1 expression levels by combined positive score (CPS)1 <5

Second-line or Subsequent Therapy

  • Choice of agents depends on previous therapy and performance status
  • Preferred regimens include:
    • Docetaxel
    • Fam-trastuzumab deruxtecan-nxki
      • For patients with HER2 overexpression-positive adenocarcinoma and received prior Trastuzumab-based therapy
    • FOLFIRI
      • For patients who did not previously receive FOLFIRI
    • Irinotecan
    • Paclitaxel
    • Ramucirumab and Paclitaxel
    • Trifluridine and Tipiracil
      • Indicated as third-line or subsequent therapy for select patients with low-volume gastric cancer without or minimal symptoms and with the ability to swallow pills
  • Other recommended regimens include:
    • Docetaxel and Irinotecan
    • FOLFIRI + Ramucirumab
    • Irinotecan and Cisplatin
    • Irinotecan and Ramucirumab
    • Ramucirumab
  • Agents useful in certain circumstances include:
    • Dostarlimab-gxly is indicated for MSI-high (MSI-H) or MMR-deficient (dMMR) tumors
    • Entrectinib or Larotrectinib is used for NTRK gene fusion-positive tumors
    • Pembrolizumab is indicated for MSI-H or dMMR tumors or for TMB high (≥10 mutations/megabase) tumors
  • In patients of adequate performance status, second-line chemotherapy is associated with proven improvements in overall survival and quality of life compared with best supportive care

Targeted Therapies

  • HER2 testing is recommended for all patients with inoperable, locally advanced, recurrent and metastatic disease at the time of diagnosis
  • In HER2-positive gastric cancer, addition of Trastuzumab to a Cisplatin-Fluoropyrimidine doublet showed clinically and statistically significant improvements in response rate, progression-free survival and overall survival
    • Trastuzumab in combination with Cisplatin and fluoropyrimidine (first-line) or with other chemotherapy agents (eg Capecitabine or 5-fluorouracil and Oxaliplatin) is the standard care regimen
    • Trastuzumab was limited only in patients with an IHC score of 3+ or 2+ and FISH positive
    • Trastuzumab is not recommended to be continued in second-line therapy
  • Pembrolizumab is a PD-1 antibody
    • Other second-line or subsequent therapy for MSI-H or dMMR tumors or for TMB high (≥10 mutations/megabase) tumors
    • May be added to first-line fluoropyrimidine, platinum and Trastuzumab in the treatment of HER2 overexpression-positive adenocarcinoma
  • Dostarlimab-gxly is a PD-1 antibody
    • Indicated for patients with progressive MSI-H or dMMR gastric cancer on or following prior therapy which did not include a checkpoint inhibitor such as PD-1i, PDL-1i, or CTLA4i, and without alternative therapy options
  • Entrectinib or Larotrectinib is recommended as second-line or subsequent therapy for NTRK gene fusion-positive tumors
  • Fam-trastuzumab deruxtecan-nxki is an antibody-conjugate composed of Trastuzumab and a cytotoxic topoisomerase I inhibitor which is connected by a cleavable tetrapeptide-based linker
    • Preferred second-line or subsequent therapy for patients with HER2 overexpression-positive adenocarcinoma and received prior Trastuzumab-based therapy
  • Nivolumab is a monoclonal PD-1 antibody
    • In combination with fluoropyrimidine- and platinum-based chemotherapy is approved as first-line therapy for patients with HER2-negative advanced or metastatic gastric cancer with PD-L1 expression levels by CPS1 of ≥5 and may be useful in tumors with a CPS1 <5
      • Addition of Nivolumab to chemotherapy resulted in significant improvements in overall survival and progression-free survival in patients with a PD-L1 CPS1 of ≥5
  • Targeting vascular endothelial growth factor receptors (VEGFR) with the anti-VEGFR-2 monoclonal antibody Ramucirumab showed promising results in patients with advanced gastric or EGJ adenocarcinoma positive for disease progression despite treatment with platinum-/fluoropyrimidine-based doublet/triplet chemotherapy
    • Ramucirumab may be given alone or in combination with Paclitaxel

Palliative/Best Supportive Care

  • Recommended for all patients with unresectable locally advanced, recurrent or metastatic gastric cancer
  • Goal is to prevent, reduce and relieve suffering and improve the quality of life for patients and their families

Interventional Radiotherapy

  • Angiographic embolization may be considered in patients with acute bleeding not relieved by endoscopy

Radiotherapy

  • Hypofractionated radiotherapy is an effective and well-tolerated treatment modality which may palliate bleeding, obstructive symptoms or pain in patients with symptomatic locally advanced or recurrent disease
  • External beam radiotherapy may be considered for patients with malignant obstruction causing pain, and acute or chronic gastrointestinal bleeding

Surgery

  • Surgeries that will aid the patients with unresectable gastric cancer control the cancer or prevent or relieve symptoms or complications 
  • Although resection of the primary tumor is not generally recommended in the palliative setting, a small number of advanced disease patients may be deemed to be operable following a good response in systemic therapy
  • Gastric resections should be reserved for palliation of symptoms such as obstruction or uncontrollable bleeding in patients with incurable disease
    • Gastrojejunostomy or gastrectomy may be done to alleviate or bypass obstruction
      • Gastrojejunostomy is preferred for gastric outlet obstruction over endoluminal stenting for patients fit for surgery and with a more prolonged prognosis 
    • Lymph node dissection is not required
  • Subtotal gastrectomy can help in problems of bleeding, pain or blockage in the stomach
  • Limited gastric resection, even with positive margins, is acceptable for unresectable tumors for symptomatic palliation of bleeding
    • Presence of peritoneal involvement, distant metastases, or locally advanced disease (eg invasion or encasement of major blood vessels) are contraindications for resection
  • Routine or prophylactic splenectomy should be avoided if possible
  • Gastric bypass (gastrojejunostomy) can treat or prevent large tumors that block food from leaving the stomach
    • For selected patients who will be receiving postoperative chemoradiation, placement of a venting gastrostomy or jejunostomy feeding tube may be considered
  • Endoscopic tumor ablation helps to stop bleeding or help relieve blockage without surgery
    • For short-term control of bleeding
  • Stent placement helps keep the opening at the beginning and end of the stomach open and allows food to pass through it
    • Endoscopic insertion of self-expanding metal stents (SEMS) has been shown to be effective for the long-term relief of tumor obstruction at the gastric outlet or EGJ
      • Preferred over gastrojejunostomy for patients with luminal obstruction secondary to advanced gastric cancer and with relatively short life expectancy
  • Venting gastrostomy may be performed to reduce symptoms of obstruction when bypass or alleviation is not possible
  • Feeding tube placement is done to help in the liquid nutrition that can be put directly into the tube
1Combined positive score (CPS) is the number of PD-L1 staining cells (eg lymphocytes, macrophages, tumor cells) divided by the total number of viable tumor cells evaluated, multiplied by 100
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