The American Cancer Society estimates that there will be approximately 28,000 new gastric (stomach) cancers and over 16,000 new esophageal cancers diagnosed in the United States in 2017.
Both gastric and esophageal cancers are more common in men. Approximately 10,000 patients will die of gastric cancer and another 15,000 of esophageal cancer in 2017. While there has been a steady decline in the incidence of gastric cancer over the last 75 years, gastroesophageal cancer, particularly in young men, has increased in incidence.
The management of gastric cancer depends upon a correct diagnosis, usually established at the time of endoscopy.
The most common form of gastric cancer is adenocarcinoma; although, lymphoma and neuroendocrine tumors can arise in this site. It is extremely important for patients with newly diagnosed adenocarcinoma to undergo the HER2 determination, as this can have a profound impact on treatment.
Gastric cancer is staged using the TNM system. T1 tumors refer to minimally invasive cancers, while T4 lesions spread deeply extending to other nearby organs. Nodal status is determined as N1 for 1-2 nearby lymph nodes, or N3 as seven or more lymph nodes are involved. Finally, the M status is M0 for no metastasis and M1 for dissemination beyond the organ and its regional lymph nodes
Once the staging is complete, and the HER2 status determined, treatment choices can be examined.
The molecular biology of gastric cancer has been under careful analysis.
The Cancer Genome Atlas (TCGA) has now recognized four distinct subtypes of gastric cancer.
One is associated with infection by the Epstein-Barr virus, a common viral infection in our environment. A second group is associated with a DNA abnormality known as mismatch repair. A third group, often diffuse in histology, is associated with relatively normal mutation levels but is often positive for mutations in the RHO oncogene.
The last group of gastric cancers have extremely high degrees of mutation and these are sometimes associated with HER2 and other driver mutations.
Where possible, surgery is the preferred mode of management.
Often, patients undergo neoadjuvant chemotherapy consisting of preoperative FOLFOX or related regimen; this is used to down-stage patients and provide the best chance of curative outcome.
Many patients undergo an initial laparoscopic staging to confirm whether there is extension beyond the stomach and to rule out the possibility of peritoneal dissemination. Patients found to have early stage disease with no evidence of distant metastasis may get primary surgery.
Patients who undergo surgery are offered postoperative chemotherapy or postoperative chemoradiation.
The original clinical trials conducted in 2000 have remained an established mainstay of therapy, as the use of 5-FU, leucovorin and radiation, published years earlier has remained an appropriately and widely used adjuvant treatment providing survival advantage.
More recently, clinical trials using combined chemotherapy have also been incorporated into postoperative management. As noted, the presence of the human epidermal growth factor receptor 2 amplification confer a higher likelihood of benefit from agents like trastuzumab and related HyER2-directed treatment. Combining these drugs with chemotherapy has proven particularly effective.
The wide use of chemotherapy combined with surgery has improved the time-to-progression and, in some circumstances, the survival in gastric cancer. As there are many active drug combinations in this setting, it is important that patients receive appropriate therapy.
Among the active treatments used in this disease are combinations EOX, ECF, FOLFOX, FOLFOXIRI, FOLFIRI, DCF, IROX, carboplatin and Taxol, and as noted for the HER2 positive population, the addition of trastuzumab.
Our investigations in gastric cancer patients have suggested that patients tend to segregate into different and distinct groups.
Some patients reveal high degrees of sensitivity to chemotherapy, while others are found more resistant.
Among drug-sensitive patients, it becomes important to compare the activity of different treatment regimens. Each combination reflects different classes of drugs including the taxanes, antimetabolites, platins (Cisplatin, Oxaliplatin, Carboplatin) and topoisomerase-1 inhibitors. Selecting amongst these different drug regimens may hold the promise of better outcomes in the future.
As many patients with gastric cancer present with advanced disease, the aspiration of ascites fluid, biopsy of lymph nodes at the time of diagnostic laparotomy or other sources of tissue can provide samples for analysis.
I am a 48-year-old male, who after a weekend of sharp abdominal pain and a visit to the emergency room, was diagnosed with widely metastatic Stage 4 stomach cancer.
The first oncologist I met was in the Emergency Room. He prescribed 5-FU chemotherapy claiming that he would try to control the spread but that basically there was no hope.
— James Tran
One year ago I was diagnosed with Stage 4 gastric (stomach) cancer and told by two doctors that I had three months to live. I had most of my stomach and colon removed, followed by chemotherapy.
A medical consultant had highly recommended that I have functional profiling testing done by Rational Therapeutics (now Nagourney Cancer Institute), since I did not have any time to waste on chemo drugs that might not work.
— Shelly Powell