Our patient with diffuse type gastric cancer would still be a candidate for total gastrectomy, but her follow-up surveillance would be affected. Because of a high lifetime risk of invasive lobular breast carcinoma, women with CDH1 mutations should undergo annual radiologic surveillance, using high risk guidelines. In a prophylactic setting, however, the type of CDH1 mutation can play a role in determining patients’ management. For example truncating germline mutations are deleterious, and a total prophylactic gastrectomy is suggested for carriers of this mutation. A D1 lymph node dissection can be considered because T1b tumors in DGC cannot be reliably identified preoperatively (T1b tumors have lymph node metastases in up to 25% of patients).
Neoadjuvant or perioperative therapy rather than initial surgery is generally preferred for patients with bulky T3/T4 gastric tumors, visible perigastric nodes by imaging or “linitis plastica” appearance. This has been found to downstage the tumor allowing more potentially curative resections, also decreasing the risk of distant metastases and improving overall survival. Epirubicin, cisplatin and infusional fluorouracil (ECF) or epirubicin, oxaliplatin and capecitabine (EOX) perioperatively had been the standard until the phase II/III FLOT4-AIO trial compared a docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) regimen (four preoperative and four postoperative) with the epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) regimen (three preoperative and three postoperative). FLOT was shown to improve the median overall survival with similar rates of perioperative complications. These are intensive regimens and typically recommended for patients without significant comorbidities. For patients not eligible to receive these regimens, 5-Fluorouracil, Leucovorin and Oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) may be considered.
The patient described herein received 1 cycle of the FLOT regimen and experienced acute neurotoxicity, likely secondary to 5-FU; Neurotoxicity is rare but both acute and delayed forms have been reported. The acute form can present as cerebellar syndrome and encephalopathy whereas delayed toxicity can present as subacute multifocal leukoencephalopathy. Our patient’s MRI of the head showed restricted diffusion in the splenium of corpus callosum, consistent with drug-related neurotoxicity/encephalopathy. Due to the neurotoxicity and complicated postoperative course, a decision was made to adjust the chemotherapy regimen.
The ChemoRadiotherapy after Induction chemoTherapy In Cancer of the Stomach (CRITICS) trial investigated whether postoperative chemoradiotherapy improves survival as compared with postoperative chemotherapy in patients all treated with preoperative chemotherapy and surgery. Adjuvant therapy involved chemotherapy (epirubicin, cisplatin/oxaliplatin and capecitabine) vs. radiation to 45 Gray (Gy) given concurrently with cisplatin and capecitabine.