Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.

BACKGROUND: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.

Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction.

BACKGROUND: : The use of platinum-based chemoradiation for esophageal cancer is routine, but it is unclear which class of cytotoxic are optimum. It was hypothesized that chemoradiotherapy with fluoropyrimidine, taxane, and camptothecin would have preserved or improved efficacy with no compromise in safety. METHODS: : Patients with histologically confirmed, resectable esophageal carcinoma were eligible. In addition to other tests, a baseline endoscopic ultrasonography (EUS) was obtained. Patients were medically fit and had near-normal organ functions. Patients received docetaxel and irinotecan, plus 5-fluorouracil as induction therapy and then the same cytotoxics with 50.4 grays of radiotherapy followed by an attempted surgery. Pathologic complete response (pathCR) at a rate of > or =20% was the primary endpoint. The pathCR and R0 resection were correlated with overall survival (OS). Safety was documented. RESULTS: : Fifty-five patients were enrolled. Seven were women, and the median age was 56 years. Fifty-three (96%) patients had EUST3, and 41 (75%) had EUSN1 disease. Forty-three (78%) patients underwent surgery, 20% achieved a pathCR, and 76.4% underwent an R0 resection. The median survival (n = 55 patients) was 43.3 months (range, 19-75 months). Baseline clinical parameters were not found to be predictive of OS; however, patients with a pathCR (P = .005) and who underwent R0 resection (P < or = .0001) had an improved OS. There was 1 treatment-related postsurgical death reported. Grade 3 or 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 62% of patients. CONCLUSIONS: : The results of the current study documented that this 3-drug, noncisplatin-based chemoradiotherapy was feasible, safe, and active but not better than the published cisplatin-based chemoradiotherapy. A fluoropyrimidine and another cytotoxic (from any class) may be adequate to establish a baseline chemoradiotherapy regimen to combine biologics. Cancer 2010. (c) 2010 American Cancer Society.

Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer.

BACKGROUND: This study evaluates the utility of positron emission tomography (PET), endoscopic ultrasonography (EUS), and computed tomographic (CT) scans to predict pathologic response and survival following preoperative chemoradiation (CRT) in esophageal cancer. METHODS: One hundred three sequential patients with locoregionally advanced esophageal cancer, who were treated with CRT and esophageal resection between May 2001 and November 2003 at the University of Texas M.D. Anderson Cancer Center, were retrospectively reviewed. PET, EUS, and CT were performed before (pre) or after (post) CRT and before surgical resection. PET standardized uptake value (SUV) was defined as maximal uptake in primary tumor. RESULTS: Most patients were male (91 [88%]) with adenocarcinoma (90 [87%]). Pretreatment clinical stages were: IIA (42 [41%]), IIB (5 [5%]), III (50 [49%]), and IVA (6 [6%]). At the time of surgery, 58 patients (56%) had a pathologic response to CRT (< or =10% viable cells). Post-CRT measurements that correlated with pathologic response were: CT esophageal wall thickness (13.3 vs 15.3 mm, p = 0.04), EUS mass size (0.7 vs 1.7 cm, p = 0.01) and PET SUV (3.1 vs 5.8, p = 0.01). Post-CRT PET SUV equal to or greater than 4 had the highest accuracy for pathologic response (76%). Univariate and multivariate Cox regression analysis demonstrated that a post-CRT PET SUV equal to or greater than 4 was an independent predictor of survival (HR, 3.5, p = 0.04). CONCLUSIONS: The FDG-PET SUV is the most accurate noninvasive test to predict long-term survival after preoperative CRT and before surgical resection. Post-CRT FDG-PET cannot, however, rule out residual microscopic disease so esophagectomy should remain a therapeutic option even if the post-CRT imaging modalities are normal.