Chemotherapy Versus Chemotherapy Plus Chemoradiation as Neoadjuvant Therapy for Resectable Gastric Adenocarcinoma: A Multi-institutional Analysis.

OBJECTIVE: We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA: The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS: Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS: Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS: In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.

FOXA1 is an independent prognostic marker for ER-positive breast cancer.

Forkhead box protein A1 (FOXA1) is a "pioneer factor" that plays a role in controlling nearly 50% of estrogen receptor target genes. FOXA1 expression correlates with estrogen receptor (ER)-positivity especially in luminal subtype A breast cancers. The aim of this study was to investigate the precise role of FOXA1 in breast cancer using a large population-based cohort. Nuclear expression of FOXA1 was analyzed in a tissue microarray of 4,444 invasive breast cancer cases using immunohistochemistry and correlated with clinicopathologic variables using previously described methods and cutoff points. The entire cohort was equally divided into a training and validation set. All survival analyses were performed using a previously defined cutoff (3) for validation. Additional X-tile analysis performed to analyze prognostic effects of low and high FOXA1 levels identified 24 as a cutoff. Bonferroni-Holmes test was used as appropriate. FOXA1 expression significantly correlated positively with markers of good prognosis or ER-positivity, and negatively with tumor size, tumor grade, nodal status, Ki67, HER2 expression, and basal subtype (each P value <0.0001). In both survival analyses, FOXA1 was a significant predictor of breast cancer-specific survival (P < 0.0001) and relapse-free survival (P < 0.0001). FOXA1 was also an independent predictor of breast cancer-specific survival at 10 years using both cutoffs. Among the ER-positive subgroup treated with tamoxifen, FOXA1 was an independent prognostic marker using the 24 cutoff (P = 0.030). FOXA1 is a significant marker of good prognosis in breast cancer; it also identifies a subset of ER-positive tamoxifen treated patients at low risk of recurrence.

Extrathoracic metastases of thymic origin: a review of 35 cases.

Thymic tumors are categorized as types A, AB, B1, B2, B3, and thymic carcinoma under the World Health Organization (WHO) classification. Thymomas are typically slow growing tumors that predominantly involve the surrounding structures through direct invasion, while thymic carcinomas tend to be more aggressive. A significant number of patients are asymptomatic and can present with metastases as the first presentation. The exact incidence of extrathoracic metastases from thymoma is not known. This study describes a series of 35 cases of histologically documented metastatic thymomas and thymic carcinomas at extrathoracic sites. These cases were classified according to the current World Health Organization (WHO) classification criteria, and we present their clinical data as well as discuss the differential diagnoses of these lesions. Our study shows that all types of thymic tumors, regardless of histologic type, can be associated with invasion and metastases to thoracic and extrathoracic sites.

High-level expression of forkhead-box protein A1 in metastatic prostate cancer.

AIMS: Expression of forkhead-box protein A1 (FOXA1), a transcription factor important for normal development of the prostate gland, is thought to be controlled by steroid hormones and GATA3. The aim of this study was to investigate the expression and potential role of FOXA1 and GATA3 transcription factors as prognostic factors in prostate cancer. METHODS AND RESULTS: Expression of FOXA1, GATA3 and androgen receptor (AR) was retrospectively analysed by immunohistochemistry in a series of 80 primary tumours and 28 metastatic prostate cancers, including 15 matched paired samples. Nuclear AR expression did not significantly differ between primary and metastatic tumours. High-level nuclear FOXA1 expression was seen in 19% of primary and 89% of metastatic tumours (P < 0.0001). FOXA1 expression correlated positively with tumour size, extraprostatic extension, angiolymphatic invasion, AR and lymph node metastases at diagnosis, but did not correlate with age, T stage, Gleason score, presence of prostatic intraepithelial neoplasia or multifocality, seminal vesicle or perineural invasion, or surgical excision margin status. Expression of GATA3 was not seen in either normal epithelium or tumour. CONCLUSIONS: Our preliminary analyses suggest that high-level FOXA1 expression is associated with the development of metastatic prostate cancer. If these data are confirmed, FOXA1 expression could be used to classify patients at higher risk for metastases.

WHO types A and AB thymomas: not always benign.

The 2004 WHO classification of thymic tumors recognizes five major subtypes of thymomas and thymic carcinoma. Subtypes A and AB thymomas are purported to be benign neoplasms, although prior studies have suggested a potential for malignant behavior. The purpose of this study was to assess the clinical behavior of A and AB thymomas identified from a large institutional pathologic database. A retrospective slide review of 500 thymic epithelial tumors identified 71 (∼ 14%) cases of types A and AB thymomas. Clinical history and follow-up information were obtained through retrospective chart review. There were 38 and 33 cases of types A and AB thymomas, respectively. Complete follow-up data were available in 37 (52%) cases. Eighteen (49%) patients (type A, n=9 and type AB, n=9) had evidence of recurrent/metastatic disease at an average of 62 months (range from 6 to 244 months) after initial diagnosis. Survival curves for patients with types A and AB thymomas, with and without recurrences, show a statistically significant difference (P=0.001 and 0.005, respectively). Analysis of this large cohort confirms the potential for subtypes A and AB thymomas to show malignant behavior. Long-term clinical monitoring, therefore, appears to be justified in these cases. This study also shows the poor correlation between the WHO classification and tumor behavior.