A Phase I Study of Bortezomib in Combination With Standard 5-Fluorouracil and External-Beam Radiation Therapy for the Treatment of Locally Advanced or Metastatic Rectal Cancer

Standard therapy for stage II/III rectal cancer consists of a fluoropyrimidine and radiation therapy followed by surgery. Preclinical data demonstrated that bortezomib functions as a radiosensitizer in colorectal cancer models. The purpose of this study was to determine the maximum tolerated dose (MTD) of bortezomib in combination with chemotherapy and radiation

Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging

To dynamically detect and characterize 18F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue

Esophageal Adenocarcinoma: Treatment Modalities in the Era of Targeted Therapy

Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at alarming rates. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinases’ (AURK) pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been

Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated. Methods: We conducted a retrospective, population-based study of patients diagnosed with gastric cancer from 2004 to 2018 using the National Cancer Database (NCDB). In addition to identifying unique demographic characteristics of patients with EOGC, we evaluated (using multivariable logistic regression controlling for year of diagnoses, primary site, and stage) how gender/sex, race/ethnicity, treatment facility type, payor status, and location of residence influenced the receipt of surgery, chemotherapy, and radiation. Results: Compared to patients 45–70 and >70 years of age with gastric cancer, patients with EOGC were more likely to be female, Asian/Pacific Islander (PI), African American (AA), Hispanic, uninsured, and present with stage IV disease. On multivariable analysis, several differences among subsets of patients with EOGC were identified. Female patients with EOGC were less likely to receive surgery and chemotherapy than male patients with EOGC. Asian/Pacific Islander patients with EOGC were more likely to receive chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. African American patients were more likely to receive chemotherapy than Caucasian patients with EOGC. Hispanic patients were more likely to receive surgery and chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. Patients with EOGC treated at community cancer centers were more likely to receive surgery and less likely to receive chemotherapy than patients with EOGC treated at academic centers. Uninsured patients with EOGC were more likely to receive surgery and less likely to receive chemotherapy than privately insured patients with EOGC. Patients with EOGC living in locations not adjacent to metropolitan areas were less likely to receive surgery compared to patients with EOGC who resided in metropolitan areas, Conclusions: Patients with EOGC are a demographically distinct population. Treatment of these patients varies significantly based on several demographic factors. Additional analysis is needed to elucidate why particular groups are more affected by EOGC and how treatment decisions are made for, and by, these patients

A Phase I Study of Cetuximab in Combination With Gemcitabine and Radiation for Locally Advanced Pancreatic Cancer

BACKGROUND: Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). The primary goal of this phase I study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine when combined with cetuximab plus radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Patients with locally unresectable adenocarcinoma of the pancreas were treated with gemcitabine (200 mg/m(2)/week before dose escalation) plus cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) concurrent with radiation (50.4 Gy). RESULTS: Nine patients were enrolled in the study. One withdrew due to declining performance status before receiving any therapy. Grade 4 allergic reactions to cetuximab caused the withdrawal of 2 patients. Another patient had elevated liver function test results and a stroke after his loading dose of cetuximab. Grade 3 or 4 toxicity developed in 3 of the remaining 5 patients treated with the level 1 dose. Therefore, no further dose escalations were planned. Grade 3 toxicities included nausea, vomiting, ileus, and pneumonitis. One patient had grade 4 diarrhea. CONCLUSIONS: The combination of cetuximab, gemcitabine, and radiation resulted in significant toxicity. A recommended phase II dose could not be determined

Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer

Quantitative Comparison of Prone and Supine PERCIST Measurements in Breast Cancer

Positron emission tomography (PET) is typically performed in the supine position. However, breast magnetic resonance imaging (MRI) is performed in prone, as this improves visibility of deep breast tissues. With the emergence of hybrid scanners that integrate molecular information from PET and functional information from MRI, it is of great interest to determine if the prognostic utility of prone PET is equivalent to supine. We compared PERCIST (PET Response Criteria in Solid Tumors) measurements between prone and supine FDG-PET in patients with breast cancer and the effect of orientation on predicting pathologic complete response (pCR). In total, 47 patients were enrolled and received up to 6 cycles of neoadjuvant therapy. Prone and supine FDG-PET were performed at baseline (t0; n = 46), after cycle 1 (t1; n = 1) or 2 (t2; n = 10), or after all neoadjuvant therapy (t3; n = 19). FDG uptake was quantified by maximum and peak standardized uptake value (SUV) with and without normalization to lean body mass; that is, SUVmax, SUVpeak, SULmax, and SULpeak. PERCIST measurements were performed for each paired baseline and post-treatment scan. Receiver operating characteristic analysis for the prediction of pCR was performed using logistic regression that included age and tumor size as covariates. SUV and SUL metrics were significantly different between orientation (P < .001), but were highly correlated (P > .98). Importantly, no differences were observed with the PERCIST measurements (P > .6). Overlapping 95% confidence intervals for the receiver operating characteristic analysis suggested no difference at predicting pCR. Therefore, prone and supine PERCIST in this data set were not statistically different