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Background: Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA., Methods: Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt., Results: A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20)., Conclusions: MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018;124:1791-7. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Introduction: Esophageal adenocarcinomas commonly express the epidermal growth factor receptor. This trial assessed the 6-month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second-line therapy., Methods: This was a multicenter, open-label phase II study of single-agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0 to 2 were required. Patients received cetuximab 400 mg/m intravenously (IV) on week 1 and 250 mg/m IV weekly thereafter. The primary objective was to determine 6-month overall survival. Secondary end points included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies., Results: Sixty-three patients were registered, with eight ineligible or never treated. Fifty-five eligible patients (49 men, 6 women; median age = 61.2 years [range, 30.7-88.5]) were enrolled. Twenty patients survived more than 6 months for a 6-month overall survival rate of 36% (95% confidence interval [CI]: 24-50%). The median overall survival was 4.0 months (95% CI: 3.2-5.9). Median progression-free survival was 1.8 months (95% CI: 1.7-1.9). One partial response and two unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of epidermal growth factor receptor, epidermal growth factor, interleukin (IL)-8, cyclooxygenase (COX)-2, vascular epidermal growth factor receptor (VEGF), CCND1, neuropilin 1 (NRP1), and K-ras mutational status were not associated with response or survival., Conclusions: The 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer.

Quantitative reverse transcription PCR (RT-PCR) was used to measure gene expressions (relative mRNA levels) of p16 and the alternate transcript pl6beta in esophageal and gastric tumors. p16 gene expression was undetectable in 13 of 25 esophageal squamous cell carcinomas. In 11 of these tumors, pl6beta was simultaneously missing whereas two of the pl6-deficient tumors still expressed p16beta. Among 34 esophageal adenocarcinomas and 11 gastric adenocarcinomas, only one tumor lacked p16 expression and all tumors expressed p16beta. p16 sequences were not detectable by PCR in genomic DNA from tumors lacking both p16 and p16beta mRNA, suggesting that the simultaneous loss of both gene expressions resulted from homozygous genomic deletion of the p16 gene. However, DNA from tumors that lacked p16 mRNA but expressed pl6beta did contain the p16 gene, consistent with loss of p16 expression in these tumors by transcriptional suppression. No point mutations in p16 cDNA were detected among 12 that were sequenced, but one p16 cDNA from a squamous cell carcinoma had a 19-base deletion, possibly indicating a splice-site mutation. Among those tumors that expressed p16 mRNA, the gene expression values of both p16 and pl6beta varied over a wide range. In some cases, p16 expression was detectable but low, suggesting that down-regulation of p16 expression may be used in some cases to achieve the funtional equivalent of gene deletion or transcriptional silencing. These results demonstrate that p16 expression patterns differ based on tumor histology and origin. Homozygous deletion of p16 appears to be common in esophageal squamous cell carcinomas but in adenocarcinomas, both gene deletion and transcriptional silencing of p16 were infrequent.

Although epidermoid cancer of the anus is an uncommon tumor, it has served well as a model for several disciplines within oncology. Advances in understanding the epidemiology and the definitive therapeutic role of combined radiation therapy and chemotherapy for anal tumors have encouraged many investigators to study similar applications in the more common epithelial malignancies. In this monograph, the anatomy of the anal area is reviewed emphasizing the differences in natural history and prognosis between anal margin and anal canal cancers. Treatment does not depend on the specific histologic variant of the epidermoid tumors which arise in this region. The roles of viruses, of immunodeficiency syndromes, and of a history of benign anal disease and trauma in the etiology and epidemiology of this tumor are discussed. Current staging will be critically reviewed stressing that invasive (pathologic) staging by surgery is not indicated, but noninvasive staging has definite limitations. Small superficial tumors may be definitively treated with either limited surgery or radiation. While regional treatments such as surgery and radiation offer cure to between 45% and 60% of nonselected patients, initial treatment with combination radiation and chemotherapy produces cure rates between 65% and 85% for similar groups of patients. The rationale for combined modality therapy is presented and recommendations for therapy by stage of the cancer are made. Finally, we present questions that remain for future research in the clinic and laboratory regarding epidermoid tumors of the anus.

Celestin intubation of the esophagus is occasionally employed in the palliation of unresectable esophageal carcinoma and in the obturation of malignant tracheoesophageal fistulas. Fourteen of 192 patients with carcinomas of the esophagus had Celestin tubes inserted at our institution between October 1977 and October 1982. Although tube insertion carries a low operative risk, there is significant subsequent morbidity associated with its use. Complications were identified radiographically in 11 of the 14 patients. Gastroesophageal reflux with aspiration pneumonia, tube obstruction, and tube migration were demonstrated most often. When Celestin tube use is deemed appropriate, the clinician and radiologist should be aware of the possible complications.

Under the auspices of the Southwest Oncology Group, Wayne State University tested a schedule using bleomycin and mitomycin C that was previously reported to give a response rate of 88%. In our patients the same regimen produced similar toxic effects but a far different response rate of 15.8% (one complete remission and two partial remissions). The only discernible difference in the two patient groups was the amount of radiation given prior to chemotherapy.