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Purpose To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Materials and Methods Patients with localized, non-metastatic T3 or T4 rectal cancer < 12 cm from the anal verge were enrolled in a prospective, multi-institutional, single arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3D-conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed in 4-8 weeks following completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2-5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of 0.10 (1-sided). Results 79 patients were accrued, of whom 68 were evaluable. 61 patients (89.7%) had cT3 and 37 (54.4%) cN (+) disease. 42/68 patients received post-operative chemotherapy. 58 patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. 35 patients (51.5%) developed grade ≥ 2 GI toxicity. 12 patients (17.6%) developed grade 3 or 4 diarrhea. pCR was achieved in 10 patients (14.7%). With a median follow-up of 3.98 years, the 4-year locoregional failure (LRF) rate was 7.4% (95% CI: 1.0% - 13.7%). 4-year OS and DFS were 82.9% (95% CI: 70.1% - 90.6%) and 60.6% (95% CI: 47.5% - 71.4%), respectively. Conclusion The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of gastrointestinal toxicity.

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This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose-dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune-endocrine function, which may be important in the course of immunodeficiency syndrome.