Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.

Gastric prostaglandin E2 receptors are the common antisecretory target of mucosal prostanoids.

The gastric mucosa produces all principal prostaglandin (PG) types, but receptor binding studies in this tissue have as yet been performed exclusively with [3H]PGE2. Therefore we compared the binding of different 3H-labelled prostanoids to fundic mucosal plasma membranes from the porcine stomach. Binding sites for [3H]PGE2, [3H]iloprost and [3H]PGF2 alpha had similar nanomolar dissociation constants with high affinities for unlabelled PGE2. Iloprost and PGF2 alpha were 10- and 100-fold less potent competitors with Hill slopes near unity in all cases. In further [3H]PGE2 competition studies the affinities of prostanoid ligands with selectivity for different PG receptor types correlated closely with their respective antisecretory potencies, as tested by [14C]aminopyrine uptake in isolated porcine parietal cells. We conclude that parietal cell PGE2 receptors are the common antisecretory target for all prostanoid types in the porcine stomach. There was no evidence for other mucosal PG receptors possibly involved in acid secretion.