Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for Rectal Cancer

Abstract

Learning Objectives After completing this course, the reader will be able to: Describe present strategies of treatment of locally advanced rectal cancer and ongoing clinical trials, including neoadjuvant radiochemotherapy with 50.4 Gy and concomitant 5-FU +/− oxaliplatin.Define the basic clinical parameters, with special emphasis on gender and BMI, correlating with radiochemotherapy-associated side effects in rectal cancer patients and differences in severity of toxicity. CME This article is available for continuing medical education credit at CME.TheOncologist.com Patients with locally advanced rectal cancer (cUICC stages II/III) are typically treated with preoperative 5-fluorouracil–based (5-FU–based) radiochemotherapy (RCT). However, trials are currently being conducted to improve the complete remission rates and the systemic control by combining 5-FU with oxaliplatin. The primary objective was to identify the subgroups of rectal cancer patients who were at risk for high-grade toxicity. All 196 patients who were included in the present study were treated with 50.4 Gy and chemotherapy that included either 5-FU (n = 115) or 5-FU+oxaliplatin (n = 81). The preoperative RCT was followed by a total mesorectal excision and adjuvant chemotherapy. Acute toxicity was monitored weekly and a toxicity grade ≥3 (Common Toxicity Criteria) for a skin reaction, cystitis, proctitis, or enteritis was defined as high-grade acute organ toxicity. After RCT with 5-FU+oxaliplatin, complete tumor remission was achieved in 13.6% of the patients and in 11.3% after RCT with 5-FU alone. Complete irradiation dosages of 50.4 Gy were given to 99% (5-FU) and 95% (5-FU+oxaliplatin) of the patients. Concomitant chemotherapy was fully administered in 95% of the patients treated with 5-FU compared with the 84% of patients treated with 5-FU+oxaliplatin. A significantly higher proportion of acute organ toxicity was found in the patients who were treated with 5-FU+oxaliplatin compared with those who were treated with 5-FU. Additionally, women with a low body mass index were at the highest risk for acute organ toxicity. These results suggest that there are basic clinical parameters, such as gender and body mass index, that may be potential markers for generating individual risk profiles of RCT-induced toxicity.

Predicting Radiotherapy-Related Clinical Toxicities in Cancer: A Literature Review

“…This large-scale trial included a sample of 1,688 patients, and results are supported by a smaller scale study (Wolff et al, 2011) that also investigated patients with rectal cancer and used the same tool to measure toxicity. In Wolff et al (2011), almost 4% of the total sample surveyed developed severe grade 4 acute toxicities, which included gastrointestinal, urologic, and dermatologic effects. All affected had a BMI of less than 22, whereas the average BMI for the total sample was 26.4 (Wolff et al, 2011).…”

“…In Wolff et al (2011), almost 4% of the total sample surveyed developed severe grade 4 acute toxicities, which included gastrointestinal, urologic, and dermatologic effects. All affected had a BMI of less than 22, whereas the average BMI for the total sample was 26.4 (Wolff et al, 2011). However, results of a study by Tho et al (2006) indicated no significant correlation between BMI and acute effects of radiotherapy in rectal cancer, although this difference may be attributed to the smaller sample size (41 patients) and, also, the lower dose of radiotherapy received by the sample (45 Gy versus 50.4-54 Gy).…”

“…Inclusion and Exclusion Criteria in the development of late effects in those treated for head and neck cancer; and lower BMI is predictive of acute toxicities in patients with rectal cancer (Ambrosone et al, 2006;Ghadjar et al, 2012;Legge et al, 2013;Meyer et al, 2012;Meyerhardt et al, 2004;Twardella et al, 2003;Wolff et al, 2011). Inclusion and Exclusion Criteria in the development of late effects in those treated for head and neck cancer; and lower BMI is predictive of acute toxicities in patients with rectal cancer (Ambrosone et al, 2006;Ghadjar et al, 2012;Legge et al, 2013;Meyer et al, 2012;Meyerhardt et al, 2004;Twardella et al, 2003;Wolff et al, 2011).…”

Polyphenols from brown alga, Padina boergesenii (Allendar & Kraft) decelerates renal cancer growth involving cell cycle arrest and induction of apoptosis in renal carcinoma cells

“…Cancer metastasis is recognized worldwide to be a major process and as a main reason for high mortality . It is the progressive step, where the spreading of cancer cells occur through circulatory system to distant organs establishing a secondary tumor originated from primary site . The reason behind the organ selectivity is determined by the pattern of blood flow where the provision of a fertile environment compatible tumor cells could grow .…”

“…The reason behind the organ selectivity is determined by the pattern of blood flow where the provision of a fertile environment compatible tumor cells could grow . The successful manifestation of metastasis involves primary tumor cell invasion with penetration of small lymphatic or vascular channels, release of neoplastic cells, survival, followed by angiogenesis, and growth at a distant site . Currently, the treatments are unsatisfactory to prolong survival of patients with metastasis .…”