The Efficacy of Dietary Fiber in Managing Gastrointestinal Toxicity Symptoms in Patients with Gynecologic Cancers undergoing Pelvic Radiotherapy: A Systematic Review.

BACKGROUND: Pelvic radiotherapy is a common part of treatment used in gynecologic malignancies. The side effects associated with treatment, such as gastrointestinal toxicity, can be acute and chronic. Previous studies have provided little clarity in regard to the best dietary intervention for management of symptoms. OBJECTIVE: The aim of this systematic review was to summarize the evidence on the efficacy of nutrition interventions involving fiber modification in patients with gynecologic cancers undergoing pelvic radiotherapy to prevent or alleviate gastrointestinal side effects, in comparison to standard care, placebo, or no intervention. METHODS: Studies, inclusive of any language and date, up to December 1, 2019, were selected from eight electronic databases: PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, Scopus, Science direct, Clinical Key, Web of Science, and Cochrane. Key study outcomes included gastrointestinal toxicity such as diarrhea/bowel changes, abdominal pain or bloating, and nausea; nutritional status; and quality of life. All studies underwent a quality appraisal using the Academy of Nutrition and Dietetics Quality Criteria Checklist and certainty of evidence was assessed via the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Four studies were included (total number of participants = 89), with quality ratings of neutral or negative. Due to the risk of bias, inconsistency, indirectness, and imprecision, there was very low certainty of evidence that dietary fiber modifications improved these outcomes. Some positive trends regarding improvements in incidence and severity of diarrhea and bowel symptoms were reported; however, the body of evidence was insufficient to form specific recommendations for clinical practice. This is reflected in the Grading of Recommendations Assessment, Development, and Evaluation criteria rating (very low level of certainty) for quality of life and gastrointestinal toxicity outcomes. CONCLUSIONS: This systematic review suggests that supplementary fiber modification during radiation therapy may have some potential benefits with improving gastrointestinal symptoms; however, more definitive evidence and further exploration of fiber in a therapeutic role is required to inform dietary practice.

Lower abdominal and pelvic radiation and testicular germ cell tumor risk.

BACKGROUND: Testicular germ cell tumor (TGCT) incidence has increased in recent decades along with the use and dose of diagnostic radiation. Here we examine the association between reported exposure to diagnostic radiation and TGCT risk. METHODS: We conducted a case-control study of men with and without TGCT recruited from hospital- and population-based settings. Participants reported on exposures to 1) x-ray or CT below the waist and 2) lower GI series or barium enema, which consists of a series of x-rays of the colon. We also derived a combined measure of exposure. We used logistic regression to determine the risk of developing TGCT according to categories of exposures (0, 1-2, or ≥3 exposures) and age at first exposure, adjusting for age, year of birth, race, county, body mass index at diagnosis, family history of TGCT, and personal history of cryptorchidism. RESULTS: There were 315 men with TGCT and 931 men without TGCT in our study. Compared to no exposures, risk of TGCT was significantly elevated among those reporting at least three exposures to x-ray or CT (OR≥3 exposures, 1.78; 95% CI, 1.15-2.76; p = 0.010), lower GI series or barium enema (OR≥3 exposures, 4.58; 95% CI, 2.39-8.76; p<0.001), and the combined exposure variable (OR≥3 exposures, 1.59; 95% CI, 1.05-2.42; p = 0.029). The risk of TGCT was elevated for those exposed to diagnostic radiation at age 0-10 years, compared to those first exposed at age 18 years or later, although this association did not reach statistical significance (OR, 2.00; 95% CI, 0.91-4.42; p = 0.086). CONCLUSIONS: Exposure to diagnostic radiation below the waist may increase TGCT risk. If these results are validated, efforts to reduce diagnostic radiation doses to the testes should be prioritized.

Dose optimization strategy of sacrum limitation in cervical cancer intensity modulation radiation therapy planning.

The aim of this study was to investigate the dose optimization strategy for the sacrum to reduce the risk of pelvic insufficiency fracture (PIF).Using a retrospective study design, we analyzed data from 28 patients with cervical cancer who underwent postoperative adjuvant radiotherapy in our department from June 2017 to January 2018. Among these patients, 20 (71.4%) underwent external beam radiation therapy in the pelvic lymphatic drainage area (node-negative patients). Overall, 8 patients (28.6%) underwent radiotherapy in the pelvic lymphatic drainage area with a simultaneous integrated boost (node-positive patients). Furthermore, 20 patients were assigned to 2 groups of plans according to the prescribed doses of 5000 and 4500 cGy/25. Each group had 3 plans according to 3 different dose limit conditions: "pelvic bones and sacrum unlimited," "pelvic bones limited," and "pelvic bones + sacrum limited." The irradiation dose of the sacrum and pelvis was analyzed in three limited optimization models.The planning target volume conformity index and homogeneity index, based on different optimization modes in the 4500 and 5000 cGy plans, showed no significant differences. The D50% and Dmean of the pelvis + sacrum limited mode were significantly lower than those of the pelvic limited mode (P < .001). The dose of the sacrum and pelvis in the 4500 cGy plan in the lymphatic drainage area was significantly lower than that of the 5000 cGy plan (P < .001). In the lymph node boost group, the irradiation dose of the sacrum and pelvis was significantly increased (P ≤ .001).Increasing the limitation of the sacrum, on the basis of pelvic bone limitation, in cervical cancer intensity-modulated radiation therapy can significantly reduce the dose to the sacrum. Compared with the dose of 5000 cGy to the lymphatic drainage area, the dose of 4500 cGy was the largest influencing factor to reduce the dose to the sacrum.

Diagnostic Reference Levels for conventional radiography and fluoroscopy in Austria: Results and updated National Diagnostic Reference Levels derived from a nationwide survey.

OBJECTIVE: Evaluation and updating of Austrian National Diagnostic Reference Levels (NDRLs). METHODS: A nationwide survey on common conventional radiography and fluoroscopy examinations was conducted. In line with Austrian radiation protection standards, all relevant Austrian hospitals and radiology offices/centers were asked to report a minimum sample of 10 representative dose-area product (DAP) values together with patient weight and fluoroscopy time, if applicable. Examinations included for conventional radiography were skull, chest, abdomen, pelvis, lumbar spine and bedside chest x-ray, for fluoroscopy barium enema (single and double contrast) and swallowing (video). Participants were invited via e-mail, followed up by reminders to increase participation rates. Plausibility checks were performed to increase data quality. 3rd quartiles of facility median and mean DAP were calculated and compared to Austrian and international NDRLs. RESULTS: 59% of invited facilities submitted DAP data, 43% submitted additional data on patient weight and 41% on fluoroscopy time. DAP case numbers varied from 1005 to 2121 for conventional radiography and from 182 to 1380 for fluoroscopy. Average patient weight was 75 kg for conventional radiography and 77 kg for fluoroscopy. CONCLUSION: 3rd quartiles derived from the survey are substantially lower than the old Austrian NDRLs (valid till early 2018). Since 3rd quartiles correspond well to European NDRLs, the update would be in accordance with European DRL harmonisation efforts.

Complementary and alternative medicine self-care strategies for nausea in patients undergoing abdominal or pelvic irradiation for cancer: A longitudinal observational study of implementation in routine care.

OBJECTIVE: To longitudinally describe practice of Complementary and Alternative Medicine (CAM) self-care strategies for nausea during radiotherapy. METHODS: Two hundred patients daily registered nausea and practice of CAM self-care strategies, beside conventional antiemetic medications, for nausea during abdominal/pelvic irradiation (median five weeks) for gynecological (69%) colorectal (27%) or other tumors (4%). RESULTS: During radiotherapy, 131 (66%) experienced nausea, and 50 (25%) practiced self-care for nausea at least once, for a mean (m) of 15.9days. The six of 50 patients who stayed free from nausea practiced self-care more frequent (m=25.8days) than the 44 patients experiencing nausea (m=14.5) (p=0.013). The CAM self-care strategies were: modifying eating (80% of all self-care practicing patients, 80% of the nauseous patients versus 83% of the patients free from nausea; ns) or drinking habits (38%, 41% vs 17%; ns), taking rests (18%, 20% vs 0%; ns), physical exercising (6%, 2% vs 33%; p=0.035), acupressure (4%, 5% vs 0%; ns) and self-induced vomiting (2%, 2% vs 0%; ns). CONCLUSION: A fourth of patients undergoing emetogenic radiotherapy practiced CAM self-care for nausea, mostly by modifying eating or drinking habits. The CAM self-care practicing patients who did not become nauseous practiced self-care more frequent than the nauseous patients did. To make such self-care evidence based, we need studies evaluating its efficacy.

Nutritional supplementation with arginine protects radiation-induced effects. An experimental study.

PURPOSE:: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. METHODS:: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. RESULTS:: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). CONCLUSIONS:: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine.

Nutritional supplementation with arginine protects radiation-induced effects. An experimental study

ABSTRACT PURPOSE: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. METHODS: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. RESULTS: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). CONCLUSIONS: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine.

Volumetric-modulated arc therapy with vaginal cuff simultaneous integrated boost as an alternative to brachytherapy in adjuvant irradiation for endometrial cancer: a prospective study.

AIM: To report preliminary results of a prospective study using pelvic volumetric-modulated arc therapy and simultaneous integrated boost (SIB-VMAT) on vaginal cuff postoperatively in patients with endometrial cancer (EC). PATIENTS AND METHODS: Fifty consecutive patients, submitted surgery for EC, were recruited to SIB-VMAT prescribing a dose of 54 Gy to the pelvis and 66 Gy to the vaginal cuff in 30 fractions. A 2 mm transvaginal probe and magnetic resonance imaging were used to define the vaginal cuff. Toxicity data were collected according to Common Terminology Criteria for Adverse Events v4.0; clinical outcomes were analyzed. RESULTS: The median follow-up was 26 (range=12 to 39) months. According to International Federation of Gynecology and Obstetrics 2009, the stages were: IB1 in 20%, IB2 in 28%, IIA2 in 16%, IIB in 6%, IIIA in 2%, and IIIC in 28%. The 2-year Overall Survival and Local Control were 96% and 100%, respectively. Two pelvic node failures were registered. Acute gastrointestinal toxicity was: G0 in 12%, G1 in 52%, G2 in 36%; no case of toxicity G3 or more was observed. Acute genitourinary toxicity was: G0 in 10%, G1 in 42%, G2 in 48%; no case of toxicity G3 or more was observed. No late severe gastrointestinal or genitourinary toxicities were reported. A statistical correlation was found between acute G2 gastrointestinal toxicity with bowel V20 Gy ≥ 30%, V20 ≥ 40%, V30 ≥ 30%, Dmax ≥ 45 Gy. Acute G2 genitourinary toxicity was threefold higher with chemotherapy. CONCLUSION: In patients with EC, SIB-VMAT is feasible, and well tolerated. Preliminary data of clinical outcome are promising. Further prospective studies are advocated.

Protective effects of nutritional supplementation with arginine and glutamine on the penis of rats submitted to pelvic radiation.

Radiotherapy is widely used to treat pelvic malignancies, but normal tissues near the target tumour are often affected. Our aims were thus to determine whether the structural organization of the rat penis is altered by radiation, and whether supplementation with L-arginine (ARG) or L-glutamine (GLN) would have protective effects against these alterations. Groups of rats were treated with: no intervention (CONTR); pelvic radiation, followed by sacrifice 7 (RAD7) or 15 (RAD15) days later; and pelvic radiation, daily supplementation with ARG or GLN, followed by sacrifice 7 (RAD7+ARG, RAD7+GLN) or 15 (RAD15+ARG, RAD15+GLN) days after radiation. Structural components in the corpus cavernosum (CC), tunica albuginea of the corpus spongiosum (TACS) and urethral epithelium (UE) were analysed using stereological and immunohistochemical methods. The results showed that in the CC, connective tissue was increased by 18% in RAD15 (p < 0.04), but this change was partially prevented in RAD15+GLN (p < 0.05) and RAD15+ARG (p < 0.04). The fibrous matrix of the CC trabeculae stained evenly for collagen type I. In RAD15, the intensity of the labelling was increased, whereas in RAD15+GLN and RAD15+ARG the staining was similar to that of CONTR. No staining changes were seen in the groups that were sacrificed 7 days after radiation. Cavernosal elastic fibre content in RAD15 was increased by 61% (p < 0.004), and this was prevented in RAD15+ARG (p < 0.004) but not in RAD15+GLN. In TACS, the amino acids protected (p < 0.02) against the radiation-induced 92% increase in elastic fibre content, but only in RAD15. Cell density in the UE, as well as UE thickness, were reduced by 30% in RAD15 (p < 0.004), and there were protective effects of both amino acids. In conclusion, radiation-induced alterations in penile structures tend to be more pronounced 15 days after radiation session. Both ARG and GLN have protective effects against these changes, with the former being slightly more effective.

The utility of hyperbaric oxygen therapy to treat recurrent acute bowel obstruction after previous pelvic radiotherapy: a case series.

BACKGROUND AND OBJECTIVE: Repeated episodes of acute bowel obstruction is a potential complication following pelvic radiation therapy. It has been previously thought that hyperbaric oxygen therapy (HBOT) may not be useful for treatment of such obstructive episodes. We report our experience with the use of HBOT for recurrent radiation-induced acute bowel obstruction. METHODS: This is a retrospective case series. Radiological imaging had excluded the presence of recurrent or new cancer. Possible predisposing causes for acute obstruction had been treated and had not led to resolution of symptoms or had been excluded. RESULTS: During 2007-2010, five patients with recurrent episodes of acute obstructive bowel symptoms following previous therapeutic pelvic irradiation were referred for HBOT (four females and one male; median age 56; range 48-72). The primary tumours sites were the endometrium (n = 2), ovary, cervix and prostate (n = 1 each), and patients were treated 2-17 (median 9) years previously with radiotherapy. Before HBOT, patients were experiencing acute obstructive bowel symptoms at 1-6 weekly intervals. Four patients had progressive weight loss. Patients received 100 % oxygen in a multiplace hyperbaric chamber at a pressure of 2.4 atm absolute for up to 90 min once a day, 5 to 7 days weekly. All patients were initially referred for 40 sessions of HBOT. Three patients required a further extra 20 sessions for complete resolution of bowel symptoms. HBOT was well tolerated with no side effects. Patients have remained well after 6-24 months of follow-up. CONCLUSIONS: HBOT may be an effective treatment of radiation-induced bowel obstruction and deserves prospective evaluation.

A systematic review and meta-analysis of probiotics for the management of radiation induced bowel disease.

BACKGROUND & AIMS: A meta-analysis to estimate the efficacy of probiotics in prevention of radiation-induced bowel disease after pelvic radiotherapy has been performed. Previous attempts have arguably failed to provide a comprehensive analysis of clinical trials and their outcomes. METHODS: We searched for studies indexed in Medline, EMBASE, Cochrane Library, and on-line clinical trials registers. There was no language or time limit. Each study was evaluated for methodological quality and outcomes. We identified four outcomes on which to perform meta-analysis: incidence of diarrhoea, loperamide use, watery, and soft stools (Bristol Stool Chart). Odds ratio (OR) was used to compare efficacy, and the pooled OR was estimated using a random effects model; heterogeneity was assessed with Cochran's Q and Higgins I(2) test. Analyses were performed using Review Manager 5.2. RESULTS: Ten studies were included in our systematic review, of which six were subjected to meta-analysis to compare probiotics against placebo. Quality assessment showed an unclear risk due to incomplete outcome data and lack of performance of intention-to-treat analysis, while blinding and randomization issues were present in certain studies. Pooled results showed heterogeneity (Cochran's Q: p < 0.05; I(2): high). However the pooled OR for the incidence of diarrhoea, synthesized from 6 studies, significantly favoured the use of probiotics over control (OR = 0.44, 95% CI 0.21-0.92). Numerically, but not statistically, probiotics seem to decrease loperamide use (OR = 0.29, 95% CI 0.01-6.80) and the incidence of watery stools (OR = 0.36, 95% CI 0.05-2.81). CONCLUSIONS: In conclusion, probiotic supplementation shows a probable beneficial effect in the prevention, and possible benefit in the treatment, of radiation-induced diarrhoea.

Nutritional supplementation with L-arginine prevents pelvic radiation-induced changes in morphology, density, and regulating factors of blood vessels in the wall of rat bladder.

PURPOSE: To determine whether L-arginine has protective effects against radiation-induced alterations in the morphology and regulatory factors of vesical blood vessels in rats. METHODS: Male rats aged 3-4 months were divided into groups of 10 animals each: (a) controls, consisting of non-treated animals; (b) radiated-only rats; and (c) radiated rats receiving L-arginine supplementation. Radiation was in one session of 10 Gy and was aimed at the pelvic-abdominal region. L-arginine was administered once a day (0.65 g/kg body weight), starting 7 days before radiation and continuing until killing on the 16th day after radiation. The density, relative area, and wall thickness of blood vessels were measured in the vesical lamina propria using histological methods, and the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF) in the bladder wall was assessed by RT-PCR. RESULTS: Compared with controls, radiation alone decreased the density and relative area of blood vessels by 32 % (p < 0.01) and 25 % (p < 0.05), respectively, and reduced the arterial wall thickness by 42 % (p < 0.004). VEGF and FGF mRNA levels after radiation were diminished by 67 % (p < 0.002) and 56 % (p < 0.04), respectively. The radiated animals supplemented with L-arginine were not significantly different from controls. CONCLUSIONS: Pelvic radiation leads to significant vesical modifications, as in the morphology of blood vessels and in VEGF and FGF expression. All these changes, however, were prevented by L-arginine treatment. These results emphasize, therefore, the potential use of this amino acid as a radioprotective drug.

Three cytotoxic drugs combined with pelvic radiation and as maintenance chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): long-term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and cisplatin.

PURPOSE: Phase III trials in the 1990s for squamous cell carcinoma of the anus (SCCA) demonstrated 5-fluorouracil (5FU) and mitomycinC (MMC) chemoradiation (CRT) improved outcome compared to radiation (RT) alone, but local recurrence remained significant. This prospective pilot study intensified treatment by integrating 3 cytotoxic drugs into CRT and maintenance chemotherapy. METHODS: CRT comprised 5-FU 1000 mg/m(2) days 1-4,29-32, MMC 10 mg/m(2) day 1 and Cisplatin (CDDP) 60 mg/m(2) days1 and 29, with 45 Gy in 25 daily fractions, followed by a 15 Gy boost. Maintenance chemotherapy started 4-8 weeks later, three courses repeated every 21 days, using 5-FU/CDDP doses above, with MMC reduced to 7 mg/m(2) and administered with the first and third cycles. RESULTS: In CRT only 14/19 (74%) patients received protocol-defined chemotherapy doses in week 5. Compliance to maintenance chemotherapy was poor. 15/19 started cycle 1, 13 started cycle 2 and 11 cycle 3. 17/19 experienced G3-G5 toxicity (16 Grade 3/4 and one Grade 5). 16/19 patients (84%) remain alive and disease-free - median follow-up 79 months (34-115). CONCLUSIONS: Despite favourable results, the significant toxicity and low compliance of the three-drug CRT regimen used, deemed it unsuitable for testing in a phase III trial. A two-drug maintenance regimen was explored in the ACT II trial.

Postoperative low pelvic radiotherapy and chemotherapy for stage II and III rectal cancer.

OBJECTIVES: To evaluate whether postoperative low pelvic radiotherapy (RT) combined with chemotherapy is an appropriate treatment for stage II and III rectal cancer. METHODS: Between November 1997 and May 2006, 104 patients with stage II and III rectal cancer underwent surgery as the primary treatment followed by postoperative RT combined with chemotherapy in our institute and were reviewed retrospectively. Sixty-nine patients received low pelvic RT only (upper margin at 1 cm above the low end of the sacroiliac joint; median dose 54 Gy) (low pelvic RT group) and the other 35 patients received whole pelvic RT (upper margin at the mid L5; median dose 43.2 Gy) and subsequently received a boost to the low pelvis (total median dose 54 Gy) (whole pelvic RT group). RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 72% versus 63%, 86% versus 84%, and 66% versus 62% for low pelvic versus whole pelvic RT group. There were no statistical differences in these 2 groups. Two patients (2.9%) of the low pelvic RT group and 2 patients (5.7%) of the whole pelvic RT group developed upper pelvis relapse, which was out of the low pelvic field. The incidence of Grade 3 to 5 small bowel late complications of the low pelvic RT group was significantly less than that of the whole pelvic RT group (4.3% vs. 20%) (P=0.029). CONCLUSIONS: Low pelvic RT significantly reduces small bowel late complications and does not compromise the overall survival rate, local control rate, and distant metastasis-free rate.

Hyperbaric oxygen therapy and delayed radiation injuries (soft tissue and bony necrosis): 2012 update.

Informal surveys at CME meetings have shown that approximately one-third of patients in the United States receive hyperbaric oxygen (HBO2) for delayed radiation injury. More than 600,000 patients receive radiation for malignancy in our country annually, and about one-half will be long-term survivors. Serious radiation complications occur in 5-10% of survivors. A large population of patients is therefore at risk for radiation injury. HBO2 has been applied to treat patients with radiation injury since the mid-1970s. Published results are consistently positive, but the level of evidence for individual publications is usually not high level, consisting mostly of case series and case reports. Only a rare randomized controlled trial has been accomplished. Radiation injury is one of the UHMS "approved" indications, and third-party payors will usually reimburse for this application. This updated review summarizes the publications available reporting results in treating radiation-injured patients. Mechanisms of HBO2 in radiation injury are discussed briefly. Outcome is reported on a mostly anatomic basis though due to the nature of the injury a positive outcome at one anatomic site is supportive of HBO2 at other sites. The potential benefit of prophylactic HBO2 before frank damage is also discussed in high-risk patients. The concerns of HBO2 enhancing growth of or precipitating recurrence of malignancy is discussed and largely refuted.

Matrix metalloproteinase-8 mediates the unfavorable systemic impact of local irradiation on pharmacokinetics of anti-cancer drug 5-Fluorouracil.

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated the influence of local irradiation on the pharmacokinetics of 5-FU in rats. The single-fraction radiation was delivered to the whole pelvic fields of Sprague-Dawley rats after computerized tomography-based planning. 5-FU at 100 mg/kg was prescribed 24 hours after radiation. A high-performance liquid chromatography system was used to measure 5-FU in the blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I was administered to examine whether or not RT modulation of 5-FU pharmacokinetic parameters could be blocked. Compared with sham-irradiated controls, whole pelvic irradiation reduced the area under the concentration versus time curve (AUC) of 5-FU in plasma and, in contrast, increased in bile with a radiation dose-dependent manner. Based on protein array analysis, the amount of plasma MMP-8 was increased by whole pelvic irradiation (2.8-fold by 0.5 Gy and 5.3-fold by 2 Gy) in comparison with controls. Pretreatment with MMP-8 inhibitor reversed the effect of irradiation on AUC of 5-FU in plasma. Our findings first indicate that local irradiation modulate the systemic pharmacokinetics of 5-FU through stimulating the release of MMP-8. The pharmacokinetics of 5-FU during concurrent chemoradiaiton therapy should be rechecked and the optimal 5-FU dose should be reevaluated, and adjusted if necessary, during CCRT.

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer.

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

Improved quality of life with hyperbaric oxygen therapy in patients with persistent pelvic radiation-induced toxicity.

AIMS: We report the results of hyperbaric oxygen therapy (HBOT) used in the treatment of radiation-induced persistent side-effects after the irradiation of pelvic tumours. MATERIALS AND METHODS: Between January 2001 and December 2005, 13 women (median age 60.3 years) with radiation combined proctitis/cystitis (n=6), longstanding vaginal ulcers and fistulas (n=5) and longstanding skin injuries (n=2) underwent HBOT in a multiplace chamber for a median of 27 sessions (range 16-40). The treatment schedule was HBOT 100% oxygen, at 2 absolute atmospheres, for 90 min, once a day. For radiation-induced toxicity grading we used the National Cancer Institute Common Toxicity Criteria (CTC) grading system, before and after HBOT. RESULTS: Thirteen patients underwent an adequate number of HBOT sessions. The mean CTC grading score before HBOT was 3.3+/-0.75, whereas the mean CTC grading score after HBOT was 0.3+/-0.63. The scores showed a significant improvement after HBOT (P=0.001; exact Wilcoxon signed-rank test). Rectal bleeding ceased in five of six patients with proctitis and dysuria resolved in six of seven cystitis patients. Macroscopic haematuria stopped in seven of seven patients. Scar complications resolved in two of two patients. None reported HBOT-associated side-effects. CONCLUSION: HBOT is apparently safe and effective in managing radiation-induced late side-effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas.

Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients.

UNLABELLED: Metronomic low-dose chemotherapy regimen was found to have an antiangiogenic effect in tumors. However, its effect on levels of circulating pro-angiogenic and anti-angiogenic factors is not fully explored. MATERIALS AND METHODS: The levels of both VEGF and PDGF-BB were measured in three time points, in the serum of 32 rectal carcinoma patients receiving daily reduced-dose/continuous capecitabine in combination with preoperative pelvic irradiation. RESULTS: We found a significant decrease in VEGF and PDGF-BB serum levels during the combination treatment (p < 0.0001), followed by an increase in the successive rest-period (p < 0.0001). In addition, substantial changes in platelets counts were observed during treatment in correlation with the changes of VEGF and PDGF-BB serum levels. DISCUSSION: These results suggest that combined chemo-irradiation affect levels of pro-angiogenic factors during treatment, and may reflect an anti-angiogenic window induced during this treatment. The potential implications of this inducible phenomenon, including a possible clinical benefit from the administration of long lasting metronomic chemotherapy immediately following combined chemo-irradiation, would warrant further investigation.