Publications by authors named "Zuleyha Akgun"

15 Publications

  • Page 1 of 1

Outcomes of patients with anal cancer treated with volumetric-modulated arc therapy or intensity-modulated radiotherapy and concurrent chemotherapy.

J Cancer Res Ther 2021 Jan-Mar;17(1):51-55

Department of Radiation Oncology, Istanbul University Medical Faculty, Istanbul, Turkey.

Aims: To evaluate the results of chemoradiation with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) for the treatment of anal canal cancer patients at three institutions that had advanced devices.

Materials And Methods: A retrospective analysis was performed for patients treated with 5-fluorouracil and mitomycin-based chemotherapy and IMRT or VMAT for anal cancer from 2011 to 2013. Complete response (CR) rates, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and toxicities were investigated. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, Version 3.0.

Results: Fifteen patients were included in the analysis. The majority of patients had T2 (53.3%) and N0 (40%) disease according to the staging system that was developed by the American Joint Committee on Cancer. CR was observed in 14 patients (93%), and the median follow-up was 26 months (13-42 months). The 3-year CFS, DFS, and OS were 86%, 86%, and 88%, respectively. Acute Grade 3 toxicities were observed as 6% of hematological, 26% of gastrointestinal, and 26% of dermatological.

Conclusion: Early results confirm that IMRT or VMAT for anal cancer treatment reduces acute toxicities while maintaining high control rates.
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March 2021

Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using 68Ga-PSMA PET/CT: TROD 09-004 Study.

Clin Nucl Med 2021 06;46(6):465-470

Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara.

Purpose: To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients.

Methods: In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed.

Results: The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed.

Conclusions: We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT.
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June 2021

Dosimetric comparison of modern radiotherapy techniques for gastric cancer after total gastrectomy.

J Cancer Res Ther 2020 Dec;16(Supplement):S133-S137

Department of Radiation Oncology, Bezmialem Vakif University, Istanbul, Turkey.

Purpose: The purpose of this study is to investigate the optimal radiotherapy technique for postoperative irradiation of gastric cancer treated with total gastrectomy.

Materials And Methods: The database of ten patients was used for this study. Three-dimensional (3D) conformal radiotherapy, intensity-modulated therapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) plans were created for each dataset. The prescription dose was 45 Gy in 25 fractions. Comparative analyses of the target volume coverage and the doses of organs at risk were performed.

Results: HT was significantly provided more homogeneity. The best conformal plans were achieved with VMAT. Both kidneys were better preserved with HT and VMAT. HT significantly lowered the V13 of the left kidney and VMAT significantly lowered V20. However, the mean left kidney doses were not statistically different. The lowest liver V30 was obtained with VMAT but not with statistically different than IMRT and HT. Mean liver doses were statistically inferior with 3D. The worst spinal cord doses were seen with 3D. The integral dose of the body did not differ among the techniques.

Conclusion: In comparison of the four techniques, 3D seems to be the most unsuitable method regarding sparing the normal tissues. According to availability, HT and VMAT should be primarily preferred. IMRT can also be used with carefully paying attention to the clinical condition of the patient.
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December 2020

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

Clin Respir J 2020 Nov 17;14(11):1050-1059. Epub 2020 Aug 17.

Faculty of Medicine, Radiation Oncology Department, Ankara University, Ankara, Turkey.

Objective: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey.

Materials And Methods: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/β ratio of 10 (BED ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity.

Results: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]).

Conclusion: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.
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November 2020

Treatment outcomes of metastasis-directed treatment using Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002).

Strahlenther Onkol 2020 Nov 2;196(11):1034-1043. Epub 2020 Jul 2.

Faculty of Medicine, Department of Radiation Oncology, Hacettepe University, Ankara, Turkey.

Purpose: The aim of this study was to evaluate the outcomes of Ga prostate-specific membrane antigen (Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC).

Methods: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation.

Results: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2‑year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2‑year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT.

Conclusion: Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.
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November 2020

Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer.

J Cancer Res Clin Oncol 2017 Aug 3;143(8):1597-1603. Epub 2017 Apr 3.

Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Purpose: Preoperative short-course radiotherapy (SCRT) followed by surgery has shown advantage over surgery alone in patients with resectable rectal carcinoma (RC); however, the importance of the timing of surgery after SCRT has not been well defined. This study aimed to investigate the effect of this duration on treatment outcomes.

Methods: Patients who underwent surgery after SCRT (25 Gy/500 cGy/daily/5fr, monday-friday) for resectable and infraperitoneal rectal adenocarcinoma (T3N0/(+)) were included into the study. Patients were divided into two groups in terms of the timing of surgery: delayed surgery (>4 weeks) or immediate surgery (<4 weeks).

Results: A hundred and thirty-six patients were included in the study. Median time between RT and surgery was 4 ± 5.7 (1-58) weeks, where 68% (n = 93) patients underwent delayed surgery (≥4 weeks). The two groups did not differ in terms of surgical margin positivity, pathological tumor regression, N downstaging, or T downstaging (p > 0.05 for all). However, the number of positive lymph nodes was higher in the immediate surgery group [median 3 (0-18) vs. 1 (0-17), p = 0.009]. Median follow-up time was 36 ± 9 (6-93) months. Delayed surgery group had significantly longer mean overall survival (p = 0.038); however, the two groups did not differ in terms of local recurrence, mean time to local recurrence, or mean disease-free survival.

Conclusions: Our findings seem to support the benefit of a longer time interval between radiotherapy and surgery after short-course neoadjuvant radiotherapy in resectable rectal cancer in terms of overall survival. However, there is a need to better define patient characteristics that might benefit from delayed surgery.
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August 2017

Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial.

J Invest Surg 2017 Jun 4;30(3):187-192. Epub 2016 Oct 4.

c Department of Radiation Oncology , Bezmialem Vakif University , Istanbul , Turkey.

Aim: This study is aimed to evaluate the effects of boron on radiation-induced skin reactions (RISR) in breast cancer patients.

Material And Methods: After 47 patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received a boron-based gel, and 24 (51%) received placebo. Assessments were performed according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five-Point Horizontal Scale (FPHS).

Results: At the end of the fifth week of radiotherapy, the RTOG scores in the boron group were significantly lower than those in the placebo group (p = .024). The FPHS score was higher in the placebo group than in the boron group, and this difference was not statistically significant (p = .079).

Conclusion: Using the RTOG scoring system, we revealed that the application of a boron-based gel diminished RISR. The mechanism of action is unclear but may be related to antioxidant, wound healing, and thermal degradation effects of boron.
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June 2017

Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer.

Asian Pac J Cancer Prev 2015 ;16(8):3365-70

Department of Radiation Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey E-mail :

Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.
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February 2016

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study.

Cancer Chemother Pharmacol 2014 Oct 8;74(4):751-6. Epub 2014 Aug 8.

Department of Radiation Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.

Purpose: The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

Methods: Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m(2) per day; 60% dose at 8:00 AM and 40% dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity.

Results: In 17 patients (20%), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5%), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5%) subjects, and grade I or II cystitis in six (6.9%). Only three patients (3.3%) developed hand and foot syndrome (both grade I-II). There were no grade IV toxicities.

Conclusions: Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.
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October 2014

V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck.

Radiat Oncol 2014 May 2;9:104. Epub 2014 May 2.

Department of Radiation Oncology, Bezmi Alem Vakif University Medical School, Adnan Menderes Bulvari, 34093 Istanbul, Fatih, Turkey.

Introduction: The purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors.

Methods: Thyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10-50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity.

Results: There were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors.

Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient's treatment.
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May 2014

Successful treatment of triple primary tumor.

Int J Surg Case Rep 2013 27;4(11):1013-6. Epub 2013 Aug 27.

Istanbul University, School of Medicine, Department of Plastic and Reconstructive Surgery, Istanbul, Turkey.

Introduction: The occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin.

Presentation Of Case: A 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression.

Discussion: The patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging.

Conclusion: This is a very rare synchronous triple tumor case.
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November 2013

Health-related quality of life during postoperative chemoradiotherapy with oral uracil-tegafur and leucovorin in rectal cancer patients.

Hepatogastroenterology 2013 May;60(123):533-7

Ministry of Health-Marmara University Pendik Education and Research H ospital Radiotherapy Clinic, Istanbul, Turkey.

Background/aims: The objective of this study was to report on the quality of life of locally advanced rectal cancer patients that were treated with uracil-tegafur (UFT)/leucovorin (LV)-based concurrent chemoradiotherapy.

Methodology: Twenty-five patients were enrolled into this prospective study. Radiotherapy (50.4Gy) was given with concurrent UFT (300mg/m2/day) and LV (30mg/day). Turkish versions of EORTC-QLQC30 and EORTC QLQCR38 were applied at the beginning (HRQoL-1) and at the end (HRQoL-2) of chemoradiotherapy. Paired samples t-test was used to compare the difference of means for each scale between HRQoL1 and HRQoL2 and p values <0.05 were considered statistically significant.

Results: Study compliance was 80.6%. From baseline to the end of chemoradiotherapy, the mean scores of dyspnea (p=0.006) diarrhea (p=0.005) and micturition (p=0.005) increased significantly. Chemotherapy side effects also increased at the end of therapy (p=0.07). Seventy-six percent (76%) of male patients replied to questions related to sexual problems and functions, whereas no female patients replied.

Conclusions: Although, diarrhea and micturition are the major problems, quality of life scores indicate that concurrent oral fluoropyrimidine-based chemoradiotherapy is a feasible treatment.
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May 2013

Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma.

J Neurooncol 2011 Jul 29;103(3):585-93. Epub 2010 Sep 29.

Radiation Oncology Department, Marmara University Hospital, Tophanelioglu Cad. 13/15 Altunizade, 34660 Istanbul, Turkey.

The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.
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July 2011

Pregnancy a short time after multimodal therapy for bilateral breast cancer: a case report and review of literature.

J Oncol Pharm Pract 2011 Dec 21;17(4):440-3. Epub 2010 Sep 21.

Department of Radiation Oncology, Regional Training and Research Hospital, Erzurum, Turkey.

Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on fetus and on the course of the pregnancy are still unknown. Here, we present a 39-year-old woman treated with chemotherapy and radiotherapy for bilateral breast cancer, and who became pregnant while taking tamoxifen.
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December 2011

Prophylactic feeding with immune-enhanced diet ameliorates chemoradiation-induced gastrointestinal injury in rats.

Int J Radiat Biol 2010 Oct;86(10):867-79

Departments of Radiation Oncology, Marmara University School of Medicine, Istanbul.

Purpose: To investigate the protective effect of immune-enhanced diet (IED) on chemoradiation-induced injury of the gastrointestinal mucosa.

Materials And Methods: Forty-eight Sprague-Dawley rats were divided into control (C, n=6), irradiation (IR, n=14), fluoropyrimidine (5-FU, n=14)-treated, IR + 5-FU (n=14)-treated groups. Half of each irradiated and/or 5-FU-treated groups were previously fed with IED containing arginine, omega-3-fatty acids and RNA fragments, while the other half were fed a standard rat diet (SD) for eight days before the induction of IR or injection of 5-FU. In IR groups, whole abdominal irradiation (11 Gy) was performed with 6 MV photons. In the 5-FU groups, fluoropyrimidine (100 mg/kg) was administered intraperitoneally 30 min prior to irradiation. All animals were sacrificed on the 4th day of IR or 5-FU injection.

Results: Bacterial colony counts in the ceca and mesenteric lymph nodes of IED-fed rats, which have received either 5-FU and/or irradiation were significantly lower than the corresponding SD-fed groups. Morphometric results revealed that gastric, ileal and colonic injuries were less in IED-treated IR or IR + 5-FU + IED groups, as compared to SD-fed groups. However, IED did not alter DNA fragmentation ratios.

Conclusion: Prophylactic feeding of IED has a protective effect on chemoradiation-induced gastrointestinal injury, which appears to involve the eradication of bacterial overgrowth.
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October 2010