Toxicity In Rectal Cancer Patients Research Articles

Modeling Acute Chemoradiotherapy (CRT) Diarrhea Severity Using Automatically Contoured Small Bowel

Acute severe diarrhea is a common toxicity in rectal cancer patients receiving CRT. A better understanding of the radiation tolerance of the small bowel is needed especially for novel radiation drug combinations. We investigate the dose impact by providing auto-contoured small bowel, using data from the ARISTOTLE phase III trial ISRCTN: 09351447. A subset of participants (n = 93/564) with locally advanced rectal cancer in the ARISTOTLE trial testing the addition of concurrent irinotecan (n = 48) to neoadjuvant capecitabine (n = 45) CRT (45/25 Gy/fx), in an MRI defined high risk of loco-regional failure. CRT was delivered with conformal techniques. Diarrhea was measured using CTCAE v4.0 weekly. We applied an AI-based auto-contouring model to segment the small bowel on planning CT. The small-bowel DVH parameters were combined with the treatment arm, age, sex and MRI-defined tumor stage in a linear regression (LR) model to predict acute diarrhea severity. Explainable Shapley values (conditional marginalized expectation of a machine learning model per feature) were used to quantify the independent and normalized impact of radiation dose vs Irinotecan on the likelihood of severe diarrhea. The auto-contouring model accuracy was consistent with clinical practice (mean dice coefficient = 0.739) and clinically acceptable when reviewed by clinicians. The treatment arm, MRI-defined T stage and small-bowel mean dose were found to be independently correlated to the diarrhea severity (p<0.001). V30Gy showed the strongest correlation to diarrhea severity in all the DVH parameters. The LR using the three variables yielded mean AUC scores of 0.898 (95% CI: [0.831,0.958]) on predicting Grade 2 and higher diarrhea, and 0.774 (95% CI: [0.678,0.869]) on predicting Grade 3 diarrhea based on 10-fold cross-validation. Shapley values showed that V30Gy>30.56 cm3 increases the likelihood of more severe diarrhea against the average (grade = 1.03) in the cohort. The impact of irradiation will be larger than the usage of Irinotecan within the patients with V30Gy >160.93 cm3. We accurately modelled acute diarrhea (AUC = 0.90) for rectal cancer patients receiving CRT using AI-contoured small-bowel structures. The treatment arm and small-bowel dose were independently correlated to the diarrhea severity. The explainable model allowed us to quantify the impact of radiation dose, usage of irinotecan, and its combination, with a threshold of V30Gy = 160.93 cm3 yielding an equivalent impact. We will be extending the analysis to the whole trial cohort to improve the statistical power.

Severe Gastro-Intestinal Complications of Radiation Therapy in Rectal Cancer: Modeling the Influence of Age Based upon Population Level Data

<h3>Purpose/Objective(s)</h3> Gastro-intestinal (GI) side effects are dose limiting for pelvic & abdominal radiation therapy (RT). Advanced-age is hypothesized to be an aggravating factor in severe radiation toxicity, but this has not been well defined. We sought to quantify the effect of age on grade IV / V gastro-intestinal complications of RT by combining information from two US population-based databases. <h3>Materials/Methods</h3> The absolute number of complications was obtained by querying the National Inpatient Database (NIS) of the Healthcare Cost and Utilization Project, which contains discharge data from a 20% stratified sample of all US non-federal hospitals. Inclusion criteria were inpatient episodes between 2015-18, with listed diagnoses of both ‘Malignant neoplasm of rectum' (ICD-10-CM Code C20), and ‘Gastroenteritis and colitis due to radiation' (ICD-10-CM Code K52.0). A grade IV complication was defined as a hospitalization, alive on discharge; whereas grade V was defined as a hospitalization culminating in death. The relative age-distribution of patients with rectal cancer treated with RT was obtained from the SEER database. Relative toxicity incidence by age group was obtained by normalizing the absolute number of toxic events obtained from NIS with the age-distribution treatment data from SEER. Statistical techniques included best-fit linear regression and multivariate logistic regression. <h3>Results</h3> Within the NIS database there were 31,878 hospitalizations with a listed diagnosis of rectal cancer (median age 63 years), of whom 290 had grade IV (median age 66) and 10 grade V (median age 76.5) radiation gastroenteritis / colitis. There were no grade 4 toxicities under the age of 20, and no grade 5 toxicities under the age of 70. After adjusting for the baseline age distribution of rectal cancer patients receiving radiation derived from SEER data, the relative risk (RR) of grade IV toxicity was 0.44 for subjects aged 20-39, and 0.53 for subjects aged 40-59 and 1.0 for 60-79 (the comparator). The RR for grade V toxicity was zero for <60, 1.0 for 60-79 (the comparator), and 1.26 for subjects aged 80-99. Best-fit linear regression line for grade IV toxicity was defined by [0.0084* age(yrs)* + 0.2], and for grade V toxicity by [0.024* age(yrs)* - 0.87]. On multivariate logistic regression, amongst all those with grade 4-5 radiation gastroenteritis / colitis, age was the only clinical predictor of death (dosimetric factors were not available). <h3>Conclusion</h3> We demonstrate that the risk of acute severe radiation-induced bowel toxicity in rectal cancer patients rises linearly with age. Modelling demonstrates that the gradient is far steeper for grade V toxicity than grade IV toxicity. Importantly, our results facilitate the incorporated of age into existing NTCP models of bowel toxicity. Age-adjusted radiation dose constraints for the bowel should be adopted.

New dosimetric parameters to predict ano-rectal toxicity during radiotherapy treatment

PurposeRadiotherapy is essential in the treatment of locally advanced rectal cancer. Side effects of radiotherapy in the treatment of rectal cancer have a great effect on quality of life. The aim of this retrospective study is to evaluate the correlation between dosimetric parameters and acute toxicity in rectal cancer patients. MethodsWe analyzed the Dose Volume Histogram parameters for both the target structures and the Organs at risk of 89 patients. A dedicated statistical analysis was performed for all the acute toxicities showing a frequency rate higher than 20%.A linear logistic regression model was elaborated using the variable showing the highest level of significance at the univariate analysis. ResultsThe occurrence of proctitis was significantly correlated with three dosimetric parameters: D98% of low ano-rectum, D98% and Dmean of low ano-rectum wall.A predictive linear logistic regression model reports that the D98% of the wall of the low ano-rectum must be < 38.5 Gy to decrease the rate of proctitis.A general analysis on grade 2 acute toxicity occurrence reported that it was correlated with D98% of low ano rectum. ConclusionsTwo dose constraints were elaborated: D98%<33.5 Gy for low ano rectum to prevent grade 2 acute toxicity and D98%<25 Gy for low ano-rectum wall to prevent proctitis (grade 1 or superior).

Effect of Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemo-Radiotherapy.

BackgroundWhile chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy.Methods112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events.ResultsThe radiation dose to PBM (V5~V45, Dmean, P<0.05), PBM sub-regions (V10~V35, Dmean, P<0.05) and both femoral heads (V5~V40, Dmean, P<0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P<0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05).ConclusionsApplying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

184 Analysis of Radiation Dosimetry Predictive for Toxicity in Rectal Cancer Patients Treated with Long Course Chemo-Radiation

184 Analysis of Radiation Dosimetry Predictive for Toxicity in Rectal Cancer Patients Treated with Long Course Chemo-Radiation

Effect of Pelvic Bone Marrow-Sparing on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemoradiotherapy

To investigate whether pelvic bone marrow sparing (PBMS) could reduce the incidence of acute hematologic toxicity in rectal cancer patients undergoing chemo-radiotherapy. 84 rectal cancer patients were selected and divided into the IMRT Group (42 cases) and the PBMS-IMRT Group (42 cases). All patients underwent concurrent chemo-radiotherapy. The PTV was prescribed with a total dose of 50∼50.4Gy in 1.8∼2Gy fractions. Capecitabine combined was administered concurrently with pelvic radiation. The pelvic bone was contoured both for the PBMS-IMRT and IMRT groups. Only the pelvic bone in PBMS-IMRT group was prescribed by:V10≤85%,V20≤65%,V30≤45%.The mean dose (Dmean) and the volume of each organ at risk (OAR) with dose range from 5 to 50Gy (e.g., V 5, V10, V15, V20, V25, V30, V35, V40, V45, andV50) was calculated for all the patients from the two groups. The patient acute hematologic toxicity (e.g. patient with symptoms of leukopenia, neutropenia, anemia, or thrombocytopenia) was recorded according to RTOG scoring scale. Independent sample t test were applied for the dose-volume parameters, and card square analysis for clinical parameters. In terms of the OAR dose-volume parameters, the V5∼V35 and Dmean for the pelvic bone, left femoral head and the right femoral head significantly (p<0.05) decreased for the PBMS-IMRT Group compared with the IMRT group. There was no significant difference in any dose-volume parameters for the bladder. As for PTV dose distribution, there was a significant (p=0.001) improvement of the target conformity in the PBMS-IMRT group. In addition, the dose homogeneity was also improved by 14.5% for this group, although not significantly (P=0.108). For the following acute hematologic toxicity observation, the numbers of the patients with grade 0, 1, 2, 3, 4 were 12, 6, 14, 10, and 0 respectively for the IMRT group. Meanwhile the corresponding numbers were 10, 19, 12, 1, and 0 for PBMS-IMRT group. The incidence of grade 2 or upper acute hematologic toxicity in the PBMS-IMRT group was significantly reduced (31%, 13/42 vs. 57.1%, 24/42, p=0.027). There was no incidence of grade 2 or upper acute cystitis in both of the two groups. The marrow-sparing of the pelvic bone significantly reduces its dosage as well as the left and right femoral head. Patients with pelvic bone marrow-sparing had lower incidence of the grade 2 or upper acute hematologic toxicity compared with those without marrow-paring. Pelvic bone marrow-sparing can benefit patients with rectal cancer undergoing chemo-radiotherapy.

Timing of surgery following neoadjuvant chemoradiation in rectal cancer: a retrospective analysis from an academic medical center.

Neoadjuvant chemoradiotherapy (nCRT) has been shown to achieve decreased local recurrence (LR) with lower toxicity in rectal cancer patients, but data confirming the optimal timing of surgery following this therapy is less robust. The University of Iowa Cancer Registry was queried to identify all patients with stages II-III rectal cancer who received nCRT and surgery from 2000 through 2012. Primary endpoints were time interval to surgery (TI), and overall survival (OS). Secondary endpoints included pathologic outcomes, perioperative morbidities and postoperative complications. Patient characteristics and treatment regimens were compared. Univariate Cox proportional hazard models were used to study the association between TI and OS. Associations of TI with secondary endpoints were tested using Chi-square tests of association. Eighty-seven patients presented with stages II-III rectal cancer. Mean TI was 9.92 weeks. There was no significant association between TI and OS when comparing <8 to ≥8 weeks (P=0.23) or when considering the interval as a continuous variable (P=0.85). Increased LOS [median 7.00 days, P=0.05, HR 1.03 (1.00-1.06)] did correlate with worse survival outcomes. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection (P=0.05). OS was not influenced by longer intervals between nCRT and surgery. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection.

Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

Dose-Volume Parameters of MRI Active Bone Marrow Versus Total Bone Marrow As Predictor of Hematologic Toxicity in Rectal Cancer Patients during Neoadjuvant Chemoradiation Therapy

Dose-Volume Parameters of MRI Active Bone Marrow Versus Total Bone Marrow As Predictor of Hematologic Toxicity in Rectal Cancer Patients during Neoadjuvant Chemoradiation Therapy

Radiation induced toxicity in rectal cancer patients

Preoperative radiotherapy ? chemotherapy became the standard treatment for locally advanced rectal cancer. Despite better local control with this approach, there was not seen a significant improvement in overall survival and disease free survival, yet. The main disadvantage is toxicity that can be developed, especially concomitantly with chemotherapy. Toxicity can be acute and late. Acute complications are transitory, but late might lead to permanent damage and consequently are more significant for patients. Today, there are technical opportunities in reduction of acute and late radiation toxicity in the treatment of rectal cancer. With the implementation of 3D conformal radiotherapy (3D CRT) and intensity modulated radiation therapy (IMRT) techniques in clinical practice significant accuracy, better dose distribution and safety in the treatment of rectal cancer patients is achieved, with maximal sparing of surrounding normal tissue. Utilization of advanced techniques and new software solutions can keep adverse effects on satisfactory levels with excellent local control.

Can Dosimetric Parameters Predict Acute Hematologic Toxicity in Rectal Cancer Patients Treated With Intensity Modulated Pelvic Radiation Therapy?

Can Dosimetric Parameters Predict Acute Hematologic Toxicity in Rectal Cancer Patients Treated With Intensity Modulated Pelvic Radiation Therapy?

Associations of Genetic Polymorphisms of PAI-1 and PAR-1 With Acute Normal Tissue Toxicity in Rectal Cancer Patients Treated With Pelvic Radiation Therapy

Associations of Genetic Polymorphisms of PAI-1 and PAR-1 With Acute Normal Tissue Toxicity in Rectal Cancer Patients Treated With Pelvic Radiation Therapy

Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy?

BackgroundTo identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy.MethodsNinety-three rectal cancer patients receiving concurrent capecitabine and pelvic intensity-modulated radiation therapy (IMRT) were analyzed. Pelvic bone marrow (PBM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSS), ilium, and lower pelvis (LP). The volume of each site receiving 5–40 Gy (V 5, V10, V15, V20, V30, and V40, respectively) as well as patient baseline clinical characteristics was calculated. The endpoint for hematologic toxicity was grade ≥ 2 (HT2+) leukopenia, neutropenia, anemia or thrombocytopenia. Logistic regression was used to analyze correlation between dosimetric parameters and grade ≥ 2 hematologic toxicity.ResultsTwenty-four in ninety-three patients experienced grade ≥ 2 hematologic toxicity. Only the dosimetric parameter V40 of lumbosacral spine was correlated with grade ≥ 2 hematologic toxicity. Increased pelvic lumbosacral spine V40 (LSS-V40) was associated with an increased grade ≥ 2 hematologic toxicity (p = 0.041). Patients with LSS-V40 ≥ 60 % had higher rates of grade ≥ 2 hematologic toxicity than did patients with lumbosacral spine V40 < 60 % (38.3 %, 18/47 vs.13 %, 6/46, p =0.005). On univariate and multivariate logistic regression analysis, lumbosacral spine V40 and gender was also the variable associated with grade ≥ 2 hematologic toxicity. Female patients were observed more likely to have grade ≥ 2 hematologic toxicity than male ones (46.9 %, 15/32 vs 14.8 %, 9/61, p =0.001).ConclusionsLumbosacral spine -V40 was associated with clinically significant grade ≥ 2 hematologic toxicity. Keeping the lumbosacral spine -V40 < 60 % was associated with a 13 % risk of grade ≥ 2 hematologic toxicity in rectal cancer patients undergoing concurrent chemoradiotherapy.

Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

Background and purposeTo identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer. Materials and methodsWe analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models. ResultsNadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p=0.04), and patients ⩾59years of age had a lower hemoglobin ratio trend during PRT (p=0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p=0.03), and women had lower hemoglobin cell count trend compared to men (p=0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p=0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p=0.03) and sacral BM V45 (p=0.03) were associated with a lower WBC and ANC ratio at nadir, respectively. ConclusionsHT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.

The incidence and Time to Presentation of Capecitabine Induced Cardiovascular Toxicity in Rectal Cancer Patients Receiving Concurrent Chemo-radiotherapy

Background: Chemo-radiotherapy with capecitabine is standard treatment for locally advanced rectal cancer1. Coronary vasospasm is a recognised toxicity of capecitabine2. Risk factors, presentation and incidence of capecitabine induced vasospasm are poorly defined, with the incidence ranging from 3–9%3. capecitabine was prescribed at 825mg/m2 twice daily, 7 days per week throughout radiotherapy.

Toxicity in rectal cancer patients treated with neoadjuvant radiotherapy combined with capecitabine vs. raltitrexed

Toxicity in rectal cancer patients treated with neoadjuvant radiotherapy combined with capecitabine vs. raltitrexed

The final results of the SWOG S9304 phase III intergroup trial’s pharmacogenetic analysis: Association of polymorphisms with survival and toxicity in stage II/III rectal cancer patients treated with 5-fluorouracil (5-FU) and pelvic radiation (RT).

3542 Background: Postoperative chemoradiation (CRT) for locally advanced rectal cancers has improved overall survival (OS) and pelvic control. The SWOG S9304 (INT 0144) trial was designed to investigate the benefit of protracted venous infusion (PVI) versus bolus 5-FU before, during and after postoperative RT. All arms provided similar disease-free survival (DFS) and OS. We tested whether 16 functional polymorphisms in 12 genes (GSTP1, TS, ERCC1, VEGF, VEGFR, IL8, CXCR2, COX2, CCND1, EGF, EGFR, ICAM1) predicted survival and toxicity. Methods: Tissue samples from 746 stage II/III rectal patients enrolled in the S9304 phase III trial were analysed. Genomic DNA was extracted from FFPE tumor tissue. The polymorphisms were analysed using direct DNA-sequencing or PCR-RFLP. 383 out of 746 patients were still alive at the time of data analysis with a median follow-up of 123 months. The median age of our cohort is 61 years old (range 16-86). Most patients are males (64%) and Caucasian (93%). 30% have N0 tumor, 42% have N1 tumor and 27% have N2-3 tumor. Results: In univariate analyses, GSTP1-Ile105Val (rs1695) appeared to be associated with DFS and OS (p=0.02 for each, no adjustment for multiple comparisons). The 3-year DFS was 60% for the low activity genotype (Val/Val), 72% for Val/Ile and 65% for Ile/Ile patients (and 78%, 83% and 79% for OS respectively). In patients treated with PVI 5-FU combined with RT, the homozygous IL8-251A/A genotype (rs4073) was associated with a lower risk of any grade 3-5 toxicities compared to A/T or T/T genotypes (41%, 62% and 62%; p=0.04). Also, the homozygous VEGFR2 exon 11 A/A genotype (rs1870377) was associated with a higher risk of grade 3-5 esophagitis/stomatitis compared to A/T or T/T genotypes (17%, 5% and 8%; p=0.037) in the PVI arm only. However, exon 11 A/A was associated with lower risk in the bolus 5-FU arm (p=0.004). Conclusions: Our data suggest that GSTP1-Ile105Val is associated with DFS and OS and IL8-251A/T and VEGFR exon 11 with toxicity in rectal cancer patients treated with adjuvant CRT. Validation would be required to confirm these relationships.

Use of genetic variations to predict toxicity associated with neoadjuvant chemoradiation for AJCC stage II/III rectal cancer.

411 Background: Genetic polymorphisms have been associated with toxicity from chemotherapeutic agents for colon cancer, but none has been identified for rectal cancer. We examined the association between polymorphisms in genes for DNA repair, cell cycle progression, angiogenesis, and drug metabolism with toxicity from neoadjuvant chemoradiation treatment (CRT) for rectal cancer. Methods: Patients with AJCC stage II/III rectal adenocarcinoma were enrolled in a phase II multicenter trial examining timing of rectal cancer response to neoadjuvant CRT. There were two treatment arms: (I) radiation (XRT) and 5-FU followed by surgery and (II) XRT/5-FU and FOLFOX followed by surgery. Treatment toxicity, classified by the NCI Common Terminology Criteria guidelines as grade 3 and above, was recorded. DNA was extracted from normal rectal mucosa and analyzed for 22 polymorphisms in 17 genes. Results: We evaluated 110 patients (group I, n = 52; group II, n = 58). A total of 19 patients experienced grade 3+ adverse events (AE) [group I, n = 10 (19%); group II, n = 9 (16%)]. Gastrointestinal symptoms were the most common AE [group I, n = 5 (10%); group II, n = 4 (7%)]. The detection of lys allele (lys/lys or lys/gln genotypes) at codon 751 of the Xeroderma pigmentosum group D (XPD) gene was associated with increased toxicity in group II (p = 0.03), whereas homozygosity for the arg allele (i.e., arg/arg genotype) at codon 399 of the X-ray cross-complementing protein 1 (XRCC1) gene was associated with a significant increase in toxicity in both treatment groups (p = 0.009). Conclusions: Genetic polymorphisms in DNA damage repair genes XPD and XRCC1 are associated with toxicity in rectal cancer patients receiving CRT. The identification of gene polymorphisms that predict adverse events may help to optimize patient therapy while minimizing morbidities. No significant financial relationships to disclose.

Circulating endothelial cells and acute toxicity in rectal cancer patients receiving postoperative radiotherapy with concurrent UFT administration

15102 Background: Concurrent chemoradiation (CCRT) is now a standard postoperative adjuvant treatment for high-risk rectal cancer patients. However, no surrogate marker for optimization of adjuvant...

Correlation between Irradiated Small Bowel Volume and Toxicity in Rectal Cancer Patients Receiving Concomitant Pelvic Irradiation and 5-Fluorouracil Chemotherapy

The aim is to study the relationship between radiation induced small bowel toxicity and radiation dose received by the small bowel during pelvic irradiation for patients with rectal cancer treated with pelvic radiotherapy and concomitant 5-Fluorouracil. Thirty-two patients with rectal cancer were referred for either a postoperative or preoperative pelvic irradiation concomitant with 5-Fluorouracil chem- otherapy at the Radiotherapy Unit of King Abdulaziz University Hospi- tal. All patients had computerized 3D treatment planning. Radiation therapy was given in two phases, to a total dose of 5040 cGy / 28 frac- tions / 5.5 weeks. Small bowel loops were contoured on CT cuts and a dose volume histogram was constructed and the mean radiation dose received by the small bowel, the volume of the small bowel irradiated and the mean radiation dose / volume of small bowel involved ratio. Univariate analysis showed a significant association between small bowel toxicity and mean radiation therapy dose received by small bowel (p = 0.001), the volume of small bowel involved (P = 0.043) and the type of surgical intervention with higher incidence for those patients who had abdominoperineal resection (P = 0.003). In conclu- sion, this study confirms the relation between small bowel toxicity and the volume of small bowel receiving radiotherapy.