Rectal Carcinoma
Conditions
Keywords
rectal, rectum, cancer, carcinoma
Brief summary
Determine if genotype-directed neoadjuvant chemoradiation, using information from the thymidylate synthase promoter polymorphism, result in a greater degree of tumor downstaging in high risk patients compared to historical controls.
Interventions
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy proven adenocarcinoma of the rectum * Lesion evaluated by surgeon and found to be resectable * Stage T3 or T4 disease on radiography or ultrasound * Karnofsky Performance Status at \>60 * Laboratory criteria: * Absolute neutrophil count \>= 1.5 K * Platelets \>= 100 K * Total Bilirubin \<= 2.0; * SGOT and Alkaline Phosphatase \<= 2 x upper limit of normal * Creatinine \< 2.0 * Informed consent signed * Patients with distant metastatic disease will be eligible if they satisfy all other conditions.
Exclusion criteria
* Pregnant women, children \< 18 years, or patients unable to give informed consent * Patients with a past history of pelvic radiotherapy. * Patients with prior malignancy in the past 5 years except: skin cancer or in-situ cervical cancer. However, patients with synchronous adenocarcinomas are eligible provided either (a) the synchronous adenocarcinoma was in a removed pedunculated polyp and did not invade the stalk or (b) the synchronous adenocarcinoma was in a removed polyp that lay within the surgical field (extent of resection would not be changed) or (c) the synchronous adenocarcinoma is smaller than the index rectal cancer and lies completely within the radiation field (clinically favorable second lesion and the extend of radiation and surgery would not be changed). * Patients with known allergy to 5-fluorouracil or irinotecan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Tumor Downstaging Compared With Historical Controls. | 1 year after enrollment | Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rates | 1 year after enrollment | Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0). Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0). pCR rate of historical controls is 8%-14%. |
| Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation. | Prior to start of study treatment and 3-6 weeks post completion of radiation therapy | The questionnaire is encouraged but not required. |
| Determine Patient Fears and Expectations of Pharmacogenetics. | Prior to start of study treatment and 3-6 weeks post completion of radiation therapy | The questionnaire is encouraged but not required. |
Countries
United States
Participant flow
Recruitment details
Enrollment to the study opened on 10/07/2002 and the study closed to enrollment on 10/23/2008.
Participants by arm
| Arm | Count |
|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. | 98 |
| Poor Risk (TYMS*3/*3, *3/*4) Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. | 37 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive irinotecan | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Poor Risk (TYMS*3/*3, *3/*4) | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 55 years | 56 years |
| Baseline clinical M stage M0 | 32 participants | 84 participants | 116 participants |
| Baseline clinical M stage M1 | 5 participants | 14 participants | 19 participants |
| Baseline clinical N stage N0 | 11 participants | 30 participants | 41 participants |
| Baseline clinical N stage N1 | 22 participants | 64 participants | 86 participants |
| Baseline clinical N stage N2 | 4 participants | 4 participants | 8 participants |
| Baseline clinical T stage T1-2 | 0 participants | 2 participants | 2 participants |
| Baseline clinical T stage T3 | 32 participants | 77 participants | 109 participants |
| Baseline clinical T stage T4 | 5 participants | 19 participants | 24 participants |
| Baseline Stage Stage IIA (T3, N0, M0) | 10 participants | 24 participants | 34 participants |
| Baseline Stage Stage IIB (T4, N0, M0) | 0 participants | 3 participants | 3 participants |
| Baseline Stage Stage IIIA (T1-2, N1, M0) | 0 participants | 1 participants | 1 participants |
| Baseline Stage Stage IIIB (T3-4, N1, M0) | 19 participants | 53 participants | 72 participants |
| Baseline Stage Stage IIIC (T-any, N2, M0) | 3 participants | 3 participants | 6 participants |
| Baseline Stage Stage IV (T-any, N-any, M1) | 5 participants | 14 participants | 19 participants |
| Clinical staging modality CT Scan +/- PET Scan | 6 participants | 22 participants | 28 participants |
| Clinical staging modality Endoscopic ultrasound | 21 participants | 60 participants | 81 participants |
| Clinical staging modality MRI | 10 participants | 16 participants | 26 participants |
| Performance status 0 | 26 participants | 63 participants | 89 participants |
| Performance status 1 | 11 participants | 34 participants | 45 participants |
| Performance status 2 | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized African American | 8 participants | 10 participants | 18 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 29 participants | 86 participants | 115 participants |
| Region of Enrollment United States | 37 participants | 98 participants | 135 participants |
| Sex: Female, Male Female | 24 Participants | 69 Participants | 93 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 42 Participants |
| Thymidylate Synthase Enhancer Region (TSER) genotype *2/*2 | 0 participants | 26 participants | 26 participants |
| Thymidylate Synthase Enhancer Region (TSER) genotype *2/*3 | 0 participants | 71 participants | 71 participants |
| Thymidylate Synthase Enhancer Region (TSER) genotype *2/*4 | 0 participants | 1 participants | 1 participants |
| Thymidylate Synthase Enhancer Region (TSER) genotype *3/*3 | 35 participants | 0 participants | 35 participants |
| Thymidylate Synthase Enhancer Region (TSER) genotype *3/*4 | 2 participants | 0 participants | 2 participants |
| Tumor distance from anal verge (cm) >10 | 4 participants | 8 participants | 12 participants |
| Tumor distance from anal verge (cm) <5 | 12 participants | 33 participants | 45 participants |
| Tumor distance from anal verge (cm) 5-10 | 21 participants | 57 participants | 78 participants |
| Tumor grade Moderately differentiated | 25 participants | 68 participants | 93 participants |
| Tumor grade Not reported | 1 participants | 5 participants | 6 participants |
| Tumor grade Poorly differentiated | 7 participants | 17 participants | 24 participants |
| Tumor grade Well differentiated | 4 participants | 8 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 96 / 96 | 35 / 35 |
| serious Total, serious adverse events | 16 / 96 | 12 / 35 |
Outcome results
Primary
Rate of Tumor Downstaging Compared With Historical Controls.
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%.
Time frame: 1 year after enrollment
Population: 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX~6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Rate of Tumor Downstaging Compared With Historical Controls. | 64.4 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Rate of Tumor Downstaging Compared With Historical Controls. | 64.5 percentage of participants |
Secondary
Complete Response Rates
Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0). Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0). pCR rate of historical controls is 8%-14%.
Time frame: 1 year after enrollment
Population: 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX~6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Complete Response Rates | ypT0 | 20 percentage of participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Complete Response Rates | pCR | 18.9 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Complete Response Rates | ypT0 | 41.9 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Complete Response Rates | pCR | 35.5 percentage of participants |
Secondary
Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.
The questionnaire is encouraged but not required.
Time frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy
Population: The data was not collected for this outcome measure as the questionnaire was encouraged but not required.
Secondary
Determine Patient Fears and Expectations of Pharmacogenetics.
The questionnaire is encouraged but not required.
Time frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy
Population: The data was not collected for this outcome measure as the questionnaire was encouraged but not required.
Post Hoc
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Good Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-TA | 6 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-TA | 27 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-CC | 14 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-TC | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-CC | 7 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | TA-TA | 7 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-CA | 13 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | TA-TA | 4 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-CA | 2 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-CC | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CA-TA | 9 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-CC | 2 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-TA | 3 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC-TC | 0 participants |
Post Hoc
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-CC | 7 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-TA | 2 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-TA | 4 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-TC | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-CA | 4 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | TA-TA | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-CC | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | TA-TA | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-CC | 3 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-TA | 4 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-CC | 2 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-TA | 3 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC-TC | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CA-CA | 4 participants |
Post Hoc
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Good Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | AA (MTHFR 1298A>C) | 26 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | AC (MTHFR 1298A>C) | 41 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC (MTHFR 1298A>C) | 8 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | AA (MTHFR 1298A>C) | 15 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | AC (MTHFR 1298A>C) | 4 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC (MTHFR 1298A>C) | 2 participants |
Post Hoc
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. MTHFR gene = methylenetetrahydrofolate reductase (NAD(P)H)
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Good Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC (MTHFR 677C>T) | 34 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CT (MTHFR 677C>T) | 34 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | TT (MTHFR 677C>T) | 7 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CC (MTHFR 677C>T) | 5 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | CT (MTHFR 677C>T) | 12 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | TT (MTHFR 677C>T) | 4 participants |
Post Hoc
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC (MTHFR 677C>T) | 12 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CT (MTHFR 677C>T) | 6 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | TT (MTHFR 677C>T) | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC (MTHFR 677C>T) | 9 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CT (MTHFR 677C>T) | 7 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | TT (MTHFR 677C>T) | 0 participants |
Post Hoc
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | AA (MTHFR 1298A>C) | 9 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | AC (MTHFR 1298A>C) | 9 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC (MTHFR 1298A>C) | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | AA (MTHFR 1298A>C) | 8 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | AC (MTHFR 1298A>C) | 6 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | CC (MTHFR 1298A>C) | 2 participants |
Post Hoc
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Good Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677T-1298A | 40 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677C-1298A | 33 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677C-1298C | 49 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677T-1298A | 16 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677C-1298A | 12 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) | 677C-1298C | 6 participants |
Post Hoc
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Time frame: First day of treatment through 30 days after completion of surgery
Population: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677C-1298A | 15 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677C-1298C | 10 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677T-1298A | 7 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677C-1298A | 11 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677C-1298C | 8 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) | 677T-1298A | 7 participants |
Post Hoc
Overall Survival
Analyzed using Kaplan-Meier Models.
Time frame: 1 year, 2 years, and 3 years
Population: Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Overall Survival | 1 year | 96.9 percentage of participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Overall Survival | 2 years | 80.6 percentage of participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Overall Survival | 3 years | 78.2 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Overall Survival | 1 year | 94.3 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Overall Survival | 2 years | 94.3 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Overall Survival | 3 years | 83.6 percentage of participants |
Post Hoc
Relapse-free Survival
Analyzed using Kaplan-Meier Models.
Time frame: 1 year, 2 years, and 3 years
Population: 14 patients in the Good Risk arm had metastatic rectal cancer at time of enrollment are not included in this analyses.~3 patients in the Poor Risk arm had metastatic rectal disease before surgery and are included in this analyses.~2 of the patients in the Good Risk arm and Poork Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Relapse-free Survival | 1 year | 85.2 percentage of participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Relapse-free Survival | 2 years | 78.3 percentage of participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Relapse-free Survival | 3 years | 73.4 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Relapse-free Survival | 1 year | 87.0 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Relapse-free Survival | 2 years | 80.5 percentage of participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Relapse-free Survival | 3 years | 72.4 percentage of participants |
Post Hoc
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Grade 3 to 4 toxicities related to treatment and surgery using CTC Version 2.0.
Time frame: First day of treatment through 30 days after completion of surgery
Population: Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Pain | 3 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Vomiting | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Perforation | 2 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Ileitis | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Pelvic abscess | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Dehydration | 3 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | PPE | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Enteritis | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Crohn's flare | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Nausea | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Syncope | 2 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Dyspnea | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Rash | 2 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Mucositis | 4 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Fatigue | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Neutropenia | 0 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Atrial fibrillation | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Diarrhea | 17 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Infection | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Headache | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Anemia | 3 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Small bowel obstruction | 1 participants |
| Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | GI bleed | 2 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Small bowel obstruction | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Nausea | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Vomiting | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Diarrhea | 16 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Dehydration | 7 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Mucositis | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | GI bleed | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Ileitis | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Enteritis | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Dyspnea | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Neutropenia | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Anemia | 3 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Pain | 4 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Perforation | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Pelvic abscess | 2 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | PPE | 1 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Crohn's flare | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Syncope | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Rash | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Fatigue | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Atrial fibrillation | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Headache | 0 participants |
| Poor Risk (TYMS*3/*3, *3/*4) | Toxicities by Genotype Group (Good Risk Versus Poor Risk) | Infection | 1 participants |