Lymphedema, Musculoskeletal Complications, Radiation Fibrosis, Radiation Toxicity, Sarcoma
Conditions
Keywords
radiation fibrosis, radiation toxicity, lymphedema, musculoskeletal complications, stage I adult soft tissue sarcoma, stage II adult soft tissue sarcoma, adult extraskeletal chondrosarcoma, stage III adult soft tissue sarcoma
Brief summary
RATIONALE: Image-guided radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a lower dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying the side effects and how well image-guided radiation therapy works in treating patients with primary soft tissue sarcoma of the shoulder, arm, hip, or leg.
Detailed description
OBJECTIVES: Primary * To determine the effect of reduced radiation volume using image-guided radiotherapy (IGRT) on lymphedema ≥ grade 2, subcutaneous fibrosis, and joint stiffness at 2 years in patients with primary soft tissue sarcoma of the extremity. Secondary * To estimate the rates of other grade 3-5 adverse events as measured by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. * To determine the pattern of first failure, including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression. * To estimate the rates of local failure, local-regional failure, distant failure, distant disease-free survival, disease-free survival, overall survival, and second primary tumor. * To estimate the rate of wound complications. * To correlate the degree of late radiation morbidity (defined as any lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years with scores on the clinical measure, Musculoskeletal Tumor Rating Scale (MSTS). OUTLINE: This is a multicenter study. * Neoadjuvant radiotherapy: Patients are assigned to 1 of 2 treatment groups (group 1 closed to accrual as of 01/08/10). * Group 1 (closed to accrual as of 01/08/10): Patients undergo 3-D conformal radiotherapy (3D-CRT) or intensity-modulated therapy (IMRT) once daily, 5 days a week, for 4½-5 weeks. Patients also receive up to 6 courses of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy. * Group 2: Patients undergo 3D-CRT or IMRT once daily, 5 days a week, for 5 weeks. * Surgery: At 4-8 weeks after completion of neoadjuvant radiotherapy, patients undergo surgical resection of the tumor. Patients with positive tumor margins (residual tumor) undergo intraoperative radiotherapy boost or proceed to adjuvant radiotherapy within 2 weeks after surgery. * Adjuvant radiotherapy: Patients undergo either external-beam radiotherapy (EBRT) once daily for 8 fractions or brachytherapy. After completion of study treatment, patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
DRUGChemotherapy
Up to 6 courses of investigator's choice of neoadjuvant, adjuvant, concurrent, or interdigitated chemotherapy
RADIATIONRadiation therapy
Preoperative IGRT (3D-CRT or IMRT): If receiving neoadjuvant or adjuvant chemotherapy or no chemotherapy: 50 Gy (2 Gy once a day, 5 times a week). If receiving concurrent or interdigitated chemotherapy: 44 Gy (2 Gy once a day, 5 times a week). Postoperative radiotherapy boost for patients with positive margins following surgery: 16 Gy (2 Gy once a day, 5 times a week) external beam radiation therapy or 16 Gy at ≤ 80 cGy per hour brachytherapy or 3.4 Gy/fraction in 4 fractions brachytherapy or 10-12.5 Gy in a single fraction intraoperative radiation therapy boost.
PROCEDURESurgery
Resection of the sarcoma with the goal of having negative pathologic margins. Every effort should be made to have limb preservation surgery unless there is documented evidence of tumor progression that would require amputation for an appropriate negative margin resection. All lesions of the extremities should be treated with wide excision.
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
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
DISEASE CHARACTERISTICS: * Histologically confirmed primary soft tissue sarcoma of the upper extremity (including shoulder) or lower extremity (including hip) * Incisional or core biopsy required within the past 8 weeks * No histopathological diagnosis of any of the following: * Rhabdomyosarcoma * Extraosseous primitive neuroectodermal tumor (PNET) * Soft tissue Ewing sarcoma * Osteosarcoma * Kaposi sarcoma * Angiosarcoma * Aggressive fibromatosis (desmoid tumor) * Dermatofibrosarcoma protuberans * Chondrosarcoma * Extraskeletal myxoid chondrosarcoma allowed * Tumor must be surgically resectable, as determined by a surgeon within the past 8 weeks * Limb-preservation surgery alone would not provide adequate local control, as determined by the surgeon * No sarcoma of the hand, foot, head, neck, or intra-abdominal or retroperitoneal region or body wall * No sarcoma ≥ 32 cm in any direction * No lymph node or distant metastases, according to the following within the past 8 weeks: * History/physical examination, including a detailed description of the location, size, and stage of the sarcoma * MRI with contrast of the primary tumor * The maximum dimension of the primary tumor is measured in MRI images * CT scan of the chest * Multiple pulmonary nodules \< 8 mm without a histological diagnosis detected incidentally on a non-screening CT scan may be allowed * CT scan with contrast of the abdomen and pelvis in patients with intermediate- or high-grade sarcoma of the upper thigh * No recurrent tumor after prior potentially curative therapy PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed) * Bilirubin ≤ 1.5 mg/dL\* * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 times upper limit of normal\* * Serum creatinine ≤ 1.6 mg/dL OR creatinine clearance ≥ 55 mL/min\* * Left ventricular ejection fraction (LVEF) ≥ 50% by multiple gated acquisition scan (MUGA) or echocardiogram\* * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix * No severe, active co-morbidity, including any of the following\*: * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * Transmural myocardial infarction within the past 6 months * Acute bacterial infection or fungal infection requiring intravenous antibiotics * Acquired Immune Deficiency Syndrome (AIDS) or immunocompromised patients * HIV testing not required * No NCI CTCAE v 3.0 grade 3-4 electrolyte abnormalities, including any of the following\*: * Calcium \< 7 mg/dL or \> 12.5 mg/dL * Glucose \< 40 mg/dL or \> 250 mg/dL * Magnesium \< 0.9 mg/dL or \> 3 mg/dL * Potassium \< 3mmol/L or \> 6 mmol/L * Sodium \< 130 mmol/L or \> 155 mmol/L NOTE: \*Applies to group 1 only, which was closed to accrual as of 01/08/10) PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior excisional biopsy in which the majority of the tumor (≥ 50%) is removed * No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by EORTC/RTOG Criteria | 2 years after start of treatment (+/- 3 months) | The rate of patients with late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years from the start of radiotherapy as measured by EORTC(European Organisation for Research and Treatment of Cancer)/RTOG (Radiation Therapy Oncology Group) criteria. Grade refers to the severity of the morbidity. The RTOG/EORTC Late Radiation Morbidity Scoring Schema assigns Grades 1 through 5 with unique clinical descriptions of severity for each morbidity based on this general guideline: Grade 1 Mild , Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to morbidity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate at Two Years | From registration to date of death or last follow-up. Report at time of primary outcome measure analysis. | Overall survival is defined as the time from registration to date of death or last follow-up. Two year survival rate and 95% confidence interval were estimated by the Kaplan-Meier method. |
| Pattern of First Failure | From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis. | Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression. |
| Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years | From start of treatment to 2 years. | The Musculoskeletal Tumor Rating Scale (MSTS) is a measure of physical function across 7 items, completed by the physician (preferably by the Orthopedic Surgeon or Surgical Oncologist) or the physician's designated staff. The 7 items are: pain, range of motion, strength, joint stability, joint deformity, emotional, acceptance, and overall function. Each item is scored from 0-5 (worst possible to best possible condition). The item scores are summed to get the total score which ranges from 0-35. Late radiation morbidity is defined as ≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. |
| Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events | From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis. | Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. |
| Local Failure Rate at Two Years | From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis. | Local failure is defined as the time from registration to date of failure (local progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method. |
| Regional Failure Rate at Two Years | From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis. | Regional failure is defined as the time from registration to date of failure (regional progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method. |
| Distant Failure Rate at Two Years | From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis. | Distant failure is defined as the time from registration to date of failure (distant progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method. |
| Distant Disease-free Survival Rate at Two Years | From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis. | Distant disease-free survival is defined as the time from registration to date of failure (distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method. |
| Disease-free Survival Rate at Two Years | From registration to date of failure (local, regional or distant progression or death) or last follow-up. Report at time of primary outcome measure analysis. | Disease-free survival is defined as the time from registration to date of failure (local, regional, or distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method. |
| Second Primary Tumor Rate at Two Years | From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis. | Second primary tumor is defined as the time from registration to date of failure (second primary tumor) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method. |
| Late Radiation Morbidity Rate (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by CTCAE v3.0 | 2 years after start of treatment (+/- 3 months) | Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. |
| Percentage of Patients With Wound Complications | From date of surgery to 4 months post-surgery | Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution. |
Other
| Measure | Time frame |
|---|---|
| Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients | 2 years after start of treatment (+/- 3 months) |
| Comparison of TESS and the MSTS Scores at 2 Years Between Cohort B Patients and the Preoperative Radiotherapy Patients in the NCIC CTG Trial [National Cancer Institute of Canada Clinical Trials Group] | 2 years after start of treatment (+/- 3 months) |
| Correlation of Late Radiation Morbidity at 2 Years With the 3 Quality of Life Assessments [Functional Assessment of Cancer Therapy-General (FACTG), Toronto Extremity Salvage Score (TESS), and Sexual Adjustment Questionnaire (SAQ)] | 2 years after start of treatment (+/- 3 months) |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A - Chemotherapy Radiation therapy with neoadjuvant or adjuvant or concurrent or interdigitated chemotherapy followed by surgery followed by, for patients with positive margins, radiation therapy boost | 10 |
| Cohort B - No Chemotherapy Radiation therapy followed by surgery followed by, for patients with positive margins, radiation therapy boost | 79 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No protocol treatment received | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 6 |
Baseline characteristics
| Characteristic | Cohort A - Chemotherapy | Cohort B - No Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 61 years | 61 years |
| Sex: Female, Male Female | 5 Participants | 37 Participants | 42 Participants |
| Sex: Female, Male Male | 5 Participants | 42 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 10 | 73 / 79 |
| serious Total, serious adverse events | 2 / 10 | 13 / 79 |
Outcome results
Primary
Rate of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by EORTC/RTOG Criteria
The rate of patients with late radiation morbidity (≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness) at 2 years from the start of radiotherapy as measured by EORTC(European Organisation for Research and Treatment of Cancer)/RTOG (Radiation Therapy Oncology Group) criteria. Grade refers to the severity of the morbidity. The RTOG/EORTC Late Radiation Morbidity Scoring Schema assigns Grades 1 through 5 with unique clinical descriptions of severity for each morbidity based on this general guideline: Grade 1 Mild , Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to morbidity.
Time frame: 2 years after start of treatment (+/- 3 months)
Population: All eligible patients on Cohort B who started study treatment and had an assessment of toxicity at 2 years. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Rate of Late Radiation Morbidity (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis, or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by EORTC/RTOG Criteria | 10.5 percentage of participants |
Comparison: Initially designed to test for a 20% absolute improvement from 37% (fixed rate) to 17% using Fisher's exact test, requiring 41 patients per cohort (51 with 20% ineligibility) with 5% type I error and 90% statistical power. During accrual, the sample size for cohort B was increased to 66 (83 with 20% ineligibility) to test for a 15% improvement with 5% type I error and 85% power.p-value: 0.0005Fisher Exact
Secondary
Disease-free Survival Rate at Two Years
Disease-free survival is defined as the time from registration to date of failure (local, regional, or distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Time frame: From registration to date of failure (local, regional or distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Disease-free Survival Rate at Two Years | 58.1 percentage of participants |
Secondary
Distant Disease-free Survival Rate at Two Years
Distant disease-free survival is defined as the time from registration to date of failure (distant progression or death) or last follow-up. Two year rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Time frame: From registration to date of failure (distant progression or death) or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Distant Disease-free Survival Rate at Two Years | 61.4 percentage of participants |
Secondary
Distant Failure Rate at Two Years
Distant failure is defined as the time from registration to date of failure (distant progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Time frame: From registration to date of failure (distant progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Distant Failure Rate at Two Years | 37.3 percentage of participants |
Secondary
Late Radiation Morbidity Rate (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by CTCAE v3.0
Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time frame: 2 years after start of treatment (+/- 3 months)
Population: All eligible patients on Cohort B who started study treatment and had an assessment of toxicity at 2 years. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Late Radiation Morbidity Rate (≥ Grade 2 Lymphedema, Subcutaneous Fibrosis or Joint Stiffness) at 2 Years From the Start of Radiotherapy as Measured by CTCAE v3.0 | 8.8 percentage of participants |
Secondary
Local Failure Rate at Two Years
Local failure is defined as the time from registration to date of failure (local progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Time frame: From registration to date of failure (local progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Local Failure Rate at Two Years | 11.4 percentage of participants |
Secondary
Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years
The Musculoskeletal Tumor Rating Scale (MSTS) is a measure of physical function across 7 items, completed by the physician (preferably by the Orthopedic Surgeon or Surgical Oncologist) or the physician's designated staff. The 7 items are: pain, range of motion, strength, joint stability, joint deformity, emotional, acceptance, and overall function. Each item is scored from 0-5 (worst possible to best possible condition). The item scores are summed to get the total score which ranges from 0-35. Late radiation morbidity is defined as ≥ grade 2 lymphedema, subcutaneous fibrosis, or joint stiffness. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time frame: From start of treatment to 2 years.
Population: All eligible patients on Cohort B who had a 2-year MSTS assessment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort B - No Chemotherapy | Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years | 31.3 units on a scale | Standard Deviation 4.5 |
| Cohort B - No Chemotherapy | Mean Musculoskeletal Tumor Rating Scale (MSTS) by Late Radiation Morbidity at Two Years | 25.0 units on a scale | Standard Deviation 0 |
Secondary
Overall Survival Rate at Two Years
Overall survival is defined as the time from registration to date of death or last follow-up. Two year survival rate and 95% confidence interval were estimated by the Kaplan-Meier method.
Time frame: From registration to date of death or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Overall Survival Rate at Two Years | 80.6 percentage of participants |
Secondary
Pattern of First Failure
Pattern of first failure including local failure (in-field, marginal, and outside-field failure), regional failure, distant failure, and death without disease progression.
Time frame: From registration to date of local, regional or distant progression. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. All eligible patients on Cohort B. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort B - No Chemotherapy | Pattern of First Failure | Alive without disease progression | 8 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Local | 1 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Regional | 0 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Distant | 1 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Dead without disease progression | 0 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Dead without disease progression | 2 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Distant | 29 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Local | 8 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Alive without disease progression | 39 participants |
| Cohort B - No Chemotherapy | Pattern of First Failure | Regional | 1 participants |
Secondary
Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events
Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time frame: From start of treatment to last follow-up. Analysis can occur at or after time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Percentage of Patients With Other CTCAE, v.3.0 Grade 3-5 Adverse Events | 38.0 percentage of patients |
Secondary
Percentage of Patients With Wound Complications
Estimate rate of patients with acute wound complications with 95% confidence interval assuming binomial distribution.
Time frame: From date of surgery to 4 months post-surgery
Population: All eligible patients on cohort B that had surgery and a wound assessment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Percentage of Patients With Wound Complications | 36.6 percentage of participants |
Secondary
Regional Failure Rate at Two Years
Regional failure is defined as the time from registration to date of failure (regional progression) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Time frame: From registration to date of failure (regional progression) or death or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Regional Failure Rate at Two Years | 0 percentage of participants |
Secondary
Second Primary Tumor Rate at Two Years
Second primary tumor is defined as the time from registration to date of failure (second primary tumor) or death or last follow-up. Two year rate and 95% confidence interval were estimated by the cumulative incidence method.
Time frame: From registration to date of failure (second primary tumor) or death or last follow-up. Report at time of primary outcome measure analysis.
Population: All eligible patients on Cohort B who started study treatment. (See limitations and caveats, Cohort A is not included.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort B - No Chemotherapy | Second Primary Tumor Rate at Two Years | 5.1 percentage of participants |
Other Pre-specified
Comparison of SAQ Scores at 2 Years for Cohort A Patients With Cohort B Patients
Time frame: 2 years after start of treatment (+/- 3 months)
Other Pre-specified
Comparison of TESS and the MSTS Scores at 2 Years Between Cohort B Patients and the Preoperative Radiotherapy Patients in the NCIC CTG Trial [National Cancer Institute of Canada Clinical Trials Group]
Time frame: 2 years after start of treatment (+/- 3 months)
Other Pre-specified
Correlation of Late Radiation Morbidity at 2 Years With the 3 Quality of Life Assessments [Functional Assessment of Cancer Therapy-General (FACTG), Toronto Extremity Salvage Score (TESS), and Sexual Adjustment Questionnaire (SAQ)]
Time frame: 2 years after start of treatment (+/- 3 months)