5. Radiation Therapy 5.1 Phase III Randomized Study of Postmastectomy Radiotherapy in Women with Stage II Breast Cancer With One to Three Positive Nodes

Objectives

I. Compare overall and disease-free survival in women with stage II breast cancer with one to three positive nodes with or without radiotherapy following mastectomy and adjuvant chemotherapy.

II. Compare local-regional control in these patients with these treatment regimens. III. Assess the potential toxicities of radiotherapy in this patient population.

Participation Criteria

• Histologically confirmed stage II adenocarcinoma of the breast (T1-2, N1, M0).
  
  
• Primary tumor no greater than 5 cm.
  
  
• At least 1 but no more than 3 positive axillary lymph nodes.
  
  
• Nodes cannot be positive solely by cytokeratin staining.
  
  
• Must have undergone a modified radical mastectomy with a level I and II axillary dissection (at least 10 nodes examined) in past 8 months.
  
  
• Surgical margins negative for invasive and noninvasive ductal carcinoma.
  
  
• No gross extracapsular disease or residual disease in the axilla.
  
  
• Microscopic extracapsular extension allowed.
  
  
• Must have received chemotherapy with or without hormonal therapy after mastectomy.
  
  
• No more than 6 weeks since prior adjuvant chemotherapy.
  
  
• Concurrent adjuvant chemotherapy allowed.
  
  
• Concurrent tamoxifen allowed.

Randomization

Lori J. Pierce, Chair
Southwest Oncology Group Principal Investigator, Ph: 734-936-7810 University of Michigan Medical School Ann Arbor, Michigan

5.2 Phase III Randomized Study of Synchronous Versus Sequential Adjuvant Chemotherapy and Radiotherapy in Women with Early Stage Breast Cancer

Objectives

I. Compare the effects of synchronous versus sequential adjuvant chemotherapy and radiotherapy on local recurrence, disease-free and overall survival, and treatment delay in women with early stage breast cancer.

II. Compare the safety with regard to dose intensity and toxicity of these treatment regimens in this patient population. III. Evaluate the quality of life and cosmetic outcome in these patients.

Participation Criteria

• Histologically confirmed early stage, invasive, unilateral breast cancer.
  
  
• Planned use of adjuvant chemotherapy and radiotherapy.
  
  
• Prior or concurrent hormonal therapy allowed.

Randomization

Patients receive any chemotherapy regimen that includes cyclophosphamide, methotrexate, and fluorouracil. Some regimens may also include leucovorin calcium, epirubicin, and/or doxorubicin.

Indy Fernando
Chair Cancer Research Campaign Clinical Trials Unit-Birmingham (CRCTU) Principal Investigator, Ph: 0121-414-3787 University of Birmingham Birmingham, England, United Kingdom

5.3 Phase II Study of Concurrent Paclitaxel and Radiotherapy Following Adjuvant Doxorubicin and Cyclophosphamide in Women with Stage II or III Breast Cancer

Protocol IDs: CWRU-2199, NCI-G00-1851, BMS-CWRU-2199 Projected Accrual: Approximately 40 patients will be accrued for this study over 12-18 months.

Objectives

I. Determine the feasibility of concurrent paclitaxel and breast radiotherapy in women with stage II or III breast cancer who have had primary breast-conserving surgery and adjuvant chemotherapy.

II. Assess the cosmetic results of breast conservation after this treatment in these patients.

III. Determine the pulmonary toxicity of this regimen in these patients.

Participation Criteria

• Stage II or III invasive breast cancer
  
  
• .Prior breast-conserving surgery (lumpectomy or quadrantectomy) with ipsilateral axillary lymph node dissection required.
  
  
• Doxorubicin and cyclophosphamide adjuvant hemotherapy completed within past 3 weeks.
  
  
• Prior tamoxifen allowed.
  
  
• No concurrent tamoxifen.

Protocol

Patients receive paclitaxel IV over 3 hours every 21 days for 4 courses beginning 3 weeks after completion of the last doxorubicin and cyclophosphamide adjuvant regimen. Patients also undergo concurrent radiotherapy 5 days a week for approximately 6-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Beth A. Overmoyer, Chair
Ireland Cancer Center Principal Investigator, Ph: 216-844-5176 Cleveland, Ohio

5.4 Phase III Randomized Study of Radiotherapy Fractionation Regimens After Local Excision or Mastectomy in Women with Early Stage Breast Cancer

Objectives

Determine the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of normal tissue responses, local-regional tumor control, quality of life, and economic consequences in women prescribed postoperative radiotherapy for early stage breast cancer.

• Histologically confirmed invasive unilateral breast cancer. T1-3, N0-1, M0 at presentation.
  
  
• Complete macroscopic excision of tumor by breast-conserving surgery or mastectomy.
  
  
• No immediate breast reconstruction.
  
  
• No requirement for axillary radiotherapy after greater than a Level 1 axillary dissection or after greater than 10 lymph nodes have been removed
  
  
• .At least 2 weeks since prior cytotoxic agents. No concurrent chemotherapy.

Randomization

A breast boost is recommended in both arms for patients with microscopic evidence of invasive or in situ cancer at, or within 1 mm of, a resection margin. These patients receive radiotherapy for 5 fractions in 1 week for a total boost dose of 10 Gy. John Robert Yarnold START Trial Management Group

Principal Investigator
Ph: 020 8661 3891 Royal Marsden Hospital Sutton, England, United Kingdom

5.5 Phase III Randomized Study of Radiotherapy Fractionation Regimens After Local Excision or Mastectomy in Women with Early Stage Breast Cancer

Objectives

Determine the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of normal tissue responses, local-regional tumor control, quality of life, and economic consequences in women prescribed postoperative radiotherapy for early stage breast cancer.

Participation Criteria

• Histologically confirmed invasive unilateral breast cancer that is considered operable. T1-3, N0-1, M0 at presentation
  
  
• .Complete macroscopic excision of tumor by breast-conserving surgery or mastectomy.
  
  
• No immediate breast reconstruction.
  
  
• No requirement for axillary radiotherapy after greater than a Level 1 axillary dissection or after greater than 10 lymph nodes have been removed.
  
  
• Prior neoadjuvant, or primary medical, therapy allowed provided subsequent surgery confirms complete macroscopic excision of residual primary tumor.
  
  
• At least 2 weeks since prior cytotoxic agents.
  
  
• No concurrent chemotherapy.

Randomization

John Robert Yarnold, Chair
START Trial Management Group Principal Investigator, Ph: 020 8661 3891 Royal Marsden Hospital Sutton, England, United Kingdom

5.6 Phase III Randomized Study of Internal Mammary and Medial Supraclavicular Lymph Node Chain Irradiation vs No Further Therapy in Women with Resected Stage I/II/III Breast Cancer

Objectives

I. Compare the effect of irradiation of the homolateral internal mammary and medial supraclavicular lymph node chains vs no further therapy on survival, disease-free survival, metastasis-free su

Participation Criteria

• Histologically confirmed unilateral adenocarcinoma of the breast
  
  
• Stage I/II/III (Tx, T0-3, N0-2) disease in one of the following categories or multifocal tumors if one of the foci is in agreement with the following:
  
  
  • Centrally or medially located with any lymph node status
    
    
  • Central location defined as underlying the areola medial location defined as at least partial involvement of upper or lower
    
    
  • Medial quadrant of breast
    
    
  • Externally located with axillary node involvement
    

Randomization

Participating Organizations/Investigators
Walter F. Van den Bogaert, Chair EORTC Breast Cancer Group Chair, EORTC Radiotherapy Group Principal Investigator, Ph: 32-16346902 U.Z. Gasthuisberg Leuven, Belgium

5.7 Phase III Randomized Study of Adjuvant Breast Radiotherapy with or without Regional Radiotherapy in Women with Resected, Early Stage, Invasive Breast Cancer

Objectives

I. Compare the overall survival, disease-free survival, isolated local regional disease-free survival, and distant disease-free survival in women with resected, early stage, invasive breast cancer treated with breast radiotherapy with or without regional radiotherapy.

II. Compare the toxicities, including cosmetic outcomes, of these 2 regimens in these patients. III. Compare the quality of life of patients treated with these 2 regimens.

Participation Criteria

• Histologically proven invasive carcinoma of the breast without evidence of T4, N2-3, or M1 disease prior to surgery. Node-positive or high risk node-negative.
  
  
• Prior breast conserving therapy (BCT) (e.g., lumpectomy, partial mastectomy, or segmental mastectomy) and axillary node dissection or sentinel node biopsy required and must be a candidate for breast radiotherapy after BCT.
  
  
• Patients with positive margins should undergo re-excision. Patients with microscopically focally positive margins defined as no greater than 3 times high power fields are candidates for breast radiotherapy plus a boost to the lumpectomy site.
  
  
• Treated with currently accepted adjuvant systemic chemotherapy and/or hormonal therapy.
  
  
• High risk of regional and systemic recurrence due to one of the following:
  
  
  • Pathologically positive axillary lymph nodes
    
    
  • Pathologically negative axillary lymph nodes with one of the following:
    
    
  • Primary tumor greater than 5 cm
    
    
  • Primary tumor greater than 2 cm and less than 10 axillary lymph nodes excised and one of the following:
      Estrogen receptor negative
       OR
    Skarf-Bloom-Richardson grade 3

Randomization

Timothy Joseph Whelan
Chair NCIC-Clinical Trials Group Principal Investigator, Ph: 905-387-9711 ext. 64501 Cancer Care Ontario-Hamilton Regional Cancer Centre Hamilton, Ontario, Canada

5.8 Phase II Study of Adjuvant Radiation Therapy After Resection of Borderline and Malignant Phyllodes Tumors

Objectives

I. Determine the local recurrence rate for patients with phyllodes tumors of the breast treated with local excision with negative margins and adjuvant radiation therapy.

II. Determine the survival rate in this patient population.

Participation Criteria

• Histologically proven phyllodes tumors of the breast with borderline or malignant grade:
  
  
  • Borderline: 5 to 9 mitoses/10 high power fields (HPF), pushing or infiltrating margins, 2+ atypia.
    
    
  • Malignant: 10 or more mitoses/10 HPF, predominantly infiltrating margins, usually 3+ atypia with occasional 2+ atypia.
    
    
• Must have been excised with breast-conserving resection.
  
  
• No positive margins.
  
  
• Local recurrence of a previously excised phyllodes tumor allowed if the recurrence is in the area of the previous excision.
  
  
• No prior breast carcinoma or in situ ductal carcinoma in the ipsilateral breast.

Protocol

Patients receive radiation therapy 5 days a week for a total of 28 treatments. The adjuvant radiation therapy must begin within 12 weeks of local excision or breast reexcision.

Richard J. Barth, Jr.
Chair Norris Cotton Cancer Center Principal Investigator, Ph: 603-650-7903 Norris Cotton Cancer Center Lebanon, New Hampshire

5.9 Phase III Randomized Study of Palliative Radiation Therapy for Bone Metastases From Breast or Prostate Cancer

Objectives

I. Compare the ability of a single fraction of radiation therapy vs multiple fractions to provide complete pain relief in patients with painful bone metastases from breast or prostate cancer.

II. Determine the frequency and duration of pain relief and narcotic relief after these treatments in these patient populations.

III. Compare the effect on quality of life of these two treatments in these patient populations.

IV. Compare the incidence of pathologic fracture within the treatment fields after these two treatments in these patient populations.

Participation Criteria

• Histologically proven breast or prostate cancer.
  
  
• Radiographic evidence of bone metastasis within 8 weeks of study.
  
  
• Eligible treatment sites:
  
  
  • Weight-bearing sites: pelvis (excluding pubis), femur, sacrum and/or sacroiliac joints, tibia
    
    
  • Nonweight-bearing sites: up to 5 consecutive cervical, thoracic, or lumbar vertebral bodies, lumbosacral spine, up to 3 consecutive ribs, humerus, fibula, radius with/without ulna, clavicle, scapula, pubis
    
    
• If multiple sites are treated, site is included as weight-bearing if any of the sites include the pelvis, sacrum, femur, or tibia.
  
  
• Worst pain score of at least 5 on a scale of 10
  
  
• .No skull, feet, or hand metastases.
  
  
• No spinal cord or cauda equina compression/effacement in vertebral metastases.
  
  
• Multiple sites eligible if they can be included in no greater than 3 treatment sites.
  
  
• No planned surgical fixation of the bone.

Randomization

William F. Hartsell, Chair
Ph: 847-723-8030 Radiation Therapy Oncology Group Principal Investigator, Ph: 847-723-8030 Lutheran General Cancer Care Center Park Ridge, Illinois

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