Evaluation of Two Boost Radiation Schedules in Post Lumpectomy Early Stage Carcinoma Breast
Condition: Breast Cancer; Adverse Effect of Radiation Therapy
MeSH terms: Breast Neoplasms
Study type: Observational [Patient Registry]

Summary: 
      In a general radiation oncology practice, breast cancer typically comprises approximately 25%
      of the total patient caseload.1 Surgery is the primary modality of treatment. Radical
      mastectomy remained the mainstay of surgical therapy into the 1970s. Breast-conserving
      surgery followed by radiation therapy to the intact breast is an established standard of care
      for the majority of women with early stage invasive breast cancer. Recommended techniques for
      breast-conservation treatment are local excision of the primary tumor, preferably with clear
      margins, axillary lymph node dissection, and breast irradiation (45 to 50 Gy), usually with a
      boost (10 to 20 Gy, depending on tumor size and status of the surgical margins).

      The aim of this study is to compare the two boost regimen 10Gy/5#/1 week with 16Gy/8#/1.5
      weeks in post lumpectomy patients of early stage breast cancer, following whole breast
      irradiation (WBI).

      The study will include 50 patients, (25 in each arm) of early stage post lumpectomy breast
      cancer patients. Each patient will be treated by WBI followed by tumor bed boost with either
      electron beam therapy or 3D CRT. The primary end point of the study will be assessment of
      acute and late radiation toxicities, cosmetic score analysis and local control between two
      schedules. Secondary end points will be recurrence-free survival.
    

Detailed description: 
      Patients to be included in this study will be pre-operatively staged according to American
      Joint Committee on Cancer (AJCC) 7th edition, International Union against cancer ( which uses
      TNM staging ) as stage I , stage II of breast carcinoma. Fifty patients of histologically
      proven post lumpectomy cases of carcinoma breast suitable for whole breast radiotherapy will
      be enrolled in this study. Patients would be evaluated at the Department of Radiotherapy
      PGIMER, Chandigarh by doing a thorough clinical examination followed by routine
      investigations which will include hemogram, liver function tests, kidney function tests,
      chest X-ray. Patients will be treated by standard rectangular tangential field radiotherapy
      to whole breast. CT based planning will be done for photons boost and electron beam therapy.

      Inclusion criteria

      1. Unicentric primary breast cancer with invasive ductal histology. 2. Stage T1, T2, N0, N1,
      M0 Exclusion criteria

        1. Tumor histology with invasive or in situ lobular carcinoma or pure ductal carcinoma in
           situ.

        2. Skin involvement.

        3. History of prior primary malignancy.

        4. History of prior irradiation to chest

        5. Patients who received neoadjuvant chemotherapy. Procedure Fifty patients (25 in each
           arm) scheduled for whole breast radiotherapy after lumpectomy will be included in this
           study. An informed written consent in prescribed proforma for all patients will be taken
           for performing planning CT scan.

      Prior to radiotherapy planning, breast conserving surgery in the form of lumpectomy will be
      carried out in the department of surgery under general anaesthesia. Patients will be
      recruited 2-3 weeks after lumpectomy. A planning CT scan will be made for each patient. The
      patients will be positioned on a breast board with sternum parallel to the table, and the
      ipsilateral arm abducted above the head. Before the CT scan skin marks would be placed to
      enable the patient repositioning during treatment. Radioopaque markers will be placed to
      locate the whole breast and lumpectomy cavity on CT images.

      Patients will be scanned from level of larynx to the level of upper abdomen, including both
      lungs with a scan thickness and index of 5mm. The CT scan will include the complete left and
      right lung, both breasts and the heart. Then CT images will be transferred to the treatment
      planning system.

      The gross tumor volume (GTV) will be defined by lumpectomy cavity contoured on each CT slice.
      The clinical target volume (CTV) will consist of GTV uniformly expanded in three dimensions
      by 1cm; however the volume will be constrained to lie 5mm within external contour and up
      against the pectoralis major muscles. The planning target volume (PTV) will be calculated
      from the CTV using uniform three dimensional expansion of 0.5 cm. The ipsilateral whole
      breast will be defined to lie within the radioopaque markers and as deep as the anterior
      chest wall muscles. The cranial extent of heart will include the infundibulum of right
      ventricle, the right atrium and right auricle but exclude the pulmonary trunk, ascending
      aorta and superior vena cava. The lowest external contour of heart will be the caudal border
      of mediastinum. The pericardium should be excluded from the heart volume. Both lungs will be
      contoured. The contralateral breast will be contoured as the breast parenchyma is visible on
      CT images.

      After contouring the target volumes and organs at risk (OAR), standard whole breast
      rectangular field plans, 3D-CRT boost and electron boost plans will be generated. Dose
      prescribed would be 40 Gy/16#/3 weeks for whole breast rectangular plans and a boost of 10
      Gy/5#/1week in arm A and 16Gy/8#/1.5weeks in Arm B. Plans will be evaluated both
      quantitatively (analyzing dose volume histograms) and qualitatively (by visually inspecting
      isodose curves). Plans will be inspected for conformity and doses delivered to target and
      organs at risk.

      First follow up will be after 1 month of treatment, subsequently every 2 months till 6
      months, 3 monthly till 1 year and 4 monthly till 3 years. Patient will be examined clinically
      for acute effects, cosmetic outcome and LRR. Required investigation will be done if
      indicated.

      Assessment of toxicity will be done as per RTOG scores AND LENT SOMA scale SKIN Grade0 Grade1
      Grade2 Grade3 Grade4 Toxicity No change over baseline Follicular, faint or dull erythema/
      epilation/dry desquamation/ decreased sweating Tender or bright erythema, patchy moist
      desquamation/ moderate edema Confluent, moist desquamation other than skin folds, pitting
      edema Ulceration, hemorrhage, necrosis Subcutaneous & cutaneous tissue Grade 0 Grade 1 Grade
      2 Grade 3 Grade 4 Toxicity None Slight induration (fibrosis) and loss of subcutaneous fat
      Moderate fibrosis but asymptomatic Slight field contracture <10% linear reduction Severe
      induration and loss of subcutaneous tissue Field contracture >10% linear measurement Necrosis

      Pigmentary change :

      0 = None

        1. = Transitory , slight

        2. = Permanent , marked

      Breast edema :

      0 = None 1 = Asymptomatic 2 = Symptomatic 3 = Secondary dysfunction

      Cosmetic assessment will be done using Harvard/NSABP/RTOG Breast Cosmesis Grading Scale

      Statistical analysis The principle end point of the study will be an analysis of acute and
      late radiation toxicities,cosmetic score analysis and local control between two boost arms.
      Skin, subcutaneous toxicity and cosmetic assessment will be done before treatment and then in
      regular follow up of the study. Chi-square test will be used to compare radiation toxicity
      parameters. Descriptive statistics including mean and standard deviation will be obtained for
      all variables. A student t-test will be used to compare the dosimetric parameters. p values
      of <0.05 will be taken as significant. All tests would be performed using SPSS (Statistical
      Package for the Social Sciences) v.12.0.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Stage I , stage II of breast carcinoma with breast conservative surgery
      
Keywords: Breast conservative surgery; boost radiation; acute toxicity; cosmesis; local control