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• The National Cancer Institute’s Breast Intergroup INT C9741 and CALGB 9741 trial published in 2003:
  • Evaluated combination chemotherapy for breast cancer given by both dose dense and sequential therapy
  • The goal of the study was to evaluate the best way to administer the chemotherapy regimen:
    • Doxorubicin (A), cyclophosphamide (C) followed by paclitaxel (T)
  • The study assessed chemotherapy administration in a:
    • Dose dense fashion (2 weeks vs. 3 weeks) and treatment sequence (concurrent versus sequential)
• Dose-dense chemotherapy refers to:
  • Decreasing the interval between cycles of treatment without the need of increasing doses and toxicity
• Sequential therapy refers to:
  • The administration of treatments one at a time rather than concurrently
• National Cancer Institute’s Breast Intergroup INT C9741 and CALGB 9741 trial:
  • Was a prospective, randomized trial designed to study adjuvant chemotherapy treatment regimens in women with axillary node-positive breast cancer conducted from September 1997 to March 1999
  • Doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) were chosen for this study
  • Using a 2 x 2 factorial design, patients were assigned to receive one of the following four regimens:
    • Sequential A then C followed by T x 4 cycles every 3 weeks,
    • Dose-dense, sequential A then C then T x 4 cycles every 2 weeks with filgrastim
    • Concurrent AC x 4 cycles followed by T x 4 cycles every 3 weeks
    • Dose-dense, concurrent AC x 4 cycles followed by T x 4 cycles every 2 weeks with filgrastim
  • Results showed that dose-dense treatment improved the primary endpoints of disease-free survival (DFS) and overall survival (OS):
    • Four-year DFS was 82% for dose-dense regimens and 75% for other groups (risk ratio, 0.74, P=0.01)
    • Three-year OS was 92% for dose-dense regimens and 90% in other groups (risk ratio, 0.69, P=0.013)
    • There was no difference in either DFS or OS between the concurrent and sequential schedules
    • Severe neutropenia was less common in patients who received the dose-dense regimens
    • As a result of this study:
      • Dose-dense and concurrent AC chemotherapy has become one of the standard components of breast cancer therapy

References

1. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431-1439.

2. Orzano JA, Swain SM. Concepts and clinical trials of dose-dense chemotherapy for breast cancer. Clin Breast Cancer. 2005;6(5):402-411

• The phase III PRIME II trial has shown a higher risk of local recurrence with the omission of adjuvant radiotherapy after breast-conserving surgery in patients aged ≥ 65 years with hormone receptor–positive, node-negative disease who were receiving adjuvant endocrine therapy.
• No difference in the risk of distant recurrence as the first recurrence event or overall survival was observed.
• Study Details: The trial included 1,326 patients from sites in the United Kingdom (n = 1,263), Greece, Australia, and Serbia with T1 or T2 primary breast cancer (with tumors ≤ 3 cm in the largest dimension) who received breast-conserving surgery with clear excision margins and adjuvant endocrine therapy.
• Patients were randomly assigned between April 2003 and December 2009 to whole-breast irradiation at 40 to 50 Gy in 20 to 25 fractions (n = 658) or no irradiation (n = 668).
• Tamoxifen at 20 mg per day for 5 years was recommended as standard adjuvant endocrine therapy.
• The primary endpoint was local breast cancer recurrence.
• Key Findings: Median follow-up was 9.1 years. At 10 years, the cumulative incidence of local recurrence was 9.5% (95% confidence interval [CI] = 6.8%–12.3%) in the no-radiotherapy group vs 0.9% (95% CI = 0.1%–1.7%) in the radiotherapy group (hazard ratio = 10.4, 95% CI = 4.1–26.1, P < .001).
• The 10-year cumulative incidence of distant recurrence as the first recurrence event was 1.6% (95% CI = 0.4%–2.8%) in the no-radiotherapy group vs 3.0% (95% CI = 1.4%–4.5%) in the radiotherapy group.
• For the no-radiotherapy group vs the radiotherapy group, 10-year rates were:

• 68.9% (95% CI = 64.7%–73.0%) vs 76.3% (95% CI = 72.5%–80.2%) for disease-free survival
• 80.8% (95% CI = 77.2%–84.3%) vs 80.7% (95% CI = 76.9%–84.3%) for overall survival
• 97.4% (95% CI = 96.0%–98.8%) vs 97.9% (95% CI = 96.5%–99.2%) for breast cancer–specific survival.
• The investigators concluded: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among [patients] 65 years of age or older with low-risk, hormone receptor–positive early breast cancer.

• The overall significant complication rate from sentinel lymph node dissection reported from the ACOSOG Z0010 trial:
  • Was low:
    • With 32% of patients reporting at least one surgical side effect and less than 1% of patients requiring hospitalization
  • The most common surgical side effect was:
    • Axillary paresthesia:
      • Affecting 307 (8.6%) of 3,573 patients
    • Allergic reaction:
      • Was reported in less than 1%:
        • Related to the administration of lymphazurin blue dye
      • Lymphedema in 7%
      • Brachial plexus injury in less than 1% of patients
    • Only one anaphylactic reaction to blue dye was reported
• References
  • Hunt KK, Ballman KV, McCall LM, Boughey JC, Mittendorf EA, Cox CE, et al. Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial. Ann Surg. 2012;256(3):428-436.
  • Boughey JC, Hunt KK. The ACOSOG experience. In: Kuerer HM, ed. Kuerer’s Breast Surgical Oncology. New York, NY: McGraw-Hill Companies; 2010:517-530.

• NSABP B-06:
  • Phase III Total Mastectomy / Axillary Dissection vs. Segmental Mastectomy / Axillary Dissection with or without Radiotherapy for Potentially Curable Breast Carcinoma:
    • Compared total mastectomy with lumpectomy alone and lumpectomy with irradiation in patients with tumors 4 cm or less in greatest diameter
  • All patients had an axillary lymph node dissection (ALND)
  • This trial, along with 5 other randomized prospective trials:
    • Was instrumental in establishing lumpectomy plus radiation therapy as the preferred treatment for women with early stage, operable breast cancer, as compared to mastectomy
    • After 20 years of follow-up:
      • There were no observed differences in:
        • Overall survival, or distant disease-free survival:
          • Between the total mastectomy group and the lumpectomy groups, with or without radiation:
            • The hazard ratio (HR) for death with lumpectomy alone was 1.05 (95% confidence interval [CI] 0.90–1.23; P=0.51)
            • The HR for death with lumpectomy plus radiation was 0.97 (95% CI, 0.83–1.14; P=0.74):
              • Which were comparable to total mastectomy
• NSABP B-04:
  • Enrolled clinically node-negative patients and randomized them to radical mastectomy (RM), total mastectomy (TM) plus radiation, or TM alone
• NSABP B-17:
  • Compared lumpectomy alone to lumpectomy plus breast radiation:
    • In patients with localized ductal carcinoma in situ (DCIS)
• NSABP B-32:
  • Assigned clinically node-negative patients to either sentinel lymph node (SLN) resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2)
• NSABP protocol B-43:
  • Aims to evaluate the effect of trastuzumab on local recurrence in patients with HER2-positive DCIS treated with lumpectomy and whole-breast irradiation

References:

Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233-1241.

Fisher B, Montague E, Redmond C, Barton B, Borland D, Fisher ER, et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer: a first report of results from a prospective randomized clinical trial. Cancer. 1977;39(6 Suppl):2827-2839.

Mamounas EP, Wickerham DL, Fisher B, Geyer CE, Julian TB, Wolmark N. The NSABP experience. In: Kuerer HM, ed. Kuerer’s Breast Surgical Oncology. New York, NY: McGraw-Hill Companies; 2010:475-508.

Fisher B, Dignam J, Wolmark N, Mamounas E, Constantino J, Poller W, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol. 1998;16(2):441-452.

Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Constantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 Randomized Phase 3 Trial. Lancet Oncol. 2010;11(10):927-933.

Siziopilou KP, Anderson SJ, Cobleigh MA, Julian TB, Arthur DW, Zheng P, et al. Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43. Breast Cancer Res Treat. 2013;142(2):415-421.

• The 21-gene recurrence-score assay (e.g., Oncotype DX, Genomic Health):
  • Is one of several commercially available gene-expression assays:
    • That provide prognostic information:
      • In hormone-receptor-positive breast cancer
• The assay originally set cut points for:
  • Low risk at a recurrence score less than 18
  • Intermediate risk at 18 to 30
  • High risk at greater than 30
• It is predictive of chemotherapy benefit:
  • When the recurrence score (RS) is high (greater than 26) and
• It is prognostic for very low rates of distant recurrence:
  • 2% at 10 years:
    • When the RS is low (less than 10)
• The TAILORx prospective randomized clinical trial:
  • Was completed to determine whether chemotherapy is beneficial for women with an intermediate RS of 11 to 25:
    • The cutoffs for this trial were adjusted to ensure all patients in the intermediate range who may benefit were included
  • At 9 years of follow-up:
    • The endocrine therapy only and the chemo-endocrine therapy group had similar rates of invasive disease-free survival:
      • 83.3% vs. 84.3% respectively
    • The endocrine therapy alone was noninferior to chemoendocrine therapy:
      • For all patients in the intermediate RS study group (RS 11 to 25)
    • The two groups also had similar outcomes in freedom from disease recurrence at a distant or locoregional sites:
      • However, the chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004):
        • With some benefit of chemotherapy found in women 50 years old or younger with an RS of 16 to 25:
          • In women less than 50 receiving chemotherapy:
            • Demonstrated a lower rate of distant recurrence than endocrine therapy if RS was:
              • 16 to 20 (percentage-point difference, 0.8 at 5 years and 1.6 at 9 years) or 21 to 25 (percentage-point difference, 3.2 at 5 years and 6.5 at 9 years):
                • Overall survival however remained similar
          • For this reason, researchers conclude that the 21-gene assay can identify women with ER+ early-stage breast cancer:
            • Who may be spared chemotherapy if they are over 50 years old with an RS of 25 or lower:
              • As well as women 50 years or younger with RS of 15 or lower
• References:
  • Sparano JA, Gray RJ, Makower DF, Pritchard K, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121

• Management of the nodal basins in a patient with drainage to both an epitrochlear and axillary or a popliteal and inguinal nodal pattern:
  • Warrants SLN biopsy of both basins and attention to each basin based on the SLN status of that respective basin
• It is not possible, based on lymphoscintigraphy:
  • To determine whether the proximal lymphatic basins drain the primary tumor site through lymphatic channels that are separate from those that drain to the distal nodal basin
• If found to have a positive sentinel lymph node:
  • Current management of the regional lymph node basin(s):
    • Have shifted towards observation by ultrasound as compared to completion lymph node dissection:
      • This shift in treatment paradigm was influenced by two randomized control trials:
        • MSLT II and DeCOG-SLT:
          • Both of which demonstrated no improved in survival in sentinel lymph node positive patients who underwent immediate completion lymph node dissection as compared to observation
• Additionally, referral for adjuvant immunotherapy or targeted therapy:
  • Should be considered as recent evidence has demonstrated improvement in disease free survival:
    • Among resectable stage III melanoma patients that went on to receive adjuvant therapy
• If unable to undergo close observation:
  • The appropriate next step is completion lymphadenectomy of all involved nodal basins:
    • Complete axillary dissection including all lymph nodes in levels 1, 2, and 3 along with the nodes superior to the axillary vein and superficial to the axillary artery and brachial plexus along with all of the nodal tissue along the subscapular musculature is the standard of care for patients with melanoma
• Unlike the situation with breast cancer, adjuvant radiation and chemotherapy are not uniformly used and does is not a substitute for appropriate surgical therapy
• References:
  • Bilimoria KY, Balch CM, Bentrem DJ, et al. Complete lymph node dissection for sentinel node-positive melanoma: assessment of practice patterns in the United States. Ann Surg Oncol. 2008;15:1566-1576.
  • Gershenwald JE, Andtbacka R, Prieto V, et al. Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J ClinOncol. 2008;26:4296-4303.
  • Pollock RE, Curley SA, Ross MI, et al, eds. Advanced Therapy in Surgical Oncology. Hamilton, Ontario, Canada: BC Decker; 2008.

• In patients with early-stage HER2-positive breast cancer:
  • Studies have shown that adjuvant trastuzumab, in addition to chemotherapy:
    • Prolongs disease-free survival (EA Perez et al., J Clin Oncol. 2014)
• Several trials have evaluated different approaches to improve outcomes beyond those achieved with one year of trastuzumab:
  • Five major studies include:
    • HERA trial:
      • Extending the duration of trastuzumab to 2 years
    • ALTTO trial:
      • Administration of lapatinib, a tyrosine kinase inhibitor, to trastuzumab
    • BETH trial (NSABP-B44):
      • Addition of bevacizumab, an anti-angiogenic agent, to trastuzumab
    • ExteNET trial:
      • Subsequent addition of neratinib, a tyrosine-kinase inhibitor, for 1 year
  • APHINITY trial (BIG 4-11):
    • Addition of pertuzumab to transtuzumab, for 1 year
• The ExteNET and APHINITY:
  • Showed benefit with the additional therapy
• HERceptin Adjuvant (HERA) trial:
  • An international, multicenter, phase 3 randomized trial:
    • Of 5,102 women with HER2-positive early breast cancer
  • After completing all primary therapy (including, surgery, chemotherapy, and radiotherapy as indicated):
    • Patients were randomly assigned to receive trastuzumab for 1 or 2 years, or to the observation group
  • Primary endpoint:
    • Was disease-free survival
  • Results reported that one year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer:
    • Significantly improved long-term disease-free survival, compared with observation:
      • While two years of trastuzumab had no additional benefit
• ALTTO (Adjuvant Lapatinib And / Or Trastuzumab Treatment Optimization) Study:
  • Was the first trial to test the hypothesis that dual anti-HER2 blockade could further improve survival outcomes of patients with HER2-positive early breast cancer compared with adjuvant trastuzumab
  • The study compared the efficacy of the addition of lapatinib to trastuzumab (sequentially after completion of 12 weeks of trastuzumab or concurrently with 52 weeks of trastuzumab) vs. trastuzumab alone for 1 year
  • Adjuvant treatment that included lapatinib:
    • Did not significantly improve survival compared with trastuzumab alone and added toxicity
• NSABP B-44, also known as the BETH Study (Treatment of HER2 Positive Breast Cancer With Chemotherapy Plus Trastuzumab vs. Chemotherapy Plus Trastuzumab Plus Bevacizumab):
  • Was a phase 3 study evaluating the addition of bevacizumab, a vascular endothelial growth factor (VEGF-A) to trastuzumab
  • Patients were randomized to 1 of 4 treatment arms in 2 cohorts:
    • Cohort 1:
      • The nonanthracycline regimen TCH (docetaxel, carboplatin, and trastuzumab [Herceptin]) or TCH plus bevacizumab
    • Cohort 2:
      • Anthracycline-based therapy with T-FEC-H (docetaxel, fluorouracil, epirubicin, cyclophosphamide, plus trastuzumab) with or without bevacizumab
  • The study concluded that the addition of bevacizumab (Avastin) to adjuvant chemotherapy:
    • Did not improve invasive disease-free survival or overall survival in patients with high-risk HER2-positive breast cancer
  • BETH also demonstrated that the non–anthracycline-containing chemotherapy arm:
    • Was as effective in prolonging survival as the anthracycline-containing arm
• Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET) Trial:
  • Is a multicenter, randomized, phase 3 trial designed to investigate extended adjuvant therapy with neratinib
  • Patients received 1 year of extended adjuvant therapy with neratinib:
    • An irreversible pan-HER tyrosine kinase inhibitor:
      • Administered after chemotherapy and trastuzumab
  • The results showed that 1 year of neratinib:
    • Significantly improved 5-year invasive disease-free survival without increasing the risk of long-term toxicity
• APHINITY trial (BIG 4-11):
  • A randomized comparison of chemotherapy (C) plus trastuzumab (T) plus placebo versus chemotherapy plus trastuzumab (T) plus pertuzumab (P) as adjuvant therapy in patients with HER2-positive early breast cancer
  • In previous neoadjuvant trials, pertuzumab significantly prolonged progression free and overall survival and increased pathologic complete response (pCR) rates when added to trastuzumab and chemotherapy
  • They investigated the role of pertuzumab when added to trastuzumab after surgery and chemotherapy in the adjuvant setting:
    • A small benefit in favor of the combination was observed, which was more pronounced in node-positive patients
• References
  • Cameron D, Piccart-Gebhart MJ, Gelber RD, Proctor M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195-1205.
  • Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol.2016;34(10):1034-1042.
  • Slamon DL, Swain SM, Buyse M, Martin M, Geyer CE. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive, or high-risk node-negative breast cancer [Abstract]. Cancer Res. 2013;73(suppl 24): S1-03.
  • Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1688-1700.
  • von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122-131.

• The treatment paradigm for melanoma patients with a positive SLN:
  • Has undergone a dramatic evolution in recent years
    • Historically, completion lymph node dissection (CLND) was considered the standard of care for patients found to have micrometastatic disease in the SLN:
      • However, two recent trials sought to investigate the efficacy of immediate CLND:
        • The DECOG-SLT and MSLT-II trials were multicenter randomized control trials:
          • That randomly assigned melanoma patients with sentinel-node metastasis to either immediate CLND versus observation by nodal ultrasound
    • In the DECOG-SLT trial:
      • 477 patients were enrolled
      • At three years, the study reported no difference in distant metastasis-free survival:
        • 77% versus 74.9%, HR 1.03; p=0.87 between the observation group and CLND group
      • At three years, the study reported no difference in overall survival:
        • 81.7% versus 81.2%, HR 0.96; p=0.87 between the observation group and CLND group
    • Similarly, in the larger MSLT-II trial:
    • Where 1,755 patients were evaluated
    • The study found that immediate CLND did not improve melanoma-specific survival when compared to patients that underwent observation:
      • 86% versus 86%; p=0.42
• If, however, patients are unable or unwilling to undergo close surveillance:
  • Completion lymph node dissection can be considered
• Completion lymph node dissection for microscopic inguinofemoral SLN involvement consists of:
  • Superficial groin dissection:
    • Which includes clearance of nodal tissue within the femoral triangle
  • These nodes are accessed via either an oblique incision below or a lazy incision crossing through the inguinal crease:
    • Flaps are made superiorly several centimeters above the inguinal ligament, laterally to the anterior superior iliac spine (ASIS) and proceeding along the lateral border of the sartorius to the apex of the femoral triangle, and medially along the adductor longus to the pubic symphisis:
      • All nodal tissue within these landmarks and around the femoral vessels is taken:
        • With effort to preserve the lateral femoral cutaneous nerve:
          • As it runs below the ASIS and superior to the sartorius
  • The saphenous vein may be sacrificed if gross nodal disease precludes safe dissection of nodal tissue circumferentially:
    • However, preservation can be performed with theoretical benefits in preventing lymphedema
  • Depending on the extent of tissue resection and the health of overlying skin, a sartorius transposition flap can be made to cover the femoral vessels
• Several centers advocate intraoperative assessment by frozen section of Cloquet’s node:
  • The lowest iliac node located within the femoral canal:
    • To determine whether immediate or delayed deep (iliac/obturator) node dissection is warranted:
      • However, the clinical adaptation of this technique is variable:
        • Sole excision of Cloquet’s node without further superficial inguinal node dissection is not standard of care
• References:
  • Al-Refaie WB, Ross MI. Inguinal lymphadenectomy for malignant melanoma. Operative Techniques in General Surgery, 2006. WB Saunders, Philadelphia, PA.
  • Faries MB, Thompson JF, Cochran AJ, et al: Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med 376:2211-2222, 2017
  • Leiter U, Stadler R, Mauch C, et al: Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 17:757-767, 2016
  • Essner R, Scheri R, Kavanagh M, et al. Surgical management of the groin lymph nodes in melanoma in the era of sentinel node dissection. Arch Surg. 2006;141:877-882.
  • Jacobs LK, Balch CM, Coit DG. Inguinofemoral iliac/obturator, and popliteal lymphadenectomy in patients with melanoma. In: Balch CM, Houghton AN, Sober AJ, Soong S-J (eds.) Cutaneous Melanoma. 5th ed. St. Louis: Quality Medical Publishing; 2009:457-470.
  • Tsao H, Atkins M, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;998-1012.

• Lymphedema management:
  • Begins with the documentation of limb measurements:
    • For both arms or legs:
      • Using either volume displacement or circumferential measurement:
        • All extremities must be measured at multiple points.
• Increased physical activity:
  • Has proven to decrease lymphedema symptoms
• Compression sleeve:
  • Should be 30 to 40 mm Hg of compression
• There are several microsurgery techniques:
  • That have proven to improve lymphedema symptoms
• References:
  • Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma Staging: Evidence-Based Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J Clin. 2017; 67(6): 472-492.
  • Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol. 2012; 30 (23): 2912-8.
  • Faries MB, Thompson JF, Cochran AJ, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017; 376(23): 2211-2222.

• A multi-institution, prospective randomized trial from participating Cancer Care Ontario Centers:
  • Was performed from 1993 to 1996
• The study sought to determine whether accelerated hypofractionated whole-breast irradiation (WBI) was as effective as conventional 5-week fractionation
• Included in the study were women who received:
  • Breast-conserving surgery (BCS) for invasive breast cancer with clear surgical margins and negative axillary nodes
• Participants were randomly assigned to receive WBI either at the standard dose of 50.0 Gy in 25 fractions over 35 days (control group), or at a dose of 42.5 Gy in 16 fractions over 22 days (hypofractionated-radiation group)
• The control group included:
  • 612 patients and the hypofractionation group had 622 patients
• Results from this study indicated that the Canadian regimen was not inferior to the standard 5-week treatment regimen for women who received BCS for invasive breast cancer with clear surgical margins and negative axillary nodes
• The risk of local recurrence at 10 years was:
  • 6.7% in the control group and 6.2% in the hypofractionated group
• Cosmesis at 10 years was found to be comparable between the two groups:
  • With good or excellent outcomes for 71.3% of women in the control group and 69.8% in the hypofractionated-radiation group
• There was also no difference between the two groups in overall survival and no increase in cardiac-related deaths was seen in the hypofractionated group

References

1. Whelan TJ, Pignol J-P, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513-520.