Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• The NSABP B-18 trial:
  • Evaluated whether four cycles of doxorubicin and cyclophosphamide (AC) given preoperatively improved DFS and OS when compared with the same regimen given postoperatively
  • Results showed:
    • No statistically significant differences in DFS or OS between the two groups
    • Secondary aims included the evaluation of preoperative chemotherapy in down staging the primary breast tumor and involved axillary lymph nodes:
      • With preoperative chemotherapy, 13% of patients achieved pCR
    • Patients who received preoperative chemotherapy were:
      • More likely to receive breast-conserving surgery (67% vs. 60%, P=0.002) than patients receiving postoperative chemotherapy
• The NSABP B-27 trial:
  • Evaluated the addition of docetaxel (T) either preoperatively or postoperatively to preoperative AC chemotherapy
  • These results showed that the addition of T:
    • Did not significantly impact DFS or OS, but when given preoperatively:
      • Significantly increased the number of patients who achieved a pathologic complete response (pCR):
        • 26% v 13%, p<0.0001
    • In both studies, patients who achieved a pCR had significantly improved DFS and OS compared to those who did not (P=0.0001)
• References
  • Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483- 2493.
  • Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001(30):96-102.
  • Bear HD, Anderson S, Smith RE, Geyer CE, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24(13):2019-2027.
  • Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27 J Clin Oncol. 2008;26(5):778-785.

#Arrangoiz #BreastSurgeon #BreastCancer #SurgicalOncology #NSABPB18 #NSABPB27 #Miami #Mexico

• The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis:
  • Found that for patients undergoing breast-conserving surgery for node-negative breast cancer:
    • Radiation reduced the risk of any recurrence:
      • 16% vs. 31%
    • Radiation reduced breast cancer mortality:
      • 17% vs. 21%
• The EBCTCG:
  • Also found that for patients undergoing mastectomy with 1 to 3 nodes positive:
    • Radiotherapy was associated with:
      • A reduction in local-regional recurrence (LRR):
        • 4% vs. 20%
      • A reduction in breast cancer mortality:
        • 42% vs. 50%
  • Many practitioners interpreted these findings to mean that all postmastectomy patients with 1 to 3 positive nodes should have postmastectomy radiation therapy (PMRT):
    • However, the patients enrolled in those trials were enrolled between 1964 and 1986, and many of them did not receive systemic therapy
  • A retrospective study of patients with 1 to 3 positive nodes compared the risk of LRR between the two different eras, before and after the routine use of sentinel node biopsy, taxane therapy, and aromatase inhibitors:
    • Use of PMRT reduced the 15-year rate of LRR in the first era:
      • From 14.5% to 6.1%
    • PMRT did not appear to benefit patients treated in the second era:
      • With 5-year LRR rates of 2.8% without PMRT, and 4.2% with PMRT
  • In view of the fact that PMRT significantly increased overall mortality in node-negative patients in the EBCTCG:
    • 47.6% vs, 41.6%; rate ratio 1.23:
      • Caution should be taken in extrapolating the results to all patients with 1 to 3 positive nodes in the modern era
• The consensus statement regarding the role of PMRT in women with 1 to 3 positive lymph nodes:
  • ASCO / ASRTO / SSO unanimously agreed that PMRT in this subset of patients reduces local-regional failure, any recurrence, and breast cancer mortality:
    • In patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes in the setting of multidisciplinary care
    • In some subsets of patients, the risk of local-regional failure may be so low that the absolute benefit of PMRT is outweighed by its toxicities, even if axillary lymph node dissection is omitted in the setting of a positive lymph node
• When given, PMRT should include the internal mammary, supraclavicular, and apical axillary nodes and the chest wall or reconstructed breast
• All patients with a positive axillary node after receipt of neoadjuvant chemotherapy:
  • Should receive PMRT
• Following mastectomy, patients with DCIS generally do not require radiotherapy:
  • Childs et al. showed infrequent chest wall recurrences:
    • Crude rates of chest wall recurrence was 1.4% for all patients, even though 15% had positive margins, and 16% had close margins (less than 2 mm) in the analysis
      • Crude rate of chest wall recurrence for patients with positive margins and close margins was 4.8% and 4.3%, respectively
• In the setting of breast-conserving surgery, observation after lumpectomy for DCIS may be appropriate in select settings:
  • There is a higher risk of ipsilateral breast event without breast RT:
    • As RT decreases the recurrence by roughly 50%
  • RTOG 9804:
    • Is a prospective randomized trial consisting of women with mammographically detected “good risk” DCIS with low- or intermediate-grade DCIS, less than 2.5 cm with margins greater than 3mm
    • They were randomized to RT versus observation after surgery
    • With median followup at 7 years:
      • The local failure rate was 1% in the RT arm versus 7% in the observation arm suggesting a subset of patients with a small volume of DCIS could be observed given the low failure rates
• Currently, three prospective randomized clinical trials in the US and UK are evaluating the safety of omitting radiation in highly selected DCIS patients
• References
  • Early Breast Cancer Trialists’ Collaborative Group, McGale P, Taylor C, Correa C. Effect of radiotherapy after mastectomy on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935):2127-2135.
  • McBride A, Allen P, Woodward W, et al. Locoregional recurrence risk for patients with T1,2 breast cancer with 1-3 positive lymph nodes treated with mastectomy and systemic treatment. Int J Radiat Oncol Biol Phys. 2014;89(2):392-398.
  • Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Ann Surg Oncol. 2017; 24(1):38-51.
  • Childs SK, Chen YH, Duggan MM, et al. Impact of margin status on local recurrence after mastectomy for ductal carcinoma in situ. Int J Radiat Oncol Biol Phys.2013;85(4):948-952.
  • McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33(7):709-715.

Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon / endocrine surgeon / surgical oncologist and is a member of Mount Siani Medical Center in Miami Beach, Florida :

• He is an expert in the management thyroid disease and thyroid cancer

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedicalCenter #Miami #ThyroidNodule #ToxicNodularGoiter #TNG #MultinodularGoiter #Hypothyroidism #Goiter

• Excluding thyroidectomy and radioactive iodine (131I) ablation:

  • The most common causes of hypothyroidism in the adult are:

    • Hashimoto’s thyroiditis (Chronic Lymphocytic Thyroiditis)

    • The hypothyroid phase of subacute thyroiditis

  • Because the long-term treatment is very different:

    • The clinicians must distinguish between these conditions.

• The common causes of low circulating thyroid hormone levels are:

  • Primary hypothyroidism  (thyroid failure with elevated TSH):Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis)
    • Hypothyroid phase of painful subacute thyroiditis:Pseudo-granulomatous–De Quervain’s thyroiditis
    • Hypothyroid phase of painless lymphocytic thyroiditis
    • Hypothyroid phase of postpartum thyroiditis
    • Radioactive iodine ablation
    • Thyroidectomy
    • Head and neck radiation
    • Drugs:Lithium
      • Amiodarone
      • Interleukin
      • Interferon
      • Propylthiouracil / methimazole
      • Iodine excess in patients with thyroiditis
    • Iodine deficiency (uncommon in the United States)
    • Biosynthetic defects (rare and presents in childhood)
    • Congenital hypothyroidism (rare and presents in childhood)
  • Secondary (hypothyroidism with low or inappropriately normal TSH):Pituitary dysfunction:Pituitary damage from tumor, surgery, and / or radiation
  • Tertiary:Hypothalamic damage from:Tumor and / or radiation

Management

Euthyroid patients with positive thyroid antibody titers can typically be

monitored without the institution of thyroid hormone replacement

therapy.26 However, there are some data that pregnant patients with

positive thyroid antibody titers may have improved pregnancy out-

comes and reduced complications with the institution of LT4 replace-

ment therapy. In non-pregnant patients with hypothyroidism, there are

standard recommendations for treatment and monitoring.27 This usu-

ally consist of LT4 therapy and TSH and FT4 monitoring every 6 weeks

with adjustments in LT4 dosing until the TSH is within the goal range

(typically 1 to 3 uIU/mL) although a higher target range is considered

acceptable in the elder

#HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedicalCenter #Miami #ThyroidNodule #ToxicNodularGoiter #TNG #MultinodularGoiter #Hypothyroidism #Thyroiditis #Goiter

• Lymph node involvement in PTC:
  • The incidence of nodal metastases in adults depends upon the extent of surgery:
    • Among patients who undergo a modified radical neck dissection:
      • Up to 80% have lymph node metastases:
        • Half of which are microscopic
    • Among patients with papillary micro-carcinomas who have prophylactic central node dissection:
      • Microscopic metastases have been reported in 37% to 64%
  • At diagnosis, clinically detectable regional lymph node metastases:
    • Are more common in children (approximately 50%) than adults (30% to 40%)
• Invasion of either the thyroid capsule or a lymph node capsule into surrounding soft tissue:
  • Has been reported in 5% to 35% of surgical specimens
• Vascular invasion is seen in only:
  • Approximately 5% to 10%
• Distant metastases:
  • From 2% to 10% of patients have metastases beyond the neck at the time of diagnosis:
    • Among such patients:
      • Two-thirds have pulmonary
      • One-fourth have skeletal metastases
      • Rarer sites of metastasis are:
        • The brain, kidneys, liver, and adrenals
• Growth pattern:
  • The growth pattern and biologic behavior of papillary thyroid cancers are variable:
    • At one end of the spectrum is the common:
      • Micro-carcinoma (formerly called occult papillary thyroid cancer):
        • Defined as a tumor equal or less than 1 cm in diameter
        • These micro-carcinomas are found in 15% to 30% of thyroid glands at autopsy
        • This high frequency, coupled with the rarity of clinically detected papillary cancer:
          • Suggests that the presence of a single focus of micro-carcinoma in a thyroidectomy specimen is likely to be an incidental finding of no clinical importance
    • At the other end of the spectrum is a large, locally invasive cancer with distant metastases noted at the time of diagnosis:
      • These tumors are also far more likely than micro-carcinoma to metastasize through intra-thyroidal lymphatic channels and form multifocal tumors or involve regional lymph nodes
• References:
  • The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. AU Randolph GW, Duh QY, Heller KS, Livolsi VA, Mandel SJ, Steward DL, Tufano RP, Tuttle For The American Thyroid Association Surgical Affairs Committee’s Taskforce On Thyroid Cancer Nodal Surgery RM SO Thyroid. 2012;22(11):1144

• Management of euthyroid patients with positive thyroid antibody titers:
  • Can typically be monitored without the institution of thyroid hormone replacement therapy:
    • However, there are some data that pregnant patients with positive thyroid antibody titers may have improved pregnancy outcomes and reduced complications with the institution of LT4 replacement therapy
• In non-pregnant patients with hypothyroidism:
  • There are standard recommendations for treatment and monitoring:
    • This usually consist of LT4 therapy and TSH and FT4 monitoring every 6 weeks with adjustments in LT4 dosing until the TSH is within the goal range (typically 1 to 3 uIU/mL) although a higher target range is considered
      acceptable in the elderly patients

• Stavros has proposed the following BIRADS categories for breast ultrasound (see Table)

• The American College of Radiology classification:
  • Subdivides category 4 into:
    • BIRADS 4a:
      • Which has a 2% to 10 % risk of malignancy
    • BIRADS 4b:
      • Which has a 10% to 50 % risk of malignancy
    • BIRADS 4c:
      • Which has a 50% to 95% risk malignancy
  • BIRADS 5:
    • Has 95% or greater chance of malignancy
• In evaluating a solid sonographic nodule:
  • One should first look for any of the 10 signs of malignancy, and if even 1 of them is present:
    • The lesion cannot be considered BIRADS 3
  • The signs of malignancy are:
    • Shadowing
    • Hypoechoic echotexture
    • Spiculation
    • Angular margins
    • Thick echogenic halo
    • Microlobulation
    • Taller than wide
    • Duct extension
    • Branching pattern
    • Calcifications
• Note that Stavros compares the echogenicity of lesions to that of breast fat, not breast parenchyma:
  • Therefore, a lesion with hypoechoic echotexture would be very hypoechoic if breast parenchyma is used as the reference

• The hypoechoic lesion in the image does not have smooth margins but appears microlobulated
• Regardless of whether the classification of Stavros or the American College of Radiology is used:
  • The risk of the lesion in this patient is not low enough to be considered BIRADS 3 nor high enough risk to warrant BIRADS 5:
    • Thus, it falls somewhere in the BIRADS 4 range:
      • Biopsy is required
• References:
  • D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA. ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. 5^th ed. Reston, VA: American College of Radiology; 2013
  • Jales RM, Sarian LO, Torresan R, Marussi EF, Alvares BR, Derchain S. Simple rules for ultrasonographic subcategorization of BI-RADS®-US 4 breast masses. Eur J Radiol. 2013;82(8):1231-1235.
  • Stavros AT. Breast Ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.

• Toboggans technique for retrosternal goitre a valuable technique to protect RLN:
  • The surgery of retrosternal goiter is at increased risk for iatrogenic recurrent laryngeal nerve lesion
• Charles Proye:Described a surgical technique to avoid this lesion
• To have a better exposition, resection of the prethyroid muscles can be considered:Particularly if it is a voluminous and / or recurrent goiter. 
• The approach starts with:The thyroid isthmus liberation that is dissected free from the anterior part of the trachea and transected
• Then:The middle thyroid vein is divided and the superior pole vessels are divided
• The superior pole is then mobilized laterally:And the recurrent laryngeal nerve is searched for at its entry point into the larynx
• The nerve function can be verified by the neuromonitoring:Which also helps to find it in this vessel-rich area
• The dissection continues between the nerve and the posterior part of the thyroid:Progressively from top to bottom:Descending as on a toboggan
• After the recurrent nerve dissection:The goiter can usually be extracted without difficulty:Dividing the last vessels holding the goiter inside

https://www.liebertpub.com/doi/full/10.1089/ve.2014.0009

Rodrigo Arrangoiz MS, MD, FACS

Surgical Training:

• General Surgery
• Michigan State University:
• 2005 to 2010• Complex Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:
• Fox Chase Cancer Center (Filadelfia):
• 2010 to 2012• Masters in Science (Clinical research for health care professionals):
• Drexel University (Filadelfia):
• 2010 to 2012• Head and Neck Surgery and Oncology
• IFHNOS / Memorial Sloan Kettering Cancer Center:
• 2014 to 2016

• Patients with HT:
  • May present in a:
    • Euthyroid state:
      • With normal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels
    • Subclinical hypothyroidism:
      • With mild TSH elevations (5 to 10 uIU/
        mL), and a paucity of symptoms
    • Significant / overt hypothyroidism:
      • With TSH > 10 uIU/mL
• Although a goiter may be noted during a
  physical examination:
  • Thyroid morphology associated with HT varies widely and ranges from:
    • Atrophic, barely palpable glands to slightly
      enlarged glands to very large goiters
• The gland texture:
  • May be smooth as in“simple” goiters or contain numerous nodules as seen with multinodular goiters
• Although the euthyroid state may persist
  for many years:
  • About 4% to 5% of initially euthyroid patients with HT will develop hypothyroidism each year:
    • The rate of progression is somewhat dependent on the intensity of the inflammatory reaction and the concomitant rate of induced thyroid follicle destruction
• HT is usually not associated with any neck discomfort:
  • But there are instances where individuals will present with anterior neck pain or tenderness:
    • So HT should be considered in the differential diagnosis of patients with neck discomfort
• Episodes of more acute thyroiditis:
  • With the development of transient thyrotoxicosis have been reported
    and been referred to as Hashitoxicosis
• Changes from HT noted by thyroid ultrasound, such as:
  • Heterogeneous parenchyma:
    • May become evident before the ability to measure thyroid antibody titers in the patient’s serum
• Although thyroid nodules certainly can be present in the context of HT:
  • Focal inflammatory changes due to HT may give the false impression of thyroid nodules:
    • The term pseudonodule refers to instances where there is the appearance of a thyroid nodule in at least one ultrasound view, but it cannot be reproduced on the additional complementary views:
      • Such lesions may not be evident upon future imaging at a later point in time
    • Therefore in patients with HT, the possibility of a pseudonodule should be considered before proceeding with FNA sampling
• Thyroid enlargement associated with HT:
  • May regress with LT4 therapy:
    • Particularly if TSH elevation is present at the time of diagnosis:
      • However, some goiters associated with HT will persist or even grow whether or not LT4 suppression is used:
        • If such patients exhibit progressive goiter growth or develop compressive type symptoms thyroidectomy may need to be considered
  • If the goiter is large and especially if
    tracheal deviation or substernal extension is present:
    • Then preoperative imaging with computed tomography (CT) of the neck is warranted to
      better define the anatomy and help plan the surgical approach
• Histopathology is typically notable for:
  • Prominent lymphocytic infiltration, foci of lymphoid germinal centers, and follicle destruction.
• Controversy exists if HT patients have an increased risk for thyroid cancer and, if so, whether or not HT is associated with a more aggressive disease pattern

• The recommended workup and staging of DCIS includes:
  • History and physical examination
  • Bilateral diagnostic mammography
  • Pathology review
  • Determination of tumor estrogen receptor (ER) status
  • MRI as indicated is special situations
• For pathology reporting:
  • The NCCN panel endorses the College of American Pathologists Protocol:
    • For both invasive and noninvasive carcinomas of the breast
• The NCCN panel recommends testing for ER status:
  • In order to determine the benefit of adjuvant endocrine therapy or risk reduction
• Although the tumor HER2 status is of prognostic significance in invasive cancer, its importance in DCIS has not been elucidated:
  • To date, studies have either found unclear or weak evidence of HER2 status as a prognostic indicator in DCIS
  • The NCCN Panel has concluded that knowing the HER2 status of DCIS does not alter the management strategy and is not required DCIS
• The role of MRI in management of DCIS remains unclear:
  • MRI has been prospectively shown to have a sensitivity of up to 98% for high-grade DCIS
  • In a prospective, observational study of 193 women with pure DCIS who underwent both mammography and MRI imaging preoperatively:
    • 93 (56%) women were diagnosed by mammography and 153 (92%) were diagnosed by MRI (P < .0001)
    • Of the 89 women with high-grade DCIS:
      • 43 (48%) who were not diagnosed by mammography:
        • Were diagnosed by MRI alone
  • However, other studies suggest that MRI can overestimate the extent of disease:
    • Therefore, surgical decisions should not be not be solely based on MRI results especially when mastectomy is being contemplated
  • If MRI findings suggest more extensive disease than is seen on mammography such that a markedly larger resection is required for complete excision:
    • The findings should be verified histologically through MRI-guided biopsy of the more extensive enhancement
  • Studies have also been performed to determine whether the use of MRI reduces re-excision rates and decreases local recurrence in women with DCIS:
    • No reduction in re-excision rates was seen in women undergoing lumpectomy following MRI compared with those who did not undergo preoperative MRI
  • The NCCN Panel recommends only performing breast MRI for DCIS in select circumstances where additional information is warranted during the initial workup, noting that the use of MRI has not been shown to increase likelihood of negative margins or decrease conversion to mastectomy for DCIS
• Primary Treatment for DCIS:
  • The goal of primary therapy for DCIS:
    • Is to prevent progression to invasive breast carcinoma
  • Management strategies for DCIS treatment include:
    • Surgery:
      • Mastectomy or lumpectomy
    • Radiation therapy
    • Adjuvant endocrine therapy:
      • To reduce risk of recurrence
  • Surgery:
    • Excision of DCIS using a breast-conserving approach (lumpectomy) with or without whole breast radiation therapy (WBRT) or alternatively, mastectomy:
      • Are the primary treatment options for individuals with DCIS:
        • The choice of local treatment does not impact overall disease-related survival:
          • Therefore, the individual patient’s acceptance of the potential for an increased risk of local recurrence must be considered
• Post-excision mammography:
  • Is valuable in confirming that an adequate excision of DCIS has been performed particularly for DCIS patients who initially present with microcalcifications
• Mastectomy:
  • Patients with DCIS and evidence of widespread disease (ie, disease involving two or more quadrants) on diagnostic mammography or other imaging, physical examination, or biopsy:
    • May require mastectomy
• Mastectomy permanently alters the lymphatic drainage pattern to the axilla:
  • So that future performance of a sentinel lymph node biopsy (SLNB) is not technically feasible
    • Therefore, for DCIS patients who intend on treatment with mastectomy, or alternatively, for local excision in an anatomic location that could compromise the lymphatic drainage pattern to the axilla (eg, tail of the breast):
      • A SLNB procedure should strongly be considered at the time of definitive surgery to avoid necessitating a full axillary lymph node dissection for evaluation of the axilla
• Complete axillary lymph node dissection (ALND):
  • Is not recommended unless there is pathologically documented invasive cancer or axillary lymph node metastatic disease in patients (by either biopsy or SNLB)
  • However, a small proportion of women (about 25%) with seemingly pure DCIS on initial biopsy:
    • Will have invasive breast cancer at the time of the definitive surgical procedure and thus will ultimately require ALN staging
• Lumpectomy plus Whole Breast Radiation Therapy (WBRT):
  • Breast conserving therapy (BCT) includes lumpectomy to remove the tumor with negative surgical margins followed by WBRT to eradicate any residual microscopic disease
  • Several prospective randomized trials of pure DCIS have shown that the addition of WBRT after lumpectomy:
    • Decreases the rate of in-breast disease recurrence, or distant metastasis-free survival
  • In the long term follow-up of the RTOG 9804 trial, at 7 years:
    • The local recurrence rate was:
      • 0.9% (95% CI, 0.0%–2.2%) in the radiation therapy arm versus 6.7% (95% CI, 3.2%–9.6%) in the observation arm (HR, 0.11; 95% CI, 0.03– 0.47; P < .001)
    • In the subset of patients with good-risk disease features:
      • The local recurrence rate was low with observation but was decreased significantly with the addition of radiation therapy
    • A meta-analysis of four large multicenter randomized trials:
      • Confirms the results of the individual trials, demonstrating that the addition of WBRT after lumpectomy for DCIS:
        • Provides a statistically and clinically significant reduction in ipsilateral breast events (HR [hazard ratio], 0.49; 95% CI; 0.41–0.58, P < .00001)
        • However, these trials did not show that the addition of RT has an overall survival benefit
    • The long-term follow-up of the NSABP B-17 showed that at 15 years:
      • Radiation therapy resulted in a 52% reduction of ipsilateral invasive recurrence compared with excision alone (HR, 0.48; 95% CI, 0.33–0.69, P < .001)
      • However, overall survival (OS) and cumulative all-cause mortality rates through 15 years were similar between the two groups (HR for death, 1.08; 95% CI, 0.79–1.48)
    • Similar findings were reported by a large observational study of the SEER database that included 108,196 patients with DCIS:
      • In a subgroup analysis at 10 years, of 60,000 women treated with breast-conserving therapy, with or without radiation therapy:
        • Radiation therapy was associated with a 50% reduction in the risk of ipsilateral recurrence (adjusted HR, 0.47 [95% CI, 0.42–0.53]; P < .001), however, breast cancer-specific mortality was found to be similar (HR, 0.86 [95% CI, 0.67–1.10]; P = .22)
  • More recently, in a population-based study, the use of WBRT in patients with higher-risk DCIS:
    • Higher nuclear grade, younger age, and larger tumor size:
      • Was demonstrated to be associated with a:
        • Modest, but statistically significant improvement in survival
• RT Boost:
  • The use of RT boost has been demonstrated to provide a small but statistically significant reduction in IBTR risk (4% at 20 years):
    • In all age groups for invasive breast cancer
  • Recently, a pooled analysis of patient-level data from ten academic institutions evaluated outcomes of pure DCIS patients:
    • All treated with lumpectomy and WBRT (n = 4131) who either received RT boost with a median dose of 14 Gy (n = 2661) or received no boost (n = 1470):
      • The median follow-up of patients was nine years
        • A decrease in IBTR was seen in patients who received boost compared with those who did not at:
          • 5 years (97.1% vs 96.3%)
          • 10 years (94.1% vs 92.5%)
          • 15 years (91.6% vs 88.0%)
            • P = .0389 for all
      • The use of RT boost was associated with significantly decreased IBTR across the entire cohort of patients (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01)
      • In a multivariate analysis that took into account factors associated with lower IBTR, including grade, ER positive status, use of adjuvant tamoxifen, margin status, and age:
        • The benefit of RT boost still remained statistically significant (hazard ratio, 0.69; 95% confidence interval [CI], 0.53 – 0.91; P < .010)
        • Even in patients considered very low risk based on negative margins status (defined as no ink on tumor as per National Surgical Adjuvant Breast and Bowel Project definition, or margins 10 mm or no tumor on re-excision in 48 % of patients)
        • Although the rate of IBTR were acceptably low for the low-/intermediate grade group at the 5 years, at a median follow-up time of 12.3 years, the rates of developing an IBTR were 14.4% for low/intermediate-grade and 24.6% for high grade DCIS (P = .003)
        • This suggests that IBTR events may be delayed but not prevented in the seemingly low-risk population
        • Therefore, the NCCN panel concluded that for DCIS patients treated with lumpectomy alone (without radiation), irrespective of margin width:
          • The risk of IBTR is substantially higher than treatment with excision followed by whole breast radiation therapy (even for predefined low-risk subsets of DCIS patients)

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #DCIS #BreastCancer #CASO #Miami #CenterforAdvancedSurgicalOncology