Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Isolated recurrent axillary disease:
  • Is an uncommon presentation of recurrence:
    • The incidence remains rare at:
      • 1% to 2%
• It is important to stage patients with locoregional recurrences:
  • As approximately one-third will present with:
    • Synchronous distant metastasis
  • If the staging workup is negative:
    • A complete axillary dissection should be performed if possible:
      • If surgical resection is not possible:
        • Systemic therapy should be offered:
          • To potentially allow surgical resection
    • Radiation should be performed if feasible for recurrences as well:
      • Depending on the prior extent of radiation delivered
• In addition, complete breast imaging should be performed:
  • To ensure there is no in-breast recurrence as well
• The use of systemic therapy should be offered after a multidisciplinary discussion:
  • Considering:
    • Tumor phenotype and prior therapies already received by the patient
• Wapnir et al:
  • Demonstrated in the CALOR trial:
    • That in ER negative isolated recurrences:
      • Systemic chemotherapy improved disease-free survival:
        • However, in ER positive recurrences:
          • Endocrine therapy should be the preferred therapy
• References
• Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016;264:(3):413-420.
• Neuman HB, Schumacher JR, Francescatti AB, et al. Risk of synchronous distant recurrence at time of locoregional recurrence in patients with stage II and III breast cancer (AFT-01). J Clin Oncol. 2018;36(10):975-980.
• National Comprehensive Cancer Network (NCCN) Breast CancerOnline: https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed September 15, 2020
• Wapnir IR, Price KN, Anderson SJ, et al. Efficacy of chemotherapy for ER-negative and ER-positive isolated locoregional recurrence of breast cancer. Final analysis of the CALOR Trial. N Engl J Med. 2018;36(11):1073-1079.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Mexico #Miami #MountSinaiMedicalCenter #MSMC #IsolatedAxillaryRecurrence

• Qiang JK, Sutradhar R, Everett K, et al. Association between serum thyrotropin and cancer recurrence in differentiated thyroid cancer: a population-based retrospective cohort study. Thyroid. Epub 2024 Dec 26; doi: 10.1089/thy.2024.0330. PMID: 39723994.
• Background:
  • In addition to surgery (thyroidectomy with or without lymphadenectomy) and radioactive iodine treatment (RAIT), patients with differentiated thyroid cancer (DTC) may benefit from thyroid hormone therapy that suppresses TSH to reduce the risk of recurrence
  • The 2015 American Thyroid Association (ATA) guidelines recommend:
    • Maintaining TSH levels below 0.1 mU/L in patients with high-risk DTC:
      • As this has been shown to improve survival in these patients
  • The level of TSH suppression should be adjusted based on:
    • Comorbidities and response to treatment
  • However, TSH suppression is not without risks, and has been associated with an increased risk of:
    • Osteoporosis
    • Atrial fibrillation
    • A reduced quality of life
• In patients with low-risk DTC:
  • The ATA guidelines recommend maintaining TSH levels between 0.5 and 2.0 mU/L:
    • As further TSH suppression in these cases increases the risks associated with subclinical hyperthyroidism without affecting cancer recurrence rates
  • The present study aimed to evaluate whether a broadened TSH range up to 4.0 mU/L is equally safe in terms of DTC recurrence as compared with the recommended low-normal TSH goal range (0.5–2.0 mU/L)
• Methods:
  • A retrospective, population-based cohort study was conducted using data from the Ontario Cancer Registry, covering the period from 2007 to 2018
  • Serum TSH values and their measurement dates were obtained from the Ontario Laboratories Information System, which captures nearly all outpatient laboratory tests in Ontario
  • The study included patients ≥ 18 years of age, diagnosed with DTC, and with available follow-up information, including at least one TSH value recorded during follow-up
  • Patients were followed for TSH measurements and DTC recurrence starting from the index date, defined as 12 months after thyroidectomy
  • The primary outcome was the time from the index date to DTC recurrence
  • Recurrence was defined as death due to DTC or the need for additional treatment, including new surgery (thyroidectomy or neck dissection) or RAIT, after the index date
  • TSH was treated as a time-dependent covariate, updated every 90 days if a new TSH measurement was available
  • TSH levels were classified into mutually exclusive categories, with TSH >2 to ≤4 mU/L as the primary exposure and TSH 0.5–2 mU/L as the reference category
  • Secondary exposures included TSH <0.5 mU/L and TSH >4 mU/L
• Results:
  • A total of 26,336 patients were included; 21% underwent hemi-thyroidectomy, 41% total thyroidectomy, and 38% total thyroidectomy combined with RAIT
  • The median follow-up was 5.9 years (interquartile range [IQR], 3.6–8.6) from the index date and the median TSH was 0.6 mU/L (IQR, 0.1–1.8)
  • During the follow-up period, there were 2,817 cases of DTC recurrence (10% of the cohort), including 103 DTC-specific deaths (0.3%)
  • No significant increase in recurrence risk was observed with each additional 3 months of cumulative exposure to TSH levels between 2 and 4 mU/L as compared with 0.5–2 mU/L (hazard ratio [HR] 0.99, confidence interval [CI], 0.97–1.02; P = 0.55):
    • However, a significantly higher risk of DTC recurrence was associated with each additional 3 months of cumulative exposure to TSH levels > 4 mU/L as compared with 0.5–2 mU/L (HR, 1.07; CI, 1.04–1.09; P<0.01)
  • The risk of composite recurrence increased in a dose-dependent manner with longer exposure to TSH >4 mU/L:
    • For instance, after 4 years of cumulative exposure to TSH > 4 mU/L:
      • The adjusted HR was 2.86 (CI, 1.88–4.08)
  • These findings were consistent when analyses were stratified by baseline treatment and when the index date was adjusted from 12 to 18 months
• Conclusions:
  • Patients with low-risk DTC may safely maintain TSH levels within the higher normal range without increasing the risk of thyroid tumor recurrence:
    • Accordingly, serum TSH targets could be broadened to 0.5 to 4 mU/L in patients with low-risk DTC
• Summary:
  • This large, population-based cohort study provides evidence that maintaining TSH levels between 2 and 4 mU/L in low-risk DTC patients results in recurrence rates similar to those of the 0.5–2 mU/L range recommended by the 2015 ATA guidelines
  • Although earlier observational studies proposed a threshold of 2 mU/L as optimal for differentiating recurrence-free survival from thyroid carcinoma–related deaths and recurrences, confirmatory large-scale studies have been lacking
  • As such, guidelines were based largely on low-quality evidence
  • The potential for broadening TSH target ranges also carries significant health care implications:
    • Managing thyroid cancer in the United States is projected to cost over $3.5 billion by 2030
  • Relaxing TSH targets could reduce health care costs by decreasing the frequency of blood tests and lessening the need for intensive monitoring
  • From a clinical standpoint, a less stringent TSH range could improve patient compliance
  • Fewer blood tests would not only reduce stress but could also enhance quality of life
  • A more uniform dosing regimen, without the need for frequent adjustments to maintain a strict TSH target, could simplify treatment and make it more manageable for patients
  • A broader TSH range is particularly beneficial for frailer patients, particularly those with comorbidities like atrial fibrillation or osteoporosis, since it may reduce the risk of inadvertently causing subclinical hyperthyroidism
  • On the other hand, TSH should not exceed 4 mU/L
  • In this study, a TSH > 4 mU/L was associated with a higher risk of DTC recurrence, and previous studies also linked TSH > 4 mU/L to increased risks of cardiovascular disease, dysrhythmias, and fractures as compared with patients whose TSH levels are within the reference range
  • Despite its findings, this study has some limitations
  • It does not provide detailed pathological data, which hampers our ability to precisely assess the ATA risk classification of these tumors
  • Additionally, recurrences were recorded only if they required treatment, meaning that some recurrences may not have been captured
  • This highlights the need for further comprehensive studies, especially with longer follow-up periods, to confirm these results
  • This is particularly important in patients who undergo lobectomy, where the optimal TSH target and the decision to start levothyroxine remain areas of ongoing debate
  • In conclusion, this study provides valuable reassurance regarding a broader TSH range of 0.5 to 4 mU/L; however, further research is needed to refine treatment protocols and guide clinical decision-making.
• Key points:
  • In patients with low-risk differentiated thyroid cancer (DTC), TSH levels from 0.5 to 4 mU/L were not associated with an increase in cancer recurrence in a retrospective population-based analysis
  • There was an increased risk of recurrence in patients with low-risk DTC when TSH was > 4 mU/L, whereas maintaining TSH levels within the higher normal range may be safe and does not increase the risk of thyroid tumor recurrence
  • Broadening the serum TSH target to 0.5 to 4 mU/L in patients with low-risk DTC could be considered
• References:
  • McGriff NJ, Csako G, Gourgiotis L, et al. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med. 2002; 34(7-8):554-564.
  • Diessl S, Holzberger B, Mäder U, et al. Impact of moderate vs stringent TSH suppression on survival in advanced differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2012;76(4):586-592.
  • Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133.
    4. Jonklaas J, Sarlis NJ, Litofsky D, et al. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid2006;16(12):1229-1242.

• Isolated recurrent axillary disease:
  • Is an uncommon presentation of recurrence:
    • The incidence remains rare at 1% to 2%
• It is important to stage patients with locoregional recurrences:
  • As approximately one-third:
    • Will present with synchronous distant metastasis
• If the staging workup is negative:
  • A complete axillary dissection should be performed if possible
  • If surgical resection is not possible:
    • Systemic therapy should be offered:
      • To potentially allow surgical resection
  • Radiation should be performed if feasible for recurrences as well:
    • Depending on the prior extent of radiation delivered
• In addition, complete breast imaging:
  • Should be performed to ensure there is no in-breast recurrence as well
• The use of systemic therapy should be offered after a multidisciplinary discussion taking into account tumor phenotype and prior therapies already received by the patient
• Wapnir et al:
  • Demonstrated in the CALOR trial that in ER negative (ER-) isolated recurrences:
    • Systemic chemotherapy improved disease-free survival:
      • However, in ER+ recurrences:
        • Endocrine therapy should be the preferred therapy
• References:
  • Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016;264:(3):413-420.
  • Neuman HB, Schumacher JR, Francescatti AB, et al. Risk of synchronous distant recurrence at time of locoregional recurrence in patients with stage II and III breast cancer (AFT-01). J Clin Oncol. 2018;36(10):975-980.
    3. National Comprehensive Cancer Network (NCCN) Breast CancerOnline: https://www.nccn.org/professionals/physician_gls/recently_updated.aspx. Accessed September 15, 2020
  • Wapnir IR, Price KN, Anderson SJ, et al. Efficacy of chemotherapy for ER-negative and ER-positive isolated locoregional recurrence of breast cancer. Final analysis of the CALOR Trial. N Engl J Med. 2018;36(11):1073-1079.

• Management of pathogenic CHEK2 variants:
  • Should take into account the specific variant identified
• Most of the risk data is based on frameshift variants:
  • Such as 1100delC:
    • With an estimated absolute lifetime breast cancer risk of 20% to 40%
• The risks associated with other types of CHEK2 variants are not as well defined:
  • However, breast cancer risks associated with the specific missense variant Ile157Thr have been studied in more depth
• Data from multiple studies, such as a large case-control study including 10,860 breast cancer patients from The CHEK2 Breast Cancer Case-Control Consortium:
  • Found a significantly increased risk of breast cancer with the 1100delC variant (OR 2.34; 95% CI 1.72-3.20; p=0.0000001)
• Another similar study including 44,777 breast cancer patients:
  • Also demonstrated a significantly increased risk for breast cancer with the 1100delC variant (OR 2.26; 95% CI 1.90-2.69; p=2.3×10-20)
• Unlike the 1100delC variant:
  • The Ile157Thr variant has been associated with a more modest elevation in risk for breast cancer
  • A meta-analysis of case-control studies, including 26,336 cases and 44,219 controls, demonstrated an association of the Ile157Thr variant with breast cancer (OR=1.58; 95% CI 1.42-1.75; p<0.000001)
• Current National Comprehensive Cancer Network guidelines regarding frameshift CHEK2 variants:
  • Recommend beginning annual mammograms at 40 years old
  • Considering breast MRI starting at 30 to 35 years old
  • Evidence is inadequate to recommend risk reducing mastectomy (RRM)
  • On the other hand, supplementary breast cancer risk management for patients with the missense variant Ile157Thr is not suggested:
    • However, management should still be personalized based on family history, for instance:
      • Beginning breast imaging 5 to 10 years earlier than the youngest family member diagnosed with breast cancer
• References:
  • National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Accessed January 1, 2024. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
  • CHEK2 Breast Cancer Case-Control Consortium. CHEK2*1100delC and susceptibility to breast cancer: A collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004;74(6):1175-1182. doi:10.1086/421251
  • Schmidt MK, Hogervorst F, van Hien R, et al. Age- and tumor subtype-specific breast cancer risk estimates for CHEK2*1100delC carriers. J Clin Oncol. 2016;34(23):2750-2760. doi:10.1200/JCO.2016.66.5844
  • Han FF, Guo CL, Liu LH. The effect of CHEK2 variant I157T on cancer susceptibility: Evidence from a meta-analysis. DNA Cell Biol. 2013;32(6):329-335. doi:10.1089/dna.2013.1970

• Subacute thyroiditis (like painless sporadic thyroiditis and postpartum thyroiditis):
  • Is a spontaneous remitting inflammatory disorder of the thyroid:
  • That may last for weeks to months (has a more sudden onset)
• This disorder has a number of eponyms, including:
  • De Quervain’s thyroiditis
  • Giant cell thyroiditis
    
  • Pseudo-granulomatous thyroiditis
    
  • Subacute painful thyroiditis
    
  • Subacute granulomatous thyroiditis
    
  • Acute simple thyroiditis
    
  • Noninfectious thyroiditis
    
  • Acute diffuse thyroiditis
    
  • Migratory “creeping” thyroiditis
    
  • Pseudotuberculous thyroiditis
    
  • Viral thyroiditis
    
• The first description of subacute thyroiditis was in:
  • 1895 by Mygind:
    • Who reported 18 cases of “thyroiditis akuta simplex
      
• The pathology of subacute thyroiditis was first described:
  • In 1904 by Fritz De Quervain:
    • Whose name is associated with the disorder:
      • He showed giant cells and granulomatous type changes in the thyroids of affected patients
• Subacute thyroiditis:
  • Is the most common cause of:
    • The painful thyroid:
      • May account for up to 5% of clinical thyroid abnormalities
• As with other thyroid disorders:
  • Women are more frequently affected than men:
    • 5 to 1 (Hashimoto’s Thyroiditis is 8 to 9 / 1)
• The peak incidence is in the:
  • Fourth and fifth decades of life (20 to 60 years of age):
    • This disorder is rarely observed in children and the elderly
• Although the term subacute thyroiditis connotes a temporal quality that could apply to any thyroidal inflammatory process of intermediate duration and severity:
  • It is actually referring specifically to the granulomatous appearance of the thyroid found on pathologic exam
• Pathogenesis:
  • Infectious Association:
    • Although there is no clear evidence for a specific etiology:
      • Indirect evidence suggests that subacute thyroiditis:
        • May be caused by a viral infection of the thyroid
    • The condition is often preceded by a:
      • Prodromal phase of:
        • Myalgia General
        • Malaise
        • Low-grade fevers
        • Fatigue
        • Frequently by an upper respiratory tract infection
• It has been reported most frequently in:
  • The temperate zone:
    • Only rarely from other parts of the world
• It has been found to occur seasonally:
  • The highest incidence is in the summer months:
    • July through September:
      • Which coincide with the peak of enterovirus:
        • Echovirus infection
        • Coxsackie virus A and B infection
• The incidence rate has been shown to vary directly with:
  • Viral epidemics:
    • Specifically mumps:
      • The incidence of subacute thyroiditis has been found to be higher during these viral epidemics
    • Interestingly:
      • Antibodies to the mumps virus have even been detected in individuals with subacute thyroiditis who do not have clinical evidence of mumps
    • Subacute thyroiditis has also been associated with:
      • Measles
      • Influenza
      • The common cold
      • Adenovirus
      • Infectious mononucleosis
      • Coxsackie virus
      • Myocarditis
      • Cat scratch fever
      • St. Louis encephalitis
      • Hepatitis A
      • The parvovirus B19 infection
        
    • Antibodies to Coxsackie virus, adenovirus, influenza, and mumps have been detected in the:
      • Convalescent phase of this disease
    • Coxsackie virus is most commonly:
      • Associated with subacute thyroiditis
    • Coxsackie virus antibody titers:
      • Have been shown to directly follow the course of the thyroid disease
  • Certain non-viral infections, including:
    • Q fever and malaria:
      • Have been associated with a clinical syndrome similar to subacute thyroiditis
        
    • A case of subacute thyroiditis occurring simultaneously with:
      • Giant cell arteritis has been reported
        
    • Another case of subacute thyroiditis developed during:
      • Alfa-interferon treatment for hepatitis C
        
• Autoimmune Association:
  • Unlike painless or postpartum thyroiditis:
    • There is no clear association between subacute thyroiditis and autoimmune thyroid disease:
      • Serum thyroid peroxidase and thyroglobulin antibodies levels:
        • Are usually normal
          
      • When decreased the levels of thyroid peroxidase and thyroglobulin antibodies:
        • Correlated with the phase of transient hypothyroidism
          
      • Antibodies to an un-purified thyroid preparation can be detected:
        • For up to 4 years after a bout of subacute thyroiditis
          
      • Antibodies to the thyrotropin (TSH) receptor:
        • Have been rarely detected during the course of subacute thyroiditis
      • In most studies:
        • There was no correlation between the presence of thyrotropin receptor binding inhibitory immunoglobulin (TBII) or of thyrotropin receptor stimulating immunoglobulin and the thyrotoxic phase of the thyroiditis
      • On the other hand, there has been some correlation between thyroid-blocking antibodies and the development of hypothyroidism
      • It is thought that the appearance of the TSH-receptor antibodies results from an immune response:
        • That occurs after there is damage to the thyrocytes, specifically membrane desquamation
          
• Following recovery from the inflammatory process of subacute thyroiditis:
  • All immunologic phenomena disappear:
    • The transitory immunologic markers that are observed during the course of subacute thyroiditis:
      • Appear to occur in response to the release of antigenic material from the thyroid
        
• Genetic Association:
  • There is an apparent genetic predisposition for subacute thyroiditis:
    • With HLA-Bw 35 reported in all ethnic groups:
    • The relative risk of HLA-Bw 35 in subacute thyroiditis:
      • Is high:
        • Ranging from 8 to 56
  • Additional evidence for genetic susceptibility is the:
    • Simultaneous development of subacute thyroiditis in identical twins heterozygous for the HLA-Bw 35 haplotypes
      
    • A weak association of subacute thyroiditis with:
      • HLA-DRw8 has been reported in Japanese patients
        
        #Arrangoiz #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #HeadandNeckSurgeon #ThyroidExpert #SurgicalOncologist #EndocrineSurgery #MountSinaiMedicalCenter #Miami #ThyroidNodule #deQuervain’sthyroiditis #Subacutethyroiditis

• 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