My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
The hallux and thumb are the most commonly affected sites
Antecedent trauma:
Has been reported in 25% to 55% of patients
Diagnosis is often delayed because of:
Inadequate biopsies
Lesion neglect
Confusion with benign melanonychia, hematoma, chronic trauma, or fungal nail infection (onychomycosis)
The classic features suggestive of melanoma include:
Melanotic lesions arising from the nail matrix and longitudinal melanonychia:
Defined as a band of pigmentation extending from the proximal nail fold / lunula throughout the nail to the free edge
Any band greater than 3 mm in width or associated with discoloration of the lateral or proximal nail folds (Hutchinson’s sign):
Mandates biopsy of the nail matrix and bed with either incisional or punch techniques:
Partial or total avulsion of the nail plate is usually needed to perform biopsy
Management of these lesions requires sound oncologic resection with consideration of functional deficits:
Margin principles in melanoma are maintained:
Which means amputation is often necessary
Special consideration is given to the hallux and thumb:
As the complete loss of either can cause substantial disability
For the hallux amputation of the digit preserves the metatarsal head, and for the thumb, efforts are made to preserve bone proximal to the interphalangeal joint, if appropriate margins allow:
Excision of the nail bed, matrix, and proximal nail fold will not provide adequate margins
Mohs micrographic surgery has been used in several small series for selected cases of melanoma-in-situ only, and this technique would not provide adequate resection of this melanoma deeper melanomas
Amputation of the thumb just proximal to the interphalangeal joint is the best approach:
As it provides for adequate margins while preserving a stump for some functional use. Radical amputation would also provide adequate margins, but the functional deficit created is unnecessary
References:
Ross MI. Excision of primary melanoma. In: Balch CM, Houghton AN, Sober AJ, Soong S-J, eds. Cutaneous Melanoma. 5th ed. St. Louis: Quality Medical Publishing; 2009:251-274.
Sureda N, Phan A, Poulalhon N, Balme B, Dalle S, Thomas L. Conservative surgical management of subungal (matrix derived) melanoma: report of seven cases and literature review. Br J Dermatol. 2011;165:852-858.
Tan KB, Moncrieff M, Thompson JF, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-1912.
The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) MA.20 trial:
Randomized 1,832 high-risk women:
Who were treated with breast-conserving surgery and sentinel node biopsy (SLNB) or axillary lymph node dissection (ALND):
To either WBI alone or WBI plus regional nodal irradiation (RNI)
Axillary lymph node dissection:
Was required for any patients with a positive SLN
RNI included:
The internal mammary, supraclavicular, and high axillary nodes
The trial enrolled patients with:
Node-positive or high-risk node-negative disease:
85% of patients had 1 to 3 positive nodes
5% had more than 4 positive nodes
10% were node negative
Node-negative patients with tumors greater than or equal to 2 cm who had fewer than 10 axillary nodes removed were considered high risk if they had at least one of the following:
ER negative
Lymphovascular invasion
Nuclear grade 3
All patients had systemic therapy
With a median follow-up of 10 years:
The addition of RNI improved:
Locoregional DFS from:
92.2% to 95.2% (P=0.009)
Distant DFS from:
82.4% to 86.3% (P=0.03)
There was no difference in OS from:
81.8% to 82.8% (P=0.38)
The addition of RNI to WBI was associated with:
An increase in:
Grade 2 or greater pneumonitis from:
0.2% to 1.2% (P=0.01)
Lymphedema from:
4.5% to 8.4% (P=0.001)
Similarly, European Organisation for Research and Treatment of Cancer (EORTC) 22922:
Randomized 4004 women undergoing breast-conserving surgery or mastectomy and ALND for histological stage I, II, or III breast cancer to:
RNI (supraclavicular and internal mammary nodal irradiation) or no regional nodal irradiation
At a median follow-up of 10.9 years:
The addition of regional nodal irradiation improved:
DFS from:
69.1% to 72.1% (P=0.04)
Again, there was a non-significant trend toward improvement in OS from:
80.7% to 82.3% (P=0.06 among the RNI group
The results of NCIC CTG MA.20 have led many to conclude that:
All patients with axillary nodal metastases, regardless of tumor size or extent of nodal involvement:
Should receive comprehensive nodal radiation therapy (RT)
A major conundrum in current practice is resolving the apparently contradictory findings of American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla, Radiation or Surgery? (AMAROS) with those of NCIC CTG MA.20:
The modest benefit in DFS with nodal RT in NCIC CTG MA.20:
May reflect differences in patient populations between the studies:
Patients with clinically positive nodes were excluded from ACOSOG Z0011 and AMAROS (and not MA.20)
In addition, fewer than 10 nodes were removed in one-third of patients in the NCIC CTG MA.20 study and the median node count was 12:
Compared to a median of 17 in the ALND arms of Z0011 and AMAROS:
The benefit of nodal RT therefore may be limited to higher risk patients with more extensive nodal disease and perhaps more limited axillary surgery
References
1. Poortmans PM, Collette S, Kirkove C, Limbergen EV, Budach V, Struikmans H, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;37(4)3:317-327.
2. Pepels MJ, de Boer M, Bult P, van Dijck A, van Deurzen CH, Menke-Pluymers MB, et al. Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells. Ann Surg. 2012;255(1):116-121.
3. Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, et al; MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307-316.
Was designed to determine the false negative rate (FNR) of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in women initially presenting with cN1 disease
The trial enrolled women from 136 institutions who had clinical T0 through T4, N1 through N2, M0 breast cancer who received neoadjuvant chemotherapy
Patients enrolled had pre-chemotherapy axillary nodal disease confirmed by fine-needle aspiration or core needle biopsy
Following NAC, patients underwent both SLNB, followed by a back-up axillary lymph node dissection
SLNB with dual tracer using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged
Rates of detection of at least one SLN were:
92.9% in patients with cN1 disease and 89.5% in patients with cN2 disease
Overall, the FNR of SLNB after NAC was 12.6%
Bivariable analyses found that the likelihood of a false-negative SLN finding was significantly decreased:
When the mapping was performed with the combination of blue dye and radiolabeled colloid (P=.05; FNR, 10.8% combination vs 20.3% single agent) and by removal of at least 3 SLNs (P=.007; FNR, 9.1% for ≥3 SLNs vs 21.1% for 2):
A clip was placed at initial node biopsy prior to NAC in 203 patients:
In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases
In 107 (75.9%) patients where the clipped node was within the SLN specimen;
The FNR was 6.8% (confidence interval [CI]: 1.9%-16.5%)
If the clipped node was found in the ALND specimen:
The FNR was 19.0% (CI: 5.4%-41.9%)
In cases where a clip was not placed (n = 355) and in those where the clipped node location was not confirmed at surgery (n = 29):
The FNR was 13.4% and 14.3%, respectively
While the FNR overall exceeded the 10% threshold considered to be clinically acceptable, the authors concluded that with modifications to the SLN technique (i.e., dual tracer mapping and retrieval of at least 3 negative SLNs):
To the FNR was less than 10% and supported the use of SLN surgery as an alternative to axillary lymph node dissection in this patient population
Subsequently, Caudle et al have reported a separate registry of 191 patients and showed that removing the clipped positive node in addition to SLN had an FNR as low as 2.0%
References
Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al.; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455-1461.
Boughey JC, Ballman KV, Le-Petross HT, McCall LM, Mittendorf EA, Ahrendt GM, et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance). Ann Surg. 2016;263(4):802-807.
Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34(10):1072-1078.
Is the most common complication following inguinal lymphadenectomy
Closed-suction drains:
Are recommended in an attempt to prevent seroma formation
Guidelines do not exist for duration of drainage:
However, most literature suggests keeping drains in place until output decreases to less than 30 cc/day:
Which usually occurs 1 to 2 weeks following surgery
References:
Delman KA, Mansfield PF, Lee JE. Indications and techniques of regional lymphadenectomy. In: Curley SA, Pollock RE, Ross MI, eds. Advanced Therapy in Surgical Oncology. Hamilton, Ontario: BC Decker Inc, 2008:771-782.
Operative Standards for Cancer Surgery: Volume 2. Ch. 10: Neck, Axillary, Ilioinguinal, and Other Lymph Node Dissections.
In 2013 the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO):
Convened a multidisciplinary expert panel to review the available evidence regarding margin width and Ipsilateral breast tumor recurrence (IBTR) in patients with invasive cancer having breast conservation therapy
Meta-analysis and secondary data from prospective and retrospective trials led them to conclude that:
Positive margins (defined as ink on invasive cancer) is associated with:
At least a 2-fold increase in IBTR
Among patients with negative margins:
A margin width of no ink on tumor represent the optimal margin width to minimize the risk of IBTR:
Notably the routine practice of obtaining wider negative margins than no ink on tumor is not indicated
While younger age is associated with both:
Increased IBTR after breast-conserving therapy as well as increased local chest wall relapse after mastectomy:
There is no evidence that increased margin width (over no ink on tumor) nullifies this increased risk of IBTR in younger patients
In 2016, margin guidelines related to the treatment of non-invasive breast cancer (DCIS) in the setting of breast conservation therapy were developed by the SSO, ASTRO, and American Society of Clinical Oncology (ASCO) in a similar manner
A consensus statement released by a multidisciplinary panel included the optimal margins for pure ductal carcinoma in situ (DCIS) and mixed tumors (invasive and non-invasive components within the same tumor) in the setting of breast conservation
Results from the meta-analysis showed that:
A 2 mm margin decreases the risk of IBTR in pure DCIS compared to closer negative margins
This differs from the previous margin recommendation for invasive cancer, which remains no ink on tumor:
However, in the setting of mixed tumors (invasive cancer with a DCIS component) the recommendation for negative margins remains no ink on tumor:
As patients with mixed disease are treated as invasive cancer and therefore receive systemic therapy more often than pure DCIS patients
In the setting of DCIS with micro-invasion (no focus of invasive disease larger than 0.1 cm):
The multidisciplinary panel recommends a 2 mm margin:
As these lesions have similar rates of IBTR as pure DCIS
References
Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88(3):553-564.
Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M. et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. J Clin Oncol. 2016;34(33):4040-4046.
The likelihood of a false-negative SLN finding was significantly decreased – when the mapping was performed:
With the combination of blue dye and radiolabeled colloid:
P=.05; FNR:
10.8% combination vs 20.3% single agent and
By examination of at least 3 SLNs:
P=.007; FNR:
9.1% for ≥3 SLNs vs 21.1% for 2
While the study overall did not meet the predetermined acceptability threshold of:
Post-neoadjuvant SLN biopsy FNR being 10% or less:
The authors concluded that:
Changes in approach and patient selection:
Resulted in a greater sensitivity that would be necessary to support the use of SLN surgery as an alternative to axillary lymph node dissection in this patient population
References:
Boughey JC, Suman VJ, Mittendorf EA, et al; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455-1461.
The Multicenter Selective Lymphadenectomy Trial 2 (MSLT-2) was published in June 2017:
Which evaluated completion lymphadenectomy versus active surveillance (with dissection if disease were identified):
Following positive sentinel lymph node biopsies for metastatic melanoma
It is important to remember this was for clinically-occult nodal disease only
The standard of care for clinically-evident (palpable or radiographic) nodal metastatic melanoma is:
Lymphadenectomy
References:
van Akkooi CJA. Surgical and Anatomic Considerations of Malignancies Affecting the Groin: Consideration for Melanoma. In: Delman K, Master V, eds. Malignancies of the Groin. Cham, Switzerland: Springer, 2018:63-74.
Song Y, Karakousis GC. Melanoma of Unknown Primary. J Surg Oncol. 2019; 119 (2) 232-241.
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).4
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.
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
Rodrigo Arrangoiz MS, MD, FACS, FSSO 