Monday, July 10, 2017

CLND - Complete lymph node dissection in melanoma - the whole shmegegge!!!!!!!!!!!

Pros and cons of whether or not to do a complete lymph node dissection (CLND) are varied.  Here is a post addressing both (with many links within):  Sentinel lymph node disection ~ "important diagnostic procedure and might be of therapeutic benefit re: DFS and OS!"

If you prefer the links following that one in a list - here they are:
Feb 2016:  "Patients with microscopically negative/PCR+ SLN have increased risk for nodal recurrence that was mitigated by CLND"!
Also Feb 2016:  Sunbelt Melanoma Trial Final Results: No survival benefit for interferon or complete lymph node dissection in patients with a single positive SLN!
Still Feb 2016, a little tangential...but addresses effect of positive SLN:  Women and melanoma risk
Post covering several reports from 2014:  With melanoma: You can never be too rich or too thin! But, you can be too young!!!
And this huge study from Faries et al in 2014:  Lymph node removal after superficial melanoma do or not to do???? is absolutely clear (at least to me) that removal of the sentinel node after a melanoma lesion is crucial to staging and treatment if nothing else.  Complete lymph node dissection in the area of that sentinel node is more complicated.

Now there's this:

Timing of completion lymphadenectomy after positive sentinel node biopsy in patients with melanoma. Oude, van Akkooi, Rutowski, et al. Br J Surg. 2017 Feb 20.

Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS).

A retrospective cohort of patients with SNB-positive melanoma from nine European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group centres undergoing surgery between 1993 and 2009 were examined. Patients were selected based on availability of CLND and follow-up data. The CLND interval was defined as the number of days between diagnosis and CLND. Patient and tumour characteristics were collected. Five-year DFS and MSS rates were calculated. Cox and logistic regression analysis were performed, adjusting for known prognostic/predictive indicators.

A total of 784 patients were included in the study. Their median age was 51 years, and 418 patients (53·3%) were men. Median Breslow thickness was 3·0 mm, and 148 patients (18·9%) had a residual tumour load. Median CLND interval was 84 days. Five-year DFS and MSS rates were not significantly different for patients operated on with a median CLND interval of less than 84 days and those with an interval of at least 84 days. In a multivariable Cox model, CLND interval was not a significant prognostic indicator. CLND interval was negatively correlated with identification of positive non-sentinel nodes, but following adjustment for known risk factors this effect was no longer found.

The time interval between diagnosis of melanoma and CLND did not influence CLND tumour load, DFS or MSS.

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. Faries, Thompson, Cochran, Andtbacka, et al.  N Engl J Med. 2017 Jun 10.

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. 
In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence. Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. 
Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases.

So...if you note the 2014 study linked above, Faries has been looking at this stuff for a long time.  In this latest report, again, it is clear that sentinel lymph node biopsy is "associated with melanoma specific survival."  In this study, they placed patients with a positive sentinel node, randomly in either an immediate completion lymph-node dissection group or a nodal observation group that were followed with ultrasound. The group with the immediate CLND was "NOT associated with increased melanoma-specific survival".  The 3 year rate of survival was similar in the dissection and observation groups.  "The rate of disease free survival was slightly higher in the dissection group (68%) vs the observation group (63%) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92% vs 77%); these results must be interpreted with caution."  (Not sure why the caution unless they don't feel it was really a statistically significant finding.)

An interesting notation is that lymphedema was found in 24% of the folks with the CLND.  We already knew (mostly from breast cancer patients) that lymphedema is more common in older, heavier patients and more common in inguinal dissections than in those to the upper extremities. 

As Faries has done, we all need to move where the data and truth takes us.  I do not regret my two CLND's done to bilateral axilla in 2003 and 2007.  It is probably easier to take that stance since, despite some weird nerve stuff to my right (have had three surgeries there over the years!!!) I luckily, have not developed lymphedema. Additionally, back then we did not have the study results we have now...nor effective melanoma therapies.  Great strides have been made in understanding and treating melanoma in just the past 5-7 years.  For too many, however, it is not nearly enough. Keep pushing, researchers!!!  Keep pushing!

Hang in there, ratties!!! - c

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