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| SEE BIA-ALCL FEATURE @ NEWS1 |
Here some reflections, and a plea for further, more systematized
and coordinated action and consensus:
First, the just published LYSA Registry data from the French
Cancer Agency [reported at ASCO 2018] has shed some further light on two prognostically distinct
classes of BIA-ALCLs (based on effusion, breast tumor mass, and lymph node
involvement), with in situ BIA-ALCLs exhibiting an indolent clinical
course that enables complete remission typically after implant removal, in
contrast to infiltrative BIA-ALCLs exhibiting a more aggressive clinical
course, with in fact a prognosis virtually identical to systemic anaplastic
large cell lymphoma (ALCL), despite real differences. Further clarification was
provided in AU-NZ studies [especially Loch-Wilkinson,
Plast Reconstr Surg. 2017 Oct], higher-surface-area (HAS)
textured implants significantly increased the risk of BIA-ALCL (over 14 times
higher with Biocell textured implants and almost 11 times higher with
polyurethane (Silimed) textured implants compared with Siltex textured
implants, so there clearly is a risk hierarchy at play here.
Second, being mindful of overtreatment (always a concern),
nonetheless given that BIA-ALCL related death, although rare, is predominantly
due to uncontrolled local disease progression, there is a role in patients with
more advanced local disease – particularly in the minority of patients whose
disease extends beyond the capsule – for chemotherapeutic intervention, and at
this time the best evidenced first-line therapy apart from the strongly toxic
CHOP family of regimens is the monoclonal antibody brentuximab vedotin
(Adcetris) based on its role in refractory in ALCL, despite the limited but
still positive data of its off-label use in BIA-ALCL; and I have seen some
cases of patients progressing on CHOP therapy but achieving pathological
complete response (pCR) with brentuximab vedotin in the second line. Given its
comparatively favorable side effect profile and higher tolerability over
traditional chemotherapies, it retains some considerable appeal.
Third, for myself, given that:
(1) the NF-kB) pathway is commonly deregulated in lymphomas, and
that
(2) curcumin can inhibit growth of these cell lines and increase
their chemosensitivity to cisplatin, and given also that
(3) it (curcumin) increases apoptosis and differentiation of
vitamin D-treated tumor cells, with direct binding of curcumin to the vitamin D
receptor (VDR), and that
(4) curcumin modulates the well-known overexpression of EZH2 in
anaplastic lymphomas and can down-regulate the JAK/STAT pathway that is
also incriminated in BIA-ALCL, then I have (strictly ad hoc-ly and off-label) counseled the
deployment, with provisional but promising success, of a regimen of
high-penetrance curcuminoids (either phytosomal or nanoparticulate) and
optimal-dosed Vitamin D3 (achieving 25(OH)D assay levels of at least 66
ng/ml and above), in the small number of BIA-ALCL cases I have consulted on,
but clearly this requires validation in clinical trial. And Mark Clemens'
recent findings suggesting that some BIA-ALCL are associated with a chronic
allergic immune response to currently undetermined antigen(s) - with IL-13
activity (associated with allergic inflammation) as well as eosinophils and
mast cells surrounding the BIA-ALCL tumors plus the presence of IgE – is
tantalizing in this connection of anti-inflammatory interventions.
Going Forward, Work Still To Do:
1.
I am also looking to press
for the expansion of the European Commission Medical Device Expert Group
(VMDEC) Task Force with respect to collection and analysis of EU-based BIA-ALCL
cases, but VMDEC registry data must be coordinated with other non-EU entities –
like the PROFILE Registry maintained by the The Plastic Surgery Foundation here
in the States, the Australian Breast Device Registry, among many others –
if we are to establish a larger and more comprehensive cross-boundary collaborative
BIA-ALCL surveillance initiatives to advance our knowledge and better serve the
many women affected (and often overlooked and sometimes misdiagnosed as Hodgkin
lymphoma or other entities).
2.
It is disconcerting that we
still, even in 2018, lack consistent standardization and reporting regarding
pathological examination of mammary implants (most institutions often continue
to recommend gross examination alone).
3.
Furthermore, we are not
doing enough to educate patients and their health professionals on the
importance of routine surveillance after implantation.
4.
And we must finally – long
overdue -bring explicit consent issues to the fore to assure fairness to
patients. It would appear that most breast-focused plastic surgeons in the U.S.
and the UK fail to consistently include risk of BIA-ALCL and that uniform
informed-consent documents lack widespread adoption and use, so a model
BIA-ALCL informed consent is required and effective efforts made to assure that
the patient is not simply “allowed” to read and decipher the information as it
is found in the informed consent agreement as is all too commonly the case, but
that health professionals first openly and candidly discuss not only the risk
of BIA-ALCL but also the common presenting symptoms (a mass, breast
swelling/pain, or delayed-presentation seroma / effusion) of BIA-ALCL the
patient should be on guard for which would trigger a mandated evaluation. I
call this the need for “informed discussion” in addition to mere “informed
consent”, and that need was best put by the UK High Court (Judgement in
Montgomery ‘v’ Lanarkshire Health Board) that stated that “risk shouldn't be
a numbers game, it should be part of dialogue”.
...............................................................................................................................................................
Constantine Kaniklidis of evidencewatch.com
Director, Medical Research, No Surrender Breast Cancer Foundation
(NSBCF)
Oncology Reviewer, Current Oncology
Member, Society for Integrative Oncology (SIO)
European Association for Cancer Research (EACR)
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