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Journal of Clinical Oncology logoLink to Journal of Clinical Oncology
. 2020 Jul 23;38(27):3238–3240. doi: 10.1200/JCO.20.01460

Reply to E. Hindié

Andrea Maurichi 1,, Rosalba Miceli 1, Hanna Eriksson 1, Julia Newton-Bishop 1, Jérémie Nsengimana 1, May Chan 1, Andrew J Hayes 1, Kara Heelan 1, David Adams 1, Roberto Patuzzo 1, Francesco Barretta 1, Gianfranco Gallino 1, Catherine Harwood 1, Daniele Bergamaschi 1, Dorothy Bennett 1, Konstantinos Lasithiotakis 1, Paola Ghiorzo 1, Bruna Dalmasso 1, Ausilia Manganoni 1, Francesca Consoli 1, Ilaria Mattavelli 1, Consuelo Barbieri 1, Andrea Leva 1, Umberto Cortinovis 1, Vittoria Espeli 1, Cristina Mangas 1, Pietro Quaglino 1, Simone Ribero 1, Paolo Broganelli 1, Giovanni Pellacani 1, Caterina Longo 1, Corrado Del Forno 1, Lorenzo Borgognoni 1, Serena Sestini 1, Nicola Pimpinelli 1, Sara Fortunato 1, Alessandra Chiarugi 1, Paolo Nardini 1, Elena Morittu 1, Antonio Florita 1, Mara Cossa 1, Barbara Valeri 1, Massimo Milione 1, Giancarlo Pruneri 1, Odysseas Zoras 1, Andrea Anichini 1, Roberta Mortarini 1, Mario Santinami 1
PMCID: PMC7499609  PMID: 32701413

We thank Hindié1 for his interest in our study,2 and we are happy to provide the clarifications requested. We agree that our nomogram has not been prospectively tested on unselected patients with thin melanoma. Although prospective testing is desirable, it would not be ethical to use unselected patients with stage T1 melanoma because sentinel node biopsy (SNB) would be overtreatment in most cases.

Similarly, Hindié1 notes that we did not test the nomogram on the two subgroups (of the development and validation cohorts) that did not receive SNB. Once again, it is precisely because these subgroups did not receive an SNB that nomogram performance could not be assessed. Thus, we did the only thing possible: assess outcomes after long follow-up, finding that foregoing SNB in these subgroups was justified post hoc.

Hindié1 also notes that younger age predicted SNB positivity in our nomogram, although perhaps paradoxically, older age is clearly associated with poorer prognosis,3 higher rates of false-negative SNB,4 and greater risk of local or in-transit recurrence.4 Because nodal function changes with age,5 lower rates of sentinel node (SN) positivity in older people are difficult to interpret. We can only emphasize that we were not addressing the issue of overall outcomes, but of whether the SNs were likely to be positive.

Hindié1 makes the point that there is a need to better define the aims of SNB in patients with thin melanoma. We wholeheartedly agree. He notes that the main aim of an SNB is to identify occult nodal disease and offer adjuvant therapy if appropriate. However, he draws attention to the fact that adjuvant therapies have not been tested in all categories of patients with stage T1 melanoma and that guideline recommendations6,7 for patients that are SN-positive (new stage IIIA of the American Joint Committee on Cancer [AJCC] Eighth Edition)8 are discordant: stage IIIA patients with low SN tumor burden (≤ 1 mm) are not recommended for inclusion in adjuvant therapy trials.6 However, according to ASCO guidelines,7 they should be considered for individualized approaches (that include adjuvant treatment). The situation is further complicated by the fact that the pertinent adjuvant therapy trials,9,10 which were all conducted with patients who received complete lymph node dissection, were performed on patients staged according to the AJCC Seventh Edition.

As requested, our own data on SN tumor burden are as follows: of the 108 patients that were SN positive in the development cohort, 21 (19.4%) had a tumor burden of > 1 mm, and 87 (80.6%) had a tumor burden of ≤ 1 mm. Those with high SN burden would now be candidates for adjuvant treatment,6 whereas those with low burden would not.6 Our opinion is that patients with low SN burden should be proposed for adjuvant therapy only after exhaustive consideration by the multidisciplinary team and a discussion with the patient. In line with trial results,11 we no longer propose completion lymph node dissection when the SN is positive.

SNB was initially devised as a therapeutic procedure but was subsequently recognized as a staging tool. However, the unexplained variance in survival of AJCC-staged patients exceeds 20%.12 So performing SNB is of insufficient prognostic value for giving nuanced advice to patients, especially those with thin primaries. Our work was intended to add further information for patients and physicians who are considering SNB when the likelihood of a positive result is low. We believe our nomogram provides useful information but, as we stated in our article, better prognostic biomarkers are needed for thin melanomas than are available at present.

ACKNOWLEDGMENT

Supported by Grants No. C588/A19167, C8216/A6129, and C588/A10721 from Cancer Research UK and by Grant No. CA83115 from the National Cancer Institute.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Reply to E. Hindié

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Andrea Maurichi

Speakers' Bureau: Novartis Italia

Travel, Accommodations, Expenses: Novartis Italia

Andrew J. Hayes

Research Funding: Amgen Pharmaceuticals (Inst)

David Adams

Consulting or Advisory Role: Microbotica

Research Funding: Bristol Myers Squibb

Roberto Patuzzo

Speakers' Bureau: Novartis

Catherine Harwood

Honoraria: Sanofi/Regeneron, Merck Serono

Consulting or Advisory Role: Sanofi

Speakers' Bureau: Sanofi, Merck Serono

Research Funding: PellePharm, Meda Pharmaceuticals, Chanel (CERIES), LEO Pharma, AbbVie

Travel, Accommodations, Expenses: Sanofi/Regeneron, PellePharm

Bruna Dalmasso

Patents, Royalties, Other Intellectual Property: AstraZeneca UK concerning methods for SLFN11 detection in cancer samples and its correlation with clinical outcome (I); Davide Bedognetti and Wouter Hendricxk from SIDRA Medicine, Doha, concerning in vitro experiments with SLFN11 and cancer models (I); European patent No. 102019000018989 concerning a “multi-domain method for prediction of one-year mortality in senior patients diagnosed with cancer” (I)

Travel, Accommodations, Expenses: Novartis (I), Roche (I)

Uncompensated Relationships: Breast International Group (I), Roche (I), Breast International Group/International Breast Cancer Study Group (I), AstraZeneca (I), European Organisation for Research and Treatment of Cancer (I)

Vittoria Espeli

Consulting or Advisory Role: MSD Oncology

Travel, Accommodations, Expenses: Janssen-Cilag

Cristina Mangas

Consulting or Advisory Role: Merck, Novartis

Giovanni Pellacani

Honoraria: Novartis (Inst)

Consulting or Advisory Role: Sanofi

Nicola Pimpinelli

Consulting or Advisory Role: MSD, Takeda Pharmaceuticals, Kyowa Hakko Kyrin

Research Funding: Novartis (Inst), Almirall (Inst)

Giancarlo Pruneri

Expert Testimony: Roche Molecular Diagnostics

Travel, Accommodations, Expenses: Roche

Andrea Anichini

Honoraria: Bristol Myers Squibb

Research Funding: Bristol Myers Squibb (Inst)

No other potential conflicts of interest were reported.

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