# Collaboration outreach — email templates for external validation cohorts

**Versión:** 1.0  —  **Fecha:** 2026-05-14
**PI:** Dr. Sergio Cervera

---

## Estrategia general

Para validar externamente el modelo Nivel 3 necesitamos **datos individuales (IPD)** de
una cohorte cN+ tratada con NAC con outcome ypN0 conocido. Los candidatos primarios son
los autores de los cuatro estudios pivotales (Z1071, SenTa, RISAS, Montagna).

**Principios:**
1. Email **breve y directo** (decision-makers reciben docenas al día).
2. Solicitud **específica**: variables exactas, sin pedir más de lo necesario.
3. **Reciprocidad clara**: ofrecer co-autoría si la contribución es sustancial; ofrecer
   acceso al modelo desarrollado.
4. Compromiso **ético y legal** explícito (DUA, sólo de-identificado, retención limitada).
5. **Persistencia educada**: recordatorio a las 3 semanas si no hay respuesta; no más de
   2 recordatorios totales.

---

## Variables solicitadas (mínimo)

Por paciente, anonimizado:

| Variable | Tipo | Justificación |
|----------|------|---------------|
| `id_anon` | hash | identificador no reversible |
| `age` | numérico | predictor |
| `cT_stage` | categórico | predictor |
| `cN_stage` | categórico | predictor |
| `subtype` | categórico (HR/HER2/TNBC) | predictor principal |
| `ki67` | numérico (si disponible) | predictor |
| `nac_regimen` | categórico | predictor |
| `pertuzumab` | binario | predictor (HER2+) |
| `pembrolizumab` | binario | predictor (TNBC) |
| `clinical_response_axilla` | categórico | predictor |
| `surgery_type` | categórico (SLNB/TAD/ALND) | metadato |
| `slns_examined` | numérico | metadato |
| `ypN_stage` | categórico | **outcome** |
| `ypN0_outcome` | binario derivado | **outcome primario** |

---

## Plantilla 1 — Dr. Judy Boughey (ACOSOG Z1071, Mayo Clinic)

**Sugerencia de envío:** email institucional + opcional via ResearchGate.
Boughey Z1071 publication: Boughey JC et al. JAMA 2013;310:1455-61.
doi:10.1001/jama.2013.278932

```
Subject: Request for collaboration — external validation of ypN0 prediction model
         (cN+ NAC, n>300 institutional cohort)

Dear Dr. Boughey,

I am Dr. Sergio Cervera, breast surgeon at [Institution, Spain]. I am writing to
respectfully request collaboration for the external validation of a multivariable
prediction model for axillary pathological complete response (ypN0) after
neoadjuvant chemotherapy in cN+ breast cancer.

Background. Building on a literature-based pooled meta-regression (Brier 0.0078) that
synthesizes Z1071, SENTINA, RISAS, SenTa, and Montagna's multicenter cohort, we have
abstracted an institutional retrospective cohort of >325 cN+ patients (2015-2024)
including the modern era of dual HER2 blockade and pembrolizumab. We are now training a
machine-learning model (logistic regression + XGBoost) and seek a single, well-curated
external cohort for validation.

The Z1071 dataset is the gold-standard reference for this question. We would be
grateful if you would consider sharing a de-identified subset of Z1071 patient-level
data (a list of ~14 variables, attached) under your institution's data use agreement.

Reciprocity. We offer:
- Substantive co-authorship for you and any nominated colleagues, in line with ICMJE
  and CRediT criteria.
- Access to the validated model and source code (open-access at publication).
- Full acknowledgment of the Z1071 dataset and its leadership in any publication.

Ethics & legal. Our institutional Ethics Committee (CEIm) has approved (or is in
process of approving) the protocol. We will sign whatever Mayo Clinic / Alliance
data use agreement is required, including limitations on retention, access, and
secondary use. No re-identification will be attempted.

Timeline. We aim to submit the manuscript within 6 months of receiving the data,
targeting JAMA Surgery or Annals of Surgical Oncology.

Variables requested. See attached PDF (15 variables, all already in the published
Z1071 dataset). We do not need any new abstraction on your end.

Would you be open to a brief 20-minute video call to discuss feasibility?

Thank you very much for your consideration and for the foundational work that
Z1071 represents for our field.

With my best regards,

Dr. Sergio Cervera
Breast Surgery
[Institution], [City], Spain
[Email] | [ORCID] | [Phone]

Attachments:
- Variable list (1 page PDF)
- Project synopsis (2 page PDF)
- Institutional CEIm approval (when available)
```

---

## Plantilla 2 — Prof. Dr. Mattea Reinisch / Prof. Dr. Sherko Kuemmel (SenTa, Essen)

SenTa publication: Kuemmel S et al. Ann Surg 2022;276:e553-62.
doi:10.1097/SLA.0000000000004572

```
Subject: External validation collaboration — ypN0 prediction model after NAC
         (institutional cohort + ML)

Sehr geehrter Prof. Dr. Kuemmel, sehr geehrte Prof. Dr. Reinisch,
Dear Prof. Kuemmel and Prof. Reinisch,

I write to you as principal investigator of an institutional retrospective cohort
study on prediction of ypN0 in cN+ breast cancer treated with NAC, and to respectfully
request collaboration with the SenTa investigator group for external validation.

The SenTa cohort, with its rigorous design, prospective ascertainment, and inclusion
of the modern era including pertuzumab, is a uniquely valuable validation dataset.

Our institutional cohort (n>325, 2015-2024) has been used to train a logistic
regression + XGBoost model. We have built the model on top of a literature-based
meta-regression (which includes SenTa as a primary anchor; Brier 0.0078 in
internal validation).

What we ask. A de-identified extract of SenTa with ~14 variables (list attached). We
do not need any new chart abstraction.

What we offer.
- Co-authorship for SenTa investigators meeting ICMJE criteria.
- Full SenTa acknowledgment and citation in all dissemination.
- Open-access manuscript and code; sharing of the trained model with the SenTa group
  for any future use.

Ethics & DUA. Approval pending from our local CEIm. We will sign your institutional
data use agreement and observe all use restrictions.

We would be honored to schedule a 20-minute call at your convenience.

With kind regards,

Dr. Sergio Cervera
Breast Surgery
[Institution], [City], Spain
[Email] | [ORCID]
```

---

## Plantilla 3 — Prof. Dr. Marjolein Smidt (RISAS, Maastricht)

RISAS / Simons publication: Simons JM et al. JAMA Surg 2022;157:991-9.
doi:10.1001/jamasurg.2022.3907

```
Subject: External validation collaboration — ypN0 prediction model in cN+ NAC

Dear Prof. Smidt,

I am Dr. Sergio Cervera, writing as PI of a retrospective institutional study on
prediction of ypN0 in cN+ breast cancer after NAC. I would like to respectfully
request your consideration for collaboration on external validation using the
RISAS cohort.

The RISAS approach (radioactive iodine seed targeted axillary biopsy) is the
methodological reference standard for axillary staging after NAC, and the RISAS
cohort represents the cleanest available reference dataset for ypN classification
with TAD.

Our work. Institutional cohort of >325 cN+ NAC patients (2015-2024), including the
modern era of dual HER2 blockade and pembrolizumab. We have trained a multivariable
logistic + XGBoost model on top of a literature-based pooled estimator (which
includes RISAS as an anchor cohort).

Request. A de-identified extract of RISAS data (~14 variables; list attached).

Offer.
- Substantive co-authorship for RISAS investigators meeting ICMJE criteria.
- Full RISAS citation and acknowledgment.
- Open-source code and trained model deposited at publication.

Ethics. Local CEIm approval pending. Willing to sign Maastricht UMC+ DUA and observe
all use restrictions.

Would you be open to a brief call?

Met vriendelijke groet / With kind regards,

Dr. Sergio Cervera
Breast Surgery
[Institution], [City], Spain
[Email] | [ORCID]
```

---

## Plantilla 4 — Dr. Giacomo Montagna (multicenter cohort, MSKCC)

Montagna multicenter publication: Montagna G et al. Ann Surg 2024 (in press).

```
Subject: Collaboration request — external validation of ypN0 prediction model

Dear Dr. Montagna,

I write as PI of an institutional retrospective study on prediction of ypN0 in cN+
breast cancer after NAC, to respectfully request collaboration with your multicenter
international cohort for external validation.

Your cohort is uniquely valuable: it is multicenter, modern (with dual blockade and
pembrolizumab), and includes the granular outcome data needed to compare prediction
models head-to-head.

Our work. Institutional cohort of >325 cN+ patients (2015-2024) trained on logistic
regression + XGBoost, building on a literature-based meta-regression baseline (Brier
0.0078 in internal validation).

Request. A de-identified subset of your multicenter cohort (~14 variables, list
attached). No new chart work needed on your end.

Offer.
- Co-authorship per ICMJE for substantial contributors.
- Acknowledgment of all participating centers.
- Open-access code and trained model.

Ethics. Local CEIm approval pending. Willing to sign MSKCC and any participating
center DUA.

Could we schedule a brief call?

With kind regards,

Dr. Sergio Cervera
Breast Surgery
[Institution], [City], Spain
[Email] | [ORCID]
```

---

## Plantilla de recordatorio (a las 3 semanas si no hay respuesta)

```
Subject: Re: Collaboration request — ypN0 prediction model external validation

Dear Dr. [Name],

I hope this finds you well. I wanted to gently follow up on my email of [date]
regarding collaboration for external validation of our ypN0 prediction model. I
fully appreciate that your inbox is busy and there is no urgency on your end.

If the request is something you would consider but lacks bandwidth right now, I
would be happy to wait or to work with a colleague you nominate as primary contact.
If it is not feasible, a brief note to that effect is also more than welcome and I
will not follow up further.

Thank you again for your time.

With my best regards,
Dr. Sergio Cervera
```

---

## Documentos a adjuntar

Para cada solicitud, adjuntar como mínimo:

1. **Project synopsis (2 páginas PDF)** — resumen del estudio, hipótesis, diseño, métricas
   esperadas, referencias.
2. **Variable list (1 página PDF)** — tabla exacta de variables solicitadas con tipo y
   ejemplo de valor.
3. **CEIm approval letter** (cuando esté disponible) — escaneado.
4. **CV breve del PI** (1 página) — opcional pero útil en primera ronda.
5. **DUA template** (si tu institución tiene una plantilla; muchos prefieren la suya).

---

## Tracker de solicitudes

| Destinatario | Cohorte | Fecha envío | Recordatorio | Respuesta | Status |
|--------------|---------|-------------|--------------|-----------|--------|
| Boughey | Z1071 | | | | |
| Kuemmel/Reinisch | SenTa | | | | |
| Smidt | RISAS | | | | |
| Montagna | Multicéntrica | | | | |
| (Backup 1) | TBD | | | | |
| (Backup 2) | TBD | | | | |

---

## Backup options si no se obtiene IPD

1. **TBCRC (Translational Breast Cancer Research Consortium)** — solicitud formal vía
   web, sometida a comité.
2. **NHS Breast Cancer Audit (UK)** — datos agregados disponibles públicamente; útil para
   plan B (calibration-in-the-large).
3. **Cohorte hermana institucional** — colaborar con un hospital próximo para una
   validación "casi-externa" (centro distinto, mismo país).
4. **Validación split-sample temporal** — usar cohorte 2015-2021 para training y 2022-2024
   para "validación externa temporal" (no es ideal pero es defendible si el resto falla).

---

## Notas legales

- Revisar siempre la **DUA del centro de origen** antes de cualquier transferencia.
- Para datos europeos: cumplimiento RGPD; cláusulas estándar de transferencia
  internacional si el receptor está fuera del EEE.
- Para datos USA: HIPAA Safe Harbor para de-identificación.
- Documentar **exactamente** qué variables se reciben, cuándo, y cuándo se destruirán.
