Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.


Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
03 2019
Historique:
received: 21 08 2018
accepted: 23 01 2019
revised: 18 01 2019
pubmed: 23 2 2019
medline: 18 12 2019
entrez: 23 2 2019
Statut: ppublish

Résumé

Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Sections du résumé

BACKGROUND
Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors.
METHODS
The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced.
RESULTS
Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005).
CONCLUSION
PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Identifiants

pubmed: 30792530
doi: 10.1038/s41416-019-0402-0
pii: 10.1038/s41416-019-0402-0
pmc: PMC6461960
doi:

Substances chimiques

Chorionic Gonadotropin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

587-594

Subventions

Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

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Auteurs

Fieke E M Froeling (FEM)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Ramya Ramaswami (R)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Panagiotis Papanastasopoulos (P)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Baljeet Kaur (B)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Neil J Sebire (NJ)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Dee Short (D)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Rosemary A Fisher (RA)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Naveed Sarwar (N)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK.

Michael Wells (M)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Kam Singh (K)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Laura Ellis (L)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Janet M Horsman (JM)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Matthew C Winter (MC)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

John Tidy (J)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Barry W Hancock (BW)

Trophoblastic Disease Centre, Weston Park Hospital, Sheffield, UK.

Michael J Seckl (MJ)

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Imperial College NHS Healthcare Trust and Imperial College London, London, UK. m.seckl@imperial.ac.uk.

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Classifications MeSH