Pituitary Neoplasms
Conditions
Keywords
Temozolomide; Aggressive Pituitary Tumor; Pituitary Carcinoma; PitNET; MGMT; Latin America; Retrospective Cohort; Multicenter Study
Brief summary
Temozolomide is the main chemotherapy drug used for aggressive pituitary tumors and pituitary carcinomas that do not respond to standard treatments like surgery or radiation. Most of what is known about how well this treatment works comes from small studies in Europe and the United States, with very little data from Latin America. Building on a previous multicenter study conducted in Brazil, this study (TEMPLA) expands data collection to additional centers across Latin America to better understand how patients in this region respond to temozolomide, how long the treatment controls the tumor, and whether certain tumor characteristics (such as MGMT status) can help predict which patients are more likely to benefit.
Detailed description
Temozolomide is the first-line chemotherapeutic agent recommended for aggressive pituitary neuroendocrine tumors (PitNETs) and pituitary carcinomas refractory to standard therapy, including surgery and radiotherapy. Current evidence supporting its use derives largely from small case series and single-country cohorts, with limited data representative of Latin American populations. TEMPLA (TEMozolomide in Pituitary tumors - Latin America) is a retrospective, multicenter cohort study that expands a previously conducted national Brazilian cohort on temozolomide use in aggressive PitNETs and pituitary carcinomas to a broader Latin American regional scope. Participating centers will retrospectively identify patients treated with temozolomide for histologically confirmed aggressive PitNET (defined by Knosp grade ≥3, radiological growth \>20% within 6 months, and/or progression despite optimized standard therapy) or histologically/clinically confirmed pituitary carcinoma. Data will be collected via a standardized electronic case report form (REDCap), with harmonized diagnostic and response criteria applied across all participating sites to minimize inter-center heterogeneity. Mandatory variables include tumor subtype and lineage, temozolomide dose and treatment duration, and radiological response assessed from pre- and post-treatment imaging. MGMT status (by immunohistochemistry and/or promoter methylation analysis, where locally available) will be collected as a secondary variable and analyzed as an exploratory predictor of treatment response. The primary aim of this study is to characterize the radiological response rate to temozolomide across Latin American centers. Secondary aims include estimating progression-free survival and overall survival following temozolomide initiation, evaluating the association between MGMT status and treatment response, and describing treatment-related adverse events.
Interventions
DRUGtemozolamide
Temozolomide, an oral alkylating chemotherapeutic agent, administered as part of routine clinical management for aggressive pituitary neuroendocrine tumors (PitNETs) and pituitary carcinomas refractory to standard therapy. Dosing regimens, cycle duration, and total number of cycles varied according to each treating center's clinical protocol and were not standardized as part of this study. Temozolomide was not assigned by the investigators for research purposes; all treatment decisions were made independently by the treating clinical team prior to data collection
DRUGTemozolamide
Unlike most published temozolomide studies in aggressive pituitary tumors, which are limited to single-center case series from Europe or North America, this cohort captures multicenter, real-world temozolomide use specifically in Latin American patients with aggressive PitNETs and pituitary carcinomas. Data include MGMT status (immunohistochemistry and/or promoter methylation) as an exploratory predictor of response, collected under heterogeneous but harmonized dosing protocols reflecting routine clinical practice across participating centers, rather than a standardized experimental regimen.
Sponsors
University of Sao Paulo General Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Inclusion criteria
Histologically confirmed pituitary neuroendocrine tumor (PitNET) meeting criteria for aggressive behavior (Knosp grade ≥3, radiological tumor growth \>20% within 6 months, and/or progression despite optimized standard therapy including surgery and/or radiotherapy), OR histologically or clinically confirmed pituitary carcinoma (defined by the presence of craniospinal or systemic metastasis) Treatment with temozolomide, at any dose or duration, administered for the above indication Availability of pre-treatment and post-treatment imaging sufficient to assess radiological response Temozolomide treatment initiated within the defined study period
Exclusion criteria
Insufficient clinical or imaging data to assess the primary outcome measure Temozolomide administered for an indication other than aggressive PitNET or pituitary carcinoma Loss to follow-up before any post-treatment imaging assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiological Response Rate to Temozolomide | From initiation of temozolomide treatment to best radiological response observed, assessed up to 5 years | — |
| Radiological response | From initiation of temozolomide treatment to radiological or clinical disease progression, or death from any cause, whichever occurs first, assessed up to 5 years | Radiological response to temozolomide will be classified as complete response, partial response, stable disease, or progressive disease, based on comparison of pre-treatment and post-treatment imaging (MRI) available for each patient. Response classification will follow criteria adapted from RECIST where applicable, acknowledging that formal RECIST assessment may not have been systematically applied at the time of clinical treatment in all participating centers. |
Contacts
CONTACTRAFAEL Loch BATISTA, MD PhD
Outcome results
None listed