Outcomes of temozolomide and capecitabine chemotherapy used in neuroendocrine and endocrine tumours: A real-world comparison of treatment evidence in Alberta, Canada, from 2011-2021.
Bibliographic record
Abstract
e23064 Background: Capecitabine and temozolomide (CAPTEM) have proven effective in improving progression-free survival (PFS) in pancreatic neuroendocrine tumors (PNETs). This study extends its evaluation to determine efficacy across the broader spectrum of neuroendocrine and endocrine tumors (NETs and ETs) Methods: This was a retrospective cohort study, for which REB approval was obtained. We identified all patients with NETs & ETs treated with CAPTEM (at least 1 cycle) in Alberta from 2011-2021. PFS & OS from start of CAPTEM were compared between groups stratified by primary: Pancreatic NETs (PNETs); gastrointestinal NETs (GINETs); Pulmonary NETs (PuNET); other NETs (ONETs). Among 159 patients identified, there were 67 PNETs, 38 GINETs, 35 PuNETs, & 19 ONETs. PFS & OS were compared between NETs when CAPTEM was used as 1st vs. later-line therapy & patients receiving ≥ 6 vs. < 6 cycles. Kaplan-Meier & Log- Rank tests were used, adjusted for age & sex using cox regression. Results: Compared to PNETs, GINETs demonstrated no statistically significant difference in median progression-free survival (PFS 10.5 vs 9 m, p = 0.11; HR = 1.14 95%CI = 0.76-1.71; HR adjusted for age & sex = 1.10, 95% CI = 0.79 -1.65) and overall survival (OS median 15.9 vs 19 months, p = 0.15; HR = 1.13 , 95% CI = 0.69 -1.85, HR adjusted to age and sex = 1.11 , 95% CI = 0.69 - 1.81). Conversely, PuNETs & ONETs were associated with significantly lower median PFS (PuNETs 3 vs 9m, p = 0.02, HR = 1.6 95%CI = 1.1 -2.4, HR adjusted for age & sex = 1.65, 95% CI = 1.15 - 2.5); ONETs 2 vs 9m, p = 0.01, HR = 1.56 95%CI = 1.1 -2.6, HR adjusted for age &sex = 1.59, 95% CI = 1.14 -2.7) and OS (PuNETs 6.8 vs 19 m, p = 0.01, HR = 1.7, 95% CI = 1.06 - 2.7, HR adjusted to age & sex = 1.73, 95% CI = 1.08 to 2.71); ONETs 5.6 vs 19 m, p = 0.02, HR = 1.49, 95% CI = 1.1 - 2.7, HR adjusted to age and sex = 1.51, 95% CI = 1.05 - 2.8). OS analyses revealed comparable trends.CAPTEM therapy administered as 1st-line treatment was associated with longer median PFS & OS compared to later-line use. PFS (10 vs 3.5m, P = .008; HR = 0.56 95% CI = 0.40 -0.78) & OS (23 vs 4.7m, P = 0.0001; HR = 0.42 95% CI = 0.29 -0.62). Additionally, patients receiving ≥6 cycles of CAPTEM exhibited higher median PFS and OS compared to those receiving < 6 cycles. PFS (18 vs 2m, P = 0.0001; HR = 0.22 95%CI = 0.16 - 0.32) & OS (29 vs 4.2m, P = 0.0001; HR = 0.22 95% CI = 0.14 - 0.34). Conclusions: CAPTEM therapy demonstrates comparable efficacy in gastrointestinal NETs (GINETs) to that observed in pancreatic NETs (PNETs) but appears to be less effective in non- gastroenteropancreatic NETs and Endocrine tumors. Importantly, the use of CAPTEM as a first- line treatment and the administration of an extended cycle regimen are significantly associated with improved progression free survival (PFS) and overall survival (OS) across the broader NET spectrum, representing a novel prognostic variable not previously reported.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.014 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".