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Overall survival of patients with pancreatic adenocarcinoma and <i>BRCA1</i> or <i>BRCA2</i> germline mutation.

2016· article· en· W2890803263 on OpenAlexaffabout
Kyaw Aung, Spring Holter, Ayelet Borgida, Ashton A. Connor, Melania Pintilie, Neesha C. Dhani, David W. Hedley, Jennifer J. Knox, Steven Gallinger

Bibliographic record

VenueJournal of Clinical Oncology · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsOntario Institute for Cancer ResearchToronto General HospitalUniversity of TorontoUniversity Health NetworkMount Sinai HospitalPrincess Margaret Cancer Centre
Fundersnot available
KeywordsMedicineInternal medicineOncologyGermline mutationPancreatic cancerAdenocarcinomaStage (stratigraphy)CancerGastroenterologyMutation

Abstract

fetched live from OpenAlex

4123 Background: Pathogenic BRCA1/2 germline mutations are found in 4.6% of patients with pancreatic adenocarcinoma (PDAC). Long-term overall survival (OS) of these patients is largely unknown. BRCA1/2 mutations are associated with DNA double strand break repair deficiency and more data are needed to establish whether PDAC patients with a BRCA1/2 germline mutation achieve better OS with DNA cross linking agents such as platinum. Methods: The objective was to evaluate OS including survival outcomes achieved with platinum based chemotherapy in a cohort of BRCA1/2germline mutant PDAC patients. Primary endpoint was 5 year OS for patients with stage I & II operable disease and 2 year OS for patients with inoperable stage III & IV advanced disease. Evaluable patients, diagnosed between January 1997 and December 2015, were identified from the Ontario Pancreas Cancer Study prospective database. Results: Fifty seven patients, 25 female and 32 male, were identified: 14 BRCA1 mutant, 42 BRCA2 mutant, and 1 double mutant. Median age was 63 years (range 29-84). Twenty six patients (45%) had prior cancer diagnoses (13 breast, 3 prostate, 3 bladder, 2 ovarian, 2 thyroid, 1 colon, 1 melanoma and 1 lymphoma). At a median follow up of 18 months (range 2-87), 40 (70%) have died. Twenty four (42%) had a primary tumor resection (4 stage I + 20 stage II). Their median OS was 19.5 months and 5 year OS 17% (95%CI 6-35%). Thirty three patients (58%) had advanced disease (8 inoperable stage III + 25 stage IV). Their median OS was 9.6 months and 2 year OS 24% (95%CI 11.5-43%). Twenty advanced patients received platinum (oxaliplatin, cisplatin or carboplatin) either as part of first line or subsequent lines of palliative chemotherapy. Their median OS was 15.3 months and 2 year OS 35% (95%CI 18-56%). Of remaining 13 advanced patients, treatment details were not available for one. For 12 advanced patients who did not receive platinum chemotherapy, median OS was 8.3 months and 2 year OS 0%. Conclusions: In this large cohort of germline BRCA1/2 mutant PDAC patients, OS for early stage disease was similar to historical controls, whereas OS for advanced disease was superior to historical controls, particularly for patients who received platinum based chemotherapy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.033
GPT teacher head0.343
Teacher spread0.310 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations10
Published2016
Admission routes2
Has abstractyes

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