Subtype
Digestive System Adenocarcinoma
CI-CAN-00002525Explore in graph →
- NCIt
- C210140
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Subtype
CI-CAN-00002525Explore in graph →
Variants & evidence
167 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| JUN Overexpression1 | ||||||||
| Irbesartan | Colorectal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1633A 67-year-old female presents with recurrent metastatic colonic adenocarcinoma. Immunohistochemical and genetic workup showed overexpression of c-JUN and FOS, which presumably signals through the RAA… (full text at CIViC) PMID 27022066 · Jones et al., 2016 · Open in CIViC | civic |
| ALK Fusion1 | ||||||||
| Alectinib | Pancreatic Acinar Cell CarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID10327Case report of a 62-year old male patient diagnosed with pancreatic acinar cell carcinoma. Liver metastases were diagnosed and treatment was started with gemcitabine plus nab-paclitaxel regimen. After… (full text at CIViC) PMID 35005993 · Gaule et al., 2022 · Open in CIViC | civic |
| KDR R961W1 | ||||||||
| Regorafenib Anhydrous | Colorectal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID1191Case Report of a 84-year-old woman with stage IVb CRC after progression under 5-fluorouracil and bevacizumab. NGS revealed a frameshift mutation in APC, a missense mutation in KRAS. Variants of uncert… (full text at CIViC) PMID 27004155 · Loaiza-Bonilla et al., 2016 · Open in CIViC | civic |
| KIF23 EXPRESSION1 | ||||||||
| (prognostic) | Hepatocellular Carcinoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID1745KIF23 variant 1 was found to be expressed in the cDNA of tumor tissues from a large cohort of HCC patients of chinese descent via PCR. This expression was absent in the normal tissues of these patient… (full text at CIViC) PMID 26674738 · Sun et al., 2015 · Open in CIViC | civic |
| KMT2D Loss-of-function2 | ||||||||
| Immune Checkpoint Inhibitor | Colorectal Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12583In a retrospective TCGA cohort of microsatellite-instable colorectal adenocarcinoma (n = 43; KMT2D LOF = 16, WT = 27), KMT2D loss of function was associated with higher TMB (p < 0.001), higher neoanti… (full text at CIViC) PMID 39578878 · Takemon et al., 2024 · Open in CIViC | civic |
| WRN Inhibitor HRO761 + WRN Inhibitor RO7589831Substitutes | Colorectal Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12584In microsatellite-instable (MSI) colorectal carcinoma cell-line assays, KMT2D loss of function (LOF) stratified sensitivity to WRN perturbation. In DepMap viability data, WRN knockout was lethal in MS… (full text at CIViC) PMID 39578878 · Takemon et al., 2024 · Open in CIViC | civic |
| KRAS A11_G12insGA1 | ||||||||
| (oncogenic) | Colon Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 4 | accepted | EID9331FFPE tumor tissue from 1506 colorectal adenocarcinoma patients was analyzed at codons 12, 13, 61 and 146 by PCR. 672 KRAS mutations were found in 670 patients, and from these, two were inframe inserti… (full text at CIViC) PMID 24642870 · Tong et al., 2014 · Open in CIViC | civic |
| ERBB2 V842I + KRAS G12CERBB2KRAS1 | ||||||||
| ARS-1620 + NeratinibCombination | Pancreatic Ductal Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID11573When tested in MIAPaCa2 (PDAC cell line and KRAS G12C) cells, Neratinib and ARS-1620 strongly inhibit AKT and MAPK phosphorylation (Figure 6F). Also, MIAPaCa2 cell line with the variant in exposure to… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| KRAS G12D2 | ||||||||
| Adebrelimab + KRAS G12D Inhibitor HRS-4642Combination | Pancreatic Ductal Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13294In this phase 1/2 trial the KRAS G12D degrader HRS-4642 in combination with PD-L1 inhibitor adebrelimab was tested in 48 pretreated KRAS G12D-positive pancreatic adenocarcinoma patients. Patients had … (full text at CIViC) PMID 42748921 · Shi et al., 2026 · Open in CIViC | civic |
| Setidegrasib | Pancreatic Ductal Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12938A phase 1 dose‑escalation and dose‑expansion study in patients with previously treated advanced KRAS p.G12D mutant pancreatic ductal adenocarcinoma (NCT05382559; n = 203 overall; n = 21 PDAC treated a… (full text at CIViC) PMID 41879829 · Park et al., 2026 · Open in CIViC | civic |
| ERBB2 E717D + KRAS G12DERBB2KRAS1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11556KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| ERBB2 Q679L + KRAS G12DERBB2KRAS1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11554KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| ERBB2 S310F + KRAS G12DERBB2KRAS1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11548KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| ERBB2 S423R + KRAS G12DERBB2KRAS1 | ||||||||
| (oncogenic) | Pancreatic Ductal Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID11550KRAS G12D-transformed HPNE cells with lentiviral vectors containing the variant significantly increased colony formation in number and size in soft agar compared to infected HPNE cells with the varian… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC | civic |
| KRAS G12/G132 | ||||||||
| Gemcitabine + TrametinibCombination | Pancreatic Adenocarcinoma | Predictive | B | Supports Resistance | 4 | accepted | EID622Adding trametinib to gemcitabine does not improve overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or duration of response (DOR) in patients with untreated metastati… (full text at CIViC) PMID 24915778 · Infante et al., 2014 · Open in CIViC | civic |
| Trametinib | Pancreatic Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID990KRAS G12/G13 status was evaluated in cell-free DNA (cfDNA) of patients with untreated metastatic adenocarcinoma of the pancreas that were randomised (1:1) to receive gemcitabine plus trametinib or pla… (full text at CIViC) PMID 24915778 · Infante et al., 2014 · Open in CIViC | civic |
| KRAS G12 + KRAS G13 + KRAS Q612 | ||||||||
| (prognostic) | Colorectal Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID11056The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| Cetuximab + ChemotherapyCombination | Colorectal Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 4 | submitted | EID11055The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| KRAS G13D1 | ||||||||
| Cetuximab + ChemotherapyCombination | Colorectal Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID11054The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| KRAS Mutation2 | ||||||||
| Refametinib + SorafenibCombination | Hepatocellular Carcinoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1642Phase 2 study in Asian patients with unresectable hepatocellular carcinoma. 70 patients received refametinib (BAY 86-9766) plus sorafenib as study treatment. A retrospective biomarker analysis was per… (full text at CIViC) PMID 25294897 · Lim et al., 2014 · Open in CIViC | civic |
| PI3Kbeta Inhibitor AZD8186 + SCH772984Combination | Pancreatic Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID1003Inhibition of ERK in 11 KRAS mutant pancreatic cancer cell lines with SCH772984 was more effective than MEK Inhibition. Combined Treatment with PI3K Inhibitor AZD8186 was more effective than either ag… (full text at CIViC) PMID 26725216 · Hayes et al., 2016 · Open in CIViC | civic |
| KRAS Q22*1 | ||||||||
| Panitumumab | Colon Mucinous Adenocarcinoma | Predictive | C | Supports Resistance | 2 | accepted | EID1131A 43-year-old female was diagnosed with an adenocarcinoma of the ascending colon and received 6-months of adjuvant chemotherapy. After 5 years of completion of adjuvant chemotherapy, the disease relap… (full text at CIViC) PMID 19661358 · Palmirotta et al., 2009 · Open in CIViC | civic |
| KRAS Wildtype1 | ||||||||
| Cetuximab + ChemotherapyCombination | Colorectal Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID11057The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Entrectinib | Colorectal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID2960A gene fusion between exon 11 of LMNA and exon 10 of NTRK1 was observed in a patient with metastatic colorectal cancer after therapy with first-line FOLFOX, second-line FOLFIRI/cetuximab, and third-li… (full text at CIViC) PMID 26546295 · Russo et al., 2016 · Open in CIViC | civic |
| NTRK1 Fusion + NTRK1 G595R + NTRK1 G667C1 | ||||||||
| Entrectinib | Colorectal Adenocarcinoma | Predictive | C | Supports Resistance | 4 | accepted | EID2961A gene fusion between exon 10 of NTRK1 and exon 11 of the LMNA genes was observed in a patient with metastatic colorectal cancer after therapy with first-line FOLFOX, second-line FOLFIRI/cetuximab, an… (full text at CIViC) PMID 26546295 · Russo et al., 2016 · Open in CIViC | civic |
| MAGEH1 EXPRESSION1 | ||||||||
| Gemcitabine | Bile Duct Adenocarcinoma | Predictive | D | Supports Resistance | 2 | accepted | EID95010 biliary tract carcinoma cell lines were sorted based on their gemcitabine sensitivity. MAGEH1 protein expression was negatively correlated with sensitivity. In a clinical validation cohort, MAGEH p… (full text at CIViC) PMID 20088962 · Ojima et al., 2010 · Open in CIViC | civic |
| MAP2K2 G132D1 | ||||||||
| Trametinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Resistance | 2 | submitted | EID7732In this case report, a 66-year old woman with pancreatic ductal adenocarcinoma was treated with trametinib for a BRAF in-frame-deletion and TP53 mutation and achieved an initial partial response for c… (full text at CIViC) PMID 29903880 · Aguirre et al., 2018 · Open in CIViC | civic |
| MAP2K2 G132S1 | ||||||||
| Trametinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Resistance | 2 | submitted | EID7733In this case report, a 66-year old woman with pancreatic ductal adenocarcinoma was treated with trametinib for a BRAF in-frame-deletion and TP53 mutation and achieved an initial partial response for c… (full text at CIViC) PMID 29903880 · Aguirre et al., 2018 · Open in CIViC | civic |
| MET Amplification2 | ||||||||
| Cabozantinib | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID7873Cabozantinib's effect on cell proliferation was studied in a variety of cell lines. In two gastric adenocarcinoma cell lines with MET amplification (SNU-5 and Hs746T) were the most sensitive to caboz… (full text at CIViC) PMID 21926191 · Yakes et al., 2011 · Open in CIViC | civic |
| Onartuzumab | Gastric Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID689A case-study describing a patient with MET polysomy, MET over-expression and evidence of autocrine HGF-production (the growth factor ligand of MET). The patient initially achieved a complete response … (full text at CIViC) PMID 22389872 · Catenacci et al., 2011 · Open in CIViC | civic |
| MET Overexpression1 | ||||||||
| Rilotumumab | Gastric Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 5 | accepted | EID5835In this randomised, double-blind, placebo-controlled phase 3 trial, 609 patients with MET+ (expression of at least 1+ intensity on 25% or more tumor cells) gastric cancer or gastroesophageal adenocarc… (full text at CIViC) PMID 28958504 · Catenacci et al., 2017 · Open in CIViC | civic |
| NCOA3 Mutation1 | ||||||||
| Anti-PDL1 Therapy + PD-1 Ligand InhibitorSubstitutes | Colon Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12626In a retrospective cohort analysis of colon adenocarcinoma treated with PD-1/PD-L1 immune checkpoint inhibitors from the MSKCC ICIs-treated COAD dataset (n = 76; NCOA3-mutant n = 7, NCOA3-wild-type n … (full text at CIViC) PMID 40215778 · Liu et al., 2025 · Open in CIViC | civic |
| NEDD9 EXPRESSION1 | ||||||||
| (prognostic) | Hepatocellular Carcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID1059IHC was performed in 123 hepatocellular carcinoma tissues and their adjacent normal liver tissues for protein expression of HEF1 (NEDD9). Overexpression of HEF1 protein was observed in HCC tissue when… (full text at CIViC) PMID 26893853 · Li et al., 2016 · Open in CIViC | civic |
| BRAF D594G + BRAF V600E + KRAS MutationBRAFKRAS1 | ||||||||
| Cetuximab + ChemotherapyCombination | Colorectal Adenocarcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID11060The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| NQO1 Overexpression1 | ||||||||
| NSC84167 | Pancreatic Ductal Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID12560In preclinical pancreatic ductal adenocarcinoma (PDAC) models with high NQ01 expression, which indicates the NFE2L2 (NRF2) pathway activation, the small molecule NSC84167 (NSLC01, 50 mg/kg) selectivel… (full text at CIViC) PMID 34247201 · Dai et al., 2021 · Open in CIViC | civic |
| NR4A2 Overexpression1 | ||||||||
| C-DIM 12 + GemcitabineCombination | Pancreatic Ductal Adenocarcinoma | Predictive | D | Supports Resistance | 3 | submitted | EID12649In pancreatic cancer cell lines MiaPaCa2 and Panc1, gemcitabine 1 μmol/L induced NR4A2/NURR1 expression and triggered cytoprotective autophagy, while both CRISPR-mediated NR4A2 knockout and the NR4A2 … (full text at CIViC) PMID 35582016 · Zarei et al., 2021 · Open in CIViC | civic |
| ATG12 Overexpression + ATG7 Overexpression + NR4A2 OverexpressionNR4A2ATG7ATG121 | ||||||||
| (prognostic) | Pancreatic Ductal Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID12650In a retrospective TCGA PDAC (tumors n = 179, normals n = 171), high ATG7 expression was significantly associated with poorer survival on Kaplan–Meier analysis (P = 0.013), and high ATG12 expression s… (full text at CIViC) PMID 35582016 · Zarei et al., 2021 · Open in CIViC | civic |
| BRAF Mutation + KRAS Mutation + NRAS MutationKRASNRASBRAF1 | ||||||||
| (prognostic) | Colorectal Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID11061The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| PALB2 Mutation1 | ||||||||
| Talazoparib | Pancreatic Ductal Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID10835A patient with pancreatic ductal adenocarcinoma (PDAC) and a somatic PALB2 mutation (NM_024675.4: c.3350+1G>T) experienced disease progression after 10 cycles of FOFIRINOX and 2 cycles of gemcitabine.… (full text at CIViC) PMID 36119518 · Kachmazov et al., 2022 · Open in CIViC | civic |
| PBK NUCLEAR EXPRESSION1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 2 | accepted | EID1052Microarray expression data from 48 patients with gastric adenocarcinoma were analyzed for genes differentially expressed with regard to overall survival. Upregulation of proteasome subunit beta type 8… (full text at CIViC) PMID 26894977 · Kwon et al., 2016 · Open in CIViC | civic |
| PBLD Underexpression1 | ||||||||
| (prognostic) | Hepatocellular Carcinoma | Prognostic | D | Supports Poor Outcome | 4 | submitted | EID6364The frequent deletion of PBLD in HCC tissues is an independent predictor of poor prognosis for patients with HCC. Elevated PBLD expression has been show to reduce the growth and spread of HCC. PMID 26594798 · Li et al., 2016 · Open in CIViC | civic |
| PIK3CA Amplification1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID504In patients with gastric cancer, those with amplification of PIK3CA had shorter overall survival than those without amplification. PMID 22292935 · Shi et al., 2012 · Open in CIViC | civic |
| PROM1 EXPRESSION1 | ||||||||
| Sorafenib | Hepatocellular Carcinoma | Predictive | B | Supports Resistance | 2 | accepted | EID926CD133 (PROM1) expression in 39 samples of hepatocellular carcinomas was correlated with JNK activity. Both were more highly expressed in patients not responding to sorafenib. CD133+ cells (sorted) wer… (full text at CIViC) PMID 22596232 · Hagiwara et al., 2012 · Open in CIViC | civic |
| PSMB8 NUCLEAR EXPRESSION1 | ||||||||
| (prognostic) | Gastric Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 2 | accepted | EID1051Microarray expression data from 48 patients with gastric adenocarcinoma were analyzed for genes differentially expressed with regard to overall survival. Expression of 294 and 116 genes was enriched i… (full text at CIViC) PMID 26894977 · Kwon et al., 2016 · Open in CIViC | civic |
| PTEN Loss1 | ||||||||
| Lapatinib + TrastuzumabSubstitutes | Gastric Adenocarcinoma | Predictive | B | Supports Resistance | 2 | accepted | EID864In 48 patients with advanced gastric cancer, retrospectively analyzed for PTEN expression using IHC, PTEN loss was associated with a shorter duration of response (median 4.2 vs. 6.1 months, p = 0.04) … (full text at CIViC) PMID 25300346 · Zhang et al., 2015 · Open in CIViC | civic |
| PTPN6 Underexpression1 | ||||||||
| (prognostic) | Hepatocellular Carcinoma | Prognostic | D | Supports Poor Outcome | 4 | submitted | EID6390SHP-1 has been shown to be a tumor suppressor in hematopoietic cancers. Reduced SHP-1 expression in HCC correlates to aggressive tumor behavior resulting in a poor prognosis for patients. PMID 29776962 · Wen et al., 2018 · Open in CIViC | civic |
| RAF1 Amplification1 | ||||||||
| Sorafenib | Hepatocellular Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID9113Through the histological examination of 25 patient tumor samples with hepatocellular carcinoma, the efficacy of postoperative sorafenib treatment may be correlated with higher levels of c-Raf-1 expres… (full text at CIViC) PMID 26981887 · Lei et al., 2016 · Open in CIViC | civic |
| RB1 Overexpression1 | ||||||||
| Doxorubicin + Fluorouracil + Gemcitabine + MitomycinSubstitutes | Pancreatic Adenocarcinoma | Predictive | D | Supports Resistance | 2 | accepted | EID1324In Capan-1 cell lines engineered to reduce pRB expression (by transfection with p16), resensitization to chemotherapy-induced apoptosis was observed. The effect was asserted to be specific to pRB depl… (full text at CIViC) PMID 11792751 · Plath et al., 2002 · Open in CIViC | civic |
| RICTOR Amplification1 | ||||||||
| Vistusertib | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID1915Tumor samples from 640 patients with metastatic solid tumors were prospectively analyzed with a next-generation sequencing assay to identify molecular targets. 13 (2%) of 640 patients had a RICTOR-aam… (full text at CIViC) PMID 28028034 · Kim et al., 2017 · Open in CIViC | civic |
| RPS6 PHOSPHORYLATION1 | ||||||||
| Everolimus | Gastric Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID93054 patients with advanced gastric cancer were treated with everolimus. Two patient responsed and potential biomarkers were explored. High pre-treatment expression of phosphorylated RPS6 (pS6; at Ser24… (full text at CIViC) PMID 22343617 · Yoon et al., 2012 · Open in CIViC | civic |
Data updated 15 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.