Dr. Heestand is a board-certified medical oncologist with a focus on gastrointestinal cancers, primarily hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer. He currently serves as the medical oncology champion of the Stanford Hepatobiliary Tumor Board, as well as the principal investigator of multiple clinical trials. He also collaborates with campus laboratories to help develop new biomarker and treatment technologies. Dr. Heestand is a member of the ECOG-ACRIN gastrointestinal committee and serves as a representative to the NCI Hepatobiliary Task Force. He is also the director of the Stanford Medical Oncology Fellowship Program.
Dr. Heestand and his team take great pride in helping patients and their families face gastrointestinal cancer.
Outside of the clinic, Dr. Heestand enjoys playing the piano, teaching his kids about music, cooking for friends and family, and surfing the internet for interesting things to read.
- Hepatocellular Carcinoma
- Gallbladder Cancer
- Gastrointestinal Cancers
- Medical Oncology
Clinical Assistant Professor, Medicine - Oncology
Oncology Fellowship Director, Stanford University (2017 - Present)
Medical Education:University of Southern California Keck School of Medicine Registrar (2004) CA
Board Certification: Medical Oncology, American Board of Internal Medicine (2010)
Board Certification: Hematology, American Board of Internal Medicine (2010)
Fellowship:Stanford University Hematology and Oncology Fellowship (2010) CA
Residency:University of California Davis (2007) CA
Undergraduate, Harvard College (1998)
A Study of Nivolumab in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation
This study will investigate if nivolumab will improve recurrence-free survival (RFS) compared to placebo in participants with HCC who have undergone complete resection or have achieved a complete response after local ablation, and who are at high risk of recurrence
Survival after neoadjuvant approaches to gastroesophageal junction cancer.
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Gastroesophageal junction (GEJ) cancers can be treated with equipoise using neoadjuvant chemoradiation (NACRT) or chemotherapy alone (NAC), but the comparative outcomes are unclear. Patients with non-metastatic T2-4 or N1-3 GEJ adenocarcinoma who underwent definitive surgery and NAC or NACRT were selected from the National Cancer Database. The primary outcome was overall survival (OS). Multivariable regression and propensity score analysis were used to adjust for age, comorbidity, and other characteristics.We identified 2435 patients treated with NACRT and 648 patients treated with NAC. OS was not significantly different between NACRT and NAC (51% versus 54% at 3 years, respectively, P = 0.11). Extent of pathological downstaging (complete, partial/mixed, none) after NACRT or NAC was highly prognostic of survival. Patients with no response did equally poorly after either preoperative regimen, and NAC was significantly less likely than NACRT to produce any response (adjusted odds ratio 0.62, P < 0.0001). Rate of adjuvant chemotherapy usage was significantly lower after NACRT than after NAC (12% versus 34%, P < 0.0001). In patients with residual tumor and nodal disease, adjuvant chemotherapy was associated with higher OS after NACRT (adjusted hazard ratio 0.81, P = 0.05), but not after NAC. These results were further validated by propensity score analysis.NACRT had similar survival to NAC despite superior pathological downstaging. Adjuvant chemotherapy is relatively underused after NACRT and warrants further study as a risk-adapted means to improve survival, especially in patients with larger burden of residual disease.
View details for DOI 10.1007/s10120-019-00980-6
View details for PubMedID 31230228
The Mutational Landscape of Gastrointestinal Malignancies as Reflected by Circulating Tumor DNA.
Molecular cancer therapeutics
2018; 17 (1): 297–305
We aimed to assess the utility of a novel, noninvasive method of detecting genomic alterations in patients with gastrointestinal malignancies, i.e., the use of liquid biopsies to obtain blood-derived circulating tumor DNA (ctDNA) through an analysis of the genomic landscape of ctDNA (68 genes) from 213 patients with advanced gastrointestinal cancers. The most common cancer types were colorectal adenocarcinoma (N = 55; 26%), appendiceal adenocarcinoma (N = 46; 22%), hepatocellular carcinoma (N = 31; 15%), and pancreatic ductal adenocarcinoma (N = 25; 12%). The majority of patients (58%) had ≥1 characterized alteration (excluded variants of unknown significance). The median number of characterized alterations was 1 (range, 0-13). The number of detected alterations per patient varied between different cancer types: in hepatocellular carcinoma, 74% of patients (23/31) had ≥1 characterized alteration(s) versus 24% of appendiceal adenocarcinoma patients (11/46). The median percent ctDNA among characterized alterations was 2.50% (interquartile range, 0.76%-8.96%). Overall, 95% of patients (117/123) had distinct molecular portfolios with 143 unique characterized alterations within 56 genes. Overall, concordance rates of 96%, 94%, 95%, and 91%, respectively, were found between ctDNA and tissue biopsy (N = 105 patients) in the four most common alterations (KRAS amplification, MYC amplification, KRAS G12V, and EGFR amplification). Of 123 patients with characterized alterations, >99% (122/123; 57% of entire population tested; 122/213) had one or more alterations potentially actionable by experimental or approved drugs. These observations suggest that many patients with gastrointestinal tumors, including difficult-to-biopsy malignancies like hepatocellular cancers, frequently have discernible and theoretically pharmacologically tractable ctDNA alterations that merit further studies in prospective trials. Mol Cancer Ther; 17(1); 297-305. ©2017 AACR.
View details for DOI 10.1158/1535-7163.MCT-17-0360
View details for PubMedID 29133621
View details for PubMedCentralID PMC5752585
Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.
European journal of cancer (Oxford, England : 1990)
2017; 83: 80–87
Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well.We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well.Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer.Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation.
View details for DOI 10.1016/j.ejca.2017.06.019
View details for PubMedID 28728050
A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3
2016; 11 (1)
NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS) in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples.Using the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker.Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251) and validation sets (229). Among all patients, elevated levels of interleukin-8 (IL-8), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1-alpha (HIF-1 alpha), and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2) expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention.ClinicalTrials.gov NCT00040183.
View details for DOI 10.1371/journal.pone.0147995
View details for PubMedID 26808546
FGFR1 and NTRK3 actionable alterations in "Wild-Type" gastrointestinal stromal tumors.
Journal of translational medicine
2016; 14 (1): 339
About 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies.We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations.We identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1-HOOK3, FGFR1-TACC1) and one harbored an ETV6-NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1-TACC1 and ETV6-NTRK3 fusions.Using patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015.
View details for PubMedID 27974047
Approach to Patients With Pancreatic Cancer Without Detectable Metastases
JOURNAL OF CLINICAL ONCOLOGY
2015; 33 (16): 1770-?
The poors outcomes associated with pancreatic cancer clearly reflect the advanced stage of disease at diagnosis for most patients. Through this lens, it is easy to lose sight of the fact that roughly 50% of patients with pancreatic cancer have no clinically detectable metastases at presentation. Herein, we discuss how patients with localized pancreatic cancer are currently managed. The primary goal of care for patients with resectable and borderline-resectable tumors is cure, facilitated by achieving margin-negative resection of the primary disease and delivering effective adjuvant and/or neoadjuvant therapy. For patients with locally advanced disease, the focus is on limiting local progression and outgrowth of metastatic disease and maintaining quality of life. Although it was once a centerpiece of therapy for localized pancreatic cancer, the value and place of radiation therapy in the treatment algorithm is now under increased scrutiny. In contrast, given its value as demonstrated in multiple prospective trials, chemotherapy is an established part of the treatment paradigm for all patients. With the demonstration that cytotoxic combinations such as fluorouracil, leucovorin, irinotecan, and oxaliplatin as well as gemcitabine/nab-paclitaxel are active in the metastatic setting, these agents are now being studied in patients with localized disease. The neoadjuvant setting provides a particularly favorable setting for evaluating new systemic strategies. Given the array of new targets, including immunomodulatory approaches, there is reason for optimism that we can markedly improve survival for all patients with pancreatic cancer and enter an era in which surgery with curative intent actually fulfills this goal on a much more regular basis.
View details for DOI 10.1200/JCO.2014.59.7930
View details for Web of Science ID 000356062200008
View details for PubMedID 25918279
Molecular landscape of pancreatic cancer: implications for current clinical trials
2015; 6 (7): 4553-4561
Despite recent improvements, overall survival for advanced adenocarcinoma of the pancreas continues to be poor. In comparison to other tumor types that have enjoyed marked survival benefit by targeting aberrant cell signaling pathways, standard of care treatment for pancreatic cancer is limited to conventional cytotoxic chemotherapy. Multiple pathway aberrations have been documented in pancreatic cancer. A review of the COSMIC database reveals that most pancreatic cancers contain somatic mutations, with the five most frequent being KRAS, TP53, CDKN2A, SMAD4, and ARID1A, and multiple other abnormalities seen including, but not limited to, mutations in STK11/LKB1, FBXW7, PIK3CA, and BRAF. In the era of tumor profiling, these aberrations may provide an opportunity for new therapeutic approaches. Yet, searching clinicaltrials.gov for recent drug intervention trials for pancreatic adenocarcinoma, remarkably few (10 of 116 (8.6%)) new study protocols registered in the last three years included a molecular/biomarker stratification strategy. Enhanced efforts to target subsets of patients with pancreatic cancer in order to optimize therapy benefit are warranted.
View details for Web of Science ID 000352792000002
View details for PubMedID 25714017
- A novel biomarker panel examining response to gemcitabine (G) with or without erlotinib (E) for pancreatic cancer (PA) therapy in NCIC clinical trials group PA.3. AMER SOC CLINICAL ONCOLOGY. 2014
- A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704 AMER SOC CLINICAL ONCOLOGY. 2014
Racial Disparity in Consultation, Treatment, and the Impact on Survival in Metastatic Colorectal Cancer
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
2013; 105 (23): 1814-1820
Black patients with metastatic colorectal cancer have inferior survival compared to white patients. The purpose of this study was to examine disparity in specialist consultation and multimodality treatment and the impact that treatment inequality has on survival.We identified 9935 non-Hispanic white and 1281 black patients with stage IV colorectal cancer aged 66 years and older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Logistic regression models identified race-based differences in consultation rates and subsequent treatment with surgery, chemotherapy, or radiation. Multivariable Cox regression models identified potential factors that explain race-based survival differences. All statistical tests were two-sided.Black patients had lower rates of consultation with surgery, medical oncology, and radiation oncology. Among patients seen in consultation, black patients received less surgery directed at the primary tumor, liver- or lung-directed surgery, chemotherapy, and radiotherapy. Unadjusted survival analysis found a 15% higher chance of dying for black patients compared with white patients (hazard ratio [HR] = 1.15; 95% confidence interval (CI) = 1.08 to 1.22; P < .001). Adjustment for patient, tumor, and demographic variables marginally reduced the risk of death (HR = 1.08; 95% CI = 1.01 to 1.15; P = .03). After adjustment for differences in treatment, the increased risk of death for black patients disappeared.Our study shows racial disparity in specialist consultation as well as subsequent treatment with multimodality therapy for metastatic colorectal cancer, and it suggests that inferior survival for black patients may stem from this treatment disparity. Further research into the underlying causes of this inequality will improve access to treatment and survival in metastatic colorectal cancer.
View details for DOI 10.1093/jnci/djt318
View details for Web of Science ID 000328370000011
View details for PubMedID 24231453
- The Evolution of Modern Systemic Agents for Colorectal Cancer LOWER GASTROINTESTINAL MALIGNANCIES 2010; 1 (2): 249–60