Integrating Academic and Community Practices in the Management of Colorectal Cancer: The City of Hope Model

Colorectal cancer (CRC) management continues to evolve. In metastatic CRC, several clinical and molecular biomarkers are now recommended to guide treatment decisions. Primary tumor location (right versus left) has been shown to predict benefit from anti-epidermal growth factor receptors (EGFRs) in rat sarcoma viral oncogene homologue (RAS) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type patients. Anti-EGFR therapy has not resulted in any benefit in RAS-mutated tumors, irrespective of the primary tumor location. BRAF-V600E mutations have been associated with poor prognosis and treatment resistance but may benefit from a combination of anti-EGFR therapy and BRAF inhibitors. Human epidermal growth factor receptor 2 (HER-2) amplification was recently shown to predict relative resistance to anti-EGFR therapy but a response to dual HER-2 targeting within the RAS wild-type population. Finally, the mismatch repair (MMR)-deficient subgroup benefits significantly from immunotherapeutic strategies. In addition to the increasingly complex biomarker landscape in CRC, metastatic CRC remains one of the few malignancies that benefits from metastasectomies, ablative therapies, and regional hepatic treatments. This treatment complexity requires a multi-disciplinary approach to treatment and close collaborations between various stakeholders in large cancer center networks. Here, we describe the City of Hope experience and strategy to enhance colorectal cancer care across its network

Use of Molecular Assays and Circulating Tumor DNA in Early‐Stage Colorectal Cancer: A Roundtable Discussion of the Gastrointestinal Cancer Therapy Expert Group

&nbsp;https://doi.org/10.1002/onco.13738</p

Application of a Drug-Induced Apoptosis Assay to Identify Treatment Strategies in Recurrent or Metastatic Breast Cancer

<div><p>Background</p><p>A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes.</p><p>Methods</p><p>In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users), or elect to not use the test (non-users).</p><p>Results</p><p>The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73%) used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR) rate compared to non-users (38.1% vs 0%, p = 0.04) and a higher disease control (CR+PR+Stable) rate (81% vs 25%, p<0.01). Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01).</p><p>Conclusions</p><p>The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00901264" target="_blank">NCT00901264</a></p></div

In Vitro Drug Induced Apoptosis by Agent in all Patients.

<p>In Vitro Drug Induced Apoptosis by Agent in all Patients.</p

Patient Characteristics.

<p>Patient Characteristics.</p

Correlation of Response with use of the Mick Assay.

<p>Correlation of Response with use of the Mick Assay.</p

In Vitro Drug Induced Apoptosis in Triple Negative Breast Cancer Patients.

<p>In Vitro Drug Induced Apoptosis in Triple Negative Breast Cancer Patients.</p

Time to recurrence in patients with recurrent or metastatic breast cancer.

<p>Blue curve, patients whose physician used the MiCK assay. Red curve, patients whose physician did not use the MiCK assay.</p

CONSORT Flow Diagram.

<p>CONSORT Flow Diagram.</p