Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Genitourinary Oncologist and Researcher, Beth Israel Deaconess Medical Center; Instructor in Medicine, Harvard Medical School

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Daniel E.C. Fein, MD, how he would handle his own case of advanced bladder cancer. Dr. Fein is a genitourinary oncologist at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, as well as an Instructor in Medicine at Harvard Medical School. (Note: This piece originally appeared in May 2023; now, Dr. Fein provides his updated expert perspective, with new information on preferred treatments for people with bladder cancer.)

Curious Dr. George: Imagine a hypothetical scenario in which, as a non-smoking, very busy genitourinary medical oncologist, you were surprised to experience painless gross hematuria. Rapid subsequent microscopic urinalysis confirmed many red blood cells and some white blood cells. Urine cytology was suspicious for malignant cells, not otherwise specified. A complete blood count and blood chemistry panel were normal. At cystoscopy a sessile mass was found and biopsied, revealing a high-grade urothelial carcinoma. You then recognized a 10-pound loss of weight. The upper urinary tract was normal by imaging studies, but your pelvic lymph nodes were enlarged, and three suspicious lesions were found in your left lung. How would you proceed?

Daniel E.C. Fein, MD: Although I care for many patients with bladder cancer and have been intimately involved in the medical field for some time, I can only imagine how I might react to such shocking news. Why me? What did I do wrong? How should I tell my family? Do I need to take time off work? My mind would be spinning out of control.

I would try to take a deep breath and tell myself that it is likely that I have been diagnosed with an advanced bladder cancer. I would know that although this is likely incurable, there are new treatments available that can help me live longer and improve my quality of life. While establishing care with a cancer treatment team, I would reach out to my primary care doctor and therapist to disclose to them this new diagnosis and ask for the best way for me to manage my mental and physical health while beginning my journey.

Some background: Bladder cancer accounts for approximately 4% of new cancer cases in the US, with around 10% of those presenting with metastatic disease. Most cases are confined to the bladder and can be treated with resections and medicines instilled into the bladder. When cancer invades into the muscle of the bladder wall, patients can be potentially cured using a combination of treatments, such as chemotherapy followed by removal of the bladder, or chemotherapy with radiation. When bladder cancer has spread to distant sites outside of the area of the bladder (such as the lung) they are typically not curable but can be controlled with a combination of medications to help patients live in the range of years.

Before treatment: The approach to treating advanced bladder cancer is changing rapidly, with new approvals of medications and combinations coming out every year. Because of this, I would seek care at a nearby academic center that has experience treating bladder cancer using a multidisciplinary team of urologists, medical oncologists, and radiation oncologists.

I would undergo a biopsy of a lung lesion to confirm this is metastatic bladder cancer. I would direct this biopsy to be sent for molecular testing for gene mutations in FGFR2/3 and for expression of the marker HER2, which would tell me what kind of treatments I could receive in the future. I would also undergo germline genetic testing to see if I was born with a gene mutation that made me more likely to get this cancer and potentially others. I would also ask if I should have any additional imaging, such as an MRI head, as this may be helpful for some patients.

Choosing treatment: Because of how quickly this field is changing, I would ask my care team if there were any clinical trials in my region with new and promising treatment combinations available. As a member of the Innovation in Cancer Program at BIDMC, I have seen firsthand the outstanding care provided to cancer patients on clinical trials and would certainly participate in one if it was right for my cancer treatment and quality of life.

If I thought a clinical trial wasn’t right for me, I would ask if I could be a candidate for the newly FDA-approved combination of enfortumab vedotin and pembrolizumab (EV + P), a combination of a targeted chemotherapy and immunotherapy. Because of a recently published clinical trial, this combination is now considered the preferred first-line therapy for all patients with metastatic bladder cancer.

If I was unable receive EV + P because of other medical conditions (such as severe autoimmune disease, difficult to control diabetes, or severe peripheral neuropathy), I would ask if I could receive a platinum-based chemotherapy combination. Conventional platinum-based chemotherapy (cisplatin or carboplatin with gemcitabine, or dose-dense MVAC) has been the standard-of-care treatment for advanced bladder cancer for many years and can still be an option for some patients if they are unable to receive or decline the EV + P combination. In recent years we would give at least four cycles of platinum-based chemotherapy, and if there is some control of the cancer, switch to a maintenance immunotherapy called avelumab. There is actually another combination of platinum-based chemotherapy with an immunotherapy called nivolumab that was also recently approved based on a clinical trial, but because of how effective enfortumab vedotin plus pembrolizumab seems to be, I generally recommend EV + P first.

What next?: I may have challenges with managing side effects of treatment, coping with my new diagnosis and limited life expectancy, or sharing my experiences with friends and family members. I would seek assistance from a palliative care team and a local cancer support group who can focus on these mental, emotional, and physical challenges to improve my quality of life.

A new diagnosis of cancer, at any stage, can be life changing. If you are going through this, please know that you are not alone and that there are people around the world with and without cancer who have dedicated their lives to making yours better.

Dr. Fein can be reached at dfein@bidmc.harvard.edu or on Twitter at @DFein_MD.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Christina Wu, MD
Professor of Medicine, Mayo Clinic, Phoenix

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks oncologist Christina Wu, MD, how she would handle her own diagnosis of metastatic colorectal cancer. Dr. Wu is a Professor of Medicine at the Mayo Clinic in Phoenix, Arizona. (Note: This piece originally appeared in 2020; now, Dr. Wu provides her updated expert perspective on molecular testing, targeted therapies, surgery, and clinical trials.)

Curious Dr. George: As an experienced academic and practicing clinical oncologist at the Mayo Clinic, you have particular interest, training, and experience in colorectal cancer. What would you do if you personally were discovered to have an asymptomatic, unsuspected, non-obstructing adenocarcinoma of the ascending colon that had already metastasized to your liver?

Christina Wu, MD: Colorectal cancer is one of the most common cancers in the U.S., and there has been a noticeable rise in early-onset colorectal cancer. Every patient with metastatic colon cancer to the liver is uniquely assessed because there are systemic and liver-directed treatment options. If I were diagnosed with colon cancer and liver metastasis, I would want a multi-pronged approach to include the following:

Next-generation sequencing (NGS): First of all, I would want both blood and tumor NGS testing. Blood NGS results can be back within a week, and tumor NGS is more expansive and complete. The tumor biomarkers I would want to know first are mismatch repair (MMR) protein or microsatellite instability (MSI) status. If deficient MMR or MSI-high, I could benefit from immunotherapy (pembrolizumab or nivolumab with or without ipilumumab) and be spared chemotherapy. Other tumor markers include KRAS/NRAS/BRAF mutation (mt), HER2 amplification, and NTRK and RET gene fusion.

I would be eligible for anti-EGFR antibody (panitumumab or cetuximab) in combination with doublet chemotherapy (FOLFOX or FOLFIRI) if my tumors were KRAS/NRAS/BRAF wild-type (wt) and HER2-negative with a left-sided primary cancer. HER2-targeted therapy such as tucatinib and trastuzumab could be a chemotherapy-free option if the tumor was KRAS/NRAS/BRAF wt and HER2 positive. Trastuzumab-deruxtecan could also be offered if I was HER2 positive. A BRAF V600E mt would be targeted with encorafenib and an anti-EGFR antibody. A KRAS G12C mt would be targeted with sotorasib/adagrasib and cetuximab/panitumumab. If I had the rare NTRK fusion mutation, I could be treated with entrectinib, larotrectinib, or repotrectinib. RET gene fusion could be targeted with selpercatinib.

Multi-disciplinary tumor board: I would want high-quality imaging and experts from medical oncology, surgical oncology, colorectal surgery, radiation oncology, gastroenterology, radiology, and interventional radiology reviewing my case in a tumor board. It would be meaningful to know upfront whether the liver metastasis was surgically resectable, because I may opt to receive systemic chemotherapy followed by surgical resection. If I required conversion therapy or reduction in my tumor burden, I would consider triplet chemotherapy (FOLFOXIRI) or systemic targeted therapy to get more of a response so that I could get to surgery. However, if I had clearly unresectable disease, I would choose systemic targeted therapy or doublet chemotherapy, such as FOLFOX or FOLFIRI and bevacizumab, to improve my quality of life.

With unresectable disease, I could also consider radiation, Y90 treatment, or ablation to the liver tumors, if I had good control or surgical resection of the extrahepatic disease. In addition, liver transplant may be a future consideration if I had well-controlled, unresectable liver metastasis, with no evidence of extrahepatic metastasis. Although not present at a tumor board, the palliative care team would be a crucial component of my care.

Genetic counseling: Some hereditary syndromes lead to colon cancer development, including Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis. I would choose to pursue germline testing to screen for such conditions.

Clinical trials: There are studies looking at targeting KRAS mutations, bringing targeted therapy to the first-line setting, and providing immunotherapy combinations. I would definitely want to expand my therapy options by enrolling in clinical studies.

Final thoughts: Systemic and liver-directed treatment options are evolving, and thus a multi-disciplinary approach would be essential from the moment of my diagnosis.

Dr. Wu can be reached at wu.christina@mayo.edu.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Marc B. Garnick, MD
Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Marc B. Garnick, MD, how he would handle his own advanced prostate cancer. Dr. Garnick is the Gorman Brothers Professor of Medicine at Harvard Medical School (HMS) and Beth Israel Deaconess Medical Center in Boston, MA. He is also Editor in Chief of the HMS Annual Report on Prostate Diseases. (Note: This piece was first published in June 2022 and has now been updated with additional information about neuroendocrine elements, mismatch repair deficiency, and cardiovascular considerations.)

Curious Dr. George: In 2021, you shared with our readers how you, as an expert, would proceed with handling your own severe back pain and spine lesions.

Let’s revisit that hypothetical scenario with some new developments: Further rapid lab studies demonstrated normal peripheral blood counts and no abnormal serum proteins. The back pain stabilized. Digital rectal exam discovered an enlarged, diffusely firm prostate gland with scattered hard foci. Ten transrectal prostate biopsy cores all contained adenocarcinoma with varying degrees of dedifferentiation, Gleason score of 8, repeat PSA was 25.

How should the pathologist handle the remaining tissues? What procedures should a reference laboratory perform? How would genomic, metabolomic, or proteomics inform next steps? And would imaging be helpful?

Marc B. Garnick, MD: With these new developments, the differential diagnosis has now been narrowed. The likelihood of the bone lesions being related to a plasmacytoma or multiple myeloma, though not completely excluded, are less likely. The lead diagnosis now has been established to be a Gleason score 8 prostate adenocarcinoma, which I presume is a Gleason 4+4. Please recognize that based upon the International Expert Consensus on Prostate Cancer nomenclature, this is now best described as Grade Group 4 (GG 4). Grade Group 1 (GG 1) contains Gleason patterns 3+3; GG 2 contains Gleason patterns 3+4; GG 3 contains Gleason patterns 4+3; GG 4 contains Gleason patterns 4+4; and GG 5 contains Gleason patterns 4+5 or 5+5. If this patient did not have suspected metastases to the bones (and even in the setting of metastatic prostate cancer), the pathology biopsy note should mention the presence of any intraductal component, perineural invasion, or lymphovascular invasion, all of which commonly accompany high-grade Gleason cancers. Neuroendocrine elements, although uncommon, can also accompany high-grade Gleason scores. If present, such transformation following treatment to neuroendocrine/small cell-like pathologies represents an ominous development, which is often accompanied by visceral involvement and the need for systemic chemotherapy.

Recent recommendations now suggest that genomic profiling of the patient both for germline and somatic mutations be assessed. The importance of BRCA (either germline or somatic) mutation has increased in significance, especially since there are emerging associations of prostate cancer being found in families of women with BRCA mutations. The finding of a BRCA2 mutation is associated with a more aggressive biology and could help inform treatments at some later day with the PARP class of therapeutics of platinum-containing agents, given the increased sensitivity of BRCA + cancers to respond to these therapies. Likewise, the presence of microsatellite instability (MSI high, or MSI-H) or mismatch repair deficient (dMMR) mutations may prompt treatment with an immunotherapy agent such as pembrolizumab.

The above consideration of more precise pathologic assessment is more important in a patient who has a GG 4 or 5, in whom there is no obvious evidence of metastatic disease. In such cases, one is trying to assess a probability of the patient having subclinical metastatic disease or being likely to develop metastatic disease. For the patient with already-established evidence of abnormal foci (in this case, the bone lesions), we in the past would have assessed with an Axumin scan; now, the availability of either Ga or F linked prostate-specific membrane antigen (PSMA) scanning would be indicated, both for diagnostic purposes as well as assessing down-the-line utility of PSMA-specific therapeutic ligands, such as Lutetium 177.

An assessment of cardiovascular history is increasingly important in helping determine a treatment program that helps minimize any therapy-induced increase in morbidity. Traditional androgen-deprivation therapy (ADT) has long been associated with cardiovascular issues, and now, with the standard addition of second-generation androgen receptor signaling inhibitors to ADT, the cardiovascular risk can double and even quadruple. Patient evaluation by experts in cardiology, internal medicine, or the emerging field of cardio-oncology is becoming increasingly important.

Curious Dr. George: What additional testing and what therapy would you deem to be most appropriate at this point?

Marc B. Garnick, MD: Please recall that this patient (hypothetically me) presented with back pain and multiple bony lytic lesions. Regardless of the etiology of these lesions, identification of any impending spinal cord compression must be assessed. While spinal cord compression is an unusual manifestation of de novo metastatic prostate cancer, it is clinically more common in the setting of treated prostate cancer that has progressed to become castration resistant. I would reassess the anatomic locations of the bone lesions, and then obtain a spinal MRI directed diagnostic evaluation, along with a good neurological examination to inform preemptive radiation or surgical considerations if either impending or actual compression is found.

For treatment of newly diagnosed presumably castration-sensitive metastatic prostate cancer, we now have multiple advances that have been established in this disease setting. First-line ADT (generally with an LHRH agonist or GnRH antagonist) is now supplanted with second-generation agents, such as abiraterone (+ prednisone) or enzalutamide, or other androgen-receptor signaling inhibitor agents, such as apalutamide. ADT + chemotherapy with docetaxel is also appropriate. Given the bone pain and potential neurological issues here, I would select a GnRH antagonist (either degarelix or relugolix) as the preferred therapy.

Dr. Garnick can be reached at mgarnick@bidmc.harvard.edu.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Adam Asch, MD
Professor of Medicine; Nancy Johnson Records Chair of Oncology, University of Oklahoma College of Medicine

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Previously, our Curious Dr. George asked leukemia expert Adam Asch, MD, how he would handle his own hypothetical case of acute myelogenous leukemia (AML). Now, Dr. Asch provides an updated answer, highlighting the new option of clinical trials offering novel targeted therapies for some AML patients. Dr. Asch is Professor of Medicine and Nancy Johnson Records Chair of Oncology at the University of Oklahoma College of Medicine.

Curious Dr. George: Please consider this hypothetical scenario: You are an active clinical oncologist in generally good health, but lately, you have lacked energy, have been feeling a little more tired than usual, have some dizziness on exertion, have been bruising easily, and have lost a bit of weight without dieting. So, you decide to visit your primary care physician for a checkup. On physical examination, she notes that you are a little pale, finds arm bruises, and feels the tip of your spleen. She orders several lab tests. Your hematocrit is 38, hemoglobin 12, white blood cells (WBCs) 49,000 per microliter with many blasts, many promyelocytes, myelocytes, eosinophils, and basophils. Platelets are low. A diagnosis of acute myelogenous leukemia (AML) is made. How would you proceed?

Adam Asch, MD: This would be a fascinating case to discuss in the abstract. But in the first person, as you have been exploring in your Curious Dr. George series, diagnosis and therapy take on a special and sometimes personal urgency. For this 70-year-old oncologist, the hypothetical is a timely one and for the field a relevant one, since AML is, in so many ways, a disease of aging.

For most AML patients, I find that the most important question to ask is if there is a curative intervention. For some, chemotherapy induction and consolidation may lead to a prolonged remission and perhaps cure. But for some disease categories—notoriously, p53-mutated disease—response to traditional chemotherapy is poor. Second, assuming an initial remission follows an induction regimen, how a remission is consolidated is another critical question. For people with high-risk AML (complex cytogenetics, FLT3-mutated) or intermediate-risk AML, allogeneic transplant remains the best means of consolidating a remission and offering a cure to many.

To a great extent, treatment for AML is informed by genetic and molecular studies that have become standard in the field. Cytogenetics to assess chromosomal defects, molecular analysis to identify potentially targetable mutations, and multi-channel flow cytometry to identify a blast phenotype that can be followed to assess measurable residual disease post induction and consolidation are all standard. Translocation 15;17 or “acute promyelocytic leukemia” (APL)—once considered to be the worst type of AML prognostically—is now routinely treated with all-trans retinoic acid and arsenic trioxide, with long-term survival now approaching 90%. The clinical presentation in this hypothetical case does not sound like APL, though the bruising raises the question, and a coagulation profile, if indicative of disseminated intravascular coagulation, might make that more of a question.

Other good prognostic cytogenetics include the translocation of chromosomes 8 and 21—also known as t(8;21)—and inversion of chromosome 16. Each of these has a historical long-term survival rate of about 60 to 70% with standard induction chemotherapy. All other cytogenetic features are classified as intermediate risk or poor risk, with long-term survival rates of 30 to 40% or 10%, respectively. For each of these latter risk groups, transplant remains the only real chance of relapse-free, long-term survival.

Now, before we discuss treatment regimens for AML in general, there are some features of my presentation that would lead me to ask for some additional data. The presence of a spleen tip and the presence of early myeloid forms, eosinophils, and basophils in addition to blasts raise the possibility that my disease is a Ph+ blast crisis rather than de novo AML. If so, treatment with a kinase inhibitor directed at the BCR-ABL kinase—after initial cytoreduction of the elevated blast count—would be a reasonable initial approach to getting control of the disease. But without allogeneic transplant as consolidation, this would not offer me long-term control of the disease. So, more on transplant in a bit.

Standard induction for “fit” patients with AML has remained largely unchanged for several decades—until recently. The chemotherapy combination of 7+3 (7 days of cytosine arabinoside and 3 days of an anthracycline) has been the backbone of induction in the U.S. Consolidation chemotherapy with 3 to 4 subsequent cycles of high-dose cytosine arabinoside has been common practice. The development of a liposomal preparation containing a defined ratio of cytosine arabinoside and daunorubicin has shown increased efficacy in AML that arises from a pre-existing condition known as myelodysplastic syndrome (MDS). Also, drugs targeting specific mutations in genes such as FLT3, IDH1, or IDH2 are additional options that can now be used in combination with standard approaches—or alone in some instances. But perhaps most impressive has been the incorporation of the BCL2 inhibitor venetoclax in combination with azacytidine as a low-intensity regimen now approved by the U.S. Food and Drug Administration (FDA) for elderly and unfit patients with MDS.

Response rates appear to essentially equal those of the standard high-intensity induction regimens. Importantly, this regimen generally has lower toxicity and is most often administered outpatient. Recent data show that patients achieving a complete response with this regimen do as well with allogeneic transplant as folks who received more intensive induction. And for younger, fit patients, venetoclax added to more intensive regimens is producing results that are likely significant improvements over the old 7+3.

So, getting back to the first question I posed, am I looking at the possibility of a cure? Possibly. It is not likely, at my age, that cytogenetics would be favorable. Complex cytogenetics and AML arising from MDS are much more prevalent. Even if this were to be a Ph+ AML blast crisis, my long-term survival would depend on allogeneic transplant as consolidation post remission.

Am I a candidate at 70 for an allogeneic transplant? Possibly. Recent studies show that arbitrary age limits on allo transplantation have virtually disappeared across transplant centers. Less ablative regimens and improved supportive care around infection control and prevention of graft-versus-host disease have led to a situation where transplantation for older patients is a viable option with reasonable outcomes. Unfortunately, it is one that is currently afforded to only about 5% of older AML patients.

So, what would I want in this situation? I would, of course, look for any relevant clinical trials, as all advances in the field are dependent on trials of novel therapies. There are now several trials looking at the addition of novel targeted therapies as a component of induction therapy for patients with appropriate molecular features. But in the absence of an appropriate trial, for my intermediate- or poor-risk AML, I would likely opt for azacytidine and venetoclax as an induction/consolidation regimen, which would give me a better chance of escaping potentially debilitating complications of induction and consolidation that might put a definitive transplant out of reach. And, I would consider transplant as consolidation if in complete remission and still in good shape.

Some reality here: if these approaches didn’t get me to a complete remission, my discussions would center on defining the best way to preserve quality of life with family and friends during my remaining time.

Dr. Asch can be reached at adam-asch@ouhsc.edu.

Related links:

• How Would an Expert Manage His Own Acute Myelogenous Leukemia?
• SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
• Treating Pancreatic Cancer: Could Metabolism—Not Genomics—Be the Key?

A message from Curious Dr. George:

The goal of Cancer Commons is to help patients identify and access their best possible treatments, one patient at a time, while moving the field forward. If you have advanced cancer, let our molecular oncology scientists provide personalized information about your options.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chris Apfel, MD, PhD, MBA
Founder, CEO, and Board Chair of SageMedic Corp.

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

For people with recurring or drug-resistant cancer, choosing the best-possible next treatment can pose a huge challenge. Our Curious Dr. George asks Chris Apfel, MD, PhD, MBA—Founder, CEO, and Board Chair of SageMedic Corp.—about his company’s solution for many of these patients.

Curious Dr. George: Despite the application of curative surgical, radiation, and systemic treatments, cancer remains the “emperor of all maladies” with 600,000 Americans dying of cancer every year. With many more patients battling recurrent or resistant disease, even with adherence to standard guidelines from the National Comprehensive Cancer Network (NCCN), selecting the next line of treatment—whether cytotoxic chemotherapies, targeted therapies, or immunotherapies—often follows a trial-and-error approach.

To address this unresolved challenge, SageMedic, a CMS and CLIA-accredited and California-based company, has developed the SAGE Oncotest™. In comparison to next-generation genomic sequencing, which provides actionable insights for a smaller number of patients, SageMedic claims that its Oncotest, an extreme drug resistance (EDR) assay, provides actionable insights for virtually all patients within 10 days, thereby avoiding likely failures.

Dr. Apfel, I understand that this is only possible because you are using fresh, live cancer tissue, right? Can you share more about how your test works and how it can help cancer patients?

Chris Apfel, MD, PhD, MBA: The SAGE Oncotest is a next-generation EDR assay in which we use a patient’s biopsy specimen to create microtumors in the lab. We then expose the microtumors to a wide range of drug concentrations, and we measure which drugs at which concentrations are most effective at killing the cancer cells.

Within one day of receiving a fresh biopsy specimen, we can create hundreds of microtumors from virtually all types of solid cancer, including breast, ovarian, prostate, and pancreatic cancers, glioblastoma, and cancers of unknown origin. Thanks to our proprietary technology, these live microtumors maintain the patient’s tumor heterogeneity and microenvironment for virtually every biopsy specimen.

Furthermore, in contrast to organoid approaches that usually take weeks or months for organoid growth, if growth occurs at all, the SAGE Oncotest one-day aggregation step allows for next-day drug exposure, with actionable information generated for virtually every patient within just 7 to 10 days.

Our predicate EDR predicted tumor resistance with about 96% accuracy, and it is highly unlikely that a tumor will respond to a therapy that does not work ex vivo in supra-physiological concentrations, as in the context of the SAGE Oncotest. By ruling out ineffective therapies, we project this assay to identify the most promising drugs with about 80% accuracy, doubling a patient’s chance for a tumor response, significantly improving quality of life, and significantly extending the patient’s life expectancy.

SAGE can test the potential sensitivity and resistance of dozens of drugs and drug combinations, though our current technology does not test for anti-hormonal or immuno-oncology drugs.

If any readers are interested in having their patient’s tissue tested to help inform their treatment plan, we ask them to please let us know at least a week ahead of the patient’s biopsy or surgery, so that we can send the shipment kit to ensure overnight delivery of viable tissue. SAGE Oncotest requires fresh, live cancer tissue rather than formalin fixation, which kills cells within minutes and renders the sample unusable for our assay.

Physicians can choose from two Sage Oncotest panels. The standard panel (“Superior Care within Standard of Care”) tests the microtumors against NCCN guideline-recommended drugs and can inform, especially, initial treatment plans, e.g., stage II or III patients expected to require adjuvant therapy. The expanded panel (“Beyond Standard of Care”) includes the standard panel plus special requests, including targeted therapies and repurposed drugs, which becomes meaningful when standard treatment regimens fail. Of note, if a fresh biopsy is not feasible, we have also been able to retrieve sufficient cancer tissue from pleural effusions, ascites, and even bone metastases.

In summary, the SAGE Oncotest complements other precision oncology approaches by providing actionable information for virtually all patients within 7-10 days to avoid ineffective drugs and significantly increase the chance for best-possible outcomes.

Dr. Apfel can be reached at capfel@sagemedic.com.

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Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.