The U.S. Food and Drug Administration (FDA) has approved hundreds of drugs for the treatment of cancer. However, some approved drugs are more effective for certain patients than others. Our curious Dr. George asks Carla Grandori, MD, PhD, Founder and CEO of SEngine Precision Medicine, about her company’s test to detect which drugs are likely to be most effective for a given patient’s solid tumor.

Curious Dr. George: Too often, the FDA approves drugs that are not effective, and there is a serious lag from the beginning of their use until discovery that the drug is without benefit. For solid tumors, your company’s PARIS Test purports to detect which drugs will not work and which are likely to be effective. How exactly does it work? How might a physician and a patient access it?

Carla Grandori, MD, PhD: As physicians and patients unfortunately know firsthand, cancer treatment usually means a series of therapies over the course of years. Often a patient doesn’t respond to a course of treatment; sometimes they do, but disease later recurs anyway. It can feel like trial-and-error, with time slipping away and frightening degrees of uncertainty.

The concept of personalized medicine has generated a lot of excitement within the cancer community, with the implication that there has to be a way to figure out the best course of treatment for each individual. The field has made notable progress in certain cases, but most efforts are looking to define new buckets for patient cohorts, like carriers of a specific mutation. The DNA approach can find a therapeutic match for only 17% of patients’ DNA. That’s important, but how about the remaining 83% of patients? Also, often a patient’s cancer has multiple mutations—which one is actionable, and when? What about the many factors behind disease progression and the unique genetic background of each patient, all so complex to translate into therapies?

This leads to the most heartbreaking consideration: what if the best treatments for a specific patient sat ready in a pharmacy, but no one realized they were right? That’s what inspired us to create the PARIS Test, named for the warrior from Greek mythology who defeated his rival by finding the weakness in Achilles’ heel.

Our concept is to derive tumor organoids from a patient, so they reflect the actual characteristics of that individual’s disease, then use them to screen an array of potential therapies from our library of cancer drugs.

The way it works is, a patient or their care team shares some basic information with our CLIA-certified lab in Seattle, WA, so we can prepare instructions for an oncologist to collect appropriate biopsies (ideally four in total), surgical excision (~1 cm³), or body fluid ( more than 250 ml). Once we’ve received the sample, we use it to grow the 3D organoids, and leverage robotics to quickly screen hundreds of cancer drugs and combinations. Data produced from this process is analyzed through our informatics pipeline and combined with DNA sequencing for context, to produce an actionable report for oncologists with treatment recommendations and the rationale behind those choices. These reports get delivered to doctors in two to six weeks, and studies have shown their strong predictive power—more than 70% of patients’ clinical responses match the PARIS Test results.

Sometimes, the report confirms that the standard of care is the best way forward. But often we discover new options that can change a person’s life. One example we’re very proud of was summarized in a recently published case study for a patient we encountered who was in rapid decline and in hospice after failing standard-of-care treatments for her low-grade serous ovarian cancer (LGSOC). The PARIS Test identified the best course as a series of therapies that were approved as targeted lymphoma or lung cancer treatments, with little or no clinical evidence that anyone had even tried them in LGSOC. Through this personalized and targeted course of treatment, her symptoms reversed and she has experienced several years of stable disease.

Having now learned from hundreds of PARIS Test results from different patients, the most encouraging findings are that cancers, despite their chemoresistance, will still harbor unique sensitivities to very specific targeted treatments. Often, these unique cancer Achille’s heels are not obviously predicted from just DNA or RNA testing. These results and the many patients who have benefited from the PARIS Test indicate much hope for cancer patients—and the more medicines we will have, the higher the chance of finding a match for every patient’s cancer.

Dr. Grandori can be reached at cgrandori@senginemedicine.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.

When standard-of-care is an excuse for licensed medical malpractice

Are you getting trustworthy prostate cancer information? The terms standard-of-care, medical practice guidelines, FDA approved and, covered by insurance certainly seem very reassuring. But let’s see if some of these long-held beliefs about prostate cancer testing and treatment are dependable or whether they are simply untrue.

Curious Dr. George: Most people with prostate cancer live a long and healthy life. But some die, with or without treatment. It can be a confusing disease. To what extent are American men and physicians receiving trustworthy information about prostate cancer?

The term prostate cancer.

Belief – All prostate cancers are deadly.

Evidence against the all-inclusive prostate cancer label – Prostate cancers are not all equally deadly. In fact, it’s mostly the 10 to 15 percent of high-grade, aggressive prostate cancers that are responsible for the 30,000 or so U.S. deaths annually.

Bottom line – The vast majority of men diagnosed with prostate cancer do not die of it. Furthermore, not only is the 10-year survival about the same whether treated or not but the 15-year survival rate, irrespective of treatment option, is about the same.

Prostate specific antigen (PSA) blood test.

Belief – The PSA test leads to early prostate cancer detection, early treatment and life-extension.

Evidence against PSA testing – The PSA has a false-positive rate of 78 percent because it is neither specific to the prostate or specific to prostate cancer; its so-called cut-off value of 0-4 n g/ml is an arbitrary and misleading metric; a PSA above 4 does not mean a diagnosis of prostate cancer; large prostates commonly generate high PSAs; the PSA value can be artificially raised or lowered without a cancer being present or progressing; the PSA cannot distinguish between aggressive and non-aggressive cancers; lowering the PSA does not lower a risk of cancer and, the subset of high-grade, aggressive and potentially deadly prostate cancers may produce little to no PSA and can go undetected. Incomprehensibly, although the reliability of the PSA was concerning from the outset, the FDA (Food and Drug Administration) approved the PSA test for prostate cancer screening in 1994. Unsurprisingly, in 2009 urologists clinical studies determined that PSA testing failed to save significant numbers of lives. More damning, the USPSTF (United States Preventive Services Task Force) gave PSA-based prostate cancer screening a “D” grade in 2011 concluding that, “the benefits do not outweigh the harms”. Shamefully, after pressure from self-interest groups the USPSTF “D” grading was watered-down to an ineffectual “C” warning in 2018.

Bottom line – PSA-based screening – includes the inaccurate digital prostate exam or digital rectal exam (DRE) – is highly unreliable, risky and fails to save significant numbers of lives. In fact, many cancers are detected by chance during evaluation for an elevated PSA as the PSA was generated by the BPH and not the cancer. Currently, there is no blood or urine test that can detect just high-grade prostate cancer reliably.

The ultrasound-guided prostate needle biopsy.

Belief – That an ultrasound-guided prostate needle biopsy can reliably detect a potentially deadly prostate cancer.

Evidence against the ultrasound-guided prostate needle biopsy – 1. Prostate cancer is commonly a multifocal disease – meaning that areas of cancer can arise in several different areas of the prostate at the same time or, later. Yet, so-called standard practice for detection calls for the use of an ultrasound, which can’t see the cancer and then randomly and blindly biopsy the prostate 12 times with a needle to evaluate whether or not a cancer is present. When the volume of these 12 needle cores is measured against the volume of an average prostate, only about 0.1 percent of the prostate ends up being sampled. It also means that the clinical state of the 99.9 percent of the un-sampled prostate remains unknown. Even if 120 biopsies were taken (10 times the standard number of 12) you would still be clueless about 99.0 percent of the prostate. 2. There are two techniques for prostate biopsy: transrectal or transperineal (with or without a template). The transrectal approach is riskier than the transperineal and is associated with potentially serious complications of sepsis and bleeding. 3. The concern about false negatives (missing cancers) is hardly surprising when only 0.1 percent of the prostate is sampled. The transrectal approach has recorded a false negative rate of more than 33 percent. On the other hand, others have claimed to find 6 percent more cancers using the transperineal route. Possibly because of the compressive effects on the prostate and the angle at which the transperineally placed needle enters the prostate.

Bottom line – The ultrasound-guided needle biopsy test is risky and embarrassingly unscientific because of its egregious sampling error. The perineal approach is less risky but equally unscientific. Additionally, there is no hard evidence that either technique detects significant numbers of the 10-15 percent of the potentially lethal high-risk tumors. However, the best current screening tool to detect significant cancer anywhere in the prostate is the non-contrast MRI conducted by a radiologist with expertise in MRI prostate imaging. Areas judged to be consistent with PI-RADS four or five disease on the MRI are suggestive of potentially lethal high-grade disease and can be confirmed with an MRI-guided targeted biopsy.

The Gleason grade and score.

Belief – A pathologist’s interpretation of what is judged to be a certain grade of cancer under the microscope is reliable.

Evidence against Gleason grading reliability – The Gleason grading and scoring system is complex and relies overly on a pathologist’s knowledge and interpretive skills for estimating what grades of cancer they believe to see under low-power microscopy. Because of potential errors of judgment, grade misclassifications and disagreements amongst pathologists are common – underscoring a profound lack of reproducibility of the Gleason system.

Bottom line – Patients can never be absolutely sure of their prostate cancer grades and scores. Getting a second opinion from an experienced prostate cancer pathologist and undertaking a screening non-contrast MRI of the prostate with an expert is appropriate.

The Gleason grade 3 and the 3+3=6 “cancer”.

Belief – The Gleason grade 3 (in the Gleason 3+3=6) is a “cancer”.

Evidence against the Gleason grade 3 being a cancer – Initially, the Gleason grade 3 appearance under low-power microscopy was thought to be consistent with an early low-grade, low-risk cancer. However, since then, both the clinical evidence and the fact that the genetic pathways enabling cancer development and spread are turned off indicate that the Gleason grade 3 lacks the features of a cancer.

Bottom line – The Gleason grade 3 fails to behave as cancerous since it is not a cancer. Shamefully, the grade 3 (3+3=6) is still labeled as a cancer, scaring untold numbers of patients towards unnecessary investigation and harmful treatment. Rather, the grade 3 disease appears to be simply a benign feature of aging.

Imaging for the staging of prostate cancer.

Belief – That bone scans, ultrasounds and CT scans can determine whether a cancer is localized or has spread.

Evidence against bone scans, ultrasounds and CT scans for staging – Bone scans, ultrasounds and CT scans are quite insensitive for detecting small volume cancer spread making their use in staging unreliable. Underscoring this concern is the fact that prostate cancer cells have been found in the bone marrow of patients with so-called localized disease. These metastases may begin when high-grade cancers are as small as 0.25 mm in size and barely detectable within the prostate.

Bottom line – Staging of prostate cancer using bone scans, ultrasounds and CT scans is unreliable due to their insensitivity. The PMSA PET/CT scan and the whole body diffusion MRI studies have greater reliability for detecting small-volume spread to lymph nodes and bones. 

Prostate cancer surgical “treatment”.

Belief – That cutting out prostate cancer – whether open or robotically gets rid of it and “saves lives”.

Evidence against surgery – H.H. Young M.D. claimed early diagnosis, cure and “the remarkably satisfactory functional results furnished” from his surgical technique. In contrast, he gave zero evidence for early diagnosis or cure, two patients died and the other two were left with lifelong urinary leakage. And, when robotics entered the business of surgery not only was the device given an FDA approval without demonstrating clear benefits but the FDA’s fallacious 510(K) process was then manipulated to permit use of the tool in radical prostate surgery. Again, without sufficient evidence for safety or benefits. Unsurprisingly, the robotic prostatectomy has a similar incidence of residual cancer (positive margins occurred in 11- 48 percent of patients) and a similar incidence of impotence and incontinence to open surgery. These complications are common and typically managed with radiation, counseling and rehabilitation programs or, implantable devices for ongoing limp and leaking issues. The breakdown of these gadgets often results in more surgery, costs and suffering. In fact, the number of complications associated with the robotic device is highlighted in the FDA’s MAUDE (Manufacturer and User Facility Device Experience) site which recorded a great increase in adverse events. Irrationally, radical prostatectomy is still considered standard-of-care despite physicians concluding in 2012 that surgery failed to save significant numbers of lives. And, despite the evidence against surgery, the SPCG4 article and its conclusion “Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer”, is often quoted by urologists to support their opinion that radical prostatectomy saves lives. Aside from this work recording a substantial number of impotence and incontinence complications, the study is also flawed because of the commingling of participants with various Gleason grades and scores (both well differentiated and moderately well differentiated), unknown tumor volumes and the arbitrary use of anti-androgens in others – issues that can skew results. Additionally, the relatively short follow up time for this study (15 years) is troubling since the particular prostate cancers that the researchers targeted grow very slowly. For the low Gleason score/low-risk/well-differentiated, grade 1 tumor a mean cell doubling time of about 577 ± 68 days has been recorded. This figure means that it can take some 40 years or more from the time of cell mutation for the cancer to reach a diameter of 1 cm and be big enough to be felt on manual prostate examination. Clearly, such a slow cell division rate and a median follow up time of 12.8 years can only deliver a semblance of cure.

Bottom line – Cutting out prostate cancer whether by robotic or open techniques is unsafe and fails to save significant numbers of lives. Worse still, life extension has not been demonstrated for any focal or whole-gland prostate cancer treatment options. In part, because most, if not all, studies are flawed by the inclusion of participants with the bogus Gleason 6 “cancer”, incorporating patients with dissimilar Gleason grades, scores and tumor volumes, reliance on insensitive staging methods and, arbitrarily treating others with testosterone suppression.

Active surveillance for low-risk prostate cancer.

Belief – That by using 6 monthly PSAs, 12 monthly DREs, 12 monthly biopsies (a random 12-core) and maybe a 12 monthly MRI urologists can assess if a low-risk prostate cancer was progressing and required treatment. Urologists initiated this program for monitoring low-risk disease after appreciating the facts that most prostate cancers grow slowly and that the treatments were often worse than the disease. Enthusiastic support also came from the NIH.

Evidence against active surveillance – 1. PSA testing (and all other tests incorporating the PSA), DREs and 12-core biopsies (whether transrectal or transperineal) are highly unreliable as detailed above. 2. A prostate cancer diagnosis was likely established on the basis of a 0.1 percent random and blind sampling of the prostate. The follow up biopsy is likely done in exactly the same way. Clearly such an unscientific process can fail to detect a cancer, is unable to target reliably the original cancer and determine if the original cancer has “progressed” or, whether the cancer now detected was already present but missed by the previous biopsy. 3. Since non-contrast MRIs of the prostate (by a radiologist experienced in prostate MRI imaging) are able to examine the whole prostate and reliably identify the 10-15 percent of potentially lethal cancers their use has become more common. However, not all MRI’s are equal. Although MRI-guided targeted biopsies have been recorded as being dependable, most prostate needle biopsies are not undertaken using MRI-guided targeted techniques but by urologists using “fusion” studies. There are a number of concerns associated with the reliability of this fusion method. The MRI is commonly undertaken by a radiologist of unknown experience, knowledge and interpretative ability for PI-RADS findings – PI-RADS 4 or 5 changes on the MRI may reflect potentially lethal disease. However, this PI-RADS classification, like the Gleason grading and scoring system, is complex and has concerns for errors of interpretation. Additionally, the quality of the MRI study generated can be impacted by the radiologist’s particular study methodology, the particulars of the MRI machine and its software. Then, this previously recorded MRI study is “fused” with the ultrasound study on the day that the prostate biopsy is undertaken. Now, there are additional concerns relating to the type of ultrasound machine to be used and the ability of the urologist to interpret the images. Once “suspicious” areas are “identified” with this fusion method they can be targeted for biopsy. Absurdly, many urologists will add a random biopsy sampling 0.1 percent of the prostate to the targeted biopsy of the high-risk area located in the fusion study. This additional biopsy may only increase the risk of complications and the detection of non-lethal disease. Also bothersome, although MRI-guided targeted biopsies of PI-RADS 4 and 5 areas by radiologists may be more reliable, the fusion technique keeps the biopsy (and revenue) in the hands of urologists. 4. The definitions used to determine “progression” of low-risk disease are variable, unreliable and also impacted by laboratory and observer error – PSA level, PSA velocity or density, clinical staging, DRE, biopsies, Gleason grades and scores, tumor volumes and the number of positive cores and core lengths – none truly reflect what’s happening in the entire prostate. 5. PSA testing and surgical treatment do not save significant numbers of lives. 6. Whether you are treated or not the 10 year survival is about the same.

Bottom line – Clearly, misinterpretations about the presence or absence of cancer, stability of a low-risk cancer or the “progression” of disease are inevitable because of multiple inaccuracies. The potential benefits of active surveillance for low and moderate risk prostate cancer and the saving of significant numbers of lives because of so-called “timely” identification of disease progression have not been supported by hard data. This is not surprising when a number of highly unreliable tests are conflated to generate an unreliable endpoint before initiating a treatment option for which there is no evidence that significant numbers of lives are saved.

Why prostate cancer information is untrustworthy.

PSA-based testing and prostate cancer surgery are both risky and fail to save significant numbers of lives. How then, did the standard-of-care dogma about prostate cancer testing and treatment become so disconnected from the clinical evidence?

Meta-researcher John Ioannidis M.D. discovered the likely cause of this uncoupling of treatment beliefs from the evidence after reviewing multiple healthcare papers. He concluded that “most published research is false”. False, because most studies were commonly not founded on sound scientific principles and corrupted by errors of judgment, approximations, opinions, assumptions and conflicts-of-interest. Making this “research information” more suspect was the inevitable manipulation of study design and results by sponsoring organizations to produce “facts” supporting their biases.

Reliable healthcare information can only be developed from data sourced from studies delivering irrefutable and reproducible results. In contrast, much of the material used to develop the guidelines for prostate cancer management came from very poorly designed studies and beliefs. An all too common junk science that results in prescriptions for care that are untrustworthy, commonly exploitative and make a mockery of the Hippocratic Oath.

More references.

The Great Prostate Hoax by R. Ablin and R. Piana.

The Rise and Fall of the Prostate Cancer Scam by A. Horan M.D. 

Dedication.

This article is dedicated to Anthony Horan MD, a urologist and author (The Rise and Fall of the Prostate Cancer Scam) who fearlessly challenged the culture and the business of prostate cancer. He was always on the right side of what should never have been a controversy. Sadly, the prostate cancer testing and treatment industry is a 32.7 billion dollar market for which there is no hard evidence that significant numbers of lives are being saved.

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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.

Immunotherapy—a type of treatment that harnesses a patient’s own immune system to fight cancer—has been a “game changer” for many patients. It can be difficult, however, to predict whether or not a given person would benefit from immunotherapy, especially when it comes to drugs that target the immune system molecules PD-1 and PD-L1. Our Curious Dr. George asks Scott Tomlins, MD, PhD, Co-founder and Chief Medical Officer of Strata Oncology, about his company’s new tool to help ensure that anyone who could benefit from these drugs is identified.

Curious Dr. George: One predictor of response to immunotherapy, tumor mutation burden (TMB), has been very helpful for patients whose tumors have a high TMB score. But the tumors of many other patients may also respond to immunotherapy, providing substantial benefits in both progression-free and overall survival. What is Strata Oncology’s Immunotherapy Response Score^TM (IRS^TM), how effective is it, and how can patients with solid tumors access it?

Scott Tomlins, MD, PhD: Current biomarkers for immunotherapy are not enough. Immune checkpoint inhibition with monoclonal antibodies targeting PD-1 and PD-L1 has revolutionized the care of patients with advanced cancer. TMB is an important pan-tumor biomarker for anti-PD-1/PD-L1 therapy, but it does not identify most patients who benefit.

For example, let’s look at the KEYNOTE-158 study of 10 tumor types that led to pan-solid tumor approval by the U.S. Food and Drug Administration (FDA) of second-line pembrolizumab monotherapy in patients who are TMB-high (TMB-H). While a higher objective response rate (ORR) was observed in TMB-H patients versus TMB-low (TMB-L), numerically more objective responses were observed in TMB-L patients (43 out of 688 in TMB-L versus 30 out of 102 in TMB-H). This study demonstrates that TMB alone is not sufficient to identify all responders.

Likewise, in an analysis of TMB in 1,772 patients treated with pembrolizumab monotherapy across 24 tumor types, although ORR was significantly higher in TMB-H versus TMB-L patients, numerically similar numbers of responding patients were again observed (136 out of 433 in TMB-H versus 127 out of 1339 in TMB-L).

Clearly, there is more to the story when it comes to who will benefit from anti-PD-1/PD-L1 therapy. An improved predictive biomarker is needed to ensure that all patients who can benefit from immunotherapy are given the opportunity.

In our recent publication in Communications Medicine, we describe the development, validation, and clinical utility of a new biomarker that fulfills this unmet medical need—the Immunotherapy Response Score or “IRS”.

Immunotherapy Response Score (IRS) is an improved predictive biomarker

IRS combines TMB with four target gene expression measurements (PD-L1, PD-1, TOP2A, and ADAM12) from simultaneous, analytically valid, comprehensive genomic profiling (CGP) plus quantitative transcriptional profiling (qTP) of formalin-fixed paraffin-embedded (FFPE) tumor specimens.

We developed IRS using molecular profiling data combined with treatment and outcome data from the Strata Trial® (NCT03061305), an ongoing observational clinical trial evaluating the impact of molecular profiling for patients with advanced solid tumors.

IRS was trained to predict real-world progression-free survival (rwPFS, by time-to-next-therapy) in a discovery cohort (26 tumor types) of patients treated with pembrolizumab systemic therapy and was then validated in an independent cohort (24 tumor types) of patients treated with non-pembrolizumab anti-PD-1/PD-L1 monotherapy.

In the validation cohort, IRS-high (IRS-H) versus IRS-low (IRS-L) patients had significantly longer anti-PD-1/PD-L1 monotherapy rwPFS (median rwPFS 23.1 months versus 10.2 months, adjusted hazard ratio = 0.52) and overall survival (OS; median OS 40.4 months versus 21.4 months, adjusted hazard ratio = 0.49).

The predictive nature of IRS was confirmed in a case-crossover analysis of 146 patients from the pembrolizumab cohort who had received a previous line of systemic therapy prior to pembrolizumab monotherapy, and by a lack of association with rwPFS in 3,184 patients treated with a non-anti-PD-1/PD-1 or anti-CTLA4 containing first line systemic therapy.

IRS-H/TMB-L patients had similar outcomes as IRS-H/TMB-H patients, demonstrating the clinical utility of IRS beyond TMB alone. Across all Strata Trial patients, IRS-H identified a population nearly twice the size of the TMB-H population (n=24,463; 20.9% versus 10.8%). Critically, 7.6% of patients with tumor types not approved for PD-1/PD-L1 monotherapy were IRS-H/TMB-L, representing a sizable population predicted to have benefit but not currently eligible for treatment.

Bringing new options to people with cancer

We are excited to put this novel biomarker into the hands of physicians to help them ensure every patient gets their best-possible therapy. We are currently providing early access to IRS to a select group of key opinion leaders. IRS will be more broadly available later in 2023.

IRS is just the beginning. By leveraging data from tens of thousands of patients collected under the Strata Trial protocol we are discovering, validating, and demonstrating clinical utility for multiple new, highly quantitative, DNA- and RNA-based multivariate predictive treatment selection biomarker algorithms that span therapeutic modalities.

Dr. Tomlins can be reached at scott.tomlins@strataoncology.com.

Today, many cancer patients benefit from targeted drugs that are matched to the distinct genetic mutations found in their tumors. However, especially in late-stage cancer, this “precision oncology” strategy has not proven to be as transformative as people once hoped. Here, Curious Dr. George asks Clifford A. Reid, PhD, CEO of Travera, how his company is addressing this problem.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved about 270 anti-cancer drugs. The National Comprehensive Cancer Network publishes guidelines for treatment of about 61 major cancer types. There is consensus on 1^st– and 2^nd-line therapy for most, but great divergence on best 3^rd-line treatment. Precision oncology based on population studies not only usually fails but is a false premise. What is Travera doing to convert the promise of effective and efficient targeted drug therapy into reality?

Clifford A. Reid, PhD: The original goal of what we now know as “precision oncology” was to understand the root genetic cause of each cancer, and then design a set of targeted drugs to attack each of these cancer-causing DNA mutations. At the time, this was called “personalized oncology,” and its promise was to deliver “the right drug to the right patient at the right time” based on the DNA mutations in each cancer. Unfortunately, this approach has not worked. While the cancer research community has identified hundreds of cancer-causing DNA mutations, drugs that target these mutations inexplicably don’t work for many patients that have the targeted mutations. To our great disappointment, the promise of personalized oncology is not being realized by these genetically targeted drugs.

A small part of the cancer research community has long recognized that it is simply impossible for the results of a clinical trial to generate personalized therapies for each individual patient. Clinical trials are fundamentally designed to include a population of “similar” patients, and get drugs approved for that population. But we know that cancers are highly heterogeneous, especially in late-stage patients, and that no “one size fits all” result of a clinical trial can address each individual patient’s unique cancer.

That part of the cancer research community has focused on developing tests that directly measure the response of an individual’s live cancer cells to a large set of cancer drugs. This direct-measurement approach not only incorporates everything we know about how cancers and cancer drugs work, but also incorporates everything we don’t know. It simply tries a variety of cancer drugs on each patient’s live cancer cells to find the drug or drug combination that will work for that patient at that moment in time.

While this direct-measurement approach may seem quite obvious, as it works beautifully for selecting the right antibiotics for patients with bacterial infections, it has never really worked in cancer, despite decades of efforts. The fundamental problem is that cancer cells, which are so robust inside a patient, become extremely fragile when removed from the patient, and typically die before most cancer drugs can be tested against them. Efforts to keep the cells alive long enough to test them have backfired: cancer cells forced to stay alive change how they respond to cancer drugs, and no longer behave like the cancer cells inside the patient.

Travera is the first company to develop a test that is fast enough to measure the response of cancer cells to cancer drugs without having to force the cancer cells to stay alive for many days outside the patient. Using a new measurement tool invented at the Massachusetts Institute of Technology (MIT), Travera measures the weight change of individual cancer cells in response to cancer drugs. It turns out that for most cancers and most cancer drugs, if the drug is going to kill the cancer cells in a few days, then it changes the weights of the cancer cells in a few hours, but by an amount too small to be detected prior to the MIT invention. Travera uses this exquisitely sensitive measurement tool to offer its Rapid Therapy Guidance test with 2-day turnaround time and high predictive accuracy. The test is now available for most cancers (including all carcinomas) and for over 100 FDA-approved cancer drugs.

For more information, please visit Travera at www.travera.com

Dr. Reid can be reached at creid@travera.com.

In 2020, writer Ronald Piana shared with our readers his own experience of using hydrogen peroxide to quickly eradicate a clinically diagnosed pre-malignant oral leukoplakia—a condition that can develop into oral cancer. Here, Curious Dr. George follows up with him and hears an additional perspective from retired urologic surgeon Bert Vorstman, MD, MS, FAAP, FRACS, FACS.

Curious Dr. George: About 2 years have passed since you shared your story.  Has the lesion reappeared or does it remain “disappeared”?

Ronald Piana: As noted in my 2020 Curious Dr. George post, in 2018 I presented to my dentist with a raised 3-cm lesion on the lateral border of my tongue, where most cases of squamous cell carcinoma (SCC) occur. After treating the lesion with four separate topical applications of high-concentration H₂O₂ (hydrogen peroxide), it disappeared. To date, there has been no recurrence, which indicates that direct-contact application of high-concentration H₂O₂ had sufficient cell-kill penetration to “cure” the premalignant lesion.

Curious Dr. George: Have you learned of any other people who have tried the peroxide treatment for similar lesions? If so, what are the results?

Ronald Piana: Since the publication of the 2020 blog post, I have received several emails from people around the country seeking advice on treating suspicious lesions with high-concentration H₂O_2. All, except for one, have been oral lesions similar to the one I presented in the original blog post. Every oral lesion was treated successfully, and on follow-up emails 6-months post treatment, there has been no recurrence.

I would like to introduce to you Bert Vorstman, MD, MS, FAAP, FRACS, FACS, a retired urologic surgeon in Coral Springs, Florida, who has offered to share a case history of the exception, which involved squamous cell carcinomas of the face and leg.

Bert Vorstman, MD, MS, FAAP, FRACS, FACS: Some months ago, I happened on the Curious Dr. George blog post about Ronald Piana’s experience with the treatment of a suspicious tongue growth with high-concentrate hydrogen peroxide—a simple over the counter application that cured his precancerous lesion.

As a physician and outdoorsman, I was intrigued by this easy self-treatment as I had been visiting the dermatologist for years to have various squamous cell cancers burnt off with liquid nitrogen, an uncomfortable and costly procedure. Superficial skin cancers and precancers consistently recur, a reason why dermatologists have you coming back for office visits every few months or so for a check and burn, and maybe a biopsy or two for good measure.

I decided to try the treatment and purchased a bottle of food-grade 33 percent H₂O₂. I used a dropper to soak a Q-tip with H₂O₂ and applied it to a squamous cell cancer on the right side of my face. After 10 to 15 seconds, I could feel some tingling and mild discomfort. After 30 seconds or so I could see that the area in question had turned a speckled white. The tingling and mild discomfort soon settled. I applied the peroxide morning and evening for 2 to 3 days and stopped. Within a few days there was no sign of the lesion.

In between dermatology visits I noticed the development of another typical skin cancer on my right lower cheek; red, scaly and sensitive. I used the H₂O₂ treatment, and the skin cancer disappeared.  After this success, I became concerned about a small spot on the right side of my nose and one on the outer part of my left lower leg. Both of these areas received the same treatment as I had done to my face. These areas also disappeared. And, three months later when I returned to the dermatologist. I didn’t tell her about the areas I had treated but she could not find any areas of concern. Periodic self-examination and self-treatment with 33 percent H₂O₂ was a lot easier, more convenient, and much less costly than visiting the skin doctor. This process also eliminates the long waiting time to get a referral and convenient appointment, which can also prevent treatment delay and potential disease progression.

Moreover, simple H₂O₂ treatment can obviate the potential for Mohs surgery, an expensive procedure that can result in surgical defect requiring a plastic surgeon to undertake a complex closure to fully reconstruct the surgical site. The self-diagnosis and self-treatment of superficial squamous cell cancers with food strength hydrogen peroxide is easy, convenient and cheap.

Ronald Piana: The cytotoxic potency of H₂O₂ is well documented; however, its clinical value in cancer treatment has largely remained overlooked. In the report by Mundi, et al, the authors offered several hypotheses about the mechanism of action by which H₂O₂ eradicated squamous cell carcinomas. It is beyond the scope of this post to delve at length into those complex biochemical processes. However, my research of the literature concerning the cytotoxic properties of H₂O₂ has found a scientifically sound hypothesis based on the cancer cell’s own inherent weakness. Studies have shown that all but one human cancer cell type, a human renal adenocarcinoma, have low levels of catalase, thus, the vast majority of cancer cells lack the biochemical machinery needed to detoxify higher fluxes of H₂O₂.

More important, lysosomes (aka “suicide bags”) do not contain hydrogen-peroxide-degrading enzymes, such as catalase or glutathione peroxidase. During oxidative stress, large amounts of hydrogen peroxide enter the lysosomal compartment, with the formation of abundant hydroxyl radicals, or highly reactive iron-centered radicals, destabilizing the lysosome to the point of rupture, leading to cell death. In short, H₂O₂ is a proven Trojan Horse compound that permeates the cancer cell and induces a cascade of suicidal events. This post argues that given its enormous anticancer potential, H₂O₂ therapy deserves further testing so that it can be integrated into appropriate clinical settings.

Ronald Piana can be reached at ron.piana@gmail.com.