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.

Genetic mutations found in a tumor can be important clues to the patient’s best treatment options. Memorial Sloan Kettering Cancer Center (MSK) in New York has developed a product called OncoKB™, which enables anyone to access and navigate key clinical information about the various genetic abnormalities that may be found in tumors. Here, Curious Dr. George asks MSK Lead Software Engineer Hongxin Zhang about this tool.

Curious Dr. George: At the 2022 Precision Medicine World Conference in Santa Clara, CA, you outlined how OncoKB can be of great value for investigators, drug developers, regulators, educators, clinical oncologists, and patients. Offered through a 501(c)(3) organization, how can OncoKB help other 501(c)(3) charities access focused information and options for people with advanced cancer?

Hongxin Zhang: Precision oncology is defined as using molecular profiles to identify clinically actionable driver alterations in patient tumor samples. It has become the standard of care for many cancer types, and there are many steps between having a patient consent to tumor sequencing and having a clinical oncologist make a decision on the basis of the patient’s tumor molecular results. Interpretation of sequencing results is confounded by the sheer number of alterations that can surface from next-generation sequencing (NGS), but is a critical step in the utility of clinical NGS testing and consequent clinical decision making.

Tumor-specific (or “somatic”) mutations are divided into those that are causal in tumor development, so-called driver mutations, and those that are benign bystander mutations, or “passengers”. Most of the variants detected in a patient tumor sample are passenger mutations. A small subset of driver mutations can serve as predictive biomarkers of response or resistance to targeted therapies, and these mutations are considered clinically actionable.

The challenge for clinicians and researchers is how to reliably identify a clinically actionable variant. Information describing a variant’s biological and oncogenic effect and clinical actionability is buried in various unstructured resources, such as the text of scientific research papers. Therefore, the process for a clinical oncologist or molecular pathologist to accurately and reliably identify actionable mutations and make a timely clinical decision is time-consuming and laborious. Also, new data regarding predictive biomarkers is always emerging, making NGS sequencing-based clinical decisions require the practitioner to be completely up to date on advancements in molecular and clinical oncology.

OncoKB is a precision oncology knowledge base developed at MSK that contains biological and clinical information about genomic alterations in cancer. Alteration- and tumor type-specific therapeutic implications are classified using the OncoKB Levels of Evidence system, which assigns clinical actionability to individual mutational events. Annotations are provided based on sample biomarkers and through high-performance programmable access. This ensures the timely delivery of clinical interpretation.

OncoKB implements multiple steps to ensure content quality. First, all content is curated by oncology medical fellows, translational cancer biology postdoctoral fellows, or graduate students. All scientific and clinical content is supervised and reviewed by the OncoKB PhD-level Scientific Content Management team per the OncoKB standard operating procedure. Second, all clinical evidence must be approved by our Clinical Genomics Annotation Committee, which consists of about 50 clinicians across all disease teams at MSK. Third, we introduced an External Advisory Board (EAB) composed of leaders in the cancer genomics field across major cancer hospitals. The EAB members oversee OncoKB development and mitigate any issues arising from conflicts of interest. Based on this model, OncoKB has been annotating patient results from MSK-IMPACT™, an NGS-based multiple-panel sequencing assay, since 2016, with roughly 12,000 samples annotated yearly.

Initially introduced to the public space in 2016, OncoKB became the first somatic cancer human variant database to be partially recognized by the U.S. Food and Drug Administration (FDA), in October 2021.

Our mission is to make accurate genomic biomarker annotation available to as many users as we can. We believe that an expert-curated resource like ours would benefit the whole oncology community. Institutions frequently lack the tools and expertise required to conduct a thorough analysis of genetic data, especially those located in underrepresented communities. OncoKB is free to use in an academic setting, which includes all research projects in all 501(c)(3) organizations. Additionally, a commercial license can be provided if annotation is used in the report. The cost is determined by report volume, business size, and particular usage. If you are interested, don’t hesitate to get in touch with us.

Zhang can be reached at zhangh2@mskcc.org.

Typical approaches to cancer research don’t necessarily capture the whole picture of what a patient might experience. Here, our Curious Dr. George asks Nicole Jardine, BASc, how real-world evidence can improve cancer research. Jardine is Associate Manager, Patient Journey Analytics at the company Self Care Catalysts, recently acquired by Alira Health.

Curious Dr. George: In your role at Self Care Catalysts, you have access to a trove of self-reported linear patient data—including treatment outcomes—from a large number of patients who, over several years, have used the Health Storylines Platform to manage their journey and generate real-world evidence. Can you share how this process provides notable insights?

Nicole Jardine, BASc: The science and research behind a particular disease are essential to prevent, diagnose, treat, maintain, or cure. But knowing a condition versus understanding the experience of someone with it are quite different. The research put into treating physical and mental health conditions is crucial to the medical field; however, treatment cannot truly progress without understanding the patient’s experience and their quality of life over time. When check-in appointments are the only time patients can share what is working and what is not, a disconnect arises between health personnel and the people they intend to help.

Real-world evidence presents an opportunity to understand decision-making and patient outcomes, providing more context to a patient’s journey. As a person who studies the in-depth experience of patients through de-identified quantitative and qualitative patient-reported data and structured interviews, I can say that supplementing this information is necessary to understand how to improve the ways we support and engage patients.

Part of my job includes comparing scientific literature to the holistic patient experience. Although they are comparable in some respects, the scientific literature does not capture the full experience patients have through interactions with the healthcare system. When you look at a patient’s experience, you are looking at every part—even what they experienced before their diagnosis—to get the full picture. A notable experience I had when doing research on a patient journey was looking at the experience of men with prostate cancer. When comparing the treatment experience of a person with prostate cancer to the literature on prostate cancer treatment, I saw a notable difference on how treatment efficacy is viewed. When literature reports positive outcomes on the efficacy of treatment, it’s seen as a good thing, but when a patient has decreased quality of life despite positive efficacy, where does that lead patients?

For patients, unless the benefits exceed the risks, quality of life trumps treatment compliance. In our patient database, we have 1,900 people with different forms of cancer, including 412 people with prostate cancer who use Health Storylines to track their experience. When we analyzed qualitative and quantitative Patient Reported Outcomes of these men, as well as five patient interviews, various themes emerged from the patient-reported treatment process, highlighting why treatment is not just about efficacy. The first theme is that oftentimes men are wary of speaking to their doctor regarding prostate cancer; it can be difficult to muster up the courage to even get to the doctor to talk about prostate cancer and feelings of worry about the experience. Men tend not to think about prostate cancer until they are diagnosed, so when deciding on treatment they care about their doctor’s opinion; however, that does not come at the expense of wanting to be heard throughout the process. Although men want to be heard and emotionally supported, they do not receive that support because it is often not talked about from the patient or the doctor’s side. Similarly, men are conditioned to be proud, and they struggle to report treatment side effects that hinder their quality of life because they feel misunderstood. This experience is overwhelming for them; it changes their life and perception of the healthcare system.

Understanding the holistic patient experience provides the opportunity to supplement clinical trials for prostate cancer treatment by displaying the experience men had, the variables around treatment persistence, the challenges men experience, what their needs are, how to support them, and what doctors should tell patients when recommending treatment. By not incorporating the authentic patient experience and opinion, the whole story is not being told. Capturing that whole story is necessary to inform future directions in treatment and create a community of patients who are confident in the system that is treating them.

Jardine can be reached at nicole.jardine@alirahealth.com.

Advanced cancer treatment often involves combining multiple drugs. But with a huge number of possible combinations, it is difficult to know which mix might work best for each patient. Here, our Curious Dr. George asks two leaders to describe how the company First Ascent Biomedical is addressing this challenge.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved many thousands of drugs for marketing, including many hundreds of drugs for use in treating cancer. Some of these drugs are effective; many are not. Many cancers remain without effective therapies. The opportunity to combine FDA-approved drugs offers an additional potential treatment for people with cancer. Many—even most—such combinations have not been rigorously tested.

How does your tumor profiling technology attempt to alleviate that gap and provide hope to cancer patients through combination therapies?

Diana Azzam, PhD, and Noah Berlow, PhD: The development of combination chemotherapy regimens was one of the earliest revolutions in cancer care that led to improved outcomes across nearly every cancer type. The power of drug combinations has been established by decades of clinical data, which is why 25% of oncology clinical trials are designed around drug combinations. Combination therapies are valuable to pharma as well since drug combinations allow for development of new IP and build additional value around assets.

But the driving challenge is always who, which, and when. Who needs which combination, and when? Given that the FDA has approved over 200 cancer drugs, there are over 19,000 possible 2-drug combinations, over 1.3 million 3-drug combinations, and 64 million 4-drug combinations. Setting up 19,000 clinical trials across every cancer type to explore every 2-drug combination is an intractable clinical problem, much less 3- or 4-drug combinations. Correspondingly, finding the right combination for the right patient at the right time is a profoundly difficult problem—but one that our technologies are working to address.

Our approach to this problem is driven first and foremost by functional drug testing, the process of testing a variety of anti-cancer drugs on live cancer cells derived from the patient’s own tumor. This process allows us to identify which drugs are more likely to be effective on the patient’s tumor. The unique way we perform drug sensitivity testing allows us to rapidly test more than 100 cancer agents on the patient’s cancer cells with a median 7-day turnaround time from tissue receipt to return of drug sensitivity results—both for solid and hematological cancers. This is fast enough to support clinical decisions for patients, especially those who have exhausted standard-of-care treatment options.

Our process primarily tests single drugs to identify which drugs show potential, which is where our artificial intelligence/machine learning (AI/ML) comes into play. The AI/ML platform uses the drug sensitivity data—which drugs worked, and which did not—and the patient’s genomic profile to identify multivariate mechanisms driving drug sensitivity. By understanding those critical vulnerabilities, identifying drug combinations becomes a matter of matching FDA-approved, clinically available drugs to the tumor vulnerabilities. We can then use the AI/ML to inform combination design, which, alongside physician input on combinations of interest, guides follow-up combination drug testing. The AI/ML enables us to close the feedback loop in drug combination testing for any cancer patient.

The AI/ML right now is focused on building a deep understanding of an individual patient. As we continue to work with new patients and accumulate more data, we plan to leverage the same AI/ML to identify patterns of patient response within cancer populations to support the development of drug combination studies or even monotherapy trials for the right population. We can support new trial development from insights built on drug response data from direct testing of hundreds or thousands of cancer patients, paving the way for more combination therapies for more cancer types, with a better understanding of who will respond and why.

Dr. Azzam can be reached at dazzam@fiu.edu and Dr. Berlow at nberlow@firstascentbio.com.

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.

Curious Dr. George: Last year, 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.

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.

Additionally, if MSI high is noted during molecular testing of tumor tissue, the patient may at some later time be eligible for treatment with an immune checkpoint inhibitor, 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.

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 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.

Related links:

How Would an Expert Handle His Own Cancer of Unknown Origin Causing Severe Back Pain?

Harnessing Each Patient’s Data to Help Many More

Cancer Commons Adapts to Remain True to Our Mission

A message from Curious Dr. George:

The goal of Cancer Commons is to help patients find 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 free, personalized information about your options.

***

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.