Atlas Oncology-Nanoknife Inst for Advc Cancer Ablation

12/03/2022

Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies ...

12/03/2022

Radiation therapy has been showing promise in improving overall survival especially when used in a total ablative dose strategy. Nevertheless, that data is still very fresh and long term studies will be necessary that most PC patients don’t have.
This is a very nice article that will give insight into how the various types of RT are administered and their local effects and outcomes.
As tumor and peritumoral fibrosis is a major outcome effecting survival one must realize that it will impact down line treatment strategies that require agents administered systemically will not be able to achieve necessary therapeutic levels. Also long term studies show that RT rarely achieves total tumor distruction, but rather isolation in a hypoxic environment that will slow the growth of whatever residual disease remains. Many patients have become disenchanted after learning the tumor “reactivated” after being told it was dead.
As can be seen we are making progress but are not nearly where we need or ought to be. Much of this occurs because of each oncologists bias surrounding the effectiveness their specialties options and lack of effectiveness of the competing specialties. In attending thousands of multidisciplinary tumor boards where open exchange should be de’riguer one finds most time is spent defending and secondarily thinking thru the “pimp me” question?
For the treatment of Pancreatic Cancer to be effective we must look toward an entirely new treatment paradigm that uses a much broader multidisciplinary approach, based on making the primary more sensitive to response while using agents that attack occult micrometastatic disease and using circulating free tumor DNA and not circulating tumor cells alone. The days of relying solely on CA19-9 and CT or MRI need to be moved toward the history books. Yes they have a role, but they are the able to do much beyond identifying which group may become resectable. Unfortunately, 85% of those resected will recur within 2 years. We owe it to all patients not to subject them to surgery they will not largely benefit from. It is for this reason we have move IRE, a form of pulsed electric field ablation with a 15 year track record into the algorithm before Whipple in select cases based on multicenter studies showing survival equal in the nanoknife ablated “in situ” group with more advanced disease to the resected population. That does not mean that the Whipple should be abandoned. Quite the contrary. But rather, placed a little further down the paradigm following a modified Neoadjuvant strategy aimed at primary tumor destruction to prevent further metastasis and allow a window of perhaps 6 months to follow for oligometastatic disease development. Those without evidence of disease would go onto Whipple; whereas those showing rising circulating tumor cells or freeDNA would need to undergo selective sampling to identify the source if not available through imaging.

I am very encouraged by how we have been able to couple the nanoknife ablated primary tumor and immunotherapy (both intratumoral and systemic) but the inability of predict Hyperprogression makes it a double edged sword will very real negative consequences, that the individual is rarely able to recover from. Talk of the impact of the Abscopal Effect is quite real but the actual percent impact remains theoretical.

The rapid addition of targeted agents is exciting and will need to be assessed thru AI models after enough data is collected to see how best to incorporate and for how long.

Currently the patient must be moved into the driver seat for their care. This is an awesome responsibility but necessary as there is no role for passivity. The patient must become their advocate and do so challenging their team and their insurance who wants to deny all therapy showing promise but without 10 years of prospective data which is impossible in PC.

I am optimistic that with an open mind and everyone sitting around the table with our defenses lowered we will make progress and accomplish what our patients expect. We’re not there yet. But in the next decade or so we will need to vastly re-work the NCCN protocols which are “Guidelines” based on past experience in a disease that needs more input from promising future directives of all disciplines other than medical oncology alone, which was largely the NCCN’s focus when it was founded in 1995. Also there needs to be an even faster means of sharing these promising outcomes to the practitioner and patient alike. In this capacity the NCCN has done a very nice job. We just need to do better. There is no time to be resting on laurels when 80-85% of our most promising group of patients due within 5 years.
Robert Donoway, MD, FACS
AtlasOncology.com

Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies ...

11/12/2020

This study which compared the more favorable outcome of patients who received chemotherapy following surgical resection and debulking in colon cancer with peritoneal metastasis. This has been found to be true in other GI and GYN malignancies with a similar trend being seen in Pancreatic cancer from studies using PIPEC in Japan. The importance of chemotherapy following surgical resection for curative intent cannot be stressed enough as that is the best time to control occult micro-metastatic disease rather than waiting for it to be visualized CT imaging.
Robert Donoway,MD,FACS
AtlasOncology.com

https://jamanetwork.com/journals/jamaoncology/article-abstract/2768020?utm_source=facebook&utm_medium=social_jamaonc&utm_campaign=article_alert&utm_content=automated_rss

This cohort study compares survival with adjuvant systemic chemotherapy vs active surveillance in patients with up-front resection of isolated synchronous colorectal peritoneal metastases.

11/09/2020

Locally advanced gastric and GE junction cancers have seen a steady increase during the past 2 decades. Except in Japan and Korea where large scale screening is promoted the survival in stage 3 and 4 remains modest at best. The identification of immune markers being present in gastric cancers has openned up an entirely new realm of treatment possibilities. Attempts to improve upon standard of care chemotherapy by adding an Immune Agent (pembrolizamab) to that chemotherapy as well as when administered alone were the purpose of this large multinational and multi-institutional study published in JAMA-Oncology in late September 2020. The results were interesting in that survival was increased in the Immune therapy alone arm; though it did not quite reach statistical significance. But of equal importance was that the adverse side effect profile was much improved- a factor that significantly affected quality of life. This marks the beginning of where new horizons in treating gastric cancer will be evolve as we learn how and when best to integrate these therapies.
Robert Donoway,MD,FACS
AtlasOncology.com

https://jamanetwork.com/journals/jamaoncology/article-abstract/2769922?utm_source=facebook&utm_medium=social_jamaonc&utm_campaign=article_alert&utm_content=automated_rss

This phase 3, randomized, controlled, partially blinded interventional study evaluates the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced gastric/gastroesophageal junction cancer with PD-L1 combined positive score ≥1...

09/27/2020

Just published this past week in JAMA Oncology it nicely goes through the processes behind selection of immune therapy in melanoma, which is the gold standard immunotherapy model we know the most about. Do not get bogged down in the details. Understanding the complexity by which therapeutic decisions are made and the outcomes they produce is enough to realize we have a very long way to go before we control the cancer response to such agents. In my field of pancreatic cancer we have so much more to learn before we reach the point melanoma has been at for years. The more we know, the more questions arise and once again our hubris is put in check.
Robert Donoway,MD,FACS
AtlasOncology.com

https://jamanetwork.com/journals/jamaoncology/fullarticle/2770701?guestAccessKey=c0567c82-dd7b-46b2-b3cb-6290a510b065&utm_source=fbpage&utm_medium=social_jamaonc&utm_term=3747225616&utm_campaign=article_alert&linkId=100392313&fbclid=IwAR16ZWh1dB_N7iD2vMaj54Cmcea9yg1nqlEGKgiMvfCFe1M-hdz0FaIXz2g

This review outlines the rationale and preclinical evidence that support immune checkpoint inhibitor plus targeted therapy combination and sequencing strategies in melanoma and highlights results from clinical trials exploring these approaches.

08/12/2020

This recently published research from a Harvard group has identified one of the differences in those resistant cancer cells that survive chemotherapy. Though this was identified in a leukemia cell line it will not be long before it's translated into other cancer types. The key here is that this becomes a new target that could lengthen the times effective therapy can be administered so that further attempts at cytoreduction could lead to improved cancer control, whether by surgery, radiation, immunotherapy or even further chemotherapies. Certainly this ground breaking research will be worth following closely.
Robert Donoway,MD,FACS
ATLASOncology.com
[email protected]

08/11/2020

Pancreatic Cancer Ablation using IRE-Nanoknife continues to tackle complex areas that have been left untreated for years because of their inaccessible location.

These Three complex Pancreatic nanoknife/IRE cases are shown below.
Left-Pancreatic retroperitoneal tumor extension 5cm
Center-treatment around celiac axis
Right-treatment inter aorto-caval lymph nodes.

Below is an editorial I wrote about the NanoKnife Surgery Warriors site and the state of Pancreatic ablation. Obviously it heavily reflects my opinion.

Editorial: NSW- Where we've been and where we and the Nanoknife are going in 2020's
Robert B. Donoway,MD,FACS

The original intention of this site was to provide individuals undergoing pancreatic IRE nanoknife ablation a place for warriors and caretakers alike to ask questions, share experiences and learn as much as about the procedure including the risks before deciding it was for them or not. The sites founder,
David Shell had in fact undergone the pancreatic Nanoknife. It was his positive experience with the procedure and his youthful spirit and optimism while down playing the minor issues that every treatment has, that led many who found the site to seek the newly emerging option for patients with advanced stage pancreatic cancer. For those new to the site it is worth taking the time to read all the posts back to 2015. At that time there were very few nanoknife practitioners and centers in the US and EU. Occasionally there were "subtle" disagreements among members, who acting as cheerleaders for their home teams, let things get out of control. Clearly most have felt they were being offered this new life extending treatment by the best wherever that was. Not everyone's life was extended and you can read those posts preserved for review. There has never been any aim to hide any aspect about pancreatic IRE and the risks and outcomes as they are published and included among the posts.
David and I spoke often about the procedure and how remarkable it was in stablizing his disease before it progressed. Even on his worst days he always had a upbeat attitude about the procedure because he knew there were no guarantees. He was very proud of the site and how it morphed into a major source of information challenging any professional site. Nevertheless, he was concerned about the occasional misinformation that got passed on by some who felt they were "nanoknife diplomats without papers." It was during one of those sessions after discussing his case that he invited me to become the "resident nanoknife authority" who could post the latest science, answer concerning questions and occasionally referee if needed. He understood the importance of honesty and understanding there are two sides to every debate and he wanted in a disease so marred by negative that he wanted "his" site to be a force for good, pushing the positive as he recognized that so many patients went to undergo the treatment as a result. He also saw that afterward so many were left out on their own to fend for themselves. It was around these issues that we briefly discussed how we might expand the spectrum of the Nanoknife Warrior Site to engage more people at all educational levels as well as from around the world. The NSW has grown to be recognized as the largest international community of IRE warriors and their caretakers. It has always been and will remain a major source for communication and sharing as well as an open forum for discussion. It will continue to maintain decorum and shy away from name calling and slander as most with this disease recognize no two courses are the same and everyone's risks are different and come with the territory. We recognize that anger is a big part of this disease especially after resection has been taken off the table. Some have been asked to leave because of either their behavior or for violating the agreed rules. Please remember that "Facebook Medical Degrees" are revocable; so please offer and accept advice in the magnanimous fashion it is offered and without trying to create a pontification platform. This is meant to be the site to provide the input to allow those seriously needing information to make life decisions. As in every aspect of cancer care there will be occasions to want to discuss unpleasant events and circumstances related to treatment. This is encouraged but it is requested that you simply leave the names of individuals you're upset at out of your posts. I have witnessed in another pancreatic cancer support group where members voicing encouragement of of another's misinformation led to disastrous results. No one wants that.

It is my hope that you will take away ideas from the Interesting cases to discuss with your home oncology teams. These cases are aimed at stressing that the end of the "standard of care" does not need to be the end. Respected experts are often wrong but their longstanding bias often prevents them from seeing things in a more open fashion. In that situation you may be forced into the position of having to decide on what is more important "your life" or the importance of maintaining the "Professors respect." My advice is always choose "Life!" So to minimize the tension that might be created when you broach these "out of the box" topics I have where possible posted supporting articles so that you can cutoff the common argument that there's "No Data." Almost everything presented has a peer reviewed citation and I want you well armed when you talk to your specialist. Also, as I understand that everyone does not feel comfortable posting questions you may privately email me your questions at:
[email protected]

I will do my best to answer within 72hours.

Lastly I want to address an issue
Some former members promoted as conspiracy theories surrounding my motivation to provide professional support. You are welcome to check my academic credentials, cancer center directorships,clinical reviews and research on nutritional contributions to tumor metastasis. It's all there in the open. I have been practicing pancreatic and Hepatobiliary surgical oncology for over 30, very fortunate and productive, years. I have performed several thousand of these operations(eg,Whipple, DP, IRE, Cryo, RFA, HAIP, Liv Rsx, HIPEC....) and like so many other surgeons who do large volumes of HPB surgery, I saw unexpected recurrence despite throwing everything we had at it. It is incredibly discouraging to travel with the patient on their journey optimistically expecting a Whipple success only to find a recurrence a year or two later. However, it became clear very early that Nanoknife offered the first real new opportunity to perform a less debilitating procedure than Pancreatic resection and provide a possibility for improved survival. If you read through many of the posts on this site you will see there are survivors who started with stage 3 disease going back 10yesrs that are very much alive today and often chime in. Multiple reports confirm this; yet oncologists unaware of its existence continue to deny its value. And patients get caught in the crossfire. But remember it is Not a guarantee, but an opportunity. There are so many variables at interplay even when the disease appears limited. So the nanoknife has become the keystone for what I have defined as a new pancreatic cancer treatment paradigm; one which incorporates a multimodality approach to treat the real pancreatic cancer stage which I feel is always at least 1 stage greater than what we can identify during initial workup and imaging. So whereas the medical oncologist who concentrates on drug therapy, we have long known that drug resistance limits its success and therefore, one must take into consideration equally effective cytotoxic treatments (eg, ablation, Y90,etc) which have all been shown to be important, and are under- used. So nothing you see in the New Paradigm will be "Sorcery or snake oil" as some may suggest. They are all approved strategies and we have 5,6,7 years and longer advanced stage 3 and 4 survivors; and one was featured on ABC News at his 5 year anniversary. And yet in similar fashion these combinations will not be beneficial to every individual. So many factors are at play such as sites of metastasis and Nutritional status which directly impacts Immune competence; and is very important in impacting every part of cancer therapy. Data not desperation needs to be your guide. But the data must always include yours in that decision not just the collection of 99 others from a hopeful "mouse trial." The key take away is that in Pancreatic Cancer we have only marginally moved the "survival needle" by 3-4% in over 80years since Alan Oldfield Whipple described his operation. 9-10% of the current 60,000 new cases will survive 5 years. But only 50% of those reach the 10 year mark. So if the Whipple "cure rate" for stage 1 and 2 is less than 10% it would not be surprising that the nanoknife which is used for more advanced stage disease would have worse survival figures? But that not necessarily true because survival in pancreatic cancer is largely a function of liver involvement; and all those stage 1 and 2 Whipple resections fail because of occult metastatic disease. So the overall survival is a function of many factors. The role of the nanoknife is to destroy the tumor and prevent further metastases. If that happens to occur when the occult liver disease is less, the individual lives longer and can seek additional therapies as gauged by the tumor burden, site, size and location. So when someone says I was "guaranteed" to live two years or more you know they missed the beginning of the sentence that starts...."can possibly all other factors being equal." Unfortunately, despite our technology we are still limited by the inability to reproduceably detect micrometastatic disease. The mission behind Circulating Tumor Cells hopefully will change much of that. So up against those numbers and the realization that your personal cure rate is either 0% or 100% we have come to recognize that the nanoknife has breathed new life into this area and especially when used as an adjunct with the newer immunotherapy and Natural Killer Cell treatments has tremendous "potential" to improve survival and quality of life. The future is limited only by the imagination. We have an obligation to reduce suffering and as death is for a very long time, we owe it to ourselves to cheat it any way we can. So in Pancreatic Cancer we must always remember the best treatments from the past and continue to improve upon them but also strive to think outside the box and integrate promising new therapies.
Lastly, we (my wife and myself) recently established a Pancreatic Cancer Foundation which is aimed at funding both basic and clinical research to focus on areas that continue to move the needle in clinical areas that affect patients. It's fledgling but already the grants to pursue these areas are emerging and I will keep you all abreast of its progress.

For as much as we build better by standing on the shoulder of giants(Isaac Newton), we must always remember Einstein's definition of Insanity.

Three of my favorite Einstein quotes as they guide my perspective of the future of individualized Cancer treatment. I used to drive by his home in Princeton every Saturday on the way to the Princeton Bookstore. You would never believe the simplicity that surrounded him. A lesson.

08/07/2020

Acinar Cell Carcinoma represents less than 2% of diagnosed Pancreatic cancers. Though surgical resection remains the mainstay of treatment for curative intent new genomic targets have been identified that offer additional options to standard chemotherapy. This case report and review describes a Tail of pancreas lesion and isolated Hepatic segment 6 metastasis treated by the minimally invasive lap-robotic approach which is gaining fervor for readily amenable and easily treated cancers where fear of contamination and dissemination are less frequently experienced.
Robert Donoway,MD,FACS
ATLASOncology.com

https://lookaside.fbsbx.com/file/Robot-assisted%20pancreatectomy-hepatectomy%20for%20ACC.pdf?token=AWz8dhIm7AMLFyYPVqEPnLKGXV6rHaYfxfNZLv_p-XdAXvUTD68ZX66Fgu4Aeyon_Fvy8Acy3b2TVcLfzvUL58TJMLIXxhTAPTYqgFxwCmEAi0if-1UXQ2chgRHaFBhxtYr1kE_AYHZ25vvOELvVhYpKBr86MI1kha5WJQ67euQslsp1pGtOki2Zcvbr5SZEBSwrpwhqFor125sAn7GCQ5GK