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Immunotherapy Series – The Power of Hyperthermia with Surgery

The Power of Hyperthermia with Surgery

The conclusion of currently available research is obvious; surgery causes cancer to spread. [1] [2] [3] [4]. Did I catch you off guard with this statement? The medical term for the spread of cancer is metastasis.  The very treatment, surgery, designed to remove a tumor or to reduce tumor burden to improve survival is the same treatment that can cause cancer to spread. This point is significant because cancer metastasis leads to 90% of the cause of morbidity and mortality in cancer patients [5] [6]. I will repeat this point time and time because if treatment leads to the metastatic spread of cancer, then that is a treatment that leads to mortality and needs to change. The surgical-induced metastatic spread of cancer is similar to that of full-dose chemotherapy and radiation. The three pillars of conventional medicine cause cancer to spread.

Surgery is a trigger for metastasis:

“…surgery to eliminate the cancer can actually serve to increase the establishment of new metastases and accelerate growth of residual and micrometastatic disease.” [7]

How can this be possible?

First, no sensationalism; this is not the news. No marketing-based information; this is not marketing. No fear is accepted here either. What I am after is a review and discussion of just the receipts—the evidence. Beyond that, I believe in hope and each individual’s ability to read, interpret and determine the validity of the science on their own, not that found in groupthink. So, here we go.

First and foremost, it is essential to understand that surgery is synonymous with tissue trauma. It is the trauma, recruitment of the healing process, and the resultant disruption of the healing process that promotes the metastatic spread of cancer. It is within the tumor microenvironment of cancer that the high jack of the normal healing process occurs. It is here that the healing process serves the benefit and survival of cancer at the detriment of the body. This is not new information. This concept was first described over 100 years ago, near the turn of the 20th century! [8]

How does surgery cause the metastatic spread of cancer?

First, the information is not new; the detailed description of how surgery causes the metastatic spread of cancer is widely known. This process is not a theory but is a scientific fact that is confirmed time and time again.

A lot of the negative impacts from surgery are within the immune system. It is important to understand that surgery suppresses the immune system 2 [9] [10] [11] [12] [13] [14]. Surgery suppresses natural killer (NK) cell and macrophage activity [15] [16]. The degree of immune suppression correlates with the volume of surgery and the risk of tumor regrowth.  This evidence should require a review and analysis of the massive surgery volume, including debulking, often used in surgery. Is surgery providing a brief reprieve, only to set the stage for massive expansion?

Immunosuppression is a normal part of the post-operative period. In cancer, immunosuppression in the post-operative period is critically important. The surgical induced immunosuppression is a natural occurrence and is beyond any deliberate immune suppression drugs that can be and are often used in the post-operative state. Take organ transplant surgery for example, immune suppression is a mainstay and necessary component of treatment. Second, opiates are the conventional primary treatment option for pain control in the post-operative period. These opiates are often scheduled whether or not there is pain. In addition, in case you haven’t heard, there is something called a prescription opiate addiction epidemic? Opiates double-down on immunosuppression [17] [18] [19] [20]. With the effective use of medical marijuana for pain control, there is less need for the use of opiates. In the post-operative period, opiate use, in addition to the immunosuppression from the surgery itself, is like throwing gasoline on the fire of cancer. Unfortunately, in both cases, physicians are the means of delivery. This statement is not easy to make. In my former physician life (wink, wink), I was a surgeon.

Beyond the generalized immunosuppression and general opiate use, surgery causes the metastatic spread of cancer in a clearly defined series of sequences 7:

  • increase in inflammatory signaling (NF-kappaB, IL-1, IL-6, TNF-α…)
  • increases stress response (cortisol, epinephrine, and norepinephrine)
  • changes the tumor microenvironment
  • accelerates growth
  • increase in invasion
  • increase tumor shedding in the blood
  • increase tumor shedding in the lymphatics
  • increase in circulating tumor cells (CTCs)
  • increase in CTC migration
  • increase in CTC survival
  • increase in immune system invasion
  • increase dissemination of cancer cells
  • metastatic site preparation
  • increase adherence of CTCs at new, potential metastatic sites
  • formation of new micrometastasis
  • changes the new micrometastatic microenvironment
  • accelerated growth of micrometastasis
  • increase invasion at metastatic sites
  • increase in treatment resistance

This sequencing of the metastatic spread of cancer, as a result of surgery, also causes the increase in local recurrence. This sequencing of the metastatic spread of cancer, resulting from surgery, also causes an increase in local recurrence. Local recurrence and metastasis are just the same processes; the only difference is the location. One spreads to distant sites, and the other is just a return to the scene of the crime. The more surgery undertaken, major versus minor surgery, open versus laparoscopy surgery, results in a decrease in survival [21].

Hyperthermia protects against surgical-induced metastasis.

With the cut first and ask questions later surgical approach to conventional cancer treatment, it is important to find ways to prevent surgically induced immunosuppression that aids the process of metastasis. Hyperthermia to the rescue again. A paper published in Critical Reviews in Hematology/Oncology in 2016 showed that hyperthermia counters the surgically induced immunosuppression and actually strengthens the immune system in the critical postoperative period [22]. Another study published in the International Journal of Colorectal Disease showed that hyperthermia, in conjunction with chemotherapy and radiation, prevented local recurrence in patients that had undergone surgical resection for rectal cancer [23]. An excellent question to consider here, is the addition of chemotherapy and radiation even required? It is known that full-dose chemotherapy [24] [25] [26] and radiation [27] [28] [29], each individually, lead to the metastatic spread of cancer. Can hyperthermia do the work alone? The 2016 study highlighted above suggests this might be so.

How about we take this a step deeper? A recent study in the International Journal of Hyperthermia published in 2019 shows that hyperthermia can reduce local recurrence at the time of surgery [30]. In this study of 63 people with metastatic brain cancer, 10 out of the 63 developed local recurrence after surgical resection. That equates to a 15.8% local recurrence rate. That sounds pretty good on its face. But, when you compare it to the current 34% receiving conventional standard of care treatment, it looks really good. Overall, that is a 55% reduction of local recurrence as a result of the addition of hyperthermia to surgery. That is the evidence of the power of hyperthermia to reduce local recurrence. The same could be said to apply to metastasis because the same steps and processes, outlined above, are involved.

Cancer is a systemic process from day one [31] [32]. This favors whole body hyperthermia over local hyperthermia in the treatment of cancer. The abscopal effect [33], which is treatment that results in tumor regression at distant tumor sites, is lauded by local hyperthermia advocates as the means to achieve systemic effects from local hyperthermia. In reality, the abscopal effect is quite rare, limited, and anecdotal 27 33. The current dogma of viewing cancer through a linear, sequential process is overly simplistic and very flawed. The sequence I highlighted above is dynamic, not linear. It is more on the level and thinking of quantum physics—it is all happening at once. In this light, hyperthermia is working systemically, yet dynamically, to augment the immune system in an anti-tumor fashion. Hyperthermia increases NK cell number, function, and cytotoxicity [34] [35] [36], increases dendritic cell activation, crosstalk, and antigen presentation to other immune cells [37] [38], and increases cytotoxic T lymphocyte number, targeting, and function [39] [40].  As so often is the case, timing, temperature (dose), and duration are critical to these effects. The overall result is a systemic increase in anti-cancer immune activation.

We are not opposed to surgery, far from it. Heck, I was a surgeon myself. Dr. Lodi and I would just rather avoid it if all possible. Just look at the evidence I reviewed, and one can see why we should not rush to cut. When indicated, when a large volume of disease exists, surgery can significantly impact tumor burden reduction or preserve vital organ function when threatened by tumor growth. That being said, every time a tumor is handled, or surgical intervention ensues, circulating tumor cells increase by at least ten times [41]. My experience is that when ten fold is quoted, the reality is actually magnitudes higher. Just because we can cut doesn’t mean we should cut. Once cutting begins, there is no going back. We can only help to limit the damage. Fortunately, hyperthermia, and other integrative, holistic therapies, can limit the collateral damage called metastasis that can result from surgery.

[1] Qadri SS, Wang JH, Coffey JC, Alam M, O’Donnell A, Aherne T, Redmond HP. Surgically induced accelerated local and distant tumor growth is significantly attenuated by selective COX-2 inhibition. Ann Thorac Surg. 2005 Mar;79(3):990-5; discussion 990-5. doi: 10.1016/j.athoracsur.2004.07.042.

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[3] Angka L, Khan ST, Kilgour MK, Xu R, Kennedy MA, Auer RC. Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery. International Journal of Molecular Sciences. 2017;18(8):1787. https://doi.org/10.3390/ijms18081787

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