Cryoablation Blog
 

Updated: May 9

By Dennis R. Holmes, M.D., FACS


The COVID-19 pandemic has placed a tremendous burden on the healthcare system, resulting in the postponement of elective surgical procedures to preserve limited hospital resources and minimize viral transmission.The American College of Surgeons, the American Society of Breast Surgeons, and multiple other surgical and cancer societies have endorsed a policy that recommends at least a 1.5-4 month delay of surgery for conditions that are not immediately life-threatening, including most cases of breast cancer. In place of surgery, the societies recommend a 6-12 month course of pre-operative anti-estrogen medications for most women with estrogen-sensitive breast cancer as a way of reducing cancer extent or preventing further cancer growth while withholding surgery until after the pandemic has ended. This recommendation potentially impacts the care of 70% of women diagnosed with breast cancer today.

Although surgery delays of a few months are unlikely to reduce breast cancer survival, an unfortunate consequence of surgical delay is the tremendous amount of patient anxiety caused by the postponement of surgery for several months. Anxiety might also be caused by fear that surgery delays might lead to further tumor growth or spread, and well as by uncertainty about how long the pandemic will last. Will this pandemic be followed by yet another cycle of widespread infections that might cause additional delay of elective surgery? When the pandemic ends, will the national backlog of elective surgery further delay the scheduling of breast cancer operations, and what will determine the order of priority of elective surgery for patients awaiting surgery—date of diagnosis, tumor stage, patient age, level of insurance, or some subjective factor? Will financially-strapped hospitals remain open and sufficiently staffed to handle the backlog of elective cases? Will the new requirement of coronavirus testing before surgery and persistent uncertainty about the accuracy of coronavirus testing cause additional delay? If elective surgery is available in one community but not another, will a patient have the freedom of movement, personal financial means, and insurance coverage to travel to another community for breast cancer surgery that might not be available to her locally?

Completely missing from the discussion about the management of breast cancer during the pandemic is cryoablation or tumor freezing. Although cryoablation has yet to be adopted as a standard treatment option for breast cancer, unconventional times call for unconventional measures, like the unprecedented policy to postpone elective breast cancer surgery. By these new standards, cryoablation warrants special consideration as a practical, non-operative, healthcare resource-saving strategy for treating breast cancer.

Cryoablation an outpatient, office-based, minimally-invasive procedure performed under local anesthesia the reduces burden on the healthcare system by eliminating the need for a patient to undergo surgery. Using a handheld, needle-like instrument and liquid-nitrogen, breast cancers are typically treated with cryoablation in two freeze-thaw cycles in as little as 30-45 minutes, reaching a central temperature of -180 C. As an alternative to surgery, cryoablation reduces the side effects, psychological burden, and cosmetic impact of breast cancer treatment. Women are spared the cost, discomfort, and potential complications of general anesthesia and breast cancer surgery. Breast appearance and patient satisfaction are likely to be superior with cryoablation given that the incision is small (~3 mm) and no breast tissue is removed that could alter breast size or shape. Furthermore, the cryoablation procedure is essentially painless due to the pain-relieving effect of cold temperatures. Women are able to return to non-strenuous activities the day after the procedure. All things considered, cryoablation might be the perfect compromise that balances the goals of early cancer detection and treatment of breast cancers with the desire for a less invasive, less morbid, and less healthcare resource-intensive approach to managing breast cancer.

Breast cancer cryoablation builds on a significant body of preliminary data and historical experience in the use of cryoablation for the treatment of benign and malignant breast tumors. The largest published study about cryoablation was the American College of Surgeons Oncology Group (ACOSOG) Z1072 trial, which sought to determine the rate of successful tumor freezing in 99 women with stage I breast cancer treated initially with cryoablation followed 4 weeks later by lumpectomy or mastectomy. The Z1072 trial documented complete tumor kill in 100% of tumors <1 cm and 92% of lesions ≦2 cm, and these findings later influenced the design of the FROST Trial (currently enrolling, www.clinicaltrial.gov, #NCT011992250) and the Ice3 Trial (active, non-enrolling, www.clinicaltrial.gov, #NCT02200705). These two U.S. clinical trials are currently examining the use of cryoablation for stage I breast cancer treated without subsequent lumpectomy or mastectomy. Interim results of both trials demonstrated 1.1% and 1.4% local recurrence rates with 1-year short-term follow-up. In Japan, a clinical trial of stage I invasive ductal carcinomas managed with cryoablation, sentinel node biopsy, anti-estrogen medication, and whole breast radiotherapy without subsequent surgical removal reported a 0.98% local recurrence rate among 304 women with 6 years of follow-up. The Japanese results provides confidence in the ability of cryoablation combined with radiation and/or anti-estrogen medications to achieve long-term local control similar to lumpectomy in eligible patients. As with lumpectomy, there is a risk of cancer recurrence in the vicinity of the cryoablation. The fact that invisible, microscopic cancer cells might remain around the borders of the cancer tumor is why radiotherapy and/or drug therapy remain important in the overall management of most women treated with either cryoablation or lumpectomy.

In the context of non-operative management of breast cancer, opportunities also exist for the non-operative management of the lymph nodes. Since 2016, the Society of Surgical Oncology’s “Choosing Wisely” Campaign, an initiative of the American Board of Internal Medicine, has encouraged surgeons to avoid “routine sentinel node biopsy in clinically node-negative women 70 years of age with hormone receptor-positive, HER2/neu-negative (stage I) invasive breast cancer.” This recommendation is based on the low estimated risk of lymph node metastasis in this group of women as well as the low rate of lymph node recurrence when lymph node surgery is omitted among these patients. Whereas selective omission of sentinel node biopsy is now widely accepted in women 70, withholding sentinel node biopsy is more controversial in younger women for whom the status of the axilla has remained a key factor in evaluation the need for chemotherapy. However, the importance of the lymph nodal stage has been gradually eroded by growing confidence in the ability of tumor genomic assays likely Oncotype Dx and MammaPrint as tools for assessing the benefit of chemotherapy, regardless of patient age or tumor size. For example, the Oncotype Dx and MammaPrint tests are now capable of identifying women that benefit little from chemotherapy despite the presence of high-risk cancer features, including positive axillary nodes, further reducing the need for lymph node surgery and the use of related healthcare resources.

Applications of Cryoablation

Although there is a lack of long-term evidence supporting the unrestricted use of cryoablation, there is considerable preliminary and anecdotal data to warrant consideration of cryoablation as a definitive or temporary, stopgap measure in specific women with the following conditions who are anxious about delaying surgery or who simply refuse traditional surgery.

A. Stage I invasive breast cancer

Patients with stage I (≦2 cm) breast cancer may undergo cryoablation of the breast cancer a definitive therapy with optional surgical removal of the cryoablation site for women who may later require surgery for other reasons, such as for removal of suspicious lymph nodes.

B. Stage II invasive breast cancer

Based upon experience with stage I breast cancer, patients with Stage II (2cm-5 cm), low-risk, lymph node-negative breast cancer may receive upfront cryoablation for management of breast cancer combined with anti-estrogen medication if the tumor is estrogen sensitive. Lymph node surgery with or without surgical removal of the cryoablation site may be performed when it can be conveniently scheduled. Lumpectomy or mastectomy can be performed at a later date if follow-up breast imaging suggests the presence of residual or recurrent disease.

C. Stage III invasive breast cancer

Drawing on experience from liver tumor cryoablation, patients with breast cancers more than 5 cm may undergo cryoablation using multiple overlapping cryoablation treatments in a single session to treat the cancer plus a surrounding margin of normal tissue. Cryoablation might eliminate the need for surgery in patients refusing breast surgery or provide temporary control of tumor growth until the patient is able to conveniently undergo mastectomy with or without breast reconstruction. The need for anti-cancer medications (e.g. chemotherapy and/or endocrine therapy), radiotherapy after surgery, or radiation after cryoablation should be guided by the cancer extent and/or cancer biology.

D. Stage 0, ductal carcinoma in situ (DCIS)

As an office-based procedure typically performed under ultrasound-guidance, cryoablation is usually restricted to cancers that are visible by ultrasound. DCIS is usually visible by mammography, but not usually visible by ultrasound. However, an area of DCIS detected by mammography can be converted to an ultrasound-visible target for cryoablation by the insertion, under mammographic guidance, of one or more ultrasound-visible biopsy site markers into the area of DCIS.

E. Recurrent breast cancer

Similar to primary breast cancer, a recurrence of invasive breast cancer or DCIS following prior lumpectomy or cryoablation can be managed with cryoablation if breast imaging studies confirm that the recurrence is limited to a small area.

F. Stage IV breast cancer

The debate continues regarding the benefit of lumpectomy or mastectomy in the setting of stage IV breast cancer. However, cryoablation may be offered as a low-risk solution to control the breast tumor while drug therapy and possibly radiotherapy are administered to control the distant metastatic site(s).

G. Positive lymph nodes

The current standard of care for patients with positive lymph nodes is the surgical removal of affected lymph nodes, the goal of which is to reduce the risk of recurrence in the lymph node area, eliminate the lymph nodes as a source of cancer spread, and to allow complete cancer staging by counting the number of positive lymph nodes. However, with the biology of the primary tumor playing an increasingly important role in predicting the risk of distance recurrence and the response to systemic therapy, the actual number of positive axillary lymph nodes is not as important as it used to be. Furthermore, the ability of radiotherapy to effectively control microscopic cancer in the lymph nodes provides an opportunity to limit the extent of lymph node surgery or cryoablation to the grossly-abnormal axillary nodes in situations when complete removal of lymph nodes with surgery is either infeasible or refused by the patient. Appropriate caution must be applied when ablating lymph nodes near large nerves and veins in the armpit.

Conclusion

Recent national policies recommended the delay of elective breast surgery to preserve limited hospital resources and to decrease transmission of COVID-19. Although short-term surgery delay is unlikely to reduce breast cancer survival, delay of breast cancer surgery has the capacity to greatly increase the psychological burden of a woman diagnosed with breast cancer. Breast tumor cryoablation is an outpatient, minimally-invasive procedure that is already emerging as a substitute for surgery in early-stage invasive breast cancer. It can serve as a stand-alone treatment for some patients and a temporary, stopgap measure for others until surgery can be conveniently scheduled. Access to cryoablation would be greatly aided by relaxation of current insurance coverage restrictions that now form a barrier to the inclusion of cryoablation in the comprehensive management of breast cancer. In the meantime, cryoablation can expedite treatment in some women, minimize the risk of further tumor growth, reduce the anxiety of prolonged surgery delay, and save limited-healthcare resources. 



The world is now abuzz with news about Coronavirus (COVID-19), the viral disease that has recently taken the world by storm.

Corporations big and small are keeping employees at home; sport institutions like basketball, baseball, hockey, and soccer teams are cancelling events and entire seasons; colleges and grade schools are closing and providing classes only online; national medical conferences are being cancelled or postponed; the tourism and airline industries are experiencing major turbulence; Broadway has drawn its curtains; Disney has closed its doors; and cleaning products, toilet paper, and paper towels are experiencing their very own gold rush!

Whether or not the current global response is an appropriate reaction, or an over-reaction is unclear at this point in time. What is clear is that the COVID-19 pandemic will likely continue to cause considerable societal disruption over the coming months as we come to understand the size of the problem and develop solutions.

While no one is immune to the COVID-19 virus or the collateral damage that it has caused, breast cancer patient may be particularly concerned about the impact of this crisis on their efforts to maintain their breast and overall health.  Anxiety will likely be heightened by recent decisions by many medical facilities to reduce their office hours, cancel or reschedule non-urgent appointments, and postpone elective operations like breast surgery as they reassign limited medical staff to more critical departments like the ICU and preserve hospital beds for sicker patients.  Such precautions are also meant to protect healthy healthcare personnel from apparently healthy patient who may be carriers of COVID-19 but have yet to exhibit symptoms.  Just imagine the impact on a medical office if an apparently healthy patient were diagnosed with COVID-19 a few days after her visit?  It could lead to a 2-week or longer quarantine of the entire medical staff, which would disrupt the healthcare of every other patient seen by that office, even if no one else ever develops a COVID-19 infection.

A more pressing concern is that many breast cancer patients have weakened immune systems due to older age, ongoing or recent receipt of chemotherapy or targeted therapy [e.g., Ibrance (palbociclib), Kisqali (ribociclib), Lynparza (oliparib)], or other health conditions (e.g., heart disease, lung disease, or diabetes) that place them at increased risk of complications from COVID-19.  These vulnerable patients may also be put at risk by younger, healthier, symptom-free COVID-19-infected patients whom they encounter during routine office visits.

With such ongoing uncertainty, I thought it would be timely to offer the following tips about how to navigate your breast health during this pandemic.

1. Practice Prober Hygiene. Regardless of the state of your health, the most important thing you can do to avoid contracting or transmitting COVID-19 is to wash your hands regularly with soap and water and/or use alcohol-based hand sanitizers often that contain at least 60% alcohol. You should also avoid unnecessary touching of your face, mouth, and eyes unless your hands are clean, since these are the places where COVID-19 enters the body.  Of course, this is easier said than done. In the few minutes it took for me to write the first few paragraphs of this advisory, I’ve absentmindedly touched my face at least a dozen times.  So clean hands are a must!  You should also do your best to avoid any family, friends, or strangers suspected of having or displaying symptoms of COVID-19 infection. Please see this link for more tips about COVID-19 symptoms and avoiding infection.

2. Reschedule Your Appointment If Sick or Exposed. If you are having symptoms of respiratory infection (cough or shortness of breath), severe cold or flu symptoms, fever, or suspect that you might have been exposed to someone with COVID-19 infection, please tell your primary care doctor about your symptoms or exposure and postpone your breast health appointment until at least 2 weeks after you have fully recovered or 2 weeks after your last contact with the sick person.  If you are currently receiving chemotherapy or targeted therapy, please notify your medical oncologist before postponing a medical oncology appointment so that he or she may come up with a game plan to adjust your medications and manage your care.

3. A Modest Appointment Delay Is O.K. Don't get too alarmed if your follow-up appointment gets postponed by your doctor’s office or if you must delay your appointment for a few weeks.  However, if you are receiving chemotherapy or targeted therapy, have a concern about the healing of your wound, or have a new breast concern, please inform your doctor’s office so that you can be given a priority appointment.

4. Maintain Safe Social Distance In The Doctor's Office. When you come to the doctor’s office for an appointment, you may wish to wait in the hallway or wait outside the building to avoid sitting in a crowded waiting room.  Just leave your cell phone number with the reception desk so that you may be called minutes before the doctor is ready to see you.

5. Wear A Mask If Immune Suppressed. Chemotherapy and many targeted therapies lower your immune system, making it more difficult to resist or fight infection. Although the general recommendation is that healthy patients should NOT wear face masks, my personal recommendation to patients currently undergoing or recently completing chemotherapy or targeted therapy is to wear a face mask when you are in public spaces where you cannot maintain 6 feet separation from other persons. If you are uncertain if you are on a medication that lowers your immune system, please ask your medical oncologist. However, commonly used anti-estrogen medications like Nolvadex (tamoxifen), Arimidex (anastrozole), Femara (letrozole), and Aromasin (exemestane) DO NOT lower your immune system.

6.     Many breast concerns may be resolved in the doctor's office. Delaying routine mammograms and breast cancer screening by 1 or 2 months might cause you a bit of anxiety but is unlikely to harm your long-term physical health even if there is a hidden cancer developing within. However, if you have a new breast lump or symptom and can’t seem to get a quick appointment in the radiology department or breast center, we have the ability to perform breast ultrasound in the office to quickly exclude the presence of cancer or perform ultrasound-guided needle biopsies of suspicious findings.

7.   You can insist on an expedited appointment. If you have been recently diagnosed with breast cancer and are hoping to expedite your consultation and subsequent treatments, please inform your doctor’s office so that you can be given a priority appointment.

8. Consider a telehealth visit instead of an in-person visit. If you are voluntarily or involuntarily quarantined or simply too afraid to go out in public, you might have the option of a telehealth visit with your doctor.  Real-time telemedicine permits a live interaction between a health professional and patient using secure audio and video communication. Think videochat or Facetime, just more secure!  For example, a surgeon might use a telehealth visit to do post-operation check-ins with patients, to make sure their wound is not infected, or to discuss the surgical pathology results.  My practice is in the process of setting up a telehealth service to enable virtual appointments.  Stay tuned for more information about our telehealth service which will be sent to you in a follow-up communication.

Some health plans will allow your doctor to bill insurance for telehealth services. However, if telehealth visits are not covered by your health plan, you might have the option of paying out-of-pocket for these services.

9.     You can also share medical records online. Patients newly diagnosed with breast cancer may be particularly anxious to see a surgeon. Here, too, telehealth may provide a temporary solution. Virtual appointments have been greatly facilitated by mymedicalimages.com, a HIPAA-compliant, online, medical recording sharing service that Dr. Holmes uses to receive medical records from of town patients.  Mymedicalimages.com allows patients to use their personal computers to upload reports and full CDs of mammogram, ultrasound, and MRI images to a secure website where Dr. Holmes can view your medical records in minutes! Not only is it this rapid, mymedicalimages.com costs as little as $19, cheaper than the cost of sending medical records by express mail.

10.  There are ways to keep most tumors "in check" while awaiting surgery. What if you’ve been diagnosed with breast cancer and are unable to promptly undergo surgery due to one of the reasons listed above? Don't worry, there a several things you can do in the meantime to keep the cancer in check.  For example, if you have been diagnosed with non-invasive (stage 0) breast cancer or ductal carcinoma in situ, you can comfortably wait 1-3 months before proceeding with surgery.  If you’ve been diagnosed with non-invasive or invasive breast cancer that is strongly sensitive to estrogen, you can be started on anti-estrogen pills (e.g., tamoxifen or Arimidex) to suppress cancer growth for few weeks or months while awaiting surgery.  On the other hand, if you have a triple negative invasive breast cancer or a cancer that is weakly sensitive to estrogen, you should seek a priority appointment for surgery or chemotherapy since anti-estrogen pills do not work well (or at all) for these tumors.  Selected patients may also undergo cryoablation or tumor freezing as a substitute for surgery or as a means of controlling a breast tumor while awaiting future breast and/or lymph node surgery.

There you have it: Your Breast Health Pandemic Survival Plan, which you may share with family and friends.  Although it is reasonable to remain nervous about the current international health crisis and where things are heading, be assured that there is room for optimism.  In the past decade, the world has been rocked by the H1N1 (SARS) virus pandemic followed three years ago by the Zika virus pandemic.  Now, H1N1 and Zika are but distant memories, and COVID-19 will likely share the same fate. Till then, I encourage you to be mindful of your personal hygiene while also remaining attentive to your breast health.

This month’s newsletter draws attention to a recent JAMA Oncology editorial, De-escalating Breast Cancer Surgery—Where is the Tipping Point (Dec 12, 2019), in which respected surgeons, Monica Morrow and Eric Winer,discussed the pros but mostly the cons of de-escalating breast cancer surgery in reference to effort to eliminate surgery in an effort to reduce the burden of breast cancer care.

As a breast cancer surgeon, I have a keen appreciation of the advantages and disadvantages of surgery. Depending on the patient’s unique circumstances, breast cancer surgery either can greatly enhance or greatly diminish the quality of life of a woman, often without improving overall survival. The art of medicine and surgery is to harmonize the treatment approach with anindividual patient’s goals and tumor characteristics in a way that maintains or improves cancer control while preserving or enhancing quality of life.


At times, this could mean escalating therapy, which means that the extent of treatment is intensified to improve cancer control.  However, increasingly this means de-escalating therapy, which means that the intensity and extent of therapy can be minimized to reduce the burden of therapy without compromising cancer control.      

                                                                                               

Common examples of escalating therapy includes:


1. Adding radiation or chemotherapy after surgery based on new pathology detected in the tissue removed at the time of surgery;


2. Converting from mastectomy to lumpectomy when pathology results reviewed more extensive disease; or


3. Removal of all underarm lymph nodes if cancer is found in one or more nodes.


Due to more frequent detection of smaller cancers and more effective drug therapies, de-escalation of therapy is becoming increasingly more common. For example, I commonly use the following descalation therapies to reduce the burden of treatment and expedite recovery:  


1. Lumpectomy combined with breast reduction or breast lift instead of bilateral mastectomy and reconstruction to improve cancer removal, maintain breast symmetry and improve overall breast appearance;

2. Single dose Intraoperative partial breast radiotherapy instead of 16-fraction or 30-fraction postoperative whole breast radiotherapy to target radiation to the tumor site while sparing health tissues the effects of radiation.

3. Preoperative chemotherapy or pre-operative anti-estrogen therapy, as appropriate, to reduce the extent of breast cancer and the extent of required surgery;

4. Cryoablation instead of surgical removal of selected cancers.


One of the greatest concerns raised by Drs. Morrow and Winer was that the effort to minimize the burden of surgery might leave some women with an elevated risk of recurrence and reduced overall survival.  Another common concern is that heightened surveillance (that is, more mammograms and more biopsies) that accompanies non-operative management of breast cancer canproduce such significant patient anxiety that possibly exceeds the physical trauma of surgery.  Though valid, these concerns should not deter our efforts toadjust our treatment approach based on the extent of disease and risk of disease recurrence, which included ongoing scientific efforts to figure out which individual cancers or more likely to grow, spread, and recur.


Another point of significant disagreement is Dr. Morrow’s and Dr. Winer’s view that the voice of the patient has been excluded in the debate about reduce the need for surgery in selected cases.  Here, they really got it wrong or perhaps they haven’t been listening close enough.  


While it might not be the predominant viewpoint of women facing a breast cancer diagnosis, I have heard from maybe women who would option for a non-surgical approach if they could be confident that it could achieve comparable cancer control and survival. Completely missing in the article’s discussion of surgical de-escalation is the option of percutaneous ablation, such as cryoablation, which addresses many of the concerns raised by Drs. Morrow and Winer.


I was recently invited to write a chapter for a surgical textbook on non-surgical management of breast cancer.  Initially, I was quite reluctant to commit the time to research the topic and write a book chapter—after all, who actually reads textbooks? However, having completed the task, I am now convincedthat non-operative management of breast cancer in selected cases is a reasonable option for a subset of women looking to the avoid surgery.  The challenge for us as breast cancer researchers is to identity the most appropriate subset of women and circumstances in which non-operative management can be safely employed without compromising cancer control and patient survival.


As you already know, I am currently leading a multicenter, ongoing trial evaluating cryoablation as an alternative to surgery for stage one invasive breast cancer.  Thus far, preliminary findings are very promising.


As I write this post, I am also in the process of drafting a research protocol to examine the use of cryoablation for the management of stage 0 breast cancer or ductal carcinoma in situ (DCIS).  

The main aim of the DCIS-cryoablation study is to examine the use of cryoablation in the management of DCIS.  Although some patients elect to manage their DCIS with observation alone or observation plus Tamoxifen, one of the greatest ironies is breast cancer therapy is that DCIS (a condition that poses no direct risk to survival) is commonly treated more aggressively than invasive breast cancer, including an unacceptably high rate of mastectomy, a requirement for wider lumpectomy margins, and a high rate of reoperation.


Cryoablation can potentially serves as a compromise solution that balances the desire to disrupt the progression of DCIS toward invasive breast cancer while also minimizing the burden of wide excision, reoperation, and/or mastectomy.


The second aim of the DCIS study is to determine if cryoablation is capable of stimulating a beneficial immune response in women with DCIS.  Although multiple factors may influence if and when are a DCIS lesion might progress to invasive breast cancer, there is strong evidence that the immune microenvironment at the site of DCIS plays an important role in limiting disease progression from DCIS to microinvasive and invasive cancer. Thus, inducing a beneficial immune response with cryoablation might reduce the risk of DCIS progression to invasive breast cancer, the most endpoint of all DCIS therapies. Furthermore, understanding the immune response to cryoablation in DCIS might provide insights into ways to reduce the risk of recurrence of invasive breast cancer.


As a breast cancer surgeon, I earn my living by performing surgery on breast cancer patients, as outlined above. As a breast cancer researcher, I am drawn to the challenge of expanding the options for breast cancer therapy to include cryoablation in appropriate patients.


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