Ways to Reduce Recurrence Risk: Ketorolac, Blocks, Opiods

TORADOL/KETOROLAC

Dear Doctor, I request that you consider the use of Toradol pre-incision for my upcoming surgery. Below are the relevant studies.

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The amount and timing recommended by Dr.Patrice Forget is 20 mg pre-incision in patients under 60 kg, and 30 mg in patients over 60 kg.

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There has been ongoing research that is looking at the specific use of Torodal/ketorolac in the perioperative(preincision) phase of breast surgery. The initial study was from Belgium. This study is known as the Forget study published in 2010. A particular isolated group of patients that had an unusually low rate of breast cancer recurrence. All had the same breast surgeon and one of two anesthesiologist. The anesthesiologists had a common approach to drugs used for surgery. Toradol was identified as the common drug given intraoperative.

This link is to an article about the Dr. Forget study, 2010. Patient cohort 327.

http://www.medscape.com/viewarticle/723293

Dr. Forget' s study. This is benchmark original research.

http://www.ncbi.nlm.nih.gov/pubmed/20435950

Dr. Forget' s study 2014. Follow up retrospective study of the 2010 retrospective study. Patient cohort 720.

http://bja.oxfordjournals.org/content/early/2014/01/23/bja.aet464.full.pdf

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Dr. Retsky' s study is a broader based analysis of Dr. Forget' s

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831877/

Curr Med Chem. 2013 Nov; 20(33): 4163–4176.

Published online 2013 Nov. doi: 10.2174/09298673113209990250

Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review

Michael Retsky,^1,2,*Romano Demicheli,³William J.M Hrushesky,⁴Patrice Forget,⁵Marc De Kock,⁵Isaac Gukas,⁶Rick A Rogers,¹Michael Baum,⁷Vikas Sukhatme,⁸ and Jayant S Vaidya⁷

Quotes and graphs from Dr. Retsky's study.

"Using Computer Simulation to Analyze Bimodal Relapse Pattern

Based on computer simulation, to explain the 10 month peak we postulated that induction of angiogenesis at the time of surgery provoked sudden exits from dormant avascular phases to active growth and then to detection. That mode is quite sharp and most often seen among premenopausal patients with axillary lymph node involvement (N+). We suggested the remainder of relapses within the first 40 or so months to be surgery-induced growth of previously dormant single malignant cells. We proposed that the broad late peak relapses result from steady stochastic progressions from single dormant malignant cells to avascular micro-metastases and then on to growing deposits with no apparent synchronization to the time of surgery.

Most Important Finding – Early Relapses are the Result of Something that Happens at Surgery

The most important finding of this early work is that something happens at or about the time of surgery to accelerate or induce metastatic activity that results in early relapses. These early relapses comprise over half of all relapses. Surgery-induced angiogenesis of dormant avascular micrometastases and surgery-induced activity of single malignant cells are implicated. Late relapses are apparently not accelerated by surgery but the shallow peak at 5 years occurs as a result of shedding from primary ceasing after primary removal. We have been vigilantly looking for new data with which we can learn more about surgery-induced tumor activity and that perhaps will also lead to improved outcomes. As we describe here, there has been an important development."

Forget et al. [40] data from Universite catholique de Louvain in Brussels, Belgium. Relapse hazard is shown for mastectomy patients given ketorolac or not. Data are smoothed as indicated for fig. fig.11.

Forget et al. data were updated September 2011 and shown in hazard form but not smoothed as in fig. fig.7.7. Patient data are presented in the table. Patients included in this figure were less than 80 years of age, tumor less than 9 cm diameter and disease free survival greater than 2 months. It can be seen that relapses in months 9 -18 accounted for the major difference between ketorolac and non-ketorolac patients.

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Very often the excuse to not use Toradol is because of concern about postop bleeding. Here are links and abstracts related to studies re: Toradol and postop bleeding.

http://www.ncbi.nlm.nih.gov/pubmed/24572864

2014 Mar;133(3):741-55. doi: 10.1097/01.prs.0000438459.60474.b5.

Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.

Gobble RM¹, Hoang HL, Kachniarz B, Orgill DP.

Abstract:

BACKGROUND:

Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use.

METHODS:

Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups.

RESULTS:

Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids.

CONCLUSIONS:

This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.

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The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.

http://www.ncbi.nlm.nih.gov/pubmed/11214049

Plast Reconstr Surg. 2001 Feb;107(2):352-5.

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.

Sharma S¹, Chang DW, Koutz C, Evans GR, Robb GL, Langstein HN, Kroll SS.

Abstract:

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.

///////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////This study states a three fold increase in hematoma formation after a reduction mammoplasty. if you evaluate the numbers sited in the study, they are small in actual occurrence, but when the phrase "three fold increase" is used in the conclusion of the actual study and then repeated in the abstract, the implication is the numbers are ominous. Another way the authors of the study describe the risk is a 1:16 ratio. When the risk of recurrence is balanced against the hematoma risk, the reduction in recurrence should be weighted in favor of disease free survival(opinion)

http://www.ncbi.nlm.nih.gov/pubmed/22434401

Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.

Abstract:

PURPOSE:

We conducted a retrospective review following concerns involving a suspected increase in the requirement for surgical re-exploration for hematoma evacuation when ketorolac was administered perioperatively in patients undergoing reduction mammoplasty.

METHODS:

Following ethics approval, a retrospective chart review was conducted of all patients who underwent reduction mammoplasty at our two institutions from the time ketorolac became available in 2004 until surgeons requested its use discontinued in 2007. The data we collected included patient demographics, ketorolac administration, requirement for surgical re-exploration, documented hematoma formation not requiring surgical re-exploration, and excessive bleeding in the perioperative period. Three hundred and seventy-nine patient records were reviewed; 127 of the patients received a single intravenous dose of ketorolac (15 or 30 mg), and 252 of the patients did not receive ketorolac.

RESULTS:

Patients who received ketorolac were at an increased risk of requiring surgical re-exploration for hematoma evacuation (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.4 to 9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3 to 3.6).

CONCLUSIONS:

A single perioperative intravenous dose of ketorolac was associated with a greater than three-fold increase in the likelihood of requirement for surgical hematoma evacuation. Our data suggest that it may be prudent to consider carefully whether the potential risks associated with the use of ketorolac outweigh the potential benefits of using ketorolac in patients undergoing reduction mammoplasty.

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thank you for consideration of this information.

Links to BCO threads that are related to this topic. These links discuss Evidence Based Research studies and articles related to preventing recurrence of BC.

Topic: TORADOL (ketorolac) linked to Recurrence Prevention. 2015, by sas-schatzi et all

https://community.breastcancer.org/forum/73/topics/833612?page=7

Topic: Paravertebral Nerve Block and Propofol Sept. 2015, by Falleaves

https://community.breastcancer.org/forum/73/topic/834546?page=1#idx_15

Topic: Effects of opioids on cancer progression Sept. 2015, by Falleaves

https://community.breastcancer.org/forum/73/topic/835291?page=1#idx_

Topic: ketorolac to reduce recurrence Mar. 2014, by Falleaves

https://community.breastcancer.org/forum/91/topic/818961?page=1#post_3936891

Topic: Anesthesia and recurrence of cancer Sept. 2015, by Fallleaves

https://community.breastcancer.org/forum/73/topic/835244

Topic: NSAIDS and Breast Cancer Sept. 2015, by 123JustMe

https://community.breastcancer.org/forum/73/topic/835343

I think I will repost this to each surgery group:

Thought I'd drop this post here. It was written to the June 2016 surgery group:

To all. check back to the post on Toradol and NSAIDS. Please, view Dr. V's video. He explains about the use of Ketorolac/toradol pre-incision. That's just the intro. If you follow all the links you will find the definitive studies and the work we all did last summer......................On the lumpectomy & rads versus mx and adjuvant. Is the most controversial of any subject. I think it's the SEER study that says the lumpectomy & Rads group do well, BUT it's how the MBC group fits into the story gets murky. Please, view Dr. V's study and then read my Toradol thread from last summer.

They're many elements that are the bases for consideration at the time of surgery time. It is known that the act of surgery causes the body's response of inflammation. That cascade of chemicals that are produced in the inflammatory response can cause 1. circulating tumor cells that are released from the tumor site to lodge at a distant point an stimulated to grow, and 2. cells that were released earlier that were dormant at a distant site are stimulated to grow.

This is the idea behind the interruption of the inflammatory cascade by the use of ketorolac/ Toradol. Not sure when inflammation was seen to be such a problem i.e what year, but Dr. Patrice Forget's first retrospective study done in 2010, looked at the drugs that were used at the time of surgery to see if the any connection could be found.

This was a highly unique situation of 325 patients at one hospital that had the same group of anesthesia docs and same surgeon(s). The finding was that ketorolac was the common drug in the group that had the longest time to reoccurrence or no recurrence. Dr. Forget then did a second retrospective study on a cohort of 725. The same finding. This was remarkable. It's earthmoving. Then Dr. Retsky did a study that looked at what was being done worldwide. There was more data worldwide supporting Forget's study in recognizing interference with the inflammatory cascade was a key connection. Though the connection to ketorolac was made by Dr.Forget, Dr. Retsky saw the immense meaning. Dr. Retsky 's study is a wild ride in the science behind Forget's discovery.

Dr. V from the video, was a co-author with Dr. Retsky. All the data that Dr. V uses in his video is from their study and Dr. Forget's study.

Dr. Forget has a prospective(double blinded) study going on in Brussels now. Dr Retsky is trying to get one going in Africa now.

The reason Dr. Retsky is in Africa is that blacks have a higher incidence(nearly exclusive) rate of triple negative patients. If ketorolac does in fact reduce reoccurrence it will be known pretty quickly b/c TNBC has the highest early reoccurrence rate. For Africa this would be revolutionary( the world too) b/c they don't have the medical resources that the developed world has. Ketorolac cost less than 10$.

I could go on for a very long time. I'm hoping this is enough to convince you of the importance of studying yourself, and then talking with your docs about ketorolac pre-incision. In the link to the topic box i have described how to use the info there. There are two posts that pull all the need to consider info & links to take to your docs. Our team from last summer did some very very intense work to put it all together to make it simpler for anyone reading this.

It has become my mission to try and make people aware of this research. If you and your physician choose not to do it b/c this is retrospective research, I get that. But the research is so compelling, don't discard it without a serious look.

Plus, there is compelling research about blocks,NSAIDS, and proporfol/Dipravan. are, also, instrumental in reducing inflammation at the time of surgery. All the links are there.

I'm going to send this off to Dr. Retsky and Dr. Forget and see if they agree as to how I've stated this. Always like to check the facts I'll post back if they have any comments.

Okay, off the soap box

Hi, Asher. The topic box with dr. V's video and an explanation of how to use the first few posts for info for your docs is all here with links to all the other research.

How did you happen upon this thread? Important may be a clue as to how to get the info out there. None of the Toradol, Blocks, Opioids, NSAIDS, Beta Blockers use is proven YET. But if we can use a therapy that does 'no harm', it might give us the needed edge to defeat cancers return.

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Techtonic, thank you for posting. Your post is very important.

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