"Osteolytic skeletal metastases: AORIF as a new strategy for enhanced comprehensive oncologic care"

June 14, 2023

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Yale Cancer Center Grand Rounds | June 13, 2023

Presentation by: Dr. Francis Lee

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00:00Is the Wayne Southwick Professor of
00:03Orthopedics and Rehabilitation and also
00:06Professor of Biomedical Engineering.
00:09His clinical interests are
00:11sarcoma complex musculoskeletal
00:13reconstruction in adults and children,
00:16musculoskeletal bone and soft tissue tumors,
00:20minimally invasive surgery for metastatic
00:23cancers to bone and spinal tumors.
00:27Doctor Lee has had several NIHRO
00:30One funded research programs in
00:33metastatic cancer induced bone loss,
00:35fracture healing, regenerative orthopedics,
00:38and bone infection.
00:41His research focuses on high
00:43impact orthopedic research that's
00:46directly relevant to pathogenesis,
00:48diagnosis and treatment
00:51of orthopedic disorders.
00:53Dr.
00:53Lee holds the rare distinction of
00:56being both an orthopedic surgeon and
00:59a musculoskeletal scientist scholar
01:01working with NIH research programs.
01:04And I've known Francis for many years now,
01:06so it's my pleasure to introduce
01:08his talk today.
01:12Good afternoon. I'm Francis Lee,
01:14and thank you so much for wonderful
01:17introduction and also many people on Zoom.
01:20It's really great to see you on Zoom as well.
01:23And today I'm here really to provide
01:26service for your enhanced care and let me
01:30introduce our three orthopedic surgeons,
01:32Doctor Gary Friedlander,
01:34myself and Doctor Lynn Scogg.
01:36And we do lots of a sarcoma surgeries and Dr.
01:39Ego Lattic is the interventional
01:42radiologist and we recently formed A-Team
01:45and we are providing lots of minimally
01:48invasive procedure for metastatic cancers.
01:51And our group is leading this new
01:55procedure nationally and internationally.
01:59So this is a main topic.
02:01The most important thing is
02:03about hip fractures, hip lesions,
02:07any patients with a bone Mets is a stage 4,
02:10but I believe this is a stage 5 pathological
02:14fracture or painful lesion around the
02:17hip is more disabling than stage 4 cancers.
02:21Traditionally orthopedic surgeons just
02:23to do surgeries for this kind of massive
02:27bone defect and the fracture in the
02:29roof of the hip joint called astabulum.
02:32But I'm taking different approach as
02:35a clinician scientist from oncology
02:37perspective, lots of cancers are
02:39chemo resistant and radio resistant.
02:42Radiation dose maxed out even after
02:45two courses of radiation and the
02:48local cancer body needs tremendous.
02:511ML of cancer contains 100 million
02:54cancer cells.
02:55It's a lot.
02:56And also at the same time,
02:59bone cancer causes inflammation.
03:02So any breast cancers or lung cancers
03:06cause inflammation in the bone release.
03:09Pain mediators,
03:10inflammatory cytokines that destroy
03:12bone and inhibit bone formation.
03:15Biomechanically, bone is weak and soft.
03:20And this is what we do surgically.
03:22But because of a big surgeries,
03:24sometimes patients miss opportunities
03:27to live longer from the surgical
03:30complications and the prolonged recovery.
03:33So our team has developed some kind
03:35of a surgery called Arif AORIF.
03:38This is ablation to kill cancer.
03:41We are providing local cancer control
03:45instantly on the day of procedure,
03:47we kill billions of cells.
03:50And also we are improving a bone cancer
03:53biology because we are killing the cancer.
03:55As a result, local bone homeostasis
03:59improves biomechanically.
04:00We are reinforcing the bone and the
04:03patient can emulate next day and the
04:06patient does not require admission and
04:08you can resume your chemotherapy right
04:11away or radiation therapy the next day.
04:13And as a result patients may live longer.
04:18Over the past five years,
04:20our team has a published about 10
04:22papers and the most recent paper
04:24was published in radiology which
04:26is impacted fact is about 30.
04:28And we are very actually proud of
04:31our collaboration with the medical
04:33oncologist such as Doctor Deshpande, Dr.
04:36Sharon, Dr. Gettinger and so many people.
04:39We are working together 24 hours
04:42and seven days by exchanging text.
04:46And the goal of this grand round is to
04:49assure you we exist to really facilitate
04:53your life saving oncologic care
04:56through innovative drugs or radiation.
04:59And we are providing not just
05:02putting the nail or implants,
05:04we are providing comprehensive
05:07bone oncologic care
05:09to this end. Do not wait
05:12until patient breaks the bone,
05:13just call us all in the.
05:16Right away when you detect metastasis
05:19then we can get, we can kill cancers,
05:22reinforce the bone and I think medical
05:25oncology care will be further enhanced.
05:28And also today we'll discuss
05:30some science as well.
05:32So if you consult this patient to orthopedic
05:37surgeons depending on trauma surgeon
05:39or oncologic surgeon whoever the treatment.
05:43All really vary.
05:45Some people put big implant,
05:47some people put plate and screws,
05:50but I don't think this is the right way.
05:52I'm an orthotic surgeon,
05:53I know how to these surgeries but this
05:56is not the right surgery for patients
05:58with the metastatic bone disease.
06:01And this is some pictures from my surgery.
06:03Big exposure raiming,
06:06massive reconstruction,
06:08but patients had the radiation,
06:10poor wound, healing, diabetes, infection.
06:13At this point, oncologist,
06:15they cannot continue drug therapy
06:17because of complications.
06:19So I was thinking about what to
06:21do over the next 5 or 10 years.
06:24The way is really minimally invasive surgery.
06:29If you look at the case of AAA
06:32aneurysm or cardiac surgeries,
06:35most of the procedures are
06:37done now percutaneously,
06:38no more open heart surgery,
06:39no heart lung machine.
06:41So why not for at least for
06:46metastatic bone disease,
06:48you may recognize this famous
06:50painting by Pablo Picasso.
06:52He was really, as you know,
06:54painting genius at age 15.
06:56He can draw like a photograph,
06:59but as he as time evolves,
07:01he became a really minimalist and we became
07:05a minimalist and we are leading the field.
07:08So Arif is metastasis specific
07:11procedure developed by our people.
07:14So let me share.
07:16One of our patients patient is a
07:2059 year old male with a massive
07:22bone destruction and a tumor.
07:25Orthopedic surgeons always
07:26look at the bone defect,
07:28but I'm an oncology surgeon and
07:30I see huge cancer there and the
07:33cats can show massive bone defect.
07:37And if it open surgery,
07:38this is going to be a nightmare,
07:40requires 2 week of admission.
07:42CQ transfusion complication
07:44rate is about 50%.
07:47Patient is very obese as well.
07:51So this is the picture that I took
07:53during the surgery and this is the
07:56pelvic area and very small draping
08:00and this is the X-ray we are using
08:03at the York Street operating room.
08:08Since there are no surgeons in
08:11this audience, I'm going to skip
08:13the surgical procedure part.
08:14But bottom line is we can
08:16do a lot of great things by
08:19using simple imaging studies.
08:22So first what we do is we put
08:24little pin forward the cancer to
08:29target the approach and this is
08:32the imaging studies we are using.
08:36And we are putting a guide wire,
08:39then putting a small screw
08:45through a 3 millimeter skin cut,
08:47no big skin incision and the Yale
08:51Cancer Centers Amazing imaging facility.
08:53This is a 3D imaging that is easily
08:56available in the operating room.
09:00Then I insert screws
09:03halfway through the pelvis.
09:06And through the screw that
09:08has holes in the middle,
09:11we can a lot of things.
09:13This is a device called the
09:15radiofrequency ablation.
09:16Before I do any orthopedic procedure,
09:19we kill the cancers.
09:21As I said, 1ML of a cancer
09:25contain 100 million cells.
09:28This is a radiofrequency ablation.
09:33And after ablation, sometimes we
09:36inject the dye then we see dyes
09:39leaking out and because of this reason
09:42we are doing balloon osteoplasty,
09:44meaning we are dilating balloon just
09:47like a kyphoplasty so that Symantec
09:50can be deposited in the target region.
10:01After balloon inflation and deflation,
10:04now we are injecting bone cement.
10:07This bone cement generate
10:09heat about 95 degrees.
10:12In addition, we are adding Zometa
10:15this phosphonate in the bone cement
10:18because this phosphonate unlike
10:20denosumab is heat stable and it
10:23had some protective bone effects
10:25and we are injecting bone cement.
10:30So after ablation bone osteoplasty cement
10:34injections, then we are advanced screws
10:39as you see there,
10:40there is no skin incision,
10:42only two or three insertion
10:45sites and this is what we did.
10:47Through that small incision we kill the
10:51cancer by radiofrequency ablation as
10:53well as thermal necrosis by bone cement.
10:57On top of it, we are also adding
11:00bisphosphonate to protect the bone.
11:02I was talking to that doctor dish
11:05pande whether we can mix some heat
11:07stable anti cancer drug like a
11:10methotrexate and hopefully that'll
11:11happen in the very near future.
11:14So we are very proud of this
11:17procedure not because patient is
11:18walking but actually we killed
11:21billions of cancer cells during the
11:24procedure and this is addressing.
11:26This is the anesthesia record.
11:29This entire process took less than one hour.
11:32This is really game changer.
11:34And because of this patient can
11:37get new targeted or checkpoint
11:40inhibitors the next day.
11:43So let's see how patient does in two weeks.
11:49Yeah, this is a two weeks after one.
11:52So the procedure works.
11:56And patient was very happy,
11:57but more importantly patient was able
12:00to receive chemotherapy without delay.
12:04And this is another patient
12:06with a prostate cancer.
12:07We know that prostate cancer
12:09sometimes make more bone,
12:10but it's very irregular and
12:12also they do not undergo normal
12:15bone remodeling and they are,
12:17they suffer from pathological fractures.
12:19Well this is a before and we did again same.
12:23Minimally invasive Arif
12:26and this is 2 months Follow
12:33up.
12:35This is Dr. Sharon's patient.
12:38Patient has newly diagnosed.
12:40Stage 5 is my My terminology.
12:44Stage five of breast cancer genetic
12:46chemotherapy right away but she cannot
12:49walk and we did the Arif procedure.
12:52The bottom line is not only
12:54we killed a lot of cancers,
12:55we stabilize the bone as well
13:02and this is a post of CAT scan showing nice
13:06coverage of defect in the astabular roof
13:11and patient is still alive and
13:14she regained full function.
13:24Next patient is Doctor
13:26Scott Gellinger's patient,
13:2849 year old female with a lung cancer.
13:31All drug therapies failed but
13:33he came up with one new drug
13:35and she needs new treatment.
13:37However, the patient had left
13:40to femoral neck fracture,
13:42left astabular defect and the right
13:45astabulum and femoral neck defect.
13:47She's very thin and fragile to receive
13:51bilateral total live arthroplasty.
13:53So we did simultaneous concurrent
13:59area of the astabulum and
14:03the femoral neck bilaterally.
14:07The case took about two hours.
14:10But look at this outcome.
14:12This is before one month and six months.
14:16She survived the seven months
14:18thankfully due to a really
14:20wonderful new drug therapy.
14:21And if you look at the PET scan before,
14:24you can see lots of SUV uptake,
14:26but after Arif AORIF,
14:29you can see decreased SUV uptake
14:32from cancer ablation and also bone
14:36cement derived thermal necrosis.
14:42Our next patient is 89 or the
14:44male with the refractory myeloma.
14:46When I met him,
14:48he was really dying in the bed.
14:50He had the left astabulum complete fracture,
14:53dislocation and L5A fracture.
14:55He cannot even see that.
14:57So we did concurrent L5 and the
15:02left astabular reconstruction
15:04and he was able to emulate and
15:07he survived several months while
15:09he's receiving new drug therapies.
15:16Renal cell cancer is also a big problem.
15:18I interact with the doctor Joseph
15:21Kim and also Doctor Petrol lack.
15:24Renal cell cancer is notorious for
15:26bleeding and if you do open surgeries,
15:29usually do embolization The day
15:31before the surgery then we do hip
15:34replacement and even during that
15:37procedure after embolization,
15:39the bleeding is very tremendous.
15:41So in this case we can do even concurrent.
15:45And geography and embolization and
15:48area for procedure in collaboration
15:51with the doctor Igor Lattic that
15:53I showed in my first slide.
15:56So this is how our smile patients are
16:00doing after our innovative procedure and
16:03I'm available doc Lattic is available.
16:06So text me or e-mail me, we would be
16:09happy to facilitate your oncology care.
16:12By providing all intervention,
16:14do not wait till the bone is broken.
16:17We can still kill the cancer and
16:19the reinforce the bone right away.
16:23Now let me change tone a little bit.
16:25You're all smart cancer doctors
16:27and I'm sure you're already
16:29tired of all the surgical cases.
16:30So let's talk about some some
16:33science why this area for procedure
16:36is really better or superior to
16:38conventional orthopedic procedure.
16:40This is the bone.
16:42And this is a very peaceful bone with
16:46a peaceful osteoblast and osteoclast.
16:49When breast,
16:50kidney and lung cancers go to bone,
16:53they convert this quiescent
16:56bone into inflammatory bone.
16:59And we did some work and we published
17:03this paper in Nature Bone Research because
17:06we failed to publish Nature Science,
17:08what still is a good impacted factor.
17:11And as you see here,
17:12this is MCF 7,
17:14Michigan Cancer Foundation cancer cell line,
17:16MDA, MDA, Anderson cancer cell line.
17:19Cancer cells are transplantable.
17:21That means if orthopedic surgeons
17:23do reaming or spill all the cancers,
17:26they can grow anywhere.
17:28And this is only three-week
17:30after ionoclation in the into the
17:33nude mouse tibia and the cancer
17:36cell growth is tremendous.
17:38In addition,
17:39this is a mouse fracture
17:42showing normal fracture healing.
17:44In mouse fracture healing is
17:46complete within three weeks,
17:47but in the presence of MDA 231 cancer cells,
17:51fractures do not heal.
17:53So if there's a pathological
17:56fracture already,
17:57there is no point of just
17:58putting the nail on.
17:59Somehow we have to do some local
18:02cancer control and if I just show
18:05some kind of a different diagram.
18:10Or it's too moving too fast.
18:14This is the bone homeostasis.
18:17Osteocytes are the master
18:19regulator of a bone Homeostasis and
18:23osteoclast are formed, as you know,
18:27in stimulation by rank ligand and MCSF,
18:31and those are produced
18:33predominantly by osteocytes.
18:34And some by osteoblast and
18:37T cells and other cells.
18:39And the problem is that cancer
18:42cells produce rank ligand,
18:44produce MCSF, produce TNF alpha,
18:47and all the cytokines plus osteocytes
18:51regulate bone by inhibiting bone
18:54formation by producing sclerostine.
18:57And which inhibits actually
18:59went to fiber signaling.
19:00So this is sclerostine is a negative
19:03regulatable bone formation.
19:04And there's a new drug called the
19:07romoszumab that actually can make a
19:09lot of new bones just like dinosumab
19:11by stimulating more bone formation.
19:14The problem is cancer cells
19:15behave like a bone cells,
19:17Like a breast cancer cells,
19:19they make sclerostine as well.
19:21And This is why bisphosphonate or
19:24zometa do not work even though
19:26you give a zometa or dinosumab.
19:28You may suppress osteoclastic bone formation,
19:32but.
19:33You cannot really prevent cancer induced
19:38inhibition of osteoblastic bone formation.
19:41Radiation is very effective,
19:43but again it suppresses both.
19:46Osteoblastic bone formation is
19:49osteoclast and sometimes most of the
19:52time kill cancer cells as well and
19:56This is why we introduced ablation,
19:59local cancer control by ablation.
20:02So that we can cure cancer locally
20:06without affecting surrounding
20:08Osteoblast or Osteoclast.
20:10I mean these days you are using
20:12lots of a targeted therapies
20:13like a met kinase inhibitor,
20:16Ras inhibitor,
20:16all those things I think they have a
20:19great role because Osteoclast require
20:22Mac Orca 1 to signaling MITF NF Kappa B.
20:28Nuclear factor,
20:29they activated the T cells,
20:32C1NFC1 and all those actually transmission
20:34factors are targeted by your new drugs.
20:37So I think that certainly improves
20:40bone formation.
20:45So again, this message is very important.
20:48It's not radio losing defect.
20:50There are billions of cancer cells in the
20:53bone and there is no point of watching.
20:56Just call us and we are going
20:58to kill instantly and we'll
21:00make a bone by doing ablation.
21:02Let me share how ablation works.
21:06This is I hope you don't have
21:08a chicken sandwich today.
21:09This is a chicken and we are putting a
21:14radio frequency ablation probe unlike
21:16steak which requires very hot temperature.
21:20Radiofrequency ablation delivers
21:22very low temperature,
21:24about 65 or 70 degrees over 15 minutes,
21:28so that we can protect the
21:31surrounding neurovascular structures.
21:33At the same time we can effectively induce
21:37cell necrosis within the target region.
21:43In addition, ablation therapy
21:46is not just mechanical.
21:48Ablation therapy is known
21:50to enhance targeted therapy.
21:52So this is an example of
21:56hepatocellular carcinoma in
21:58mouse and actually they gave
22:01radiofrequency ablation alone or
22:07in or better inhibitor and
22:10actually enhanced necrotic zone
22:14moreover ablation.
22:17Exposes antigen because it's a
22:20low temperature by 65 degrees,
22:23we do not induce complete necrosis.
22:26As a result, all the tumor antigens
22:28can be exposed and that will enhance
22:32your targeted antibody therapy.
22:34So this is really exciting and this
22:38is the publication by my colleague
22:41at Duke and also PD1 blockade
22:45actually improves bone mass as well.
22:48Because PD1 signaling is important
22:52during osteoclastogenesis.
22:53So I think there are a lot of
22:57commonality if we work together.
22:59I think we can enhance not only
23:01bone health but actually we can
23:03prolong the survival as well.
23:07So people measure the circulating cancer
23:10cells and the inflammatory cytokines
23:13and of after ablation in animals.
23:16Those circulating cancer cells and
23:20inflammatory cytokines decrease.
23:22So there are a lot of things going on
23:25beyond a physical killing of cancer cells.
23:28And it has been shown that ablation
23:31alone does not cause bone damage.
23:35So these are the biological
23:37factors that I introduced and
23:39briefly I'll go over biomechanics,
23:41why we are doing this small surgery
23:43instead of doing big surgery.
23:49So we are putting bone cement and screws
23:52and we published one paper in the hip joint.
23:55The effective wave bearing zone is
23:57very small. It's a size of 1/4 and I
24:01used to make 50 centimeter incision to
24:04really cure this small lesion and I
24:07think that's really nonsense these days.
24:10And so we did a bio mechanical study.
24:13And cement, small cement and screw
24:17combination really restores the
24:20biomechanical integrity of the pelvis.
24:23So this is the scientific rationally and
24:26we did a biomechanical study and screw
24:30alone or cement alone is not sufficient.
24:33But if we combine screws and the cement,
24:38we can restore a normal
24:41heat function immediately.
24:43So this is really a kind
24:45of scientific background.
24:46My last part of talk is
24:49about now clinical outcome,
24:52so do our patients survival longer
24:55than patients in other cancer centers.
24:58I was very curious and now I
25:01have some data
25:05indication of this procedure
25:07is really unlimited.
25:09We can do any patients with a painful lesion.
25:13Or chemo or radiation resistant lesions,
25:16we can kill the cancer right away.
25:19In astabulum we have about 70
25:24patients cohort and many patients were
25:27better written or wheelchair bound.
25:30I devised A functional score
25:32guidelines because Ecog score
25:34scale is only zero to four.
25:36It's very vague.
25:38So the functional score
25:401/2 is better written.
25:42And the functional pain score 3-4 wheelchair,
25:47567 assisted ambulation and
25:518910 independent ambulation.
25:54It's very intriguing to see all
25:57the patients show very vertical
25:59stiff improvement in pain in
26:02the functional score immediately
26:05within three months animations.
26:07Actually many patients live longer than
26:09one year and that function is retained.
26:17And if you look at the survival card,
26:18somehow those patients who received Arif
26:22procedure survived the longer than predicted
26:27the survival of path of fracture 3.
26:31This is AI driven big database,
26:34prolonged survival prediction tool and our
26:37smile of patients actually live longer.
26:41I mean this could be due to only
26:44functional ambulation that allowed.
26:45New drug therapy right away,
26:48why could it be a combination of radiation,
26:50chemotherapy and all others,
26:52but also at the same time it could be
26:56due to massive cancer site reduction
26:59by ablation and the bone cementation.
27:02So now I'm really thinking our
27:05procedure is not palliative procedure,
27:08it's really lifesaving procedure and.
27:12For those patients who may not live
27:14longer than six months or a year,
27:16we are providing palliative care.
27:20But for those patients who live
27:21longer than one year,
27:23we are providing really functional
27:25cure and complication wise,
27:27there are not many complications,
27:29no infection,
27:30no transfusion and the patients go
27:33home on the same day without any delay.
27:37And 1 controversy in orthopedic
27:39surgery field is.
27:41Protrugio that means femoral head already
27:44really forced into the astabulum.
27:47This is a really big problem.
27:49But we have about 14 patients with
27:53protrusional or protrusion and those
27:55patients also did very, very well.
27:57This is our recent patient with
28:00a thyroid cancer,
28:02massive cancer metastasis and the pets
28:04can show that this increased uptake.
28:08You can see femoral head through the pelvis.
28:14And we did minimally invasive
28:16procedure that took about one hour
28:19and patient was discharged and
28:22patient felt great right away.
28:24The pain was much less and this is
28:28before in the pre upholding area
28:34and this is in two weeks.
28:39He has not been working for a long time.
28:41There's a muscle atrophy,
28:42but at the same time he was able to
28:45really move much more comfortably.
28:47And I'm collaborating with
28:49the radiation oncology.
28:50They can actually do more radiation
28:52to cover the entire pelvis.
28:54My part was to save the wave
28:56bearing as tablet and the medical
29:00oncologist will give drug therapies.
29:03Now let me talk about bone mass.
29:05We talk about bone biology.
29:08So what happens to born after Arif?
29:13And this is the our patient again,
29:1664 year old woman with a breast
29:18cancer she presented with a breast
29:21cancer cat scan showed no born at
29:24all and this is a do Nova cancer,
29:26no prior chemotherapy.
29:28So we did a temporary Arif.
29:31I was a doubtful.
29:32Whether this procedure will last three
29:34months, six months, I was nervous.
29:36Each time she comes to my office,
29:38I'm praying please.
29:40And actually surprisingly she
29:42was really ambulating very well.
29:44But at the same time, look at the bone,
29:47the bone mass change is really unbelievable.
29:50There was no bone,
29:52lot of bones after massive
29:55ablation and the cementation,
29:57of course she received the chemotherapy.
30:00But interesting thing is.
30:01This pelvis was very well
30:04protected and preserved,
30:05but she developed lots of a new
30:08osteolitic metastasis in other bones.
30:11So I think we are doing something
30:12good to the bone and to the cancer.
30:14So we did some little clinical studies
30:17by measuring Ponsfield unit change
30:20on CAT scan and as you know air.
30:27There is like a zero and maximum
30:30house filled units like a 4000.
30:32We can quantify screws, cement,
30:36cancellosy bone, cortical bone and
30:40the Cancelladen fibrous defect.
30:43And this is the Spigotti plot
30:46showing house filled unit changes
30:48over time in about 20 patient
30:51cohort who had a CAT scan.
30:54Before the procedure,
30:55three months after the procedure
30:56and one year after the procedure
30:58and we can easily recognize upward
31:02slope suggesting improved bone mass.
31:06And this is a most striking preliminary
31:09finding for those patients who
31:12showed 10% improvement over bone
31:16mass or a hands free unit on CAT
31:20scan show prolonged survival.
31:22So I think really bodies are
31:24kind of cancer biomarker,
31:26but there's also could be a kind
31:29of a prognostic indicator as well.
31:32And interestingly chemotherapy
31:35radiation or other metastasis do
31:39not really correlate very well
31:41and those patients usually die of
31:43multiple organ metastasis rather
31:47than this bone healthy self.
31:54Among those 70 patients,
31:55we only had one patient who required
31:59hemiaferoplasty and this patient had
32:01a myeloma that did not respond well
32:05to myeloma therapy as you reckon
32:08recognize bone reconstitution is
32:10not really complete and later he
32:13wanted to have a hemiaferoplasty
32:15after myeloma was finally working.
32:19He is now very happy and he can even
32:22run and this is the only one case
32:25that required arthroplasty after
32:28our minimally invasive procedure.
32:31So regarding astabulum,
32:32Arif is a very safe,
32:35effective now I can really say
32:39first line treatment.
32:40It should be the first line
32:43treatment before formal open
32:45orthopedic procedure is concerned.
32:47So don't be afraid of orthopedic surgeons.
32:49We're not going to create any
32:51infections or complications.
32:52They may delay your chemotherapy
32:54just to text me or e-mail me.
32:57Then our team will coordinate
32:59care right away.
33:01And we are doing similar things
33:03for the femoral neck fracture.
33:05Traditionally we put hemi after A
33:07plus your long nails and nowadays
33:10we are doing a kind of very short
33:12mini area for the femoral neck
33:14and the advantage is that.
33:17We can avoid or gain lots
33:19of medical complications,
33:20shorter procedure time and
33:22the blood loss is much less.
33:24Length of stage is also much much less.
33:27And we are doing also the same thing.
33:29For the IM nail,
33:31I really apologize as an orthopedic
33:33surgeon we put IM nail for
33:37those patients who have large
33:39Osteo lesions in the femur and.
33:42Our Intrametalline nail is a nice New
33:45York subway or monorail that transport
33:48all the cancer cells all over the place.
33:51And because of the pressure,
33:53the circulating cancer
33:54cells also increase as well.
33:56So these days we try to kill the
33:58cancer first because a lot of
34:00patients already had the radiation.
34:02We know that radiation didn't work,
34:04chemotherapy didn't work,
34:06so now we are killing cancer and
34:09we do the orthopedic procedure.
34:12Very intriguingly,
34:13again just we learned from science,
34:15once we kill the cancer,
34:17local bone mass increases even without
34:21radiation or additional chemotherapy.
34:24So in summary,
34:26this is my final slide.
34:28I'm here to really introduce our service.
34:32We are really here to share.
34:35Our ability to facilitate,
34:37facilitate your oncology care,
34:39not to share our new surgical techniques
34:42and we provide comprehensive bone care.
34:45We are not just fixing the bone,
34:47we are killing the cancer and we
34:49are changing local bone biology.
34:51So please do not wait until bone is broken.
34:55Please get us involved early
34:56so that we can actually avoid
34:58any surgeries in the future.
35:00And thank you so much for this
35:02wonderful opportunity.
35:02Thank you.
35:16So any questions from
35:19anyone in the audience? Do
35:21we have, Oh yes,
35:27you, when you use the procedure,
35:30you focus on one area.
35:33What happened to the other area?
35:36We didn't apply this technology.
35:38I know what and
35:41what could be the reason for
35:43tumor shrinkage which was not
35:45exposed to this procedure.
35:47Thank you. So we are asking every
35:49scope or effect. And in our case,
35:52it's very, very interesting that
35:56even though local cancer control
35:59is well preserved, patients develop
36:02oscillating metastasis in other bones.
36:05So that means I think a lot of cancers have
36:08a really different chronological biology.
36:10So even though I have a great cancer
36:14control and some patients receive
36:17chemotherapy and all bones become
36:19really wide great improvement,
36:21then there are new,
36:22probably cancer clones that cause new bone
36:25inflammation and bone destruction happens.
36:27So to answer your question,
36:29I do not know the answer.
36:30I wish I know.
36:32Do you have any hypothesis on your end?
36:36By the way, could you kindly introduce
36:38yourself so that people know
36:40who my name is Jung Chi Chan,
36:42pharmacology professor.
36:45Or you you developed a new drug, right?
36:47Yes. Thank you. Also, please introduce
36:49your new amazing drug as well.
36:53I'm just coming back you and
36:55almost at the end of your talk,
36:58you start to talk about
37:00killing the tumor cells first.
37:02Then do your procedure.
37:03Is that what you're saying?
37:05Yes, if you do that where
37:08you see Nas Metasta says
37:10potential of this procedure
37:15kill the tumor cell then
37:17apply your procedure.
37:19The reason I'm asking is your procedure
37:23actually is not only trigger the
37:27local event at the site of procedure.
37:31You may actually trigger the
37:33system wise immuno function, yes.
37:36And that immuno function may be
37:40beneficial with the patients
37:43and the even at the site which
37:47tumor may metastasize too.
37:49Yeah the previously we always talk
37:52about a target oriented approach I
37:55think for cancer treatment we start
37:57to think should start to think.
38:00Much more system wide approaching
38:02controlling the tumor cells.
38:05Thank you. So I'm waking up a sleeping tiger.
38:08So exactly why you said Doctor Chan,
38:11we actually exposing a lot of antigens
38:14and release a lot of intracellular
38:16factors so that your new drug
38:18therapies and also host immune
38:20system can fight against the cancer.
38:22But I do not see all as a positive
38:24results but at least in our patients
38:27surprisingly they really live longer.
38:29And the regarding a secondary
38:31meth from bone to other organs,
38:33this is a very similar concept to
38:35like a dormant cancer by you know
38:37doctor Masago and Dr. even Kang.
38:39Yeah I think that really happens
38:41as well those any.
38:43So bone is the,
38:46I think the largest organ cancer
38:48reservoir in bone next to skin.
38:51So I think a decreasing cancer burning
38:53in bone is clinically very important.
38:58Hey, thank you. Any other questions
39:06okay, I just have one. I noticed
39:09over the years we have in medical
39:12oncology gone from treating cancer
39:17with chemotherapy and radiation
39:20and not isolating treatment for
39:25individual metastatic lesions to now.
39:28Being very, very aggressive and treating
39:32metastatic sites much more aggressively.
39:34Is this something you've seen as well?
39:36Yeah, I mean that's I really
39:39share that same philosophy.
39:40If you have a patients
39:42with the five lung nodules,
39:44sometimes they take out because
39:46they call it oligo metastasis.
39:48But when patients develop bone meds,
39:51a lot of cancer doctors or patients
39:54give up and the probably it's
39:55time to change our approach.
39:57We can be more aggressive without
39:59doing any harm on the patients by
40:02doing minimally invasive procedure
40:07Okay. Thank you any other
40:12questions in that case. Thank you
40:15Francis again for a great talk.