"Osteolytic skeletal metastases: AORIF as a new strategy for enhanced comprehensive oncologic care"
June 14, 2023Yale Cancer Center Grand Rounds | June 13, 2023
Presentation by: Dr. Francis Lee
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- 10058
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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.