Head & Neck Cancers Program 2022: Advancing the Role of Surgery in Head & Neck Cancers

Transcript

• 00:00Welcome everybody to the second
• 00:02installment of the head and neck
• 00:05cancer programs 2022 CME Series Co,
• 00:07hosted by myself and Doctor Burtness.
• 00:10Unfortunately,
• 00:11Doctor Burtness can't be here today,
• 00:13which is fairly appropriate because we're
• 00:15really talking a lot about advancing the
• 00:18role of surgery and head neck cancers.
• 00:20I'll be filling in for Doctor Burton,
• 00:23speaking about a exciting new trial that,
• 00:25well, not for us in the academic world,
• 00:28not so new,
• 00:29but it's recently been published.
• 00:31Um, the ECOG Akron 3311 trial.
• 00:35And so I'll be filling in
• 00:36for Doctor Burtness on that.
• 00:38So the this is part two of three
• 00:41for our head Neck cancer program
• 00:43at Yale New Haven Hospital,
• 00:46Smilow Cancer Hospital and Yale University.
• 00:49We have 3 speakers today.
• 00:51The first will be me filling in for
• 00:54Doctor Burtness on the 3311 trial.
• 00:56I'm talking about D intensification
• 00:59of radiation therapy for HPV.
• 01:01Positive oropharynx cancer.
• 01:03And then we have Doctor Verma who will
• 01:06be speaking about the appropriate
• 01:08use of tours and open surgery in
• 01:11management of head neck cancer.
• 01:14And of course,
• 01:14we have Doctor Sam and Payab Avash
• 01:17who will be speaking about radiomics
• 01:19of head and neck cancer and I'll
• 01:21introduce them before they speak.
• 01:23So without further ado,
• 01:25I think our numbers are kind of leveling off,
• 01:28so.
• 01:29I'm going to get started talking
• 01:32about this very interesting and
• 01:35exciting new trial recently published.
• 01:41So I'm not going to introduce myself,
• 01:44but there I am, Sir Omara,
• 01:45I'm associate professor of surgery at
• 01:48Yale and the chief of Head Neck surgery.
• 01:51Here we have a wonderful head neck
• 01:53cancer team and I'm fortunate enough
• 01:56to lead the surgical aspect of that.
• 01:59So this trial is entitled Transoral
• 02:02oral robotic surgical resection followed
• 02:05by randomization to lower standard
• 02:08dose IRT for resectable P-16 positive.
• 02:11Locally advanced oral pharynx cancer.
• 02:14This is in our circles really known as 3311,
• 02:18basically ECOG 3311.
• 02:22And the authors you can see are here,
• 02:24and I am using some of their slides,
• 02:26particularly Doctor Ferris from
• 02:28Pittsburgh, the lead author,
• 02:29and of course Dr Burtness,
• 02:31the senior author on the paper as
• 02:34well in the last last author here.
• 02:39So this this is a interesting study
• 02:42because on the population included
• 02:45P 16 positive newly diagnosed
• 02:48oropharynx cancer patients who are
• 02:51amenable to transoral resection.
• 02:53The treatment was essentially
• 02:55transoral surgery and then risk
• 02:58adjusted post operative therapy.
• 03:01So the risk status was determined
• 03:04by postoperative pathologic
• 03:05parameters like extranodal extension
• 03:07margin status and the number of.
• 03:09Positive metastatic nodes.
• 03:10I'm going to show a schema in the
• 03:13next slide that will really describe
• 03:16the different groups and how risk
• 03:18stratification was performed.
• 03:20In addition,
• 03:21intermediate risk patients for
• 03:23subgroup analysis were stratified by
• 03:25smoking history less than 10 versus
• 03:27greater than 10 pack years of history.
• 03:30And in this study,
• 03:31important functional assessments
• 03:33were also done,
• 03:34including modified barium swallows and
• 03:36patient reported outcomes including the fact.
• 03:39Your neck and the M daddy dysphagia index.
• 03:44So this is really the key slide to
• 03:46understand how this study was conducted.
• 03:48So that we had HPV P 16 positive squamous
• 03:51cell carcinoma or the oral pharynx
• 03:53stage in the 7th edition three or four,
• 03:56but they were all T1 or T2 and
• 04:00N1 or 2B in 122B cancers and they
• 04:04were baseline functional and
• 04:06quality of life assessments done.
• 04:08All patients that underwent transoral
• 04:11resection, this could be laser.
• 04:14More robotic or bovian headlight,
• 04:17but they all had transoral
• 04:20resection and a neck dissection.
• 04:22Following that patients were
• 04:24stratified into the low risk arm,
• 04:26which were negative margins and
• 04:29no intermediate risk features.
• 04:31And these patients went on to
• 04:33observation alone, no radiation,
• 04:35no chemotherapy.
• 04:35Then there was the high risk arm.
• 04:38These patients had positive margins
• 04:40greater than one millimeter of
• 04:42extranodal extension or five or more.
• 04:45Metastatic lymph nodes and they
• 04:47went on to chemotherapy and
• 04:50radiation therapy with 66 great.
• 04:52The randomization actually happened
• 04:55in these intermediate risk patients
• 04:58and these were close margins.
• 05:00The less than or equal to 1 millimeter
• 05:02VNE and the two to four metastatic
• 05:04lymph nodes and PN I perineural
• 05:07invasion and lymphovascular invasion.
• 05:09These patients were actually
• 05:11randomized into either 50 Gray
• 05:13over 25 fractions or 60 Gray.
• 05:15Over 30 fractions and the outcomes
• 05:18were two year progression,
• 05:20free survival,
• 05:21local regional recurrence and
• 05:24functional outcomes and quality of life.
• 05:29There were really two important objectives.
• 05:32One of them was the feasibility of
• 05:35doing a multi institutional study
• 05:38with transoral surgery followed by
• 05:40risk adjusted adjuvant therapy.
• 05:43As I can see many of the participants
• 05:47here know it's pretty challenging to get
• 05:51surgeons into randomized control trials.
• 05:54That's sort of the domain.
• 05:56Generally if of our radiation and more.
• 06:00Commonly our chemotherapy
• 06:02or oncology colleagues,
• 06:03but so one of them was just the
• 06:05feasibility to do this and we looked
• 06:07at overall accrual surgical quality
• 06:08and the risk distribution of patients
• 06:10that we brought into this study.
• 06:12The second outcome which I'll be talking
• 06:15a lot about today is 2 year progression
• 06:17free survival at 50 Gray versus 60
• 06:20Gray for those intermediate risk patients.
• 06:23So can we effectively de intensify
• 06:25therapy to 50 Gray in these
• 06:27intermediate risk patients versus 60?
• 06:30Without impacting 2 year progression
• 06:33free survival then secondary
• 06:35objectives were toxicity,
• 06:37overall survival,
• 06:38swallowing function and the
• 06:40patient reported outcomes.
• 06:42The original study design had
• 06:45180 called for 180 patients who
• 06:48were randomized with intermediate
• 06:50risk and that's assuming that 35%
• 06:53of patients would be valuable in
• 06:57that intermediate risk category.
• 06:59As the study proceeded,
• 07:00there was a higher proportion of patients
• 07:02saying that higher risk category,
• 07:04the RMD where they were getting chemo
• 07:06radiation and so the total accrual goal
• 07:08was actually increased to 515 patients.
• 07:11And there was a plan for interim
• 07:15analysis at one year for R&B and
• 07:17CAB&C arms A/B and C and of course
• 07:20assessing the surgical quality
• 07:21and risk distribution for the 1st
• 07:2459 patients completing surgery.
• 07:29So from this study accrued from 2013 to 2017,
• 07:34there were 87 credentialed
• 07:37surgeons and 68 of them accrued
• 07:39into the study and these patients,
• 07:41these surgeons perform transoral
• 07:43resections in 519 P, 16 positive
• 07:47oropharynx cancers stage T1 to two.
• 07:51Without matted neck nodes and then
• 07:53post operative management was
• 07:55determined based on the risk factor.
• 07:57So arm A which was observation alone
• 08:01enrolled 38 patients and then arm D
• 08:05which was chemotherapy plus radiation,
• 08:08the high risk patients enrolled
• 08:11113 patients and then ARM B,
• 08:14these were the patients that
• 08:15were randomized to 50 or 60 Gray
• 08:18enrolled 100 or 109 patients.
• 08:21And then as I stated before,
• 08:23ARM D assignment was based on Extranodal
• 08:26extension more than one millimeter,
• 08:29greater than 4 nodes and or positive
• 08:32margin overall in this study the
• 08:36positive margin rate was 3.3%.
• 08:40There were some patients that
• 08:42were deemed ineligible,
• 08:43which I will discuss briefly as well.
• 08:46And 27 of those patients had labs
• 08:49or scans just not done to protocol.
• 08:52But the treatment arm distribution for
• 08:54these patients did mirror those for
• 08:56this 360 eligible and treated patients.
• 09:01So you can see the reasons for
• 09:03exclusion from the 519 patients down
• 09:05to the final group of patients.
• 09:11And there were a number of reasons.
• 09:13Some did not receive a transoral resection.
• 09:16Some patients were just deemed ineligible.
• 09:18Patients were not assigned or
• 09:20randomized or never started treatment.
• 09:22For example, patients who
• 09:24had end to CN three disease.
• 09:26And in the end these were the
• 09:28numbers that I just described.
• 09:31The reasons patients were ineligible
• 09:34more specifically were that, for example,
• 09:37pre study scans or labs were not done within
• 09:40the four weeks prior to registrations.
• 09:42If patients had clinical T3 disease
• 09:44at baseline, they were excluded
• 09:46or ineligible for this study.
• 09:48A few patients were unknown while they
• 09:51were ineligible and to see disease.
• 09:54The primary was not measurable
• 09:57radiographically or clinically,
• 09:58so it could not be appropriately
• 10:01clinically staged.
• 10:02There were no nodes at baseline
• 10:05clinically and then and you can see
• 10:08the other reasons for ineligibility
• 10:10in this cohort of patients Step 2.
• 10:14So step one is a transoral resection
• 10:16ineligibility and then step two was a
• 10:19post operative treatment eligibility.
• 10:21And you can see the reasons for this
• 10:23for example surgery was performed
• 10:25more than four weeks from the
• 10:28registration to step one or.
• 10:30Starting radiation was greater
• 10:31than seven weeks post surgery.
• 10:36The results were actually quite intriguing.
• 10:38Here you can see the three-year progression
• 10:42free survival data in that in ARM a,
• 10:45the low risk group or
• 10:47there's observational loan,
• 10:48no radiation transoral surgery alone.
• 10:50three-year progression free
• 10:52survival was 96.9%.
• 10:54The high risk group who received
• 10:58chemotherapy and radiation
• 11:00after transoral surgery,
• 11:02the three-year progression
• 11:03free survival was 91%.
• 11:05In these two groups that were
• 11:08randomized to either 50 Gray or 60 Gray,
• 11:1050 Gray or 60 Gray,
• 11:12you can see the three-year progression
• 11:15free survival was 94.9% and 93.5%.
• 11:19There were some deaths without
• 11:21recurrence and you can see here in
• 11:23the chemoradiation group there were
• 11:25three deaths in the observation group
• 11:27there were none and one in each of the.
• 11:31Randomized groups and you can
• 11:33see the recurrence numbers,
• 11:35the absolute numbers as well.
• 11:39The transoral surgery and low dose
• 11:42radiation radiation based on this study,
• 11:45based on these preliminary results is
• 11:47were there was worthy of further study
• 11:50based on criteria created a priori.
• 11:54We also looked at in this study
• 11:56at the M Daddy scores and the
• 11:58fact head and neck score,
• 12:00so patient reported outcomes and what
• 12:02you can see here is the following.
• 12:04This is arm a, the M Daddy dysphagia MD
• 12:09Anderson Dysphasia index composite scores.
• 12:11You can see the baseline dysphagia
• 12:14index at 89% post surgery.
• 12:16There was obviously a drop in the Dysphasia
• 12:20index and then patients actually recovered.
• 12:24Quite nicely and you can see the same numbers
• 12:27here which I'll show graphically shortly.
• 12:31For arm B, the randomized groups to 50 Gray,
• 12:3460 Gray and the chemo radiation groups
• 12:38here and you can see the the decline
• 12:42in dysphasia index PRO's here in this
• 12:44in this group of patients and the same
• 12:48thing was done for the fact head and
• 12:51neck patient reported outcomes tool.
• 12:55And the survival curves you can see
• 12:57for the these are this is for the
• 12:59eligible and treated patients the
• 13:00numbers we went over and you can see
• 13:02how tight they are arm D did have
• 13:07a slightly lower overall survival,
• 13:10progression free survival here.
• 13:13And in the ineligible and treated groups,
• 13:15this was measured here as well.
• 13:19And graphically you can see the uh
• 13:22in the M daddy composite scores,
• 13:25the observational loan group did best,
• 13:28RMD chemo radiated did worse
• 13:31compared to baseline.
• 13:32But overall these tumors are still quite,
• 13:34quite, quite good and the intermediate
• 13:36risk groups and same for the
• 13:38fact head and neck total scores.
• 13:40So the conclusion of this study
• 13:43were the transoral resection for
• 13:45P-16 positive or famous cancer is
• 13:48safe and results in good oncologic.
• 13:50Outcomes and this can offer a promising
• 13:54de intensification approach to treatment
• 13:57for oropharynx cancer patients.
• 14:00In patients who have low risk disease
• 14:03progression free survival is favorable
• 14:06without any postoperative therapy and
• 14:09in those patients who have uninvolved
• 14:11margins less than five nodes,
• 14:13minimal or no ENE we can reduce postoperative
• 14:18radiation therapy without chemotherapy.
• 14:21Without impacting progression free survival.
• 14:25So finally transoral surgery with
• 14:2750 Gray should be in the future
• 14:31compared to optimal nonsurgical
• 14:33therapy in some phase three trials
• 14:37for patients with intermediate risk.
• 14:42This was coordinated by the ECOG Akron
• 14:45group here and there were these were
• 14:48the centers that accrued and Yale was
• 14:51definitely a major accrued to this study.
• 14:56I did want to spend a few minutes talking
• 14:59about two more items related to this study.
• 15:02One is an abstract that was just recently
• 15:05presented a few weeks ago at ASCO,
• 15:08based on data from 3311 not yet published,
• 15:11but was presented in abstract form with this.
• 15:17Abstract tried to analyze the
• 15:20patients from 3311,
• 15:22looking at patients who smoked 10
• 15:25greater than 10 Packers or versus
• 15:28less than 10 Packers.
• 15:30As most of the people on this call know,
• 15:32smoking can be a.
• 15:33A risk factor for worse survival in
• 15:36oropharynx cancer and HPV associated
• 15:39cancer puts classically has been
• 15:42described as an intermediate risk as
• 15:45opposed to the the high risk patient
• 15:47and to the favorable risk patients.
• 15:49This study however showed let me just
• 15:52get to the the data that there was
• 15:54no difference in overall survival
• 15:56or progression free survival for
• 15:58smokers in this cohort of patients
• 16:01in 3311 who had transoral resections.
• 16:03So these even these intermediate.
• 16:05Risk HPV oral various cancer patients
• 16:08who are current smokers or who have a
• 16:10history of greater than 10 pack years
• 16:12had favorable 3 year progression free
• 16:15survival and overall survival that
• 16:16were not worse than those non-smokers
• 16:19or less than 10 pack your history.
• 16:21So this data actually shows the first
• 16:25treatment approach meaning surgery plus.
• 16:29Radiation therapy without chemo,
• 16:32in which outcomes were not influenced
• 16:35by smoking status.
• 16:37A final study I want to share with
• 16:38you is tours in the real world.
• 16:43Where you're treated matters.
• 16:44This is a study we published a few years ago.
• 16:47This is actually in 2019 was published,
• 16:49but I think is quite apropos
• 16:52to this this discussion.
• 16:54We looked at the National Cancer
• 16:57database and looked at positive
• 16:59margin rates and predictors in
• 17:01transoral robotic surgery after
• 17:03federal approval of the robot for.
• 17:08Oropharynx cancer treatment.
• 17:11We looked at 3000 patients in the
• 17:14National Cancer Cancer database
• 17:16who underwent tours from 2010
• 17:18to 2014 soon after approval and
• 17:21we had to exclude some patients,
• 17:23but ended up with about 2600
• 17:26patients for analysis.
• 17:29In the real world during this study
• 17:32period the positive margin rate was not
• 17:35the three-point 3% presented in this
• 17:37study at the at at academic centers,
• 17:40at credentialed by credentialed
• 17:42surgeons and it was actually a higher
• 17:45than a lot of the studies that look at
• 17:48transoral surgery in at high volume centers.
• 17:51Nationally the overall positive
• 17:53margin rate was 17% of patients with
• 17:56T1 and T2 had a positive margin.
• 17:59Type of less than 20 percent, 13% and 17%.
• 18:03And when you get to T3 and T4 cancers,
• 18:06which I will mention it,
• 18:08for which the da Vinci robot at
• 18:10least is not FDA approved,
• 18:12positive marginal rates
• 18:14are significantly higher.
• 18:17In this study,
• 18:18we looked at factors associated
• 18:20with positive margin rate and
• 18:21we found that T classification,
• 18:23Lymphovascular invasion and volume
• 18:25of cases by the facility patients
• 18:29treated at high volume centers were
• 18:32less likely to yield positive margins.
• 18:35You can see how we define this was
• 18:37less than three cases per year,
• 18:39three to 10 cases,
• 18:41and then more than 10 cases per year.
• 18:43And you can see the difference.
• 18:44A high volume facilities had a rate
• 18:47still much higher than this study
• 18:50with credentialed academic surgeons,
• 18:53but 13% versus 21 percent,
• 18:5622% for low volume sensors.
• 18:58So the conclusion of this retrospective
• 19:02database study was in the year
• 19:05since FDA approval.
• 19:06Positive margin rates has been
• 19:08substantially higher than reported
• 19:09in high volume tour centers
• 19:11with academic surgeons.
• 19:12When you get to higher T stages,
• 19:16these rates can exceed 28% and then
• 19:20high volume facilities are half
• 19:22as likely to yield to positive
• 19:24margins as compared to low volume
• 19:26centers on multivariate analysis.
• 19:29So that's what I wanted to tell
• 19:31you all about the ECOT 3311 trial,
• 19:33which basically showed that D
• 19:36intensification approaches are
• 19:38possible for HPV associated P-16
• 19:41positive oropharynx cancer.
• 19:49Right. So you guys are welcome to
• 19:53put any questions in the chat.
• 19:55I'm going to be moderating.
• 19:57You probably won't see them all,
• 19:58but I'll I'll moderate them and.
• 20:01We'll move on to our next.
• 20:04Next, speakers and we'll do the
• 20:06questions probably at the end
• 20:08unless I see something that I think
• 20:10needs to be addressed right away.
• 20:13So our next speaker, thanks,
• 20:16Evan, you must start sharing.
• 20:18Our next speaker is Doctor Avanti Verma,
• 20:20who returned to us at Yale after
• 20:25her years as an undergraduate here.
• 20:27And even additionally you're
• 20:29doing research here.
• 20:30She went off to New York and Atlanta to do.
• 20:33Our ENT and advanced head and neck
• 20:36cancer training and we were lucky
• 20:38enough to recruit her back to New
• 20:40Haven as into our section of head
• 20:42and neck surgery here at Yale.
• 20:43She's assistant professor of surgery
• 20:46and the lead of head neck surgery at
• 20:49the VA in Connecticut here as well.
• 20:53So Doctor Verma will be speaking
• 20:55to us about the appropriate use
• 20:56of tours in open surgery.
• 20:58Thank you so much.
• 20:59Doctor Verma.
• 21:00Yes, thank you for the kind introduction.
• 21:03So I. We'll be speaking about using
• 21:06transoral robotic surgery and it was one
• 21:09of the modalities used in ECOG 3311,
• 21:12but probably the most
• 21:14prominent one and sort of.
• 21:16Think of this as an option and
• 21:18alternative compared to open
• 21:19surgery and we'll soon learn that
• 21:22patient selection really matters.
• 21:24So I will go through that and some of the
• 21:27technical aspects of the surgery as well.
• 21:32OK. So you know, just as an overview
• 21:34of the head and neck anatomy, Umm,
• 21:37we think about tumors in these in
• 21:41this whole region as occurring in
• 21:43different sites and then within sites,
• 21:45different sub sites. So there's many,
• 21:47many different sites of the head and neck.
• 21:49And how we manage a patient really
• 21:52depends on the the location of the tumor.
• 21:55And in all these areas there's blood vessels,
• 21:57lymphatic channels, nerves that we are
• 22:00trying to preserve the best we can.
• 22:02Muscles, bone, cartilage, everything.
• 22:05So you know, anatomic considerations
• 22:07are very important to us in general,
• 22:11the principles of head neck cancer
• 22:13surgery include complete visualization
• 22:15of the surgical field,
• 22:17which can be a challenge given that
• 22:20we're working in in small areas and
• 22:23with that visualization we want to
• 22:25achieve on block tumor resection all
• 22:28in one piece with negative margins,
• 22:31traditionally margins.
• 22:325 millimeters or greater and and then in
• 22:35addition to doing that as best as we can,
• 22:38we'd like to preserve surrounding
• 22:41structures that are important
• 22:43for function of our patients.
• 22:45So the the gold standard or
• 22:47traditional or open approaches.
• 22:49Generally all of these approaches are
• 22:51transcervical or through the neck,
• 22:53requiring a neck or facial
• 22:55incision on the left hand side.
• 22:57In the oropharynx category,
• 22:59the the few approaches to the orphans
• 23:01that were traditionally used for quite
• 23:04a while are the mandibular automy
• 23:06approach which requires a lip split
• 23:09incision most often and you can see in
• 23:12that cartoon down there that the mandible.
• 23:15Sort of split open and you
• 23:16can see this tongue.
• 23:18The tongue is retracted to one
• 23:19side and you can see this tongue
• 23:21based tumor in the visualization.
• 23:23As I said,
• 23:23which is important here is
• 23:25is very good in this case,
• 23:27but it requires a lot of work and a lot
• 23:29of potential morbidity to the patient.
• 23:32Another approach to large tongue based
• 23:35tumors includes going through the
• 23:37floor of mouth sling and musculature
• 23:39there to bring the tongue down into
• 23:41the neck and so you can visualize
• 23:43the almost the entire tongue,
• 23:45essentially the entire tongue.
• 23:46Through the neck and respect
• 23:48your tumor that way,
• 23:49which again is associated with morbidity.
• 23:52For smaller tumors of the tongue base,
• 23:55a trans hyoid approach with the
• 23:58fairing gotami can also be used.
• 24:01Don't focus too much on the larynx today,
• 24:03but you know the open approach to the larynx.
• 24:08The gold standard again is a
• 24:10total laryngectomy for Laura.
• 24:11You know especially advanced
• 24:13stage laryngeal tumors,
• 24:14partial interjections can be
• 24:15considered depending on the location
• 24:17and the stage of the tumor and the
• 24:20patients comorbidities and those
• 24:22include vertical partial laryngectomy
• 24:23is super cricoid laryngectomy
• 24:25and a supraglottic laryngectomy.
• 24:27And later in this talk I'm going
• 24:29to mention that the robot can
• 24:31be used for the Super Glottic.
• 24:33Enemy on the right hand side,
• 24:35the parapharyngeal space usually
• 24:38requires a transcervical approach,
• 24:40which can be achieved with mobilization
• 24:42or excision of the submandibular gland
• 24:46into the parapharyngeal space there.
• 24:49Or it can be done in a trans parotid
• 24:51approach, which requires a facial nerve
• 24:55dissection and removal and mobilization of
• 24:58the deep lobe of the of the parotid gland,
• 25:01which can be quite extensive.
• 25:04So some minimally invasive approaches that
• 25:06have come up recently and are robotic
• 25:09surgery, which I'll focus on today.
• 25:12And robotic surgery can be used to
• 25:15access the oropharynx in lieu of those
• 25:17bigger approaches that I mentioned.
• 25:19The supraglottic larynx can also be accessed
• 25:21as well as the parapharyngeal space.
• 25:24And in that photo below,
• 25:25you can see that the surgeon is at the
• 25:28surgeon console controlling the robotic arms,
• 25:30which are closer to the patient
• 25:33and there's an assistant.
• 25:34Of making sure the arms and
• 25:36the patient are OK.
• 25:37On the right hand side,
• 25:38again there's laser surgery
• 25:40which has existed for longer,
• 25:41a couple more decades than
• 25:43robotic surgery which has really
• 25:45come up in the past two decades.
• 25:46And there's many kinds of lasers,
• 25:49but primarily this is used for the
• 25:51Super glottic larynx and larynx.
• 25:53It can be used for the oropharynx
• 25:55as well and and for the trachea.
• 25:58So for transoral robotic surgery,
• 26:00when it was first being used for head
• 26:03and neck and it was really the US side,
• 26:06that was the model that was being used.
• 26:08And on the left hand side,
• 26:10you can see that there's a surgeon
• 26:12console with sort of those eye
• 26:15pieces where the surgeon can see
• 26:17and have a great view of the field.
• 26:19And then there's the controls there
• 26:21that you know the fingers go into and
• 26:24sort of control the robotic arms,
• 26:26there's petals that provide.
• 26:28Pottery and a left sided pedal
• 26:30that controls the camera as well.
• 26:32So you really have control of of everything.
• 26:36In the middle is the patient cart
• 26:38which is basically what's right at
• 26:40the patient and the arms have trocars
• 26:43and instruments going through them
• 26:45that go into the patient's mouth which
• 26:48you can see on the right hand side.
• 26:50And then the final component is the
• 26:53vision cart which is this tower and a
• 26:56a screen with really high definition.
• 26:59Images there for the assistant
• 27:00to be able to see,
• 27:02and for the scrub tech and anyone
• 27:04assisting in the surgery to be
• 27:06able to see what's going on.
• 27:10More recently, the A new 4th generation
• 27:13of robot, also from da Vinci,
• 27:16has been FDA approved for
• 27:18surgery of the head and neck,
• 27:20and it's the single port robots.
• 27:22On the left hand side,
• 27:23you can see that there's just one
• 27:25cannula instead of the three,
• 27:27and there's a camera and robotic arms
• 27:29that come out through the single cannula,
• 27:31which measures 2.5 centimeters in diameter.
• 27:34So it is quite small and the
• 27:37camera itself has some flexibility.
• 27:40As you can see in the middle photo,
• 27:42you can bend, there's certain pose,
• 27:44you know, we call it the Cobra
• 27:46pose so that it can sort of bend
• 27:47to look up or bend to look down.
• 27:49And the robotic arms have
• 27:52more mobility in the wrist.
• 27:54There's much more degrees of mobility there.
• 27:57So there's usually one arm that has a four
• 28:01steps to help retract or grab tissue.
• 28:03The other arm usually has cautery
• 28:06and even the forceps arm can be
• 28:09connected to bipolar cautery,
• 28:10so you can cauterize.
• 28:12Both arms and then this model of robot
• 28:15actually has the option of a fourth
• 28:17arm that you can use however you'd like,
• 28:21and some of us will put a second
• 28:23four steps there to keep longer
• 28:25retraction on tissue if needed.
• 28:27On the right hand side,
• 28:29there's a photo of what the port looks
• 28:31like going into the patient's mouth.
• 28:33And then there's a retractor.
• 28:35This is the FKW retractor that's
• 28:37holding the mouth open and keeping
• 28:39the tongue out of out of the way.
• 28:44So the indications for towards Umm,
• 28:46you know we discussed it a little
• 28:47bit when we were talking about ECOG
• 28:493311 on particularly early stage or
• 28:52financial squamous cell carcinoma.
• 28:54So T1 and T2 lesions of the tonsil
• 28:57and tongue base cancers of the soft
• 29:00palate primarily you know are not
• 29:02always so amenable to this because
• 29:05of functional downsides such as
• 29:07Villa Ferringer and sufficiency.
• 29:09Isolated lesions of the posterior
• 29:11pharyngeal wall may be considered,
• 29:13but if quite a bit.
• 29:14That is being resected and we usually
• 29:17do not proceed with this approach.
• 29:19I mentioned early stage supraglottic
• 29:21squamous cell carcinoma which
• 29:23I'll mention again later and then
• 29:25benign tumors of the oropharynx,
• 29:27supraglottis and the parapharyngeal
• 29:30space could also be considered
• 29:32for transoral robotic resection.
• 29:35Transoral robotic surgery can
• 29:36also be used for sleep apnea,
• 29:37but I I won't focus on that today.
• 29:40Lingual tonsillectomy or tongue based
• 29:42reduction can be done for patients who.
• 29:44To have this contributing
• 29:46to their sleep apnea,
• 29:48the first photo is sort of our
• 29:50view when we have good retraction,
• 29:53there's a tonsil tumor on the right
• 29:55hand side and you know the head is
• 29:57at the bottom of the screen and the
• 29:58chin is at the top of the screen.
• 30:00And so we're looking from above and you
• 30:03know we can see the tip of the epiglottis,
• 30:06the tongue base on both sides.
• 30:07We have full view of the tonsil
• 30:10cancer and even margins of tissue
• 30:12around it and you can see that.
• 30:14Four steps in the left hand corner
• 30:17corner just ready to start.
• 30:18And then on the right hand side there's
• 30:21a specimen post resection that I was
• 30:24trying to Orient for the pathologist.
• 30:27So using some of the anatomic
• 30:29landmarks can help because this
• 30:31is very much A3 dimensional tumor
• 30:33and A3 dimensional resection and
• 30:35all of this technology helps us,
• 30:38you know,
• 30:38see where we need to see to to achieve this.
• 30:42So the clinical evaluation for tours
• 30:44when we see a patient who's referred to
• 30:47to see if this is even something that
• 30:50we can offer depend on many things.
• 30:53The tumor factors include the
• 30:55size and size is close is closely
• 30:57in hand with the stage.
• 30:59So T1 or T2 tumors,
• 31:01anything bigger than that we
• 31:03probably would not consider this.
• 31:05The location is also important
• 31:08midline tumors sometimes.
• 31:10Are at risk of injury to both lingual
• 31:13arteries which I'll mention again later.
• 31:16So you know we we prefer to do this
• 31:19approach for lateralized tumors.
• 31:22The depth also factors into stage and
• 31:25we can tell that sometimes by palpation
• 31:28on clinical exam and some you know
• 31:31it definitely with imaging as well.
• 31:34If there's trismus this patient can
• 31:36only open 2 centimeters and and you know
• 31:39someone's really pushing with their thumb.
• 31:41You know then that that you
• 31:43know won't be good for us,
• 31:45especially with the 2.5 centimeter,
• 31:47uh,
• 31:47cannula that it has to get in the mouth.
• 31:49So that's something that's important
• 31:51to consider.
• 31:52The tongue size is also important.
• 31:55There's a lot of tease here.
• 31:56So people sort of remember this as the rule
• 31:59of the teas status of the teeth and the jaw,
• 32:02whether they're mandibular Tori and then
• 32:05neck mobility or tilting of the neck,
• 32:08anyone who's had spinal
• 32:09instability or spinal surgery.
• 32:11You know we have to evaluate for
• 32:13that to make sure we can get
• 32:15the exposure we need for this.
• 32:17I added to this prior treatment as well in
• 32:20patients who have had previous surgery,
• 32:23previous radiation in particular and
• 32:25this is sort of a salvage surgery.
• 32:29We have other considerations including
• 32:31you know whether that when we do
• 32:35these resections we don't necessarily
• 32:37put tissue you know to reconstruct,
• 32:40but in these patients we
• 32:41might have to do that.
• 32:42To protect the carotid artery
• 32:44or any other vital structures,
• 32:46because healing might not be as
• 32:48optimal as As for patients who
• 32:52haven't been treated before.
• 32:54So the you know the clinical
• 32:56exam it you know we rely on a
• 32:59transoral inspection and palpation,
• 33:01but we also rely on a flexible
• 33:04laryngoscopic exam.
• 33:05And between those two things we
• 33:07kind of have a sense of the extent,
• 33:09location,
• 33:10depth of the tumor whether we
• 33:12could access this.
• 33:14But a radiology is also very
• 33:16helpful for us when we evaluate
• 33:19patients and and tumors the location
• 33:22of the carotid artery is.
• 33:24Is very important,
• 33:25especially if we're looking at a
• 33:27patient who has a retropharyngeal
• 33:28carotid and you can see that
• 33:30pretty prominently in the left
• 33:32side in that image with the arrows.
• 33:34So if this patient needed a
• 33:37radical tonsillectomy,
• 33:38we we probably would not consider
• 33:39that in this case if we thought that
• 33:42the carotid artery would be exposed
• 33:44or even potentially injured by this,
• 33:46by this approach.
• 33:49Tongue based tumors,
• 33:50sometimes we can,
• 33:51we can still do um resections on a
• 33:54patient with a retropharyngeal carotid,
• 33:56but that takes a lot of you know
• 33:59very intense study of the of the
• 34:01skin and making sure that it it will
• 34:04stay away from your resection bed
• 34:06or that you won't keep it exposed.
• 34:09Then you know the I mentioned
• 34:10before that the tumor could be
• 34:12closely associated with the lingual
• 34:14arteries on both sides and that
• 34:16would be a contraindication to
• 34:18transoral robotic surgery.
• 34:19In the middle image,
• 34:21you can see a very endophytic
• 34:22tumor um that is invading and
• 34:25extrinsic tongue musculature.
• 34:27So this would already be a higher
• 34:29stage and a contraindication to tours,
• 34:31but this likely would involve
• 34:33the lingual artery on that side.
• 34:35On the right hand side is probably
• 34:38a similarly sized tumor but much
• 34:40more exophytic.
• 34:41So that's sort of a counterpoint to
• 34:43that middle image that sometimes we
• 34:45see these endophytic tumors that
• 34:47wouldn't be ideal for transoral surgery,
• 34:49but then sometimes we see these.
• 34:51Exophytic ones where we know we can
• 34:53stay away from the lingual artery
• 34:56and and resect it with minimal
• 34:59functional morbidity to the patient.
• 35:01So the the benefits of tours
• 35:03is avoidance of tracheostomy
• 35:05which would be necessary in some of these
• 35:08open approaches and faster rehabilitation,
• 35:10recovery of speech and swallow function.
• 35:13The surgery is shorter as
• 35:15well as the hospital stay.
• 35:17And we would really consider this as
• 35:20Doctor Mayer mentioned in his talk if
• 35:22we were able to reduce or eliminate even
• 35:25the need for post operative treatment.
• 35:27So post operative or adjuvant
• 35:29radiation or chemo.
• 35:31Therapy and I just put the ECOG
• 35:333311 schema up there.
• 35:35Just as a reminder as to you know
• 35:37one of the reasons we do transoral
• 35:39robotic surgery to minimize
• 35:41adjuvant treatment if we can.
• 35:43If we think that we could not say
• 35:45there's a small primary tumor,
• 35:46but there's matted nodes and obvious
• 35:49extranodal extension that you know that
• 35:52would put them in in the high risk arm,
• 35:55then maybe you know we should
• 35:58consider upfront chemo radiation.
• 36:01The risk of tours include taste disturbance
• 36:04and tongue numbness on those 2GO hand
• 36:07in hand primarily because of retraction.
• 36:10Using these FK retractors or the Med
• 36:12robotic retractors or even the Crow
• 36:14Davis and having that that blade blade
• 36:17against the tongue for quite a while
• 36:19can cause these things and and some
• 36:22patients last longer than others.
• 36:24Even though one of the things
• 36:26that is improved with Torres is
• 36:28swallowing return to swallow function,
• 36:30there still can be problems with
• 36:31swallowing in the immediate.
• 36:32Post operative period Velopharyngeal
• 36:35insufficiency is something that I mentioned,
• 36:38particularly if there is a significant
• 36:40portion of the soft palate that's
• 36:43resected if in in oropharyngeal
• 36:45squamous cell carcinoma in particular,
• 36:47a neck dissection typically is performed
• 36:51with the transoral robotic surgery.
• 36:53And so when that happens,
• 36:55there is a risk of fistula between
• 36:58the oropharynx resection and the neck
• 37:00and so we have to monitor for that.
• 37:03Carefully, um,
• 37:04during the surgeries in some cases,
• 37:06in some surgeons would tend you
• 37:08know would tend to stage the neck
• 37:10dissection for do that first and
• 37:12then do the robotic surgery later
• 37:14or if we do it at the same time,
• 37:17there are some local reconstruction
• 37:19options that we can consider to
• 37:21close a fistula and you know those
• 37:24that's important to keep an eye out
• 37:26for the other thing about the neck
• 37:29portion of the surgery particularly in
• 37:32oropharyngeal squamous cell carcinoma.
• 37:33Is ligation of the external
• 37:35carotid artery or its branches.
• 37:37Because bleeding is a very
• 37:40feared risk of tours,
• 37:41it can be life threatening and
• 37:44it doesn't happen immediately.
• 37:45It tends to happen over
• 37:47a week postoperatively.
• 37:49So it is standard of care to ligate these
• 37:53branches to minimize the risk of bleeding.
• 37:58Contraindications to transoral robotic
• 38:00surgery include inability to visualize
• 38:02the lesion or any relevant anatomy.
• 38:05Trans orally if there is carotid
• 38:07artery involvement of the tumor which
• 38:10would upstage the tumor as well,
• 38:12prevertebral fashion involvement,
• 38:14any mandibular invasion,
• 38:16and if there's greater than 50% tongue
• 38:19based involvement or greater than 50%
• 38:21posterior pharyngeal wall involvement.
• 38:23I also mentioned the medicalized
• 38:26or retropharyngeal carotid.
• 38:28Um, which is generally a contraindication.
• 38:31Um, but sometimes it particularly
• 38:33in tongue based resections.
• 38:35If it's really posterior,
• 38:37it can be still considered.
• 38:41So this is sort of some
• 38:44relevant internal anatomy.
• 38:45The the two pictures on the
• 38:48left depict the initial approach
• 38:50to a radical tonsillectomy.
• 38:53So the forceps is holding the
• 38:56pharyngeal constrictor muscle and this
• 38:58is sort of the first incision that
• 39:00we make in a radical tonsillectomy.
• 39:02We expose that medial teratoid muscle
• 39:05and and use that pharyngeal constrictor
• 39:07as as our deep margin essentially.
• 39:10And as that's being retracted medially
• 39:12and that sort of whitish fluffy thing
• 39:15stuff you see is the parapharyngeal fat.
• 39:18And so that's where the,
• 39:20the blood vessels are the things
• 39:22you want to avoid.
• 39:23And so that sort of bluntly gets.
• 39:27Dissected laterally so we can
• 39:29continue working on the muscle
• 39:31that can get transected and often
• 39:33does is the styloglossus muscle
• 39:35where that blue arrow is.
• 39:37So there's a lot of internal
• 39:39anatomy that we're thinking about
• 39:41as we do these resections and on
• 39:44the right hand side that's that's
• 39:46a depiction of the location of the
• 39:48lingual artery because during a
• 39:50tongue based resection or focused
• 39:52on where that is and you can see
• 39:55that that dorsal lingual artery.
• 39:57In in the circle there that that's
• 39:59often that often can show up and we
• 40:01are watching out for it especially
• 40:03it almost comes up as like a
• 40:05knuckle of a vessel as you're in
• 40:07the tongue based musculature.
• 40:09So we're always watching out
• 40:10for that when we do these,
• 40:12do these cases and thanks to the
• 40:15technology of the robot we really have
• 40:18great visualization as we're working.
• 40:20So moving on to Super Glottic squamous
• 40:23cell carcinoma exposure is still important.
• 40:26Sometimes it can be more
• 40:28challenging in in in that photo,
• 40:29some of those longer blades are used to
• 40:32get deeper and exposed to super glottis.
• 40:35Again,
• 40:35transoral robotic surgery is used
• 40:38for early stage tumors at T1 and T2.
• 40:41Some surgeons do report using
• 40:43this for T3 tumors as long as
• 40:45both vocal cords are mobile,
• 40:47which basically precludes paragliding.
• 40:50Face involvement.
• 40:52The airway considerations you know
• 40:54are interesting and super chaotic.
• 40:57Squamous cell carcinoma.
• 40:58I think there are some cases in
• 41:00which doing a tracheostomy up front
• 41:03to protect the airway and and in
• 41:05the event of any bleeding could
• 41:07be considered more so than for or
• 41:10pharyngeal squamous cell carcinoma.
• 41:12And the major source of bleeding
• 41:14if it were to occur would be from
• 41:16the superior laryngeal artery in
• 41:18this case and in the bottom photo.
• 41:20You can see that there's on the
• 41:22lingual surface of the epiglottis,
• 41:23there is a tumor there and so
• 41:26there the robot is being used to
• 41:29sort of visualize it and also then
• 41:32for resection contraindications
• 41:34to this include limited exposure.
• 41:37Poor pulmonary reserve is actually
• 41:39a contraindication to a supraglottic
• 41:41laryngectomy as well as you know
• 41:43it can be a difficult recovery,
• 41:46there can be aspiration postoperatively.
• 41:50Involvement of the anterior commissure
• 41:52thyroid cartilage is also contraindication,
• 41:54as is periodic space invasion.
• 41:56That could cause vocal cord fixation
• 42:00or a hypomobility.
• 42:03Some tumors that with minimal
• 42:04involvement of the pyriform
• 42:06sinus can be resected this way.
• 42:07But if there is involvement of
• 42:09the apex of the pyriform sinus
• 42:11or any post cricoid mucosa,
• 42:13that's also a contraindication.
• 42:17And just briefly for the final slides,
• 42:19wanted to review trends or robotic
• 42:21surgery for the parapharyngeal space.
• 42:23Generally it's used for a well
• 42:26circumscribed tumors most commonly
• 42:28for a deep lobe parotid neoplasm such
• 42:31as a pleomorphic adenoma and these
• 42:34generally are in the pre styloid space.
• 42:37And the the bottom picture if you
• 42:39can see it sort of depicts the pre
• 42:42styloid versus the post styloid,
• 42:44but generally the pre styloid
• 42:46space is occupied by.
• 42:47Parapharyngeal fat in the post dilate
• 42:49space is where the great vessels are
• 42:52and and and the associated nerves.
• 42:54So This is why we would probably not
• 42:57use this for post thyroid tumor.
• 43:00There have been reports of resecting
• 43:03benign tumors as large as 8
• 43:06centimeters trans orally there are.
• 43:08I think again selection is very important.
• 43:11The relationship to the internal
• 43:13carotid artery is key here.
• 43:14So if the artery is displaced
• 43:16laterally and you can see it.
• 43:18A plane between the tumor and the carotid,
• 43:21I think you know that that's a
• 43:23sign that this could be safe to do
• 43:25with a transoral robotic approach.
• 43:27In some cases with these deep lobe
• 43:30salivary gland tumors or prodded
• 43:31gland tumors,
• 43:32extension through the stylo mandibular
• 43:35tunnel may require a combined or
• 43:38an open approach because of that.
• 43:41Because it's hard to get laterally
• 43:43beyond and I'll show you photos
• 43:45of that and that this creates a
• 43:47dumbbell appearance on imaging.
• 43:48So the the graphic on top just
• 43:50shows where the stylo mandibular
• 43:52ligament is and that barrier sort
• 43:55of causes the tumor to grow around
• 43:57it and create a dumbbell.
• 43:59And so part of that could be accessed
• 44:02very easily trans orally as you
• 44:04can see the bottom right image.
• 44:06But the part that's abutting the deep
• 44:08lobe of the product can be difficult.
• 44:10So sometimes this.
• 44:11This would require just an open
• 44:13approach or or a combined approach.
• 44:16The advantages of of going trans orally
• 44:19to approach these is that there's less
• 44:21risk of first bite syndrome and fry syndrome,
• 44:24which are well described after
• 44:27transcervical or Transpara added
• 44:29approaches to the parapharyngeal space.
• 44:32There's less risk of Cialis steel because
• 44:34you're not dissecting the parotid gland,
• 44:36and then there's less risk of facial
• 44:38nerve injury because you're you're
• 44:39not dissecting that either.
• 44:40And of course there's no external incision.
• 44:45That,
• 44:45you know,
• 44:46the main disadvantage is that there's a
• 44:48very narrow corridor of exposure and if
• 44:51there's any bleeding that occurs there,
• 44:54there can be a lot of
• 44:56difficulty controlling that.
• 44:56So sometimes when when surgeons
• 44:59are doing this,
• 45:00they'll have a backup open approach
• 45:02so you can convert to an open approach
• 45:05if needed to control any bleeding,
• 45:07even though there's a decreased
• 45:09risk of facial nerve injury and
• 45:12other adverse effects,
• 45:13the glossopharyngeal nerve.
• 45:14Is actually closely associated
• 45:16with the styloglossus muscle,
• 45:18so that's an increased risk of injury here.
• 45:22So the you know in conclusion traditional
• 45:24open surgery is the gold standard
• 45:26and and what's been done for many,
• 45:28many, many years to approach the tumors
• 45:30of the head and neck with the following
• 45:33purposes to visualization on block
• 45:35resection with negative margins and
• 45:37preservation of surrounding structures.
• 45:39Robotic surgery over the past
• 45:41two decades or slightly more has
• 45:43demonstrated that you know we can
• 45:45achieve similar outcomes with improved
• 45:47functional outcomes but we have
• 45:49to select our patients carefully.
• 45:51Based on clinical aspects and
• 45:54radio graphic aspects too.
• 45:58So here are my references and I
• 46:01had a question slide while we were
• 46:03waiting till the end so. Thank
• 46:05you. We'll wait till the end. That's great.
• 46:08Thank you so much Doctor Verma for
• 46:11that great run through a transoral
• 46:14robotic surgery and Susan head neck.
• 46:18Great. So our final speaker for
• 46:20this evening is not a surgeon,
• 46:23but we work very closely with him as
• 46:26surgeons and he's done some really
• 46:28exciting work on road radiomics.
• 46:30Dr Pavish is did his MD at Tehran University,
• 46:34was a research fellow at Mass General,
• 46:37went through his radiology training and
• 46:40did a neuro Neuroradiology fellowship,
• 46:44highly coveted at UCSF.
• 46:47Probably more than five years
• 46:48ago at this point.
• 46:49And now he's assistant professor
• 46:52at of Radiology in Neuroradiology
• 46:55here with us at Yale University.
• 46:57And he's going to be speaking about
• 46:59Radiomics, so I'll hand it over to him.
• 47:03Um. Thank you very much.
• 47:06Thanks Doctor Mehta for
• 47:07introduction and invitation.
• 47:09Um, so I will be speaking about
• 47:14Radiomics in head and neck cancer.
• 47:19Do not have any conflict of interest
• 47:23and the talk will be focused on
• 47:26the application of radiomics.
• 47:30A short and brief description of
• 47:33what we are talking about when
• 47:35we are referring to radio mix,
• 47:38how this can help with diagnosis
• 47:42and molecular subtyping of tumors,
• 47:45prognostication,
• 47:46prediction of survival and perhaps
• 47:49treatment planning in patients
• 47:51with head and neck cancer.
• 47:53And this was a review article that
• 47:56we published with Doctor Burtness
• 47:58a couple of years ago. And so.
• 48:03When we talk about radiomics,
• 48:07this basically represent a hard coded
• 48:12series of hard coded algorithm that
• 48:17extract numeric features from medical images.
• 48:22So it was basically started
• 48:26along with the omics spectrum,
• 48:29as you might have heard about genomics,
• 48:33proteomics.
• 48:34The idea is that we extract a large
• 48:38amount of numeric and quantitative
• 48:42information from medical images
• 48:45and try to harness information
• 48:48from them for precision diagnosis.
• 48:52And precision treatment planning.
• 48:55Now the RADIOMICS features or the
• 48:58radiomics numbers are in generally
• 49:00representative of the intensity,
• 49:03shape and texture of a target lesion.
• 49:07In this case head and neck cancer intensity,
• 49:12basically the brightness of the tumor
• 49:15or lesion of interest on medical images.
• 49:20We are pretty much always
• 49:22working with grayscale images,
• 49:24Umm, the shape of the tumor.
• 49:26And also the texture,
• 49:28how much it is heterogeneous and this
• 49:31large amount of information that we
• 49:34extract or actually well suited for
• 49:37machine learning algorithms because
• 49:40those are preferred and suitable
• 49:43statistical models to make a prediction.
• 49:50So some of the references that I make
• 49:52are related to brain tumors, but you can.
• 49:57Basically apply the same
• 49:59concept to head and neck tumors.
• 50:01So when we talk about intensity features,
• 50:05you can think about the mean or
• 50:08range of the intensity or brightness
• 50:11that you see in a specific lesion,
• 50:15but it can also get a little
• 50:18bit more sophisticated.
• 50:20We can think about the magnitude of the
• 50:24changes of the voxel values in an image.
• 50:27Now would be referred to as energy
• 50:30or entropy like or like randomness
• 50:32of the values and the image.
• 50:35So that's why, you know,
• 50:36we basically get a larger number of
• 50:40numeric values that are representative
• 50:44of the intensity feature and.
• 50:48In medical images,
• 50:49when we talk about the radiomics
• 50:52intensity feature, this is again.
• 50:56Course we did with posterior
• 50:58fossa tumors and this was like the
• 51:01information from the histogram,
• 51:03ADC histogram in these tumors and you
• 51:06can see how this is different from
• 51:09one tumor subtypes to another and
• 51:11we apply this for differentiation of
• 51:13this posterior fossa brain tumors.
• 51:16The shape of a tumor may also have an impact.
• 51:20We usually think about the volume
• 51:22how big a tumor is but sometimes
• 51:24the surface and it's.
• 51:26We may also have an impact.
• 51:29I haven't found like a good example
• 51:31in terms of head and neck tumors,
• 51:34but for example.
• 51:37This paper which was done on
• 51:41glioblastoma showed that how much
• 51:44did the basically minimum volume
• 51:46of a bounding ellipsoid may have
• 51:50an impact on the overall survival
• 51:53of the glioblastoma.
• 51:55So there is some work that can be done
• 51:58on looking into how does the shape
• 52:01of a tumor affect the prognosis or.
• 52:08Perhaps the way affect treatment planning.
• 52:12And then the last thing that I
• 52:14mentioned or the texture of the tumor,
• 52:15how how much the tumor is heterogeneous.
• 52:18Now the numbers or the metrics that we
• 52:21use for this are a little bit complex.
• 52:24But in general you can think about
• 52:26it as we are looking into seeing
• 52:29how much the intensity of 1 region
• 52:33is different from the region next
• 52:35to it kind of the same concept that
• 52:39the more heterogeneous tumor is we
• 52:41perhaps expected. Could be more advanced.
• 52:44It's perhaps has like more time to grow.
• 52:47There are some areas that have necrosis,
• 52:49some are still, you know,
• 52:51growing and some are more vascular.
• 52:55And this was the work that was done
• 52:57for example for subtyping of the
• 53:01medulloblastoma along the same line.
• 53:04When we are looking at the texture
• 53:06or heterogeneity of the tumor,
• 53:09we can apply some filters and this
• 53:14is like a example of how does these
• 53:17filters change the original image.
• 53:20For example we can pass,
• 53:21we can apply low pass and High
• 53:24Pass filter a low pass.
• 53:25Winter kind of smooths out the image,
• 53:28gets the overall view of the what
• 53:33the original vision is by in a
• 53:36high pass filter you can look more
• 53:39into the contrast or the edges
• 53:41of the image. So.
• 53:43This is, for example, a prostate cancer.
• 53:46This is how we apply these filters
• 53:49in three directions and we get
• 53:52eight different derivatives.
• 53:55Again, these are all sorts of
• 53:57manipulation that we do just to get
• 54:00more and more information about the.
• 54:03Are the tumor going above and
• 54:07beyond the intensity and shape and
• 54:10specifically trying to figure out
• 54:12what we can get in terms of the
• 54:14information from the heterogeneity
• 54:16or the texture of the tumors, so.
• 54:20I just referred to like.
• 54:23Think that you know like three
• 54:25of the works that we have done
• 54:27here could showcase of what we
• 54:29can achieve with radiomics.
• 54:30One as I mentioned is
• 54:34molecular subtyping of tumor.
• 54:37So as you all know HPV status is very
• 54:40important in terms of prognostication.
• 54:43It's indeed the first step for
• 54:46us to decide how we're going
• 54:48to stage a tumor after 2018.
• 54:53Adjustment of the AGC.
• 54:55So we tried to use radiomics features
• 54:58from Pet city to predict the HPV
• 55:02status of head and neck tumors.
• 55:05So we segmented the the.
• 55:11The primary lesion is segmented the
• 55:14metastatic lymph nodes on pet CT
• 55:18we extracted it roughly like 1000.
• 55:21Features are representing the intensity,
• 55:24shape and texture of these primary
• 55:28lesion and tumors we were using.
• 55:34Roughly A144 from the Cancer
• 55:38Imaging Archive and 291 from Yale,
• 55:41and we split it into a training slash,
• 55:46cross validation and an
• 55:49independent validation cohort.
• 55:51We were trying to see which image
• 55:55modality and which combination of
• 55:58the input variables are important for
• 56:01are are would be most accurate in
• 56:04terms of prediction of HPV status.
• 56:07So here you can see that it
• 56:09was very extensive work.
• 56:10We were trying to see whether pets alone,
• 56:12city alone or pet city
• 56:16information using primary tumor.
• 56:20Lymph nodes or the consensus of the
• 56:23tumor and nodes or consensus of all lymph
• 56:27nodes will be give us the best model.
• 56:30Long story short, is that what?
• 56:33We found that a combination of the
• 56:36pet CT using the consensus of the
• 56:40primary lesion and the lymph nodes
• 56:43can give us the best prediction.
• 56:46And these are the AU says that
• 56:49we could get in our independent
• 56:52and external validation cohorts.
• 56:54So you may question that, OK,
• 56:58so how does this really affect our,
• 57:03you know, staging really,
• 57:05because you always will have
• 57:07a tumor sample to decide.
• 57:09Now if you look at how the
• 57:11pathologists actually do it,
• 57:13there are different stages sometimes,
• 57:16well,
• 57:16technically the guideline from
• 57:19the American Pathological
• 57:20Association is that they first do.
• 57:24And immunohistochemistry and then they
• 57:26do if depending on how certain they
• 57:29are based on the IHC, they do the PCR.
• 57:32Here at Yale we pretty much go
• 57:35for everything we go for PCR.
• 57:37However,
• 57:38what we proposed in our paper is that
• 57:42this is not a substitute for tissue sampling,
• 57:46but this can mostly work as an adjunct
• 57:49to the tissue sampling results.
• 57:51In other words,
• 57:53if you have a PC order or even
• 57:59histochemistry that is equivocal,
• 58:02maybe we can use this to supplement that.
• 58:07Analysis and that pathology report, so.
• 58:11Again,
• 58:12something that is perhaps not going
• 58:14to at this point we are still far
• 58:18away from replacing tissue sampling,
• 58:21but perhaps we have some quantitative
• 58:25and reliable and reliable methods
• 58:29to supplement those whenever needed.
• 58:33Now how about prognostication?
• 58:35So we try to see whether or not using
• 58:41the RADIOMICS features can help
• 58:43with prediction and prognostication
• 58:45and prediction of the survival
• 58:48beyond the JC staging.
• 58:50And the reason why we looked at
• 58:53a JC staging was because.
• 58:56It's kind of like you can say like
• 58:59the benchmark for a prognostication.
• 59:02So we use the HCA is addition.
• 59:06We were again using a series of
• 59:09HPV positive and HPV negative
• 59:11patients and our modeling was to
• 59:15predict those both progression for
• 59:18survival and overall survival
• 59:21using these radiomics features and.
• 59:24This is,
• 59:25I think it can give you the gist of it.
• 59:28So these are a different time points,
• 59:312 year, three-year, four year and five year.
• 59:34And as you can see for both HPV
• 59:38positive and for HPV negative,
• 59:41the RADIOMICS features could
• 59:43differentiate between high risk and low risk.
• 59:47Uh, patients? Fairly well.
• 59:50As you can see, uh,
• 59:52for HIV positive in all four time
• 59:55points that we
• 59:57tried, we could achieve significance.
• 01:00:00P value for differentiation,
• 01:00:03but really the agency is staging.
• 01:00:08Was not able to differentiate the
• 01:00:10low risk and high risk patients.
• 01:00:13Uh with this I mean even achieving
• 01:00:16the statistical significance,
• 01:00:18I should note that we actually excluded
• 01:00:20any stage four patients from our
• 01:00:24analysis and the same thing as you.
• 01:00:28This was actually, I'm sorry,
• 01:00:30this was an HP negative series, ohh,
• 01:00:33sorry, this is the overall survival,
• 01:00:35this is the progression free survival,
• 01:00:37so kind of. Same story here.
• 01:00:41Could be I forgot to include this
• 01:00:43slide about the HPV negative series.
• 01:00:46But the bottom line is that we and
• 01:00:51the way we envision this is that in
• 01:00:54future in addition to just tumor size,
• 01:00:59lymph node size or the anatomical
• 01:01:02extension of the tumor,
• 01:01:04we probably can get a bunch
• 01:01:07of numbers that can help us.
• 01:01:10Bitter stage, the patient.
• 01:01:11This is based on the very baseline pity.
• 01:01:14This is how currently we proceed
• 01:01:19to stage our patients.
• 01:01:21So if we have a better way of staging
• 01:01:25them at the baseline in terms of
• 01:01:28the survival and prognostication.
• 01:01:31Then we will have better way of
• 01:01:34treatment planning and smarter
• 01:01:36way of treatment planning, so.
• 01:01:38I we envision that perhaps in New
• 01:01:42York near future in addition to.
• 01:01:46General you know like a staging
• 01:01:47numbers we may have like more
• 01:01:49sophisticated numbers that can
• 01:01:50tell us this is a low risk,
• 01:01:52this is a high risk patient in terms
• 01:01:55of the survival and then finally.
• 01:02:00We did look to see if there are.
• 01:02:04If Radiomics can help predict locoregional
• 01:02:09progression after radiotherapy in
• 01:02:13HPV associated oropharyngeal cancer.
• 01:02:18And this is a very good follow up
• 01:02:21to presentation by Doctor Mehra
• 01:02:23and the E 3311 in the sense that
• 01:02:29these patients are potential.
• 01:02:33Candidates for intensity reduction
• 01:02:36in terms of radiotherapy.
• 01:02:38So if we know that who are more at
• 01:02:42risk of post radiotherapy regional
• 01:02:46progression and who is less likely
• 01:02:50to have the original progression,
• 01:02:53then you can perhaps use that
• 01:02:56for treatment planning.
• 01:02:59We use kind of similar methodology
• 01:03:02that we use for survival prediction,
• 01:03:05this time only focused on HPV positive
• 01:03:09patients would receive radiotherapy and
• 01:03:12as you can see here we could basically.
• 01:03:21Predict the overall survival
• 01:03:23progression for so and local regional
• 01:03:26recurrence Indian which is better?
• 01:03:30Accuracy compared to the agency.
• 01:03:34If we want to use again agency
• 01:03:37aging as a prognosticator,
• 01:03:39one thing that I should mention is
• 01:03:42that you may see that, you know,
• 01:03:44like over time we kind of lose the accuracy.
• 01:03:48It's simply because we had.
• 01:03:51Smaller number of patients who
• 01:03:53were followed beyond three years.
• 01:03:56So when you have less data
• 01:03:59point your your model,
• 01:04:00your machine learning model just
• 01:04:03would not have enough input to
• 01:04:05generate good prognostic model.
• 01:04:09So in general this is basically a.
• 01:04:17A very detailed information detailed
• 01:04:21of the local regional recurrence,
• 01:04:24local regional preparation
• 01:04:26and based on the AGC staging,
• 01:04:29different stages, oral stage,
• 01:04:31the age of the patient and
• 01:04:34how did they reconcile.
• 01:04:36So in general, Radiomics offers an
• 01:04:40automated way of image analysis.
• 01:04:43It will provide a numeric numbers
• 01:04:47and quantitative metrics for
• 01:04:49machine learning algorithms.
• 01:04:52And I tried to present some of the
• 01:04:55work that we have done here as how
• 01:04:59we can use this for differentiation,
• 01:05:03molecular subtyping of the tumors,
• 01:05:06prediction of the treatment response
• 01:05:10and survival prognostication.
• 01:05:15So yeah, let's hope that it
• 01:05:18was helpful for you. Thank
• 01:05:21you Doctor Pravesh, that was.
• 01:05:23Really exciting stuff.
• 01:05:27There are, there are some questions.
• 01:05:30Thank you everyone for staying on time.
• 01:05:32We're pretty much right on time where
• 01:05:34we want it to be which is great.
• 01:05:36There are some questions that
• 01:05:38people had for the first talk there
• 01:05:41was a question but are we doing
• 01:05:44deep intensification already?
• 01:05:47I'll answer that one is the
• 01:05:49short answer is yes.
• 01:05:50You know a lot of the as you could
• 01:05:52see there were I don't know maybe 5060
• 01:05:55academic centers I'm recruiting to the.
• 01:05:58He called 3311 trial and you know we
• 01:06:01were seeing results you know before
• 01:06:05publication and patients were asking
• 01:06:08and so off trial you know there
• 01:06:10was some discussions about this
• 01:06:12and now once the abstract came out
• 01:06:14did intensification is happening.
• 01:06:16I mean some might say tours alone
• 01:06:18is densification but also deep
• 01:06:21intensification of the dose of
• 01:06:23radiation is happening already
• 01:06:25at at major academic centers.
• 01:06:27But I think it has to be done in a mindful.
• 01:06:29Thoughtful way, multidisciplinary way,
• 01:06:31you know,
• 01:06:33with with all options presented to patients.
• 01:06:36Doctor Verma,
• 01:06:37there was a question about
• 01:06:39tonsils versus base of tongue.
• 01:06:42Is 1 easier to approach than the other?
• 01:06:46Does it impact your decision
• 01:06:47of what you know?
• 01:06:49How does that impact your decision
• 01:06:50to do tours if it's in the base
• 01:06:52of tongue versus the tonsil?
• 01:06:56Yeah, that's a good question.
• 01:06:57I think considerations might
• 01:07:00be different and particularly
• 01:07:02the anatomical considerations.
• 01:07:04If it's a tonsil tumor,
• 01:07:05you already know it's lateralized,
• 01:07:08a tongue based tumor.
• 01:07:09You still have to evaluate.
• 01:07:10If it's approaching midline for example,
• 01:07:13then you know we would probably
• 01:07:16not recommend doing a transoral
• 01:07:18resection also because we would have
• 01:07:20to consider management of both sides
• 01:07:23of the neck in terms of potential.
• 01:07:25Regional metastasis to lymph nodes.
• 01:07:28But you know I think if it's,
• 01:07:31it's not that we would choose
• 01:07:32one over the other necessarily.
• 01:07:34I think it's just different considerations,
• 01:07:36but that's a great question.
• 01:07:38And then there was a question
• 01:07:39which you kind of answered in that
• 01:07:40is when do you do bilateral neck
• 01:07:42dissections along with tours and how
• 01:07:43does that factor into your decision
• 01:07:45of whether or not to do tours?
• 01:07:48Yep. So yeah bilateral neck dissection
• 01:07:50would most would probably not be
• 01:07:53considered in a well lateralized
• 01:07:54tonsil tumor which inherently is that.
• 01:07:57But in a tongue based tumor that
• 01:07:59you're doing it towards resection on
• 01:08:01and there is approach even you know a
• 01:08:04couple millimeter or millimeter or so
• 01:08:07between you know close to midline we we
• 01:08:09have to consider you know management
• 01:08:11of both necks and this is actually
• 01:08:13where again the multidisciplinary
• 01:08:15approach really matters and before
• 01:08:17we consider or proceed with this.
• 01:08:19Kind of surgery,
• 01:08:20we have a radiation oncology and
• 01:08:22medical oncology colleagues see the
• 01:08:25patient and we could consider either
• 01:08:27not doing the transoral resection and
• 01:08:30doing chemo radiation or if there's
• 01:08:32some factor that you know really
• 01:08:34pushes us towards transoral surgery,
• 01:08:36we could consider bilateral neck dissections.
• 01:08:40Great. And then Doctor Paul Bashere was
• 01:08:43a question about, well, first of all,
• 01:08:46someone coming is very exciting
• 01:08:47how you can use radiomic data to
• 01:08:50help with prognostication and very
• 01:08:53interesting to hear your reviews about.
• 01:08:58You know one day potentially putting in it
• 01:09:01into something like a staging system even,
• 01:09:03which is really exciting.
• 01:09:04I mean right now we use pretty crude metrics
• 01:09:07on imaging like invasion into this muscle.
• 01:09:10Therefore it is this stage,
• 01:09:11but you're you're proposing in
• 01:09:14the future to use on almost,
• 01:09:16you know numeric data from RADIOMICS
• 01:09:19to help with pronunciation.
• 01:09:21Is that is that a true statement
• 01:09:24and I just want to add that, for example.
• 01:09:29Right now the Umm, we are working again.
• 01:09:35It's kind of pioneered by
• 01:09:37my colleague Dr Maria Mboya,
• 01:09:40who is working on brain tumors.
• 01:09:41We have already implemented the.
• 01:09:46The pipeline that extracted
• 01:09:49radiomics numbers.
• 01:09:50So technically speaking
• 01:09:51she has like an automated.
• 01:09:54She also had work on an automated
• 01:09:56segmentation of brain tumors, so.
• 01:09:59Umm, from the packs,
• 01:10:02like from the visage packs that, yeah,
• 01:10:04you can directly get the numbers,
• 01:10:07the radio mix number for brain tumors.
• 01:10:09So we can, you know, technically easily
• 01:10:12apply this to your or pet cities.
• 01:10:19And get those numbers and we talked about.
• 01:10:25We literally talked about the
• 01:10:27models that I developed.
• 01:10:28It's just that I use.
• 01:10:30Our coding for um,
• 01:10:32the machine learning algorithms
• 01:10:34and the the they were you know.
• 01:10:40The our practice system has a a Python
• 01:10:44on basically language compatibility.
• 01:10:46But yes, I mean literally here we
• 01:10:51are very close to you know, getting
• 01:10:55those numbers on on on our tax system.
• 01:10:59Great. That's wonderful.
• 01:11:01And then there's another question
• 01:11:03about how about using radiomics
• 01:11:05to predict extranodal extension
• 01:11:07in a lymph node in the neck,
• 01:11:09which could totally change whether
• 01:11:12or not we recommend surgery or not
• 01:11:15based on the current NCCN guideline,
• 01:11:18treatment recommendations and
• 01:11:19what are your thoughts on that?
• 01:11:21Yeah, so actually. Benjamin Connor,
• 01:11:26who is a radiation oncology resident,
• 01:11:30he's now at the Dana Farber's.
• 01:11:32He developed that they use
• 01:11:34a deep learning model.
• 01:11:35We actually even tried radomes which
• 01:11:38was creating like a similar accuracy.
• 01:11:43And at the time, yeah,
• 01:11:46like he was about to leave Yale.
• 01:11:48We talked about bringing in his
• 01:11:51model to in our park system.
• 01:11:53It didn't work.
• 01:11:54And now he's at Dana Farber.
• 01:11:56They also have like
• 01:11:58similar pack system as us.
• 01:12:00I know that he's working on
• 01:12:02it and his model has like an
• 01:12:05accuracy close to 0 point like
• 01:12:0780% and it was even more accurate
• 01:12:10than radiologist for prediction
• 01:12:12of the extranodal extension.
• 01:12:15So I do believe that we are very
• 01:12:21close to really implementing all of
• 01:12:23these in our clinical day-to-day.
• 01:12:27And there's one more
• 01:12:29question for you, Professor.
• 01:12:30There are groups of patients
• 01:12:33for whom radiomics or machine
• 01:12:35learning models are not,
• 01:12:37are not as predictive that
• 01:12:38you just know up front.
• 01:12:40So we are our models are as
• 01:12:43good as the data that we have.
• 01:12:46So that's why I mean when I
• 01:12:48mentioned that for example we do
• 01:12:49not have if we don't have data
• 01:12:51for you know long term prediction
• 01:12:53or models are not working.
• 01:12:55So we barely have data on HPV.
• 01:13:00Negative patients.
• 01:13:01So our models are less accurate for HPV,
• 01:13:06negative or for angio cancer.
• 01:13:10It's. It's only works if we have
• 01:13:14enough data and yet for example.
• 01:13:18Since the introduction of PD1 inhibitor,
• 01:13:22the two the treatment response has changed.
• 01:13:25So now we have to train a new set
• 01:13:28of models for prediction of how,
• 01:13:30how this is gonna you know like
• 01:13:33how how would that affect the
• 01:13:35the survival of the patients.
• 01:13:37So the the all the models that we
• 01:13:41developed were based on information that
• 01:13:45came from somewhere from 2011 to 2.
• 01:13:491016 so there is a lag between the
• 01:13:52models of your developing and the
• 01:13:56current cutting edge treatments.
• 01:13:57We we have to retrain the models
• 01:14:00based on the the most up-to-date
• 01:14:03treatments that we have.
• 01:14:08Very interesting, very interesting.
• 01:14:09All right. Well,
• 01:14:10I think that answers all the questions.
• 01:14:13I wanted to thank our speakers,
• 01:14:15doctor Avanti Verma,
• 01:14:17doctor Sam Kavesh for joining us and
• 01:14:20we want to thank all the participants
• 01:14:22who logged in today and the ones who
• 01:14:26will also see this on the website.
• 01:14:28This will be posted on the
• 01:14:31Twitter for Yale Cancer Center,
• 01:14:33will be on the Yale Cancer website and.
• 01:14:36Please reach out to if
• 01:14:38you have any questions.
• 01:14:39Thank you all very much for joining us.
• 01:14:41Thank you. Thank you.