Care of Sickle Cell Disease and Cancer Patients

July 26, 2021

Information

July 25, 2021

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

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00:00Funding for Yale Cancer Answers
00:02is provided by Smilow Cancer
00:04Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers with
00:10your host doctor Anees Chagpar.
00:12Yale Cancer Answers features the
00:14latest information on cancer care by
00:17welcoming oncologists and specialists
00:18who are on the forefront of the
00:21battle to fight cancer. This week,
00:22it's a conversation about sickle
00:24cell disease and cancer in pediatric
00:26patients with doctor Farzana Pashankar.
00:28Dr Pashankar is an associate
00:31professor of Pediatrics in hematology
00:33oncology at the Yale School of Medicine,
00:35where Doctor Chagpar is a
00:38professor of surgical oncology.
00:41Maybe we can start off by you telling
00:43us a little bit about yourself and
00:46how you got involved in doing what
00:48you do and what exactly do you do?
00:53Essentially I had a really long,
00:58circuitous career journey,
00:59but I got involved in doing pediatric
01:03oncology when I was training in England,
01:07after which I did a pediatric hematology
01:11oncology fellowship in Canada.
01:13And after fellowship,
01:14the two areas that I really loved
01:18and wanted to focus my career
01:21on were sickle cell disease
01:24and solid tumors
01:25and development of clinical
01:28trials and improving care for children
01:31with sickle cell disease and cancer,
01:33particularly solid tumors.
01:35So those are the two areas that
01:38I have focused on in
01:40my career for the last
01:44about 17 to 20 years and my
01:48passion primarily has been to focus on
01:51development of clinical trials for children for
01:55certain rare types of solid tumors,
01:57and also in bringing new and
01:59innovative therapies for sickle cell
02:02disease to our patient population.
02:04So maybe we
02:05can start with that.
02:06Is there much overlap between sickle
02:09cell disease and pediatric cancers?
02:11I mean, do children get sickle cell disease?
02:14Does sickle cell kind of lead to
02:17cancer or are these just two separate
02:19passions of yours that happen to
02:22coincide in the same individual?
02:26These are two separate passions,
02:29and because in Pediatrics we
02:32train in both hematology and oncology,
02:34these are two passions which
02:39developed during my training,
02:41but it is not connected in any way in terms
02:44of children with sickle cell disease being
02:47more prone to getting cancer or
02:50children with cancer more prone to
02:52having any issues with sickle cell.
02:56Let's talk about each of the two in turn
02:59and let's start maybe with
03:02talking about pediatric cancers.
03:07Any time we hear about children getting cancer,
03:09the uniform emotion that
03:11people feel is heartbreak.
03:13So tell us a little bit more
03:15about how you get involved.
03:18I know so many medical
03:21students come up to me and they say,
03:24how can you possibly dedicate your career
03:27to doing something that is so heartbreaking,
03:32but honestly after doing this for over 20 years
03:34this is such a rewarding journey.
03:37It is the time that a lot of
03:39families are going through
03:41probably the most intense and difficult
03:44time of their life and to be able
03:47to be a part of it and to help them
03:50navigate and think about the treatment
03:53decisions for their child and to be
03:55able to treat their child effectively,
03:58honestly, I don't think
03:59there's a substitute for that.
04:01I think it's so emotionally rewarding.
04:04It is also heartbreaking at times.
04:06I mean, we do have children who could
04:09have a recurrence and it is
04:12a lot of intense time thinking about
04:15not only the management but also
04:18supporting these families through that.
04:20But the relationships I've built with
04:23even the children that we've lost,
04:25the relationships
04:26built with those parents
04:28is just unbelievable.
04:30And after losing the child,
04:32they still think of
04:33us as being part of their family.
04:37And I think that bond is
04:39so valuable and precious.
04:41So yes, it can be heartbreaking at times,
04:45but it's also extremely rewarding.
04:47And today I would say that we cure
04:49about 85%
04:51of children with cancer very successfully.
04:53So clearly we have done a really
04:55good job at trying to make advances
04:57and improve the life of these
04:59children diagnosed with cancer.
05:03And I think that's such a key point is that
05:06whereas many people will
05:09think of cancer as a death sentence,
05:11now more and more what we're
05:13finding out in a variety of cancers
05:16is that really we're beginning to
05:18discover that many of these cancers
05:21are treatable and with good outcomes,
05:23but you're interested in solid tumors,
05:26so tell us more about the solid tumors
05:29that occur in Pediatrics and what kind
05:32of treatments we have to offer these kids.
05:35What the prognosis is,
05:37and the other thing that
05:39I'm always curious about
05:41on this show, we spend so much time
05:43talking about personalized medicine.
05:46The fact that now
05:48we've begun to really unlock the
05:51genomic abnormalities that
05:52occur in cancers we're able to
05:55better target these abnormalities.
05:57Can we do the same thing in kids and
06:01is that resulting in higher cure rates?
06:05Great question and a lot to unpack.
06:09In terms of solid tumors, they
06:16really change across the age spectrum,
06:19so the solid tumors that we see
06:22in the much younger child are
06:25tumors such as neuroblastoma,
06:28Wilms tumors, retinoblastoma so
06:30much more embryonal based tumors,
06:32and then as you gradually
06:35advance and you're coming to the
06:37prepubertal young adolescence,
06:39we start seeing more tumors
06:41such as the sarcomas, so the osteosarcoma
06:44the soft tissue sarcomas
06:47which have an overlap
06:49with the adult population as well,
06:52and in addition, we see,
06:54besides these sarcomas,
06:56of course we see Rhabdomyosarcoma
06:58which occurs across the age
07:01spectrum from childhood onto the
07:03adolescent young adult population.
07:05So in terms of solid tumors,
07:07really the main areas or the
07:10main types of solid tumors we see
07:12would be the embryonal tumors.
07:14As I already mentioned and
07:16then sort of the sarcomas
07:18and the bone sarcomas.
07:21Those are the two big groups
07:24of solid tumors that we see.
07:26We also see interestingly a lot of rare
07:29tumors and one of my particular area
07:32of interest has been in rare tumors,
07:34and I've been very involved
07:36in developing clinical trials
07:38for these children with rare tumors
07:41through the Children's oncology group,
07:43so the rare tumors that we see are
07:45things like nasopharyngeal carcinoma,
07:48adrenocortical carcinoma, thyroid cancer,
07:49which of course can occur in adults
07:53but also starts in young adolescence.
07:56So we see several of those patients,
07:58and now we've started seeing some
08:01of the tumors that are adult tumors
08:05earlier in Pediatrics,
08:06such as even colorectal carcinoma.
08:09So that's sort of the spectrum of
08:11tumors we see in pediatric solid tumors.
08:15I've not included brain tumors because
08:17we almost separate brain tumors,
08:19just like we do leukemia and lymphomas.
08:22And I don't treat brain tumors.
08:25I focus on the extracranial solid tumors,
08:28so those are the ones I've just mentioned
08:31with regards to the treatment and
08:34the role of personalized medicine or
08:36immunotherapy in treating these cancers.
08:42Again, the role of personalized medicine
08:45is very well known in the adult oncologic world.
08:49In Pediatrics we still do profile
08:51most of our patients with solid tumors,
08:54and there have been tumors
08:57which have happened recently and
08:58there's a lot of excitement on
09:01tumors where there's a specific
09:03targeted drug that is available,
09:05and one classic example of this is the
09:09TRK fusion cancers
09:10where there is a specific drug
09:15that has been developed with
09:18excellent outstanding results.
09:20So TRK fusion cancers can occur
09:23from infants where you
09:27have infantile fibrosarcoma's that occur in
09:29the first year of life,
09:32and then TRK Fusion
09:34sarcomas are also seen in older
09:37adolescents and young adults,
09:39so in specific situations
09:41we do also use what the adults
09:44use much more frequently,
09:46which is a very targeted therapy based on
09:50tumor profiling.
09:55How does prognosis vary
09:57amongst the pediatric cancers?
09:59Because you've kind of mentioned
10:01this whole spectrum,
10:03we have the leukemia lymphoma
10:05as one separate group and brain
10:08tumors as another separate group.
10:10But even within the non cranial solid
10:13tumors in pediatric populations
10:16we're looking at everything from eye tumors,
10:19retinoblastoma's to kidney
10:21tumors like Wilms tumor
10:24to sarcomas.
10:25So how do these vary in terms of prognosis,
10:29and have we seen a shift in terms of
10:34moving towards being able to treat
10:37these children better with new therapies?
10:41Yeah, so it is a whole spectrum.
10:44As you've already mentioned,
10:47I think we've done really well in
10:51some of these tumors.
10:54For example, in patients with retinoblastoma
10:56you have an excellent outcome,
10:59particularly now with intra arterial
11:01chemotherapy delivering very focused
11:04chemotherapy.
11:06We've also reduced the issue with long
11:09term side effects giving systemic therapy.
11:15Treatment has evolved
11:18significantly over the last maybe 10-15
11:20years with the development of
11:23an antibody called dinutuximab
11:25which focuses on the GD2
11:28which is expressed by neuroblastoma cells.
11:31So now we have this multi modality therapy
11:34that we do in addition to chemotherapy,
11:38surgery, and radiation.
11:39We also have this immunotherapy that is done
11:42in combination
11:44particularly for those who have high
11:46risk neuroblastoma in Wilms tumor,
11:48our outcomes have always been excellent,
11:51and we're continuing to improve
11:53those outcomes.
11:53And similarly I didn't
11:56mention germ cell tumors,
11:57which honestly, is
12:00a really strong interest of mine,
12:02so we do very well in germ cell tumors.
12:06And in all these four categories,
12:09I would say we have excellent outcomes.
12:12In sarcomas,
12:12I think we still have challenges.
12:15And the challenge really depends on
12:18the time of presentation,
12:21what the staging is, and
12:23for patients who present
12:25with metastatic sarcomas,
12:27be it Rhabdomyosarcoma or osteosarcoma,
12:30we still are challenged in terms
12:33of long term outcomes at times,
12:36and we have numerous clinical trials
12:40looking at different options which
12:46this is where we are
12:49looking to improve our outcomes
12:51by newer therapies.
12:52And as you mentioned, personalized therapies are
12:55so important to really try to get
12:58people involved in clinical trials
13:00to really move those therapies forward,
13:03but it's really great to hear that
13:06we're moving in the right direction,
13:08at least for the majority of solid tumors in kids.
13:11We're going to take a short
13:14break for medical minute and then learn
13:17more not only about pediatric cancer,
13:20but also delve into your interest in
13:23sickle cell disease right after this break.
13:25Please stay tuned for more
13:28with my guest Doctor Farzana Pashankar.
13:29Funding for Yale Cancer
13:32Answers comes from AstraZeneca, working
13:35to eliminate cancer as a cause of death.
13:38Learn more at astrazeneca-us.com.
13:42Genetic testing can be useful for
13:44people with certain types of cancer
13:47that seem to run in their families.
13:49Genetic counseling is a process that
13:51includes collecting a detailed personal
13:53and family history or risk assessment and
13:56a discussion of genetic testing options.
13:58Only about 5 to 10% of all cancers
14:01are inherited, and genetic testing
14:03is not recommended for everyone.
14:05Individuals who have a personal and
14:07or family history that includes
14:09cancer at unusually early ages,
14:11multiple relatives
14:12on the same side of the
14:14family with the same cancer,
14:16more than one diagnosis of
14:18cancer in the same individual,
14:21rare cancers or family history of a
14:23known altered cancer predisposing gene
14:25could be candidates for genetic testing.
14:28Resources for genetic counseling and
14:30testing are available at federally
14:32designated comprehensive cancer
14:33centers such as Yale Cancer Center
14:36and at Smilow Cancer Hospital.
14:38More information is available at
14:40yalecancercenter.org. You're listening
14:42to Connecticut Public Radio.
14:43Welcome
14:44back to Yale Cancer Answers.
14:46This is doctor Anees Chagpar
14:48and I'm joined tonight by my
14:50guest Doctor Farzana Pashankar.
14:52We're talking about sickle cell
14:54disease and cancer in pediatric
14:56patients. Before the break for
14:58any of you who missed it,
15:00there is no connection between sickle
15:02cell disease and pediatric cancers,
15:04except that our guest happens
15:06to be an expert in both.
15:08Right before the break we were
15:11talking about pediatric cancers and the fact
15:13that some kids get solid tumors.
15:17This must not be very common, right?
15:21How common are pediatric cancers?
15:25Especially the non hematologic cancers?
15:28I think of course each one of those
15:31cancers is overall pretty rare
15:33and even leukemias, which are the
15:36most common pediatric cancer we say
15:38happens one in a million.
15:41So the solid tumors are much rarer
15:45and each one has a different frequency,
15:48so it's hard to give a
15:51number for all of them combined.
15:56This is very interesting
15:58because as you may know,
16:00there's a lot of interest in rare cancers,
16:04and the NIH was looking at developing a
16:07rare Cancer Institute in order to try and
16:10improve the outcomes in these rare cancers.
16:14And when we were looking at
16:16defining what rare cancers is,
16:19it's very clear up front that every
16:22pediatric cancer is rare in that sense,
16:25but the solid tumors,
16:27particularly,
16:27many of the tumors we discussed are
16:34even much rarer than leukemia,
16:36which is already
16:38pretty uncommon.
16:39And I'm sure that every parent
16:41out there thinks that their
16:43child is one in a million,
16:45but really wouldn't want their
16:47child to be one in a million in
16:49this particular circumstance.
16:51And one of the
16:53questions that comes up and
16:55you mentioned that you had an
16:57interest in clinical trials,
16:59especially in rare tumors,
17:00is that so much of the data that
17:04we get that leads to best practice
17:06that dictates how we treat cancer
17:09comes from clinical trials.
17:11And when you have these tumors that
17:14are so rare that are one in a million,
17:17how on Earth do we get the data
17:20to actually know what's best
17:22practice to treat our children,
17:24and for every parent going through this,
17:27I mean that is their deepest anxiety.
17:31That's a very good point
17:34and I think what I must say is that in
17:38pediatric oncology we have honestly and I
17:41am not taking all the any credit for this,
17:45but we have done an amazing job at
17:48being able to conduct clinical trials
17:50and the way we've done this is through
17:53the development of a consortium
17:55called the Children's Oncology Group,
17:57which really has about 230
18:00institutions across the United States,
18:01Australia, New Zealand and Canada
18:04and the beauty of this is that
18:08as a group then we can,
18:10because each individual
18:12institution will only have
18:15a patient very rarely with a
18:17particular type of cancer,
18:19we can bring all of us together,
18:22and we can then get the numbers to
18:24be able to conduct a clinical
18:26trial and more importantly,
18:28conduct some randomized clinical trials
18:30to be able to answer the question of
18:33which treatment is the best and most
18:36appropriate for these rare cancers.
18:38So the children's Oncology Group has
18:40existed for a while and we
18:43have designed clinical trials
18:45on each type of pediatric cancer,
18:47but more recently what is happening
18:49that I am very
18:52happy to be involved with is that we are now
18:56looking at international collaborations.
18:58So for example in germ cell tumors
19:00because germ cell tumors are again so
19:03rare even in the US and Canada and
19:06Australia we cannot have the appropriate
19:08numbers to do a randomized trial.
19:11So currently we are conducting two trials,
19:13one for low risk and
19:16intermediate risk,
19:17and one for high risk.
19:20So we've collaborated with the
19:22UK with India with Australia,
19:24New Zealand and we are all
19:26running the same trials,
19:28so that again we can bring all this
19:31information together and be able to
19:33make advances for future patients.
19:35I think that's so critical.
19:38You know one of the issues that we
19:41face in adult tumors, however, is,
19:43although all of us know that clinical trials
19:46are the drivers of improved care
19:49it's how we make practice
19:51changing discovery, is that still there is
19:53a reluctance on the part of some patients
19:56to participate in clinical trials.
19:57So if you look across the board,
20:01our rate of clinical trial
20:03accrual is somewhere South of 5%,
20:05and with children I mean I can imagine
20:08that parents have obvious anxiety when
20:11you talk about clinical trials,
20:14but I understand that the rate
20:17is much higher for accrual
20:19to these clinical trials.
20:21Honestly in Pediatrics,
20:23the rate is significantly higher,
20:25and I think part of the reason
20:27at least at Yale,
20:31of all the patients eligible for a trial,
20:34because sometimes,
20:35of course a trial may not be available
20:38for that particular type of tumor.
20:40But for any eligible patient,
20:42we enroll up to 80% of the children
20:45who are eligible for a trial.
20:47When you're taking care of
20:50your child, who has cancer
20:52I think the motivation from the parents
20:54is very different than maybe
20:57the motivation for yourself.
20:59I'm not sure,
21:00but clearly we all do go
21:02above and beyond for our kids.
21:04Then we probably even do
21:06for ourselves.
21:07And I think that that desire
21:10to figure out the best treatment,
21:13especially when we're talking
21:15about rare diseases is so important.
21:17And I think the other piece is that
21:21parents sometimes have trepidation
21:23about what is the
21:25right answer to treat my child,
21:28especially when all of these cancers
21:30are so rare and clinical trials
21:32gives you some modicum of this
21:35actually might be best practice because,
21:38as you say,
21:39all of these professionals get
21:41together in designing these trials,
21:43so they've put in that brain trust of,
21:46you know this is potentially best
21:49practice or best practice versus
21:52what best practice will be and we want to see
21:54which is best for patients who are
21:57not candidates for a clinical trial
22:00where there still may be
22:03questions about what is best practice.
22:05How do you reassure patients and parents
22:08that this really is
22:11the way to go?
22:14Are there still collaborations where you
22:17get together with a consensus,
22:20either nationally or internationally,
22:22to figure out what might be best
22:25practice for these patients?
22:27Absolutely. I think one thing
22:30is that the best practice is obviously
22:33the standard of care in many cases.
22:36But in many cases there is
22:38no proper standard of care,
22:40but the beauty again of having these
22:44close collaborations working together
22:46on trials means that we have a
22:48really great phenomenal community of
22:50oncologists that you can call upon to
22:53discuss and get guidance on in
22:55really rare cases.
22:57So I think that is a really
23:00fulfilling part of being able to
23:03connect with friends and colleagues across
23:05the country, across the world to be
23:08able to discuss some difficult cases.
23:10What is really fun is
23:13we've now developed these virtual
23:16International tumor boards
23:17for some of these really rare cancers,
23:19so we have an international tumor board
23:21for patients with hepatoblastoma,
23:23where experts from across the
23:25country meet once a month and you
23:27can put in a case and they will
23:29review everything and discuss it,
23:32just like we do at a local tumor board.
23:35Similarly,
23:35we have a rare tumor board
23:37which is across the country,
23:39so again,
23:40people do go above and beyond to try and
23:43put in their time and effort to bring their
23:47thoughts and their experience to help
23:49kids across the country and across
23:51the world.
23:54I love the fact that there is such humility
23:57among pediatric oncologists to
23:59really collaborate with each other and to
24:02figure out what's the best for this child.
24:04Which is so important and so
24:07heartening for parents going through this.
24:09Now I did promise that we'd
24:12spend at least a few minutes
24:15talking about your other passion,
24:17which is sickle cell disease and
24:20sickle cell disease is still rare,
24:22but presumably less rare
24:24than pediatric cancers.
24:25Is that right?
24:27I think it is rarer than pediatric cancers,
24:31and in the US now with
24:33also a changing demographic,
24:36we have patients of many
24:39different ethnicities who can
24:41also have sickle cell disease so
24:44it's definitely something that we
24:47in Connecticut see 24 to 26 new
24:51diagnoses of sickle cell disease
24:53each year and about 600 new patients
24:57with sickle cell trait per year.
25:07Talk a little
25:10bit about sickle cell disease and
25:12the problems that people can run into.
25:14I mean, when people think about cancer,
25:17you really don't need to say anything
25:19more than cancer for it to strike
25:22the fear of God into some people.
25:24But what problems do people with
25:26sickle cell disease run into that
25:28are problematic and talk a
25:30little bit about some of the new
25:33therapies that are out now?
25:37So sickle cell disease
25:40interestingly, is the first single
25:42gene disorder that was described
25:44over 120 years ago.
25:49It is a lifelong chronic disease that
25:52obviously you inherit from your parents
25:55and the hallmarks of sickle cell disease
25:58are these painful crises,
26:02which really mean that patients
26:04with sickle cell disease
26:06can come into the hospital or have pain
26:09at home several times a year.
26:13These chronic VS occlusive crises can
26:15also lead to multiple complications,
26:18including stroke
26:21and acute chest syndrome.
26:29You can also have a lot of long term chronic
26:33morbidity because of this ongoing
26:36microvascular occlusion that happens in
26:37all your organ systems.
26:39So patients with sickle cell disease can
26:42have long term problems with their kidneys,
26:45leading to sickle nephropathy.
26:46They can have problems with their
26:49liver leading to sickle hepatopathy.
26:51They can have sickle retinopathy,
26:53so it's a disease which has
26:56acute complications which brings
26:58someone to the hospital.
27:00But also has ongoing long term chronic
27:03disease burden which continues to affect
27:06pretty much every organ system in their body.
27:09So it is a disease
27:14where you have to pay attention to
27:18obviously the acute management during pain,
27:20crisis, stroke,
27:21acute chest syndrome, etc.
27:23but you also have to take care of these
27:27adults and children for preventative care.
27:30To make sure that you are monitoring
27:33for these long term complications and
27:36you are intervening when feasible.
27:39But the good part about sickle
27:42cell disease or the exciting part
27:45currently is that we have a lot of new
27:48therapies which have come about in
27:50order to improve not only the pain crises,
27:54the FDA has now approved several
27:56new drugs besides hydroxyurea,
27:59which was the only drug available for
28:01a long time to
28:04modify sickle cell disease and the
28:06most exciting thing really is the
28:09advent of bone marrow transplant,
28:10which is currently the only curative
28:13option for sickle cell disease but
28:15also gene therapy and many of you
28:17might have seen data on gene therapy,
28:20some case reports of gene therapy for
28:23sickle cell disease which is exciting
28:25and we are looking forward to that
28:27becoming more streamlined in the next
28:30few years.
28:31Dr. Pashankar is an associate professor of
28:33Pediatrics in hematology oncology
28:35at the Yale School of Medicine.
28:37If you have questions
28:39the address is canceranswers@yale.edu
28:40and past editions of the program
28:42are available in audio and written
28:44form at yalecancercenter.org.
28:46We hope you'll join us next week to
28:48learn more about the fight against
28:51cancer here on Connecticut Public
28:53radio. Funding for Yale Cancer
28:55Answers is provided by Smilow
28:57Cancer Hospital and AstraZeneca.