Sarcoma Lecture Mayo Medical School March, 2018...Prospective Study of 146 sarcoma patients in 3...

Sarcoma Lecture Mayo Medical School

March, 20183/08/18

Clinical PresentationBrad Stish, MD

Mayo Clinic3/08/18

©2017 MFMER | slide-3

Sarcomas for the General Internist

Steven Robinson, MBBSAssistant Professor of Oncology

February 1, 2018


Objectives

• Recognize the red flags of sarcoma• Appreciate the heterogeneity in sarcoma and its impact on

management• Highlight key post-care challenges patients who undergo

curative treatment for sarcoma face


Sarcomas

• 1,734,350 new cases of cancer expected in 2018

• 16,490 cases of sarcoma (~1%)• 6,760 deaths from sarcoma

predicted• Average age ~58 yrs.


Sarcomas

• Comprise a group of neoplasms of mesenchymal origin• Heterogeneous, >70 subtypes

• Soft tissue ~ 80%• Bone ~20%

• Requires experienced bone and soft tissue pathologist• ~40% cases read by general pathologist modified by expert

BST pathologist

Ray-Coquard. Ann Oncol. 2011


Sarcomas

• Patients with localized sarcomas can be treated with curative intent

• Long term f/u studies suggest ~62% survival• Adverse risk factors

• Size > 5cm• Deep tumors• Higher grade

• Patients with disseminated disease • Median survival ~1-2 years reported trials with systemic

therapy


Sarcomas

• Strategies to improve patient outcome• Earlier diagnosis• More effective therapies

• Subtype specific• Biomarker driven


Question 1

• On average, how many soft tissue lumps seen in the primary care practitioner’s clinic end up being malignant?

• A. 30 in 100• B. 1 in 100• C. 5 in 100• D 10 in 100


Question 2

• Pain is a great discriminator in discerning malignant potential of a soft tissue lump

• A. True• B. False


New Soft Tissue Lumps

• Estimated 1 in 100 new cases of soft tissue lumps seen by PCP is malignant

• Inexperience• Delay in referral to sarcoma center

• Contributes to poorer patient outcomes• Inadvertent excisions

Nandra et al. EJSO. 2015Brouns et a. EJSO. 2003


Delays in Diagnosis and Referral

• Delayed diagnosis results in…• Larger tumor size at presentation

• Poorer resection margin• Lower likelihood of limb salvage• Increased rate of post-surgical complications

• Increased likelihood of metastatic disease• Ultimately poorer survival

Nandra et al. EJSO. 2015Brouns et al. EJSO. 2003George and Grimer. Ann R Coll Surg Engl. 2012


Delays in Diagnosis and Referral

• Studies evaluating cause for delays• Patient related delays

• Absence of pain in lump• Physician related delays

• Misdiagnosis• Clinical exam only in 59%

Brouns et al. EJSO. 2003Calrk and thomas. EJSO. 2005George and Grimer. Ann R Coll Surg Engl 2012


Inadvertent Excisions

• Estimated to account for 40% of initial sarcoma surgeries• Problem-residual disease

• Reports ranging from 24-74%• Higher rate of local relapse (70-90%)• Decreased disease specific survival

Qureshi et al. Ann Surg Oncol. 2012Venkatesan et al. EJSO. 2012Potter et al. Clin Orthop Relat Res. 2008



• Role of definitive wide re-excision• Adequate local control can be achieved• Disease specific survival similar to those who undergo

primary excision of known sarcoma

Fiore et al. Ann Surg Oncol. 2006; Thacker et al. Foot and Ankle International. 2008Arai et al. Clin Orthop Relat Res. 2010

Almanda et al. J Surg Oncol. 2012; Venkatesanet al. EJSO. 2012



• Downstream impact of wide re-excision• Increases likelihood of free flap for limb salvage procedures• Greater likelihood of neoadjuvant/adjuvant radiation• Doubles the financial burden

Thacker et al. Foot and Ankle International. 2008Alamanda et al. Ann Surg Oncol. 2013



• Review of University Health System Consortium and Association of American Medical Colleges database

• 2007-2009• 50% of deep and malignant soft tissue tumor resections

performed by non-oncologic surgeons• 17% performed by practitioners who did 1-2 per year

Canter et al. J Surg Oncol. 2013



• Single Institution major sarcoma center retrospective cohort review

• 400 patients (253 primary vs 147 inadvertent excisions)• No impact of insurance status or proximity to the center

on the likelihood of undergoing inappropriate excisions

Alamanda et al. J Surg Oncol. 2013


RED FLAGS

• Size > 5cm• Increasing size• Deep location • Painful• Recurrent mass after previous excision

George and Grimer. Ann R Coll Surg Engl. 2012


Best Predictors?

• Royal Orthopedic Hospital, UK• 3018 patients with soft tissue lump, 1996-2007

• Malignant vs Benign• Increase in size• Age of the patient• Size of the lump• Duration of symptoms• Pain was a poor discriminator

• Greatest pairing was growing golf ball sized lesion

Nandra et al. EJSO. 2015


Radiation in Localized STS

• Improves local control• No impact on overall survival

Yang et al J Clin Onc 1998


Chemotherapy in Localized STS?

• Overall survival benefit:• Controversial

• SMAC 1997 • negative

• SMAC 2008 • ARR death of 11%• Doxorubicin and Ifosfamide

• EORTC 62931• No benefit• 24% patients had small tumors &

lower grade

• Aid operability shrinking locally advanced

• Heterogeneous• Impact of subtype on treatment

choice• Some are refractory to

conventional cytotoxic therapy• Rarely see shrinkage with

targeted agents unless driver mutation

SMAC. Lancet. 1997Pervaiz. Cancer 2008

Woll et al Lancet Oncology 2012


Phase III Trial Arms(Imatinib)

RFS OS

ACOSOG Z9001 1 yr. vs 0 Improved No Difference

EORTC 62024 2 yrs. vs 0 Improved No Difference

SSG XVIII/AIO 3 yrs. vs 1 yr. Improved Improved

Adjuvant Systemic Therapy in GIST?

DeMatteo et al. Lancet. 2009Casali et al. JCO. 2015

Joensuu et al. JAMA. 2012


Chemotherapy in Localized Ewing sarcoma

Cripe TP. Ewing sarcoma: An eponym window to history. Sarcoma 2011.


Chemotherapy in Localized Osteosarcoma

• Pivotal trial by Link et al• 2 yr RFS of 66%

(chemotherapy) vs 17% (observation)

Link et al. NEJM. 1986Marina et al. Lancet Oncology. 2016

EURAMOS1: 76% 3-yr-EFS


Survivors of extremity sarcoma treatment

• As compared to healthy controls:• Decreased physical functioning

• Pain, reduced joint mobility, increase fall risk (amputees and poor prostheses), lymphedema (large/deep tumors)

• Psychologic morbidity• Reports vary from 15-70%

• Negative social impact• Less likely to marry, live independently, be

employed, attend college

Kee Kwong. EJSO. 2014Gerrand and Furtado. Clin Oncol. 2017


Anxiety and Depression

DiagnosisN (%)

TreatmentN (%)

Follow upN (%)

p

AnxietyNormal

MildModerate Severe

15 (36.6%)14 (34.1%)8 (19.5%)4 (9.8%)

17 (47.2%)10 (27.8%)8 (22.2%)1 (2.8%)

34 (55.7%)14 (23%)

12 (19.7%)1 (1.6%)

.31

DepressionNormal

MildModerate Severe

26 (61.9%)8 (19%)

5 (11.9%)3 (7.1%)

20 (55.6%)9 (25%)

4 (11.1%)3 (8.3%)

47 (77%)10 (16.4%)

3 (4.9%)1 (1.6%)

.32

Prospective Study of 146 sarcoma patients in 3 Portuguese cancer units

Key Findings: Majority of patients have mild anxiety and depression.Symptomatic patients: Recurrence (diagnostic phase), Female (Treatment phase), Older patients and shorter time from d/c treatment (Follow up phase)

Paredes et al. Eur J Onc Nurs. 2011


OncofertilityEligible Patients % oncologists who agree

should be done% oncologists who perform at

least 50%Fertility preservation counseling 86% 47%

Sperm banking 92% 72%

Refer to fertility specialist 73% 30%

Lopategui. Trans Androl Urol. 2017

• Sarcomas account for 10% cancers in adolescents and young adults

• >40% will have some form of reproductive dysfunction (radiation to pelvis or systemic therapy)

• Animal models of newer sarcoma agents have less infertility risk compared with conventional chemotherapy (DNA binding, targeted, tyrosine kinase inhibitors)


Conclusions

• Recognition of suspicious lumps and imaging before biopsy can improve outcome

• Minimize referring patients with “sarcoma suspicious lumps” to non-oncologic surgeons

• Early involvement of experienced sarcoma center improves outcome and is strongly encouraged

• Recognition of treatment consequences and prompt implementation of personalized rehabilitation and psychosocial services is needed


reininsarcoma.org

http://www.reininsarcoma.org/

http://www.reininsarcoma.org/

Sarcoma Survivor StoryJudy Jones

3/08/18

•Rare and highly aggressive cancers of the connective tissue such as bones, muscles or soft tissue

•Can appear anywhere in the body•Among the most common cancers of children & young adults

•Attacks people at any age•Are commonly discovered late and misdiagnosed

Sarcoma Cancers

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•15,000 new cases of soft tissue and bone sarcoma are diagnosed each year in the United States

•More than 6,000 deaths annually•One of the few cancers increasing in frequency

Sarcoma Cancers

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Imagine aWorld Without Sarcomas

Karen Wyckoff, creator of Rein in Sarcoma

Mission

Support survivors and familiesEducate physicians and the public

Fund research for promising cures

38

Our Vision for our future

Significant Research Funding to find cures for sarcoma cancers:

“A World Without Sarcoma”

Provide significant educational sarcoma resources nationwide

39

Patient and Family Support

Current Programs

40

RIS hosts educational and social support events Peer to Peer Support Support for Loved ones

Patient & Family Support

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reininsarcoma.org• Patient and Family Support• Latest Information about sarcoma

cancers for professionals and public

• Research updates• Sarcoma Stories• Opportunities to meet others in

similar situations

Patient & Family Support

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Patient & Family SupportSarcoma Family Picnic• Major annual support activity - More than 500 attendees• Hosted by: University of Minnesota Hospitals, Children’s

Hospitals and Clinics of Minnesota and Mayo Clinic• The 2018 free picnic will be held in conjunction with the

Party in the Park

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Patient & Family SupportCommunity Building• Annual Party in the Park- Our signature event with over

1,500 attendees• Como Park, St. Paul- July 23, 2018• In five hours we act out our mission to “Rein in Sarcoma”

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Education of the Public & Medical Professionals

Current Programs

46

Education

Educating both…

Medical Community

General Public

about Sarcoma cancers

critical component of the work ofRein in Sarcoma

+

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Patient Education

Comprehensive Notebook• Mailed Free to sarcoma patients throughout

North America• Customized editions for:

University of Minnesota Hospitals, Children’s Hospitals and Clinics of Minnesota and Mayo Clinic

• Published 6th edition November 2016

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Education

• Educates consumers and medical community about warning early signs

• Creates brochures for the public and medical community

• Sarcoma Medical Grand Rounds and educational events at the University of Minnesota, Mayo Clinic Health Systems and Clinics throughout the upper Midwest

• Endorsed by the University of Minnesota, Children’s Hospital and Clinics of Minnesota, and the Mayo Clinic medical staffs

Red Flags of Sarcoma

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EducationMedical Education • Instrumental in ensuring sarcoma

clinical education was added to medical school curriculums at the University of Minnesota and expanding sarcoma education at the Mayo Medical School

• Sarcoma Cancer Medical School Education at:

• Mayo Clinic Medical School• University of MN – Medical School• University of Minnesota – Duluth

Medical School 50

EducationSarcoma Scholar Program• In 2011 established the Sarcoma

Scholar Program at the University of Minnesota and Mayo Medical Schools

• Four University of Minnesota students and two Mayo Medical students are the Sarcoma Scholars for the 2017-18 academic year

• Sarcoma scholars work to educate other students and the public

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Sarcoma Boot Camp: 2017 Cannon Falls, MN• By definition, a boot camp is a

short, intensive, and rigorous course of training.

• Our goal is to take this knowledge and disseminate it amongst our classmates and future colleagues, and also use it in our own future careers – wherever we may end up.

• We are fortunate to have been given such an incredible opportunity through the Rein in Sarcoma Foundation and are determined to advance the Foundation’s mission of increasing awareness and increasing survivors.

2017-2018 Sarcoma Scholars

Claire Cambron Ying Gibbens


Andrew Hughes Allison Martin


Tessa St. Cyr Madison Weg

EducationHallie Brown Educational Initiative

• To increase early and better diagnosis of sarcoma cancers.

• To encourage getting patients to sarcoma centers

• Up to a 20% increase in sarcoma survivorship• Now being piloted at Regions Hospital and

the HealthPartners Health Plan. Led by Dr. Randy Hurley.

• Resulted from $100,000 donation in 2016 by the Barbara Baekgaard Family Foundation through Todd and Kathy Brown. e

Research

Donated $1.9 million+in funding for sarcoma cancer research through the University of Minnesota’s Masonic Cancer Center

These seed grants have leveraged

$7 million+in additional peer-reviewed grants from private and public funders

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In 2017, RIS began Funding research at Mayo Clinic

Research

In January 2018 Rein in Sarcoma funded $148,000 for four foundational research projects:

Antonella Borgatti, Ph.D. Jessica Lawrence L. Chinsoo Cho

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Jaime F. Modiano

• Commitment of $12,000 for 2018-19 Sarcoma Scholars at U of MN and Mayo.

Research In addition, in 2018 RIS has committed an addition

$45,000in research at:Mayo ClinicChildren’s Hospitals and clinics of MNNationally- Through SARC

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Educational- National Conference

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