Successful treatment of pediatric desmoid tumors using hydroxyurea
Personalizing desmoid care – the pros and cons of therapeutic ...
Transcript of Personalizing desmoid care – the pros and cons of therapeutic ...
Personalizing desmoid care – the pros and cons of therapeutic
intervention
Aimee M. Crago, M.D., Ph.D., FACS Assistant Attending Surgeon
Memorial Sloan Kettering Cancer Center
Desmoid Tumor Research Foundation Philadelphia, PA
October 17th, 2015
Desmoid fibromatosis • Locally aggressive tumor without metastatic potential. • Associated in >95% of patients with mutation in CTNNB1
gene, APC loss or rarely in context of Gardner’syndrome. • Historically treated with surgery though high rates of
local recurrence were reported (25-50%). • Radiation has been considered in the adjuvant setting,
but rarely used now. • Now have options of:
– Chemotherapeutics like sorafenib or Doxil – Observation – Cryoablation
Desmoid fibromatosis
Clinical questions in management of desmoid fibromatosis
• Five potential treatment modalities – Surgery, the historical gold standard – Radiation – Observation, proposed to be the new gold standard – Systemic therapies – Cryoablation
• How do we counsel patients regarding appropriate treatment?
Desmoid fibromatosis
Observation • PROS:
– No complications of treatment
• CONS: – Tumors may be symptomatic at presentation – Disease progression is not uncommon
87 patients
30 wait & see (including
COX2 inhibitor)
57 immediate
intervention
2-year PFS ~30%
34 to the OR
21 medical management
Desmoid fibromatosis
<45y.o
>=45y.o primary
recurrent p=0.48 p=0.55
<=5cm
>5cm, <=10cm
>10cm
chest
abdominal wall
extremity, GI, other
p=0.08 (GI vs. chest) p=0.04
Risks for progression Age
Size
Presentation status
Site
Desmoid fibromatosis
Surgery • PROS:
– Able to accurately predict risk of recurrence based on clinic factors and chose ideal candidates
– Potentially curative
• CONS: – Recurrence rates as high as 50%
in some series – Short and long-term morbidities
– Limb dysfunction – Short bowel syndrome
Desmoid fibromatosis
Crago, et al. (2013) Ann Surg. 258: 347-53.
Prognosis in desmoids – A nomogram to predict post-operative recurrence
Desmoid fibromatosis
Crago, et al. (2013) Ann Surg. 258: 347-53.
Radiation • PROS:
– Effective Local control rates 70% – Avoid surgical morbidities
• CONS: – Complications
• Fibrosis of joints • Fracture • Radiation enteritis • Secondary malignancy
Desmoid fibromatosis
Ballo et al. (1999) J. Clin. Oncol. 17:158-67.
Systemic therapy
• PROS: – Avoid significant morbidities historically associated
with surgical resection • Short bowel syndrome • Amputation
• CONS: – Side effects of chemotherapy
• Fatigue, anorexia, neutropenia, infection, hand-foot syndrome
– Thought to have limited efficacy but targeted therapies with improved outcomes (sorafenib, notch inhibitors)
Desmoid fibromatosis
• Retrospective review of: – 68 patients with advanced desmoid tumors, median follow-up 63 months – treated with 157 lines of systemic therapy – Best RECIST responses
Therapy administered Lines of treatment given
Partial response
Stable disease
Progressive disease Median PFS
Anthracycline-based 35 13 (37%) 18 (51%) 4 (11%) Not reached
Methotrexate (single agent) 12 4 (33%) 6 (50%) 2 (17%) 9.4
Hormonal therapy 26 6 (23%) 17 (65%) 3 (12%) 12
Vinca-containing combination 10 2 (20%) 6 (60%) 2 (20%) Not reached
DTIC or temazolamide 16 2 (13%) 12 (75%) 2 (13%) 14.3
Tyrosine kinase inhibitor 35 3 (9%) 25 (71%) 7 (20%) 26.8
Other cytotoxic agents 8 0 7 (88%) 1 (12%) 3.7
Total 142 31 (21%) 91 (64%) 30 (21%) 14.1
*Sorafenib now also an option based on NCCN guidelines, 70% clinical benefit, may be more effective in extremity versus intraabdominal tumors
De Carmargo, Maki et al (2010) Cancer 116:2258-65.
Desmoid fibromatosis
Sorafenib in desmoid fibromatosis 24 patients managed with sorafenib, effects delineated in retrospect
Desmoid fibromatosis
Gounder, Maki et al. (2011) Clin. Cancer Res. 17:4082-90.
Cryoablation
• PROS: – Avoid complex surgery and prolonged recovery – Minimal morbidity
• CONS: – Generally limited indications:
• Small size • Anatomic constraints (not near major neurovascular
bundle, bowel, skin, etc.) • Often abdominal and chest wall tumors
Desmoid fibromatosis
Modality Ideal patients
Observation • Small lesions • Abdominal wall lesions • Asymptomatic patients
Surgery • Small tumors • Abdominal wall lesions or mesenteric desmoids • Older patients • Known growth or symptoms
Systemic therapy • Known growth or symptoms • High risk of post-operative recurrence • Significant morbidity related to surgery
Cryoablation • Small tumors • Surrounded by soft tissue or bone
Radiation • Refractory to systemic therapies • Inoperable • Known growth or symptoms
Desmoid fibromatosis
2012 – 53yo with rapid recurrence of multifocal disease after resection of an 11cm desmoid of the calf in 2011, mild symptoms.
PROS CONS
Observation Avoid side effects Symptomatic
Surgery Potentially curative 30% chance of recurrence Significant risk of Achilles injury
Radiation Control disease Long-term risk of sarcoma Radiation to ankle and knee
Cryoablation Possibility to control disease Significant risk of injury to skin
Systemic therapy 70% disease control with sorafenib
Side effects of systemic therapy- fatigue, hand-foot syndrome
Desmoid fibromatosis
PRE-TX
POST-TX
• 2.5 years of sorafenib • Dose reduced due to mild hand-foot syndrome
• Reached maximal response, off drug for 6 months with no regrowth of tumor
Desmoid fibromatosis
Soft Tissue Sarcoma 47 y.o pharmacist with asymptomatic abdominal mass
Observation
13.1 cm 19.6 cm
PROS CONS
Observation Avoid side effects Potential to develop fistula, obstruction
Surgery Option to debulk Certain short bowel syndrome
Radiation N/A Radiation enteritis
Cryoablation N/A Too large
Systemic therapy 70% disease control Side effects of systemic therapy- fatigue, hand-foot syndrome
Started on Doxil, grade 1 fatigue and hand/foot syndrome
Started on Doxil, grade 1 fatigue and hand/foot syndrome
PROS CONS
Observation Avoid side effects Potential for regrowth
Surgery Potential to debulk Likely incomplete resection, risk of regrowth
Radiation N/A Radiation enteritis
Cryoablation N/A Too large
Systemic therapy Minimal additional response possible
Side effects of systemic therapy- fatigue, hand-foot syndrome
Desmoid fibromatosis
PROS CONS
Observation Minimal chance of progression N/A
Surgery >90% chance of cure Long-term potential for hernia
Radiation N/A Radiation enteritis
Cryoablation Optimal size Minimal experience
Systemic therapy Minimal additional response possible
Side effects of systemic therapy- fatigue, hand-foot syndrome
• 37y.o. post-partum presents with asymptomatic rectus sheath mass
• Biopsy proved desmoid-type fibromatosis
Rectus sheath desmoid
Desmoid fibromatosis
PROS CONS
Observation Minimal chance of progression N/A
Surgery >90% chance of cure Long-term potential for hernia
Radiation N/A Radiation enteritis
Cryoablation Optimal size Minimal experience
Systemic therapy Minimal additional response possible
Side effects of systemic therapy- fatigue, hand-foot syndrome
• Return to clinic for follow-up in 3 months
• Increased pain
• Imaging with growth of desmoid
Rectus sheath desmoid
Desmoid fibromatosis
NED 4 years post-operatively, minimal residual discomfort related to mesh repair
29y.o. with fungating desmoid in the left axilla causing contracture of the shoulder
PROS CONS
Observation N/A Significant symptoms
Surgery Potential for cure, alleviate symptoms
50% chance of recurrence Adjacent to nerves of brachial plexus
Radiation N/A Fibrosis to joint
Cryoablation N/A Too big
Systemic therapy 70% rate of disease control, common improvement in symptoms
Side effects of systemic therapy- fatigue, hand-foot syndrome
PROS CONS
Observation N/A Significant symptoms
Surgery Potential for cure, alleviate symptoms
50% chance of recurrence Adjacent to nerves of brachial plexus
Radiation N/A Fibrosis to joint
Cryoablation N/A Too big
Systemic therapy N/A Failed systemic therapy
Unable to tolerate the drug due to side effects
Pathology: Desmoid-type fibromatosis. - The tumor measures 10.5 cm in greatest dimension. - The tumor extends to the inferior margin (R1 resection).
Desmoid fibromatosis
11 months post-operative - small 2cm recurrence by MRI
PROS CONS
Observation Small, asymptomatic Some residual compromise in function
Surgery Potential for cure, alleviate symptoms
50% chance of recurrence
Radiation N/A Fibrosis to joint
Cryoablation Small, surrounded by soft tissue Minimal experience
Systemic therapy N/A Failed systemic therapy
NED now two year post-procedure with no evidence of neurovascular compromise, improved range of motion vs. preop
Desmoid fibromatosis
Conclusions • Multiple treatment options now exist for
patients presenting with desmoid-type fibromatosis.
• Each has specific indications as well as contraindications.
• Careful consideration of each treatment modality can lead to long term disease and symptom control with minimal morbidity.
• Choice is based on discussion of pros and cons between patient and disease specialist.
Desmoid fibromatosis