rhabdomyosarcoma radiotherapy indications and outcome

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RhabdomyosarcomaRadiotherapy: Indications and Outcome

Víctor BarrondoRadiation Oncology Department/Brachytherapy Section

Hospital Universitario Basurto, Bilbao

Intergroup Rhabdomyosarcoma

GEIS XIth International Symposium / Seville - November, 29th 2013

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IRS I (1972 – 1978) OS 55%IRS II (1978 – 1984) OS 63%IRS III (1984 – 1991) OS 71%IRS IV (1991 – 1997) OS 71%COG D9602,D9803, D9802 (1998…)

Intergroup Rhabdomyosarcoma Study


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Introduction

• Highly malignant neoplasm arising from embryonal mesenchyme• With capacity for skeletal muscle differentiation.• 40% of all soft tissue sarcomas and 7% childhood malignancies in the US

http://www.bea.gov/newsreleases/relsarchivespi.htmGEIS


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• Histology• Stage

• Primary site (most important prognostic factor)• Tumor size• LN involvement (especially in extremities)• Metastatic disease

• Group• Extent of resection

Prognostic Factors


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M0N1≤5All Other Sites3

M1N0, N1Any SizeAny Site4

M0N0, N1>5All Other Sites

M0N0≤5All Other Sites2

M0N0, N1AnyOrbit, Non PM H&N, GU non bladder/prostate, biliary tract1

Distant MetastasesRegional Lymph NodesTumor Size (cm)SiteStage

Intergroup Rhabdomyosarcoma Study Group Presurgical Staging System


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Intergroup Rhabdomyosarcoma Study Group Surgical-Patologic Grouping System

Distant metastases present at diagnosisIV

Localized tumor, with gross residual disease after grossly incomplete removal, or biopsy only.III

Localized tumor, grossly removed with (a) microscopically involved margins, (b) involved grossly resectedregional lymph nodes, or (c) both.II

Localized tumor, completely removed with patologically clear margins and no regional lymph nodeinvolvement.I

DefinitionGroup


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Current Children’s Oncology Group (COG) Risk Groups

High4IVERMS

High4IVARMS

Intermediate1, 2, 3I, II, IIIARMS

Intermediate2, 3IIIERMS

Low (Subset B)2, 3I, IIERMS

Low (Subset A)1I, II, IIIERMS

Risk GroupStageGroupHistology


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Radiotherapy Indications

The Short Answer is…• Radiotherapy indicated in Group II-IV patients and Group I Alveolar histology.• As a result from COG D9803, RT recommended at an early time point (4 Week).

. Wolden SL, Anderson JR, Crist WM, et al. Indications for radiotherapy and chemotherapy after complete resection inrhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol 1999;17(11):3468e3475.

. Raney RB, Anderson JR, Brown KL, et al. Treatment results for patients with localized, completely resected (group I) alveolarrhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984e1997: a report from the Children’sOncology Group. Pediatr Blood Cancer 2010;55(4):612e616.


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Radiotherapy Doses COG D9602/D9803

Microscopic Residual Disease 3600 cGyResected Node Positive 4140 cGyOrbital Location Gross Disease 4500 cGyGross Residual Disease 5040 cGySecond Look accepted

IRS- IV: Hyperfractionation (59.4Gy / 1.1Gy fraction b.i.d.) did NOT improve local,regional or distant control over conventional fractionation for Group III tumors.


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Modern Radiotherapy Techniques: IMRT

• Early adopters since 1999.• The next step in radiation treatment planning after 3D.• Inverse planning with computer-assisted optimization.• Dose painting.

Sharp dose fall off outside target volume with selective avoidanceof critical structures and tissues

• Multiple Fields.Dose modulation within each field

• Better immobilization, longer treatment time.


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IMRT vs 3DCRT improved target dose coverage with no improvement in LC or FFS


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Smaller Margin: 15mm using MRI&PET fusion vs 20mm.LFR 3 years: 5% Parameningeal & 0% Orbit/H&N.


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• Standard doses with PNI for adolescentsand young adults (n=21) and reduced dosesper fraction for children (n=20).

• 16%-18% (median, 17%) decrease in themean dose for rectum, bladder and bowel.

• 90%LC (100% children, 79% young adults).



A) Anatomical planning target volume (PTV).

B) Biological PTV.

C) Fusion of anatomical and biological PTV.

D) Contour based optimization.

E) Voxel signal intensity based optimization.

IMRT Functional Dose painting


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Modern Radiotherapy Techniques: Protons

• Inelastic collisions through matter

• Large proportion of the energy at theBragg peak and then falls off

• Particular advantage in H&N wheresparing of critical structures may bebetter accomplished using protons,particularly in young children.

• Long-term clinical outcomes comparingproton therapy and IMRT not yetavailable.

• Cost concern.


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Modern Radiotherapy Techniques: Protons

• LF 18% vs 17% in the IRSII-IV despite poor prognostic features compared with theIRS trial population. (59% intracranial extension vs 38%) and median time to thestart of proton RT was 8 weeks (3/4LF late referral and ICE).

• Reduction in late effects compared with previously published series of patientstreated with photon RT (despite a higher proportion of younger patients).


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Favourable SitesOrbit Rhabdomyosarcoma

• Most commonly embryonal histology.• Small size.• Rarely lymph node involvement.• Standard treatment; QT+RT preserving eye.• 3 year FFS 89%, OS 100%, 5 year LC 98%.• Toxicity: Cataract, keratopathy, dry eye, loss of vision is rare.


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Favourable SitesGynaecological Rhabdomyosarcoma

• Good prognosis.• Common strategy: Initial QT with local therapy to remanent disease

(if present).• Surgery rate decreased from IRS I-IV.• Very good location for Brachytherapy.• 5 year OS 82%.


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Favourable SitesParatesticular Rhabdomyosarcoma

• Initial management with Radical inguinal orchiectomy +/- RLND(CT with enlarged nodes or 10 years or older patients).

• Avoid RT to scrotum to preserve contralateral testicular function ifcomplete resection achieved.

• 3 year FFS 90%.


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Unfavourable SitesExtremity or Trunk Rhabdomyosarcoma

• High rate of lymph node involvement, node sampling required.• Surgery maintaining form and function with RT preferred rather

than amputation.• 10 year OS 63%, FFS 57%.


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Unfavourable SitesParameningeal Rhabdomyosarcoma

• Intracraneal extension of disease main prognostic factor.• Surgery often limited (95% Group III).• 5 year OS 73%, FFS 69%, LC 83%.


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Take Home Messages

• Close collaboration mandatory.• Modern Radiotherapy techniques needed.• Work Hard.


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rhabdomyosarcoma radiotherapy indications and outcome

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rhabdomyosarcoma radiotherapy

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alveolar rhabdomyosarcoma

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