RADIATION THERAPY FOR

BONE TUMORS

Mayur Mayank22.02.2014

INTRODUCTION

Primary bone tumors are rare malignancies.They account for <0.2% of all neoplasms.Most common amongst them are :

Osteosarcoma – 35%Chondrosarcoma – 30%Ewing’s sarcoma – 16%

Most common tumors of the bone are secondary tumors metastasizing from some other primary.

Enneking Staging system

AJCC Staging system

OSTEOSARCOMAS

OSTEOSARCOMAS

Osteosarcomas are highly radio resistant tumors and the management basically comprises of surgery and chemotherapy.

Radiation therapy has limited role to play in the management of osteosarcomas.

Appropriate approach is to facilitate a limb saving surgery.

It can be done upfront in small diseases

In case of high disease burden, neo adjuvant chemotherapy is given followed by limb conserving surgery (whenever feasible).

Response to neo adjuvant chemotherapy has prognostic significance.

It is the amount of necrosis in the post operative specimen which gives a measure of the response to NACT

Huvo’s Grading> 90% necrosis - Good response< 90% necrosis - Poor response

The role of radiotherapy in the routine management of extremity osteosarcoma is virtually nonexistent today.

Radiotherapy has been reported to improve local control of borderline or unresectable extremity osteosarcoma, vertebral osteosarcoma and pelvic osteosarcoma.

It has also been used to successfully treat osteosarcomas of the mandible.

INDICATIONS FOR RT IN OSTEOSARCOMA

Patients who refuse surgery/medically inoperableMargin positive disease after surgery/Close margins after surgerySites not amenable for surgery :

PelvisJaw

Palliation

RADIATION THERAPY FOR OSTEOSARCOMAS

1. Definitive : Unresectable disease2. Adjuvant : After R1 or R2 resection3. Palliative

RADIATION THERAPY TECHNIQUESPatient positioning and immobilization :

Depends on the site to be treatedImmobilization should be done adequately so that the fields are adequately reproducible.The lesion should be positioned such that the entrance and exit of the beam(s) do not expose contralateral limbs or other tissues unnecessarily.

Techniques :2D conventional3D Conformal Radiation therapyIMRTProton beam therapy

RADIATION THERAPY TECHNIQUES

Fields and borders :Axial : 2 cms marginExtremity : 4-5 cms marginStrip of skin to be spared to prevent lymphoedemaTo restrict fields at anatomical barriers

Dosage :60 Gy in 30 # for microscopically involved margins66 Gy in 33 # for macroscopic disease70 Gy in 35 # for inoperable disease

From initial tumor dimensions on the pre operative imaging

X RAY AND MRI FINDINGS OF OSTEOSARCOMA

IMMOBILIZATION USED FOR FOREARM OSTEOSARCOMA

OTHER AVAILABLE TECHNIQUES

Extracorporeal and Intraoperative RT :The extracorporeal technique includes en bloc resection of the tumor and surrounding soft tissues, irradiation of the specimen, and reimplantation, often with the aid of prostheses.In IORT, the operative field is exposed and radiotherapy is administered. No resection of the tumor is performed.

Palliative :Palliative RT for pain managementIn cases of big lesion causing mass effectsSamarium 153Whole lung irradiation - with the recognition of the other advantages of systemic therapy, prophylactic lung irradiation has fallen out of favour.

LATE EFFECTS

Depends on the site which has been irradiatedThe normal tissue constraints of the particular site should be kept into consideration while planning fields.Also, patients receive systemic chemotherapy which causes side effects :

Doxorubicin can cause cardiomyopathy and radiation recall.

EWING’S SARCOMA

In contrast to Osteosarcomas, The Ewing’s Sarcoma family of tumors are sensitive to radiation.

Historically, Radiation therapy was the treatment of choice for these tumors

However, in view of increased toxicity and better survival with combined modality of treatment, the role of radiation therapy has declined.

Presently, based on studies done by the IESS, POG and CESS trials, the treatment comprises of systemic chemotherapy followed by adequate local control of the disease.

Local control :SurgeryRadiation therapy

Induction Chemotherapy

Local Control• Surgery• Radiotherapy

Maintenance• Chemotherapy

GENERAL PRINCIPLES OF MANAGEMENT

12 TO 24WKSVAC/IE

AT 12WK/18WK UP TO 1YEAR

5 YEAR SURVIVAL RATES IN EWING’S SARCOMA

ROLE OF RADIATION THERAPY IN EWING’S SARCOMA

Local control :Definitive Radiation therapyNeo adjuvant Radiation therapyAdjuvant Radiation therapy

Metastatic disease :Pain controlSymptomatic management

Pre operative / Definitive :Large inoperable tumorsTumors involving the proximal humerus and upper scapula

since limb reconstruction is difficult and shoulder morbidity may be substantial.

Patients with lesions of the skull, facial bones, or vertebrae

difficulty in achieving negative margins without substantial functional deficit

Pelvic bone tumors

Adjuvant RTIn case of initially bulky tumors – can be given pre operative or post operative – for better local controlMicroscopic or Macroscopic margin positivityInadequate marginsAdjuvant hemithorax irradiation

Adjuvant Hemithorax Irradiation :improves outcomes in patients with high-risk chest wall primary tumors

close or involved margins initial pleural effusion pleural infiltration, and intraoperative contamination of the pleural space

HEMITHORAX IRRADIATION FOR EWING TUMORS OF THECHEST WALL Int. J. Radiation Oncology Biol. Phys., Vol. 54, No. 3, pp. 830–838, 2002

Historically, Ewing’s sarcoma was thought to be a tumor arising from the bone marrow.

The treatment protocol consisted of treating the entire length of the bone.

An analysis of the RT fields for the Intergroup Ewing's Sarcoma Study Group (IESS) trial I suggested that most relapses were at the site of initially bulky tumor.

POG 8346 trial was the first trial which used “tailored field RT” with reduced portals.

IESS III was the first cooperative group trial to include tailored RT ports, and the first to be carried out with modern MRI imaging of the primary site and CT-based treatment planning

FIG. Changes in treatment volume. (A) Field encompassing the entire length of the medullary cavity for a tumor involving the proximal left humerus. (B) Tailored field encompassing only the proximal aspect of the leg for a limited tumor of the left tibia.

RADIATION THERAPY TECHNIQUESPatient positioning and immobilization :

Depends on the site to be treatedImmobilization should be done adequately so that the fields are adequately reproducible.The lesion should be positioned such that the entrance and exit of the beam(s) do not expose contralateral limbs or other tissues unnecessarily.

Techniques :2D conventional3D Conformal Radiation therapyIMRTProton beam therapy

RADIATION THERAPY TECHNIQUES

Current recommendations for RT Initial clinical target volume to include the original bone and soft tissue tumor with a 2.0 cm margin The initial clinical target volume is treated to 45 Gy in 25 fractions Boost field to encompass the post-chemotherapy gross soft tissue tumor as well as all of the originally involved bone with a margin of 1.5 cms.10.8 Gy in 6 fractions in patients undergoing definitive RT and to 5.4 Gy in three fractions for patients undergoing adjuvant RT for microscopic residual disease after surgery (with boost up to 10.8 Gy for any sites of gross disease after surgery).

Additional margin expansions on these volumes are used for the planning target volume expansion to account for any variability in daily setup

0.5cms-1cms depending on the institutional protocol

Some centers (University of Florida) use Hyperfractionated therapy

1.2Gy per fraction, twice daily, 6 hours apartThis has shown adequate local controlLess long term toxicity

Limited field sizes with hyperfractionated high-energy RT could minimize long-term complications and provide superior functional outcomes.

Normal tissue considerations :Epiphyseal growth plates - Avoided in order to minimize treatment induced limb shorteningCircumferential irradiation of a limb - Avoided to reduce the risk of limb edema and fibrosisGonadal avoidance or additional shielding (for the testes) - important to retain fertilityNail beds should be excluded from the radiated field when possiblePelvic tumors – Bladder

distention prior to treatment can reduce the amount of small bowel in the radiated fieldTo avoid radiation to significant portions of the bladder in patients receiving ifosfamide to reduce the risk of hemorrhagic cystitis

Long bone fracture :The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy.

For bone hypoplasia :Dose - 35 Gy was the most significant threshold•Volume significant effect in the young population (<5 yrs)

Newer modalities of radiation delivery are preferable to reduce the toxicity

3D Conformal radiation therapyIMRTProton beam therapyHeavy ion treatment

Reference : Uptodate

Reference : Uptodate

SEQUELAE OF TREATMENT Acute effects

Desquamation of the skin, myelosuppression, mucositis, diarrhea, nausea, and cystitis. Patients receiving whole lung irradiation are at risk for radiation pneumonitis.

Acute reactions are usually self-limited and subside within 10 to 14 days of RT completion

Late effects :Younger, prepubertal children are at greatest risk for radiation-induced arrest of bone growth. Sparing of uninvolved epiphyseal plates minimizes limb shortening after RT of extremity lesions.RT doses above 60 Gy are associated with markedly increased rates of soft tissue induration and fibrosis High-dose circumferential irradiation of an extremity is associated with edema, fibrosis, and compromised limb function . This can be avoided by sparing of an adequate strip of tissue.Weight-bearing bones are at risk for pathologic fractures. The highest risk is within the first 18 months of RT completion

Second malignancy after RT • With protocols utilizing lower doses of RT and

tailored RT fields suggest that the magnitude of the risk is somewhat lower.

• Cumulative risk at 15yrs = 6 – 6.7% ( CESS-81 & CESS-86; IJROBP:1997; 39) • No secondary sarcomas seen at doses <48 Gy

( Kutterch et al; JCO:1996, 14 )

RT for metastatic disease :Control of local diseasePulmonary metastatsisBone and soft tissue metastasis

Pulmonary metastasis :Bilateral lung irradiation :

Low-dose bilateral lung irradiation (15 to 18 Gy, in 1.5 to 2.0 Gy fractions) with a focal boost dose to a total of 40 to 50 Gy to large deposits is recommended for patients with pulmonary metastases who have had a good response to chemotherapy.

Reduced pulmonary relapse and improved event-free survival, and the low rate of pulmonary toxicity, it is suggested to give bilateral low-dose lung irradiation (15 to 18 Gy) even if all lesions are resected or completely respond to chemotherapy

Whole lung irradiation

Superior border : 3cm above the middle 1/3 rd of clavicle

Inferior border Below the xiphisternum / level of L1 (to include anterior and posterior costophrenic angles)

Lateral borders : Lateral border of areola of nipple

Bone and Soft tissue metastasis :Palliative RT can be considered for symptom management

CHONDROSARCOMA

Dedifferentiated chondrosarcoma : treated as osteosarcomaMesenchymal chondrosarcoma : treated as Ewing's sarcomaFor low grade histology's treatment is with surgery/RT. Indications for RT:

Inaccessible tumorWhere clear margins are not achievable. Recurrence

Dose : 50-70 Gy/ 200cGY/#/5days/week.

5 year survival – RT alone – low grade 48% high grade 22%.

CONCLUSIONS

CONCLUSIONSThe role of radiation therapy in the management of bone tumors depends on the histology of the tumor and the resectability.

Surgery forms the mainstay of management of most of the tumors of the bone.

However, radiation therapy has a significant role to play in inoperable or incompletely excised tumors for adequate local contol.

The newer modalities of delivering radiation therapy and “tailored field” radiation therapy approach has led to significant decrease in the toxicity.

The toxicities are also contributed by the chemotherapy used for the treatment of the tumor and cumulative effect of both should be considered while planning a treatment.

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