Retinoblastoma medical therapy: Difference between revisions

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Revision as of 20:13, 13 October 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The priorities in the treatment of retinoblastoma are to preserve life, preserve globe and preserve vision, in that specific order. Minimizing side effects and complications of treatment are also of paramount importance in these very young patients. Treatment modalities that may be successful in globe salvage include systemic chemotherapy with focal consolidation, intra-arterial chemotherapy, and for small tumors, focally destructive therapy (cryopexy, laser photocoagulation, hyperthermia and plaque irradiation).^[1]

Medical therapy for intraocular tumors

The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment will depend on the individual case and will be decided by the ophthalmologist in discussion with the paediatric oncologist. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies) The various treatment modalities for retinoblastoma includes:

Enucleation of the eye

Most patients with unilateral disease present with advanced intraocular disease and therefore usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision.

External beam radiotherapy (EBR)

The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. However, patients with hereditary disease who received EBR therapy are reported to have a 35% risk of second cancers.

Brachytherapy

Brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It used as the primary treatment or, more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBR therapy.

Thermotherapy

Thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors Laser photocoagulation – Laser photocoagulation is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor.

Cryotherapy

Cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. Cryotherapy may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods.

Systemic chemotherapy

Systemic chemotherapy has become forefront of treatment in the past decade, in the search of globe preserving measures and to avoid the adverse effects of EBR therapy. The common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. It is also used in patients with unilateral disease when the tumors are small but cannot be controlled with local therapies alone.

Intra-arterial chemotherapy

Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, through the aorta and the neck, directly into the optic vessels).

Nano-particulate chemotherapy

To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects

Patient Group	Treatment line	Treatment
With vitreous seeding
With gross anterior chamber involvement or neovascular glaucoma or orbital inflammation	First	Enucleation
	Adjunct	Postoperative systemic chemotherapy
Without gross anterior chamber involvement or neovascular glaucoma or orbital inflammation	First	Systemic or intra-arterial chemotherapy
	Plus	Concurrent laser ablation or chemotherapy
	Second	External beam radiation therapy
Third	Periocular carboplatin therapy
Fourth	Enucleation
Without vitreous seeding
Tumor >2 disc diameters in size	First	Systemic or intra-arterial chemotherapy
	Plus	Concurrent laser ablation or cryotherapy
	Second	External beam radiation therapy
Third	Periocular carboplatin therapy
Fourth	Enucleation
Tumor 2 disc diameters or less in size	First	Focal laser ablation alone
	Second	Systemic or intra-arterial chemotherapy
	Plus	Concurrent laser ablation or cryotherapy
Third	External beam radiation therapy
Fourth	Periocular carboplatin therapy
Fifth	Enucleation
Metastatic disease
	First	Multimodal therapy

References

↑ http://eyewiki.org/Retinoblastoma#General_treatment

@@ Line 6: / Line 6: @@
 ==Medical therapy for intraocular tumors==
-. '''External Beam Radiation (EBRT)'''
+The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment will depend on the individual case and will be decided by the ophthalmologist in discussion with the paediatric oncologist. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies)
-:* Prior to the 1990s, external beam radiation (EBRT) played a central role in the treatment of retinoblastoma. Due to disappointingly high recurrence rates, chemotherapy was limited largely to the treatment of metastatic cases. However, with long term follow-up clinicians began realizing how significant an impact external beam radiation had on the prevalence of secondary tumors, especially in patients with germline mutations.The growing reluctance to use external beam radiation coincided with the rise of more effective chemotherapeutic regimens.
+The various treatment modalities for retinoblastoma includes:
+===Enucleation of the eye===
-. '''Systemic Chemotherapy'''
+Most patients with unilateral disease present with advanced intraocular disease and therefore usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision.
-:* Systemic chemotherapy is administered with focal consolidative therapy. This treatment approach has been coined "chemoreduction" because the goal is to shrink the tumor. Shrinking the tumor increases the success of focal therapies, which are less successful with thicker tumors. Focal therapy is directly destructive to tumor cells and also breaks down the blood ocular barrier and increases penetration of chemotherapeutic agents into the eye. Today, systemic chemotherapy, applied in conjunction with local therapy, is one of the main globe salvaging options in retinoblastoma management.
+===External beam radiotherapy (EBR)===
+The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. However, patients with hereditary disease who received EBR therapy are reported to have a 35% risk of second cancers.
-. '''Advanced Bilateral Retinoblastoma Medical Therapy'''
+===Brachytherapy===
-:* In patients with advanced bilateral retinoblastoma, traditionally the more severely affected eye has been enucleated, while the less severely affected eye has undergone chemoreduction with or without external beam irradiation. In cases where only one eye harbors tumor, enucleation is usually considered when the tumor is large and there is poor vision potential. As chemoreduction has proven its efficacy, clinicians are expanding its clinical indications to allow more eyes to be saved.
+Brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It used as the primary treatment or, more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBR therapy.
+===Thermotherapy===
-. '''Intra-arterial Chemotherapy for Retinoblastoma'''
+Thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors
+Laser photocoagulation – Laser photocoagulation is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor.
-The Children’s Oncology Group (COG) currently has multiple trials evaluating chemotherapy regimens in conjunction with focal consolidation.
+===Cryotherapy===
-:* Since group A eyes are often easily managed with focal therapies alone, no COG trial exists for this group.
+Cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. Cryotherapy may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods.
-:* For group B tumors, a two agent protocol involving [[Vincristine]] and low-dose [[Carboplatin]] along with local therapy was being evaluated but has now reached a stopping point.
+===Systemic chemotherapy===
-:* Group C and D tumors were being treated with three agent chemotherapy involving [[Vincristine]], high-dose [[Carboplatin]], and [[Etoposide]] along with local therapy as well as subtenon injection of [[Carboplatin]]. These trials have also reached stopping points.
+Systemic chemotherapy has become forefront of treatment in the past decade, in the search of globe preserving measures and to avoid the adverse effects of EBR therapy. The common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. It is also used in patients with unilateral disease when the tumors are small but cannot be controlled with local therapies alone.
-:* Enucleation is recommended for group E eyes.
+===Intra-arterial chemotherapy===
-:* Children with tumor massively involving the optic nerve, orbit, brain or present at distant sites are currently being enrolled in a COG group F trial.
+Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, through the aorta and the neck, directly into the optic vessels).
+===Nano-particulate chemotherapy===
-==Adverse effects==
+To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects
-The risk of second malignancy is increased more than threefold by external beam radiation (EBRT), especially if the patient is less than 1 year of age.
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
+|valign=top|
-==Medical Treatment of Extraocular Retinoblastoma==
+|+
-Historically, extraocular retinoblastoma was nearly universally fatal.  If the retinoblastoma remained confined to the orbit, there was only  a 10% survival rate, and cases of survival with metastatic retinoblastoma was anecdotal.[16] However, as chemotherapeutic regimens have improved, the prognosis has also improved.
-For extraocular retinoblastoma limited to the orbit, clinicians are finding success with neoadjuvant chemotherapy to shrink the tumor.  This is followed by surgical debulking and post-operative chemotherapy and radiation if necessary.[17][18] For systemic metastases, especially cases with CNS involvement, aggressive treatment with high dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) is recommended.  HDC involves the administration of high doses of chemotherapeutic agents with the aim to overcome tumor resistance and completely eradicate neoplastic cells.  Unfortunately, these lethal doses are also myeloablative and concurrent ASCR must be performed to allow future reconstitution of the bone marrow. Though toxic, case series of survival after this treatment regimen are being reported.[19][20]
-Currently there is a Children’s Oncology Group (COG) trial evaluating high dose systemic chemotherapy using four cycles of induction chemotherapy with vincristine, cisplatin, cyclophosphamide and etoposide followed by one cycle of high-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for malignant brain and spinal tumors. Though promising, treatment efforts remain focused on early detection and treatment to prevent extraocular disease in the first place.
-==Trilateral Retinoblastoma treatment==
-The treatment regimen for patients with primitive neuroectodermal tumors (PNET) is similar to patients with CNS metastases<ref>http://eyewiki.org/Retinoblastoma#Trilateral_Retinoblastoma</ref>. The prognosis is also dismal. As such, early detection and treatment of primitive neuroectodermal tumors (PNET) is recommended.  Recently it was noted that there was a decrease in the incidence of primitive neuroectodermal tumors as clinicians came to rely more on chemotherapy over EBRT. This is hypothesized to be secondary to either a prophylactic effect due to systemic chemotherapy or because fewer patients are receiving radiation. Regardless, systemic chemotherapy should be strongly considered for germline cases of retinoblastoma over local (i.e. intra-arterial ) delivery.
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