Retinoblastoma medical therapy: Difference between revisions
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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).<ref>http://eyewiki.org/Retinoblastoma#General_treatment</ref> | 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).<ref>http://eyewiki.org/Retinoblastoma#General_treatment</ref> | ||
==Medical therapy== | ==Medical therapy for intraocular tumors== | ||
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 EBRT had on the prevalence of secondary tumors, especially in patients with germline mutations. It is estimated that 38.2% of patients with hereditary retinoblastoma will develop a secondary malignancy with an associated long-term mortality rate of 26%.[7][8] The risk of second malignancy is increased more than threefold by EBRT, especially if the patient is less than 1 year of age.[9] The growing reluctance to use EBRT coincided with the rise of more effective chemotherapeutic regimens. | |||
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.[10] 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.[11] Today, systemic chemotherapy, applied in conjunction with local therapy, is one of the main globe salvaging options in retinoblastoma management. | |||
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. | |||
The Children’s Oncology Group (COG) currently has multiple trials evaluating chemotherapy regimens in conjunction with focal consolidation. Since group A eyes are often easily managed with focal therapies alone, no COG trial exists for this group. For group B tumors, a two agent protocol involving vincristine and low-dose carboplatin along with local therapy was being evaluated (COG ARET0331) but has now reached a stopping point. 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 (COG ARET0231). These trials have also reached stopping points. Enucleation is recommended for group E eyes. 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. | |||
==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. | |||
==References== | ==References== | ||
{{reflist|2}} | |||
==See also== | ==See also== | ||
Revision as of 20:37, 3 September 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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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
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 EBRT had on the prevalence of secondary tumors, especially in patients with germline mutations. It is estimated that 38.2% of patients with hereditary retinoblastoma will develop a secondary malignancy with an associated long-term mortality rate of 26%.[7][8] The risk of second malignancy is increased more than threefold by EBRT, especially if the patient is less than 1 year of age.[9] The growing reluctance to use EBRT coincided with the rise of more effective chemotherapeutic regimens.
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.[10] 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.[11] Today, systemic chemotherapy, applied in conjunction with local therapy, is one of the main globe salvaging options in retinoblastoma management.
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.
The Children’s Oncology Group (COG) currently has multiple trials evaluating chemotherapy regimens in conjunction with focal consolidation. Since group A eyes are often easily managed with focal therapies alone, no COG trial exists for this group. For group B tumors, a two agent protocol involving vincristine and low-dose carboplatin along with local therapy was being evaluated (COG ARET0331) but has now reached a stopping point. 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 (COG ARET0231). These trials have also reached stopping points. Enucleation is recommended for group E eyes. 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.
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[2]. 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.