October 18, 2021

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“Black Technology”: Proton therapy for retinoblastoma

“Black Technology”: Proton therapy for retinoblastoma


“Black Technology”: Proton therapy for retinoblastoma.  Retinoblastoma is the most common ocular malignant tumor in children. Retinoblastoma occurs in 1 in 15,000 newborns, and the average age of onset is about 2 years old.

Retinoblastoma grows on the retina and its source is retinoblastoma. This kind of fetal primordial cells can differentiate and develop into mature retinal cells, which have the ability to sense light and form vision. However, due to the mutation of the RB1 tumor suppressor gene in germ cells, the retinoblasts lose their ability to differentiate into retinal cells. It becomes an uncontrolled cancer cell that divides and proliferates rapidly.

At first, retinoblastoma is difficult to be detected by parents in the early stage. It is often found that one of the children’s pupils has abnormal yellow-white reflection when the photo is taken. The professional term is called “black cat’s eye.” If treatment measures are taken at this time, the 5-year survival rate of children is quite high (in developed countries, the 5-year survival rate of retinoblastoma reaches 95%, and the 5-year survival rate of children in some countries is low, about 63%) , And most of the eyesight can be protected.



Many therapies are more sensitive to radiation, proton therapy is recommended

Currently, treatments that can preserve the eyeballs of children with retinoblastoma include cryoablation, laser therapy, chemotherapy, and radiotherapy. This disease is a radiation-sensitive tumor, and radiotherapy is usually used as a rescue treatment, but conventional photon beam therapy can increase the risk of radiation-induced second malignant tumors, especially in children with inherited RB gene mutations.

In addition, conventional radiotherapy can produce long-term toxic reactions, including conjunctivitis, corneal opacity, cataracts, glaucoma, vitreous hemorrhage, retinopathy, optic neuropathy, and orbital hypoplasia.

A variety of conformal radiotherapy techniques (stereotactic radiotherapy, intensity-modulated radiotherapy, proton therapy) have been applied to the treatment of retinoblastoma to protect organs at risk and reduce radiotherapy-related toxicity. Studies have shown that proton therapy is currently a highly conformal external beam radiotherapy option for retinoblastoma.



A new choice for children’s eye cancer-proton therapy

Proton therapy has been a recognized alternative to traditional radiotherapy, and can reduce the risk of damage to adjacent tissues such as the brain, optic nerve, and growing facial and orbital bones. In some cases, proton therapy combined with chemotherapy can avoid the risk of eyeball enucleation. The focused radiation dose delivered by proton therapy is very important for children with retinoblastoma who have a genetic predisposition to radiation-induced secondary tumors.




"Black Technology": Proton therapy for retinoblastoma

Proton therapy treatment of retinoblastoma schematic diagram


1  High local control rate and small side effects

In order to explore the long-term disease and toxicity results of children with retinoblastoma after proton therapy, a retrospective study analyzed 49 patients with retinoblastoma who received proton therapy from 1986 to 2012. 84% of patients had bilateral retinoblastoma, and almost half of the patients had received chemotherapy.

"Black Technology": Proton therapy for retinoblastoma

The median follow-up time was 8 years, and the survival rate without enucleation after proton therapy was 81.6%, especially for those early patients.
The ophthalmological follow-up results after proton therapy showed that 61% (30/49) of the patients retained their eyeballs, 47% of the patients regained visual acuity, and no patients suffered from secondary tumors.

The long-term follow-up results of patients with retinoblastoma who received proton therapy clarified that the local control rate of proton therapy is high, even for advanced cases, while retaining the useful vision of most patients.

Treatment-related ocular side effects are not common, and radiotherapy-induced malignancies have not occurred.


2  best target coverage and maximum orbital bone preservation

Whether it is partial or whole eye treatment, proton therapy is a good treatment option for patients with retinoblastoma. In a retrospective study from MD Anderson Cancer Center, a 36Gy/18F radiation dose to the whole retina and vitreous cavity can provide patients with the best target coverage and maximum orbital bone preservation.

"Black Technology": Proton therapy for retinoblastoma

Studies have shown that while providing 100% coverage of the target area, when the radiation dose is ≥5Gy, Protons can limit the average irradiated orbital volume to about 10%,  While three-dimensional conformal radiotherapy (3D-CRT) is 25%, and intensity-modulated conformal radiotherapy (IMRT) is 69%.

In summary, In retinoblastoma, proton therapy can provide the best target coverage and the most orbital bone preservation. Such a low dose is sufficient to potentially reduce the possibility of orbital bone growth defects.

3 Low radiation dose to ensure maximum eye function

In a clinical study of 6 patients with intraocular tumors in proton beam radiotherapy (PBRT), there were 3 patients with retinoblastoma.

"Black Technology": Proton therapy for retinoblastoma

The results of the study show that PBRT has physical advantages compared to traditional photon radiation therapy (EBRT). In the schematic diagram of a typical case in the figure below, Traditional photon therapy has a larger dose in the eye near the tumor, and the dose of the posterior orbit and the distal end of the brain tumor is significantly higher than that of proton therapy.

The picture on the left is conventional photon beam therapy, and the picture on the right is proton beam therapy

Studies have shown that, while maintaining the eyeball, the proton beam has a lower radiation dose than the conventional photon beam, and can ultimately maximize eye function.

Proton therapy has more extensive indications for childhood tumors

  • After subtotal resection of ependymoma, craniopharyngioma, medulloblastoma, rhabdomyosarcoma, neuroblastoma, retinoblastoma, optic nerve meningioma, PNET/low-grade glioma;
  • Protons can reduce cognitive impairment, reduce cochlear dose, and reduce hearing damage;
  • High-grade gliomas of the brain and brainstem can use protons, but it is difficult to reach the real tumor boundary, and it is difficult to achieve conformity.

Sum up

In addition to the recommended treatment of rare eye cancer with protons, in recent years, scientists have made considerable efforts to develop new methods to overcome the obstacles of solid tumors and adopt optimized strategies for CAR-T for these specific indications. therapy.

We look forward to the fact that more and more pre-clinical/clinical trial data can piece together a complete puzzle, fully demonstrating the true strength of CAR-T cell therapy in the treatment of solid tumors.




(source:internet, reference only)

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