Primary chemo lets retinoblastoma spread undetected
Last Updated: 2011-02-04 16:50:11 -0400 (Reuters Health)
By Anne Harding
NEW YORK (Reuters Health) - In children with retinoblastoma at high risk of spreading beyond the eye, primary chemotherapy may actually increase the risk of death, a new study from China shows.
Out of 100 children in the study, five of the 55 who received pre-enucleation chemotherapy died due to extension of the tumor into the brain or metastasis, Dr. Brenda L. Gallie of the University of Toronto and her colleagues found, while none of the 45 children who had primary enucleation died.
"The data we report here raise the alarming potential that children with (advanced) tumors treated with intra-arterial chemotherapy face an increased risk of metastasis, when simple enucleation of the eye would have saved their life with minimal morbidity for unilaterally affected children," the authors wrote in the Journal of Clinical Oncology.
Intra-arterial chemotherapy is increasingly popular; it's now being given worldwide to children with intraocular retinoblastoma at all stages of disease. While the approach has garnered a lot of publicity, Dr. Gallie noted in an interview with Reuters Health, there's virtually no data on long-term outcomes.
Metastasis of retinoblastoma in the developed world is rare, say the researchers. The incidence of retinoblastoma is low in countries other than India and China.
Retinoblastomas classified as A, B, C or D based on International Intraocular Retinoblastoma Classification (IIRC) "can initially respond dramatically to chemotherapy," the researchers note in their report. This has led increasing use of this approach in IIRC group E eyes, which are more severely affected and show signs associated with a greater risk of extraocular disease spread.
"However, chemotherapy may downstage pathologic features associated with risk for extraocular extension, which otherwise would suggest adjuvant therapy and/or surveillance," the researchers add. "This could result in undertreatment and loss of opportunity for cure."
Dr. Gallie and her colleagues looked retrospectively at 100 eyes with advanced retinoblastoma treated with enucleation with or without primary therapy, beginning on October 31, 2008. Eighteen of the enucleated eyes were group D and 82 were group E.
Forty-five eyes received enucleation as primary treatment, while 55 received primary chemotherapy. Median follow-up for patients still alive was 31.2 months for the patients treated with primary enucleation, compared to 25 months for patients treated with primary chemotherapy.
Patients who received pre-enucleation chemotherapy underwent a median of three cycles every three to four weeks, and eyes were removed when disease progressed with no prospect of continued vision.
For the primary enucleation patients, median time to diagnosis was 0.1 months, compared to three months for patients that received primary chemotherapy (P < .001).
This difference, Dr. Gallie noted, might have made a difference in patient survival. "If you wait three months...you give the tumor the chance to kill the child."
At the last follow-up, four patients with group E eyes who received primary chemotherapy had died due to disease in the study eye. Time from diagnosis to enucleation was more than three months for all of these patients. Disease-specific survival was significantly lower for the children with group E eyes who received primary chemotherapy, compared with those who received primary enucleation. None of the patients with group D eyes died due to disease spread, nor did any of the patients treated with primary enucleation.
"We speculate that if the four children who died from metastasis from their study eye had undergone immediate enucleation, the cancer might have not yet extended outside the eye, or if high-risk pathologic factors had been recognized, post-enucleation surveillance and adjuvant therapy might have avoided metastatic deaths," the researchers write. "The pre-enucleation chemotherapy given in this study poorly treated tumors already outside the eye, and failed to prevent extension outside the eye."
SOURCE:http://bit.ly/gHCZ9M
J Clin Oncol 2011.
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