October 22, 2009 — A new standard protocol appears to improve survival in children with rare choroid plexus tumors, according to research presented at the 41st Annual Meeting of the International Society of Pediatric Oncology (SIOP).
The interim findings suggest that the protocol, which consists of combination chemotherapy and in some cases radiation, improves survival nearly 2-fold.
The Choroid Plexus Tumor (CPT)-SIOP-2000 study began 10 years ago. It has grown to include over 100 institutions from more than 20 countries, and is the largest collaborative study to date that addresses treatment of choroid plexus tumors. "The whole international community has come together to help these children," said lead author Johannes Wolff, MD, head of pediatric neuro-oncology at the Children's Cancer Hospital, University of Texas MD Anderson Cancer Center in Houston.
No Standard Treatment, Algorithm Developed
Because of the rarity of this tumor, there is no standard treatment protocol other than surgical resection. Choroid plexus tumors originate in the choroid plexus epithelium and are typically located in the ventricles. Although they account for only 1% to 4% of all pediatric brain tumors, they represent 13% of tumors that occur in the first year of life, the authors note. Choroid plexus tumors are the most frequent brain tumor diagnosed at birth, and the majority of children are younger than 3 years at the time of diagnosis.
According to the World Health Organization classification, there are 3 histological tumor grades: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (APP), and choroid plexus carcinoma (CPC). As far as prognostic features and clinical outcomes, APPs are in an intermediate position between CPP and CPC. However, Dr. Wolff explained, the grades can be misleading because tumors can progress to higher grades and metastases can occur in all histological grades.
The protocol was drawn from an algorithm that was developed by Dr. Wolff and colleagues and from clinical research. A total of 155 patients were registered between January 2000 and January 2009, and the interim analysis presented at the meeting reported on data for 101 children.
All of the patients had undergone a surgical resection, and the study design divided participants into an observation group and a treatment group who received further therapy. "We used the algorithm to decide who needed immediate treatment and who didn't," Dr. Wolff told Medscape Oncology. "Patients in the observation group were at lower risk and they were closely followed for disease progression."
Study Groups
| Observation Group | Treatment Group |
| CPP without metastases APP without residual tumor and without metastases | CPP with metastases APP with residual tumor or metastases All cases of CPC |
All patients in the treatment group received etoposide and vincristine, which was combined with either carboplatin or cyclophosphamide. Risk-adapted radiotherapy was only administered to patients older than 3 years. A total of 44 patients were treated and, of those, 41% received radiotherapy.
"The overall response rate was more than 50% after 2 cycles of chemotherapy and more than 80% after 6 cycles," said Dr. Wolff. "That is the main message from our study — chemotherapy is effective in shrinking these tumors."
As of January 2009, 16 of 101 patients experienced a relapse; 75% had a local relapse (6 patients with local and 6 patients with local and distant), and 58% had a distant relapse (4 patients).
Interim Survival Data
| Survival | Observation Group (n = 57) | Treatment Group (n = 44) |
| Overall | 57 censored | 35 censored |
| Event-Free | 53 censored | 31 censored |
Patients who received radiation therapy also did better, Dr. Wolff explained. When evaluating the impact of histology on survival, patients with CPC had the poorest overall and event-free survival.
As for the 2 different chemotherapy regimens, there are no data on which is more effective. "We don't have the final answer for that, but the preliminary result looks like there will be no difference," said Dr. Wolff.
Toxicity was fairly mild, he added. There was some grade 3 and 4 leukopenia after the second chemotherapy cycle, but the incidence of serious infections and mucositis was low.
Dr. Wolff pointed out that "we know that chemotherapy works and radiation helps," but there are still unresolved challenges, such as what to do with young children with metastatic tumors. Another challenge is that although radiation improves the prognosis, most patients with this type of tumor are too young.
Moving Into the Future
The next phase of the trial, CPT-SIOP-2009, will develop a new study structure to evaluate the whole field of possible chemotherapy. Although the current study established that these tumors are sensitive to combinations of etoposide, vincristine, carboplatin, and cyclophosphamide, information about other protocols is lacking, he explained.
Patients will receive 1 of 4 chemotherapy combination regimens, using drugs that are already approved, that have demonstrated success in treating other types of pediatric tumors, and for which toxicity in infants is known. In addition, said Dr. Wolff, intrathecal chemotherapy with etoposide will be given to certain subgroups.
"This will be a randomized, 4-armed, open-label, multicenter study, with a safety review component, designed to find the best treatment protocol for patients of any age with newly diagnosed choroid plexus tumors," he said.
In the international community, there has been great interest in CPT-SIOP-2009, which will require 190 patients to be enrolled for 5 years. "We have received letters of intent from 35 nations, and the estimated number of patients will be more than enough," he said.
Looking further ahead to CPT-SIOP-2014, Dr. Wolff explained that, by then, the final results of CPT-SIOP-2000 will be available, although they are expected to be similar the interim results that were presented at the meeting. Preliminary results of CPT-SIOP-2009 are also expected at that time.
The study was funded through the German Children's Cancer Foundation.
41st Annual Meeting of the International Society of Pediatric Oncology: Abstract O.156. Presented October 9, 2009
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