European Organization for Research and Treatment of Cancer

Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20-25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) consensus classification for cutaneous lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms was introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centres, which may be due to the fact that consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the three main groups of CBCL. Since no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state of the art management as currently practised in major cutaneous lymphoma centres. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL. of (11%) with a (FCL) first presenting in the as compared to two of 82 patients with a marginal zone lymphoma (MZL) In nine of these 22 the only evidence of extracutaneous disease. The 5-year overall and disease-specific survivals of these nine patients were 44% and 63%, respectively, compared to 84% and 95% in 157 patients without extracutaneous disease. indicate that bone marrow examination should be considered as an essential part of staging procedures in patients with a FCL first presenting in the skin and that, from a clinical point of view, bone marrow examination appears to have limited value in

In early studies, simian virus 40 (SV40), a DNA tumor virus, was seldom detected in human tumors by use of Southern blot hybridization and/or immunohistochemical techniques [reviewed in (7)]. More recently, Bergsagel et al. (2) detected SV40 T antigen (Tag)-coding sequences with the polymerase chain reaction (PCR) in 10 of 20 choroid plexus papillomas and in 10 of 11 ependymomas, whereas Carbone et al. (3) found SV40 in 60% of human pleural mesotheliomas. We looked for SV40 Tag coding sequences in a variety of human brain specimens and in blood samples from healthy donors. We examined 58 primary brain tumors of different histotypes, 10 brain tumor-derived cell lines, 13 normal brain tissues, and 33 peripheral blood cell (PBC) samples. By using PCR followed by Southern blotting and hybridization with an oligomer probe specific for the SV40 early region, we found SV40 DNA sequences in five (83%) of six choroid plexus papillomas, eight (73%) of 11 ependymomas, three (43%) of seven astrocytomas, five (29%) of 17 glioblastomas, two (40%) of five glioblastoma multiforme-derived cell lines, and four (13%) of 30 PBC samples. None of the 13 normal brain tissues were positive for SV40 DNA, nor were seven meningiomas and one meningioma cell line, seven oligodendrogliomas, two spongioblastomas, one neuroblastoma, and four neuroblastoma cell lines. The two glioblastoma multiforme-derived cell lines that were positive for SV40 DNA showed expression of SV40 early-region sequences when analyzed by coupled reverse transcription and PCR, and SV40 Tag was detected by indirect immunofluorescence with the specific monoclonal antibody Pab 101. DNA sequencing of the amplification products from four brain tumor specimens "(one ependymoma, one glioblastoma, and two glioblastoma multiforme-derived cell lines) confirmed that they were derived from SV40.
Our data indicate that SV40 Tagcoding sequences can be detected in a large variety of human neoplastic brain samples, suggesting that SV40 virus is more widespread in human neoplasms than reported before. It is interesting that SV40 early-region sequences were also detected for the first time in PBCs from healthy individuals used as control subjects. This result, in agreement with similar findings (4,5) of sequences from the human polyomaviruses BK (BKV) and JC (JCV), suggests that human PBCs may be vectors for the transfer of SV40 to other tissues. Because SV40 was not detected in normal brain specimens, the virus seems to be specifically associated, at least in human brain, only with neoplastic tissue. SV40 is oncogenic in rodents, and it is mutagenic and can transform human cells. Its oncogenicity is mainly related to the production of Tag, a transforming protein that is 85% homologous to BKV Tag. SV40 Tag induces extensive chromosome rearrangements, and it binds and inactivates the products of the p53 (also known as TP53) and RB tumor suppressor genes (7).
All specimens, brain tumors, and PBCs that were positive for SV40 sequences in this study were found in a previous investigation (5) to contain BKV sequences. This observation suggests that BKV could act as a helper virus for SV40 replication. Indeed, SV40 does not normally infect humans, and human cells are only semipermissive for the virus. SV40 has infected humans mainly through contaminated polio vaccines (7). Its multiplication in human cells and its circulation in the human population may have been helped by the ubiquitous BKV infecting the same host. In this way, SV40 could establish latent infections in specific human cells, exerting its oncogenic potential during the development or progression of brain tumors.

Primary Extraskeletal Osteosarcoma-Experience With Chemotherapy
Extraskeletal osteosarcoma (EOS) is an extremely rare malignant neoplasm of soft tissues characterized by the production of osteoid or bone by the neoplastic cells (/). Primary EOS, unrelated to radiation therapy, is the subject of this correspondence. The traditional treatment for EOS has usually been restricted to local intervention, including surgery alone or a combination of surgery and radiation therapy. At our institution, we have treated EOS with systemic chemotherapy, following regimens similar to those used for treating conventional bone osteosarcoma. We review here our experience with the last 12 consecutive patients whom we have treated during the last decade.
Twelve patients with a histologically confirmed diagnosis of EOS were seen during the last 10 years ( Table 1). Two of the patients refused chemotherapy for personal and religious reasons. Of the 10 patients who received chemotherapy after informed written consent, six were treated before surgery, two were treated for metastatic disease, and two were treated for local recurrences after surgery and prior adjuvant chemotherapy. There were five males and five females; the median age of the patients was 50 years (range, 34-71 years), and the median size of the primary tumor was 15 cm (range, 8-20 cm). Eight patients received our front-line regimen consisting of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) fol-lowed by cisplatin. The doxorubicin was administered on an outpatient basis at a starting dose of 75-90 mg/m 2 in the form of a 4-day continuous infusion; the cisplatin was administered as an inhospital infusion (lasting 2-24 hours) at a starting dose of 120-160 mg/m 2 (given intra-arterially when possible); the complete regimen was repeated every 4 weeks for a median number of three cycles (range, two to five cycles). The remaining two patients had previously received doxorubicin-based chemotherapy in the adjuvant setting, and they were, therefore, treated for recurrent disease with a dose of 2 g/m 2 ifosfamide per day for 5 days. In addition to these two patients, three other patients who did not respond to our front-line therapy were treated with the same dose of ifosfamide, for a total of five assessable patients who received ifosfamide. Three patients received high-dose methotrexate after ifosfamide treatment at a starting dose of 8 g/m 2 over a period of 4 hours, with leucovorin rescue, repeatedevery 2 weeks. The dose of methotrexate was adjusted to achieve a target peak level at the end of the methotrexate infusion of 1000 \iM.
One of the eight patients who received our front-line regimen of doxorubicin and cisplatin achieved a partial remission of lung metastases as judged by standard criteria; one patient had a minor response, and one had a mixed response. Of the five patients who were treated with ifosfamide as second-line therapy, one patient achieved a minor response, and one achieved a mixed response. None of the three patients who received high-dose methotrexate had any response. At the time of last follow-up, nine patients, including the two who did not receive chemotherapy, had died at a median time of 12 months (range, 2-88 months) from diagnosis. Two patients, including the one with a partial remission, are alive and have no evidence of disease at 11 and 60 months, and one patient is alive and has gross disease 55 months from diagnosis.
Primary EOS is a very aggressive tumor with a relatively poor prognosis, especially when the primary tumor is large. In a previous publication from our institution (2), tumor size (<5 cm versus   >5 cm) was found to be the main prognostic indicator for this disease. The median survival time in our current series, representing a very poor prognostic" group" with very large tumors, is 13 months. Although a small retrospective study has limitations, the data presented indicate that cisplatin-based chemotherapy has limited therapeutic benefit in the treatment of patients with EOS. Our current strategy is to treat these high-risk patients in the neo-adjuvant setting with soft-tissue sarcoma chemotherapy regimens (CyADIC [cy-clophosphamide, doxorubicin, and dacarbazine]

U.S. National Cancer Institute
The European Organization for Research and Treatment of Cancer (EORTC) and the U.S. National Cancer Institute (NCI) are offering an exchange program to enable cancer researchers to work at NCI or EORTC-related institutions for one to three years.

General Conditions
Awardees will receive an annual subsistence allowance of $30,000. Half of this amount will be provided by U.S. sources, the remainder by European sources.
European awardees will receive the U.S. contribution either from the NCI or from their extramural host institution. The European contribution of the exchangeship will be provided either by the scientist's home institution or by a European granting agency.
For American awardees, the host institution must be affiliated with the EORTC.

Documentation
The following documents are required, in English, from all applicants: • Completed application form. • Description of the research to be undertaken, not to exceed three typewritten pages. • Letter of invitation from the prospective host. • Agreement to release the applicant from the home institution for the duration of the exchangeship. • Assurance of intention to return to the home institution at the end of the exchangeship.
• Statement concerning the provision of 50 percent of financial support by European sources. Non-EORTC member country candidates must continue at full salary at the home institution for the duration of the exchangeship.
• Three letters of recommendation mailed directly to the NCI Liaison Office by the recommending individuals.
For More Information Contact: EORTC