Biomedical subjects

Karen Marcus

Publications and source records attributed to Karen Marcus.

6 recordsLinked to original sources

PubMed2006

High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update.

PURPOSE: To provide an update on long-term survival of patients with high-risk neuroblastoma treated with tandem cycles of myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR). PATIENTS AND METHODS: Ninety-seven patients with high-risk neuroblastoma were treated between 1994 and 2002. Patients underwent induction therapy with five cycles of standard agents, resection of the primary tumor and local radiation, and two consecutive courses of myeloablative therapy (including total-body irradiation) with PBSCR. RESULTS: Fifty-one patients have experienced relapse or died. Median follow-up time among the 46 patients who remain alive without progression is 5.6 years (range, 15.1 months to 9.9 years). Progression-free survival (PFS) rate at 5 years from diagnosis was 47% (95% CI, 36% to 56%), and PFS rate at 7 years was 45% (95% CI, 34% to 55%). Overall survival rate was 60% (95% CI, 48% to 69%) and 53% (95% CI, 40% to 64%) at 5 and 7 years, respectively. The 5- and 7- year PFS rates from time of first transplantation for 82 patients who completed both transplants were 54% (95% CI, 42% to 64%) and 52% (95% CI, 40% to 63%), respectively. Five patients died from treatment-related toxicity after tandem transplantation. Relapse occurred in 37 (42%) of 89 patients, mainly within 3 years of transplantation and primarily in diffuse osseous sites. No primary CNS relapse or secondary leukemia was seen. One patient developed synovial cell sarcoma 8 years after therapy. CONCLUSION: High-dose therapy with tandem autologous stem-cell rescue is effective for treating high-risk neuroblastoma, with encouraging long-term survival. CNS relapse and secondary malignancies are rare after this therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Transverse myelitis after therapy for primitive neuroectodermal tumors.

Traditional therapy for malignant primitive neuroectodermal tumors in children includes surgery, multi-agent chemotherapy, and radiation. Given the poor prognosis with conventional therapy alone, newer treatment approaches have incorporated high-dose chemotherapy followed by autologous stem cell rescue. Treatment with chemotherapy and radiation is not without unanticipated and unwanted side effects. Specifically, radiation-induced damage to the central nervous system can occur, though the frequency is thought to be acceptably low. This report describes two cases of treatment-related transverse myelitis in patients who received induction chemotherapy and craniospinal irradiation followed by high-dose chemotherapy with autologous stem cell rescue. Other patients treated with a similar strategy but different sequence and timing of treatment did not experience symptoms of myelitis, suggesting that the specific timing of radiation in relationship to the chemotherapy may be of critical importance.

Adolescent↗

PubMed2005

Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor.

Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7 months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease. For this reason, many centers now direct such patients, particularly those under 5 years of age, or those with recurrent disease, towards comfort care rather than attempt curative therapy. We now report on four children, two with newly diagnosed CNS AT/RT and two with progressive disease after multi-agent chemotherapy who are long term survivors (median follow-up of 37 months) using a combination of surgery, radiation therapy, and intensive chemotherapy. The chemotherapy component was modified from the Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol as three of the seven reported survivors in the literature were treated using this type of therapy. Our four patients, when added to the three reported survivors in the literature using this approach, suggest that patients provided this aggressive therapy can significantly alter the course of their disease. More importantly, we report on the first two survivors after relapse with multi-agent intravenous and intrathecal chemotherapy treated with this modified regimen.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant.

BACKGROUND/PURPOSE: The treatment approach for patients with high-risk neuroblastoma has been one of dose intensification chemotherapy and aggressive treatment of the primary tumor. Local tumor control is examined in high-risk patients treated with tandem stem cell transplant, aggressive surgery, and selected radiation therapy (XRT). METHODS: Seventy-six patients with high-risk stage III/IV neuroblastoma were treated on a standard protocol incorporating aggressive surgical resection with or without local XRT followed by tandem high-dose chemotherapy and stem cell rescue. Patients were evaluated for degree of surgical resection, site of progression, and outcome. RESULTS: Overall event-free survival for the series is 56%. Forty-eight had gross total resection, 12 had greater than 90% resection, 10 had 50% to 90% resection, and 6 had biopsy only or no surgery. Surgical complications occurred in 29% with no deaths. There were no isolated local failures. Two patients had local recurrence after gross total resection. Surgeon assessment of completeness of resection agreed with postoperative radiological findings 66% of the time. CONCLUSION: Aggressive surgical treatment with local XRT and myeloablative chemotherapy with stem cell rescue provides excellent local control in high-risk neuroblastoma, although distant failures, particularly osseous, remain a problem. Poor correlation exists between the surgeon's perception of completeness of resection and findings on postoperative imaging studies.

Abdominal Neoplasms↗

PubMed2005

Tumor cell-associated neuropilin-1 and vascular endothelial growth factor expression as determinants of tumor growth in neuroblastoma.

We sought to characterize the expression of vascular endothelial growth factor (VEGF) and its receptors in neuroblastoma (NBL) and to correlate the results with N-myc (MYCN) expression and in vivo growth of these tumors. Two representative human-derived NBL cell lines, SK-N-AS (AS) with low and SK-N-DZ (DZ) with a high MYCN copy number, were used for the study. We examined their proliferation, VEGF and VEGF receptor expression in vitro and xenograft tumor growth in vivo. In parallel, human NBL specimens were analyzed for expression of VEGF and neuropilin-1 (NRP-1). DZ cells exhibited a 4-fold higher proliferation rate than AS. In contrast, VEGF protein expression was significantly higher in AS cells. NRP-1 was the only VEGF receptor produced in AS and DZ cells in vitro and in vivo. Both AS and DZ cells formed tumors in athymic mice but AS tumors grew 3.5 times larger than DZ tumors and had larger diameter tumor vessels. VEGF and NRP-1 expression was also demonstrated in human NBL specimens. Our studies indicate that VEGF and VEGF receptor expression in NBL tumor cells are associated with tumor growth and that angiogenic factors may serve as a biological marker together with already established MYCN amplification.

Animals↗

PubMedDate not supplied

Medical versus nonmedical mental health referral: clinical decision-making by telephone access center staff.

A database review investigated decisions of clinicians staffing a university-based telephone access center in referring new adult patients to nonpsychiatrists versus psychiatrists for initial ambulatory behavioral health care appointments. Systematically collected demographic and clinical data in a computer log of calls to highly trained care managers at the access center had limited predictive value with respect to their referral decisions. Furthermore, while 28% of the 610 study patients were initially referred to psychiatrists, billing data revealed that in-person therapists soon cross-referred at least 20% more to a psychiatrist. Care managers sent 56% of callers already taking psychotropic medications to nonpsychiatrists, 51% of whom were then cross-referred to psychiatrists. Predictive algorithms showed no potential to enhance efficiency of decisions about referral to a psychiatrist versus a nonpsychiatrist. Efforts to enhance such efficiency may not be cost-effective. It may be more fiscally efficient to assign less-experienced personnel as telephone care managers.

Academic Medical Centers↗