by

Bruce Shriver

Equal quality of life after limb-sparing or ablative surgery for lower extremity sarcomas,

Written by A Zahlten-Hinguranage, L Bern, V Ewerbeck and D Sabo, British Journal of Cancer advance online publication 3 August 2004. “This study investigated quality of life (QoL) and function of 124 patients with lower extremity sarcoma who underwent either amputation or limb-salvage surgery (LSS) in order to assess potential differences in subjective treatment outcome. The results reflect similar QoL in both treatment groups. However, in contrast to patients with LSS, who described QoL in terms of a high physical performance status with sports and recreational activities, amputees' QoL was strongly associated with their social acceptability. High QoL in amputees brings into question the expectations held with time-consuming advanced technical skills for LSS by physicians.”

Techniques to Modulate Radiotherapy Toxicity and Outcome in Soft Tissue Sarcoma

This article, written by Brian O'Sullivan, Iain Ward, Tara Haycocks and Michael Sharpe appears in Current Treatment Options in Oncology 2003, 4:453-464. The authors state, “Radiotherapy (RT) targeting of soft tissue sarcoma presents considerable opportunity and challenges in realizing the dual goals of tissue and function preservation and maintaining high local control. Traditional RT target volumes used for soft tissue sarcoma have largely been constrained by available technology and are not ideal in some situations. The advent of very precise treatment planning and delivery systems, including three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, means it is possible to select target volumes that more closely approach the optimum. Consequently, these new approaches provide great opportunity for treatment enhancement in the future. It can be expected that newer techniques for RT planning and delivery will challenge the existing dogma concerning target delineation for optimal radiotherapy outcome. It can be foreseen that the precise knowledge of appropriate targets will continue to evolve for different clinical scenarios and likely be greatly influenced by enhanced imaging capability. Advancement of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy over the next decade must rely on the consistent reporting and sharing of results concerning outcome of normal tissue from volumetric treatment planning”.

New Tumor Classification System Proposed

The review of this effort that appeared in Medinews.com states, “To help clinicians decide on the most effective treatment for patients with cancer, molecular data on the genetic makeup of tumors must be incorporated into a tumor classification system that includes morphologic and clinical information. This is the new tumor classification system proposed by Jules Berman, M.D., Ph.D., program director for Pathology Informatics within the U.S. National Cancer Institutes Cancer Diagnosis Program (Bethesda, MD, USA). 'This classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features, he explains'."

Enzyme that maintains chromosome 'ends' linked to bone cancer recurrence, decreased survival

This is a retrospective study from St. Jude Children's Research Hospital links expression of the telomerase gene to risk of disease recurrence and death among children with osteosarcoma. "Children with the bone tumor osteosarcoma are more likely to experience a recurrence of the cancer after treatment and less likely to survive if the cancer cells are expressing the telomerase gene." This finding, from investigators at St. Jude Children's Research Hospital, appears in the current issue of the Journal of Clinical Oncology (JCO).

The Impact of Chemotherapy on the Survival of Patients With High-grade Primary Extremity Liposarcoma

This article was written by Eilber, Fritz C., Eilber, Frederick R., Eckardt, Jeffery, Rosen, Gerald, Riedel, Elyn, Maki, Robert G., Brennan, Murray F., Singer, Samuel,and appeared in Annals of Surgery. 240(4):686-697, October 2004. Abstract: Objective: To determine if chemotherapy offers a survival benefit to patients with large, high-grade, primary extremity liposarcoma. Summary Background Data: The impact of chemotherapy on the survival of patients with primary extremity soft tissue sarcoma is controversial and its effect on individual histologic subtypes is not defined. Patient and Methods: Two prospectively collected sarcoma databases were used to identify all patients with >5 cm, high-grade, primary extremity liposarcoma that underwent surgical treatment of cure from 1975 to 2003 (n = 245). Clinical, pathologic and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS). Conclusions: In patients with large, high-grade, primary extremity liposarcoma; DOX is not associated with improved DSS and IF is associated with an improved DSS. Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma.

Ewing's Sarcoma Marker

In their article, Procholecystokinin as Marker of Human Ewing Sarcomas, Jean Claude Reubi and his colleagues state that, “Although it was shown previously to express the cholecystokinin (CCK) gene, it is unknown whether CCK gene expression is detectable at protein level in Ewing sarcoma tumor cell lines, in tumor tissue, and in plasma from Ewing sarcoma patients, and, if so, whether CCK peptides might play a role as tumor markers.” The authors conclude that “This is the first study that consistently documents an altered CCK metabolism in human cancer; Ewing sarcomas synthesize and secrete proCCK that can be identified in plasma as circulating tumor marker.” Their article appeared in Clinical Cancer Research Vol. 10, pp 5523-5530, August 15, 2004.

New Anti-inflammatory Strategy For Cancer Therapy Identified By UCSD Researchers

A new strategy for cancer therapy, which converts the tumor-promoting effect of the immune system's inflammatory response into a cancer-killing outcome, is suggested in research findings by investigators at the University of California, San Diego (UCSD) School of Medicine. The findings provide new insight into the immune system's response to inflammation, the connection between inflammation and malignancy, and how the delicate balance between cancer promotion and inhibition can be manipulated in the patient's favor, according to the study's senior author, Michael Karin, Ph.D., UCSD professor of pharmacology, American Cancer Society Research Professor, and a member of the Rebecca and John Moores UCSD Cancer Center.

Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas,

Pilot study for the upcoming European Rhabdomyosarcoma Protocol, Michela Casanova, et al BACKGROUND: Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low-dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low-dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high-risk patients with rhabdomyosarcoma. CONCLUSIONS: Combination therapy involving vinorelbine and low-dose cyclophosphamide was found to be feasible and to possess activity against recurrent sarcomas. The maintenance therapy doses recommended for use in the upcoming European trial are cyclophosphamide 25 mg/m2 per day for 28 days and vinorelbine 25 mg/m2 on Days 1, 8, and 15.

hTERT Is Highly Expressed in Ewing's Sarcoma and Activated by EWS-ETS Oncoproteins

Written by B. Fuchs, C. Inwards, S. Scully, and R. Janknecht appeared in Clinical Orthopaedics & Related Research, 1(426) pp 64-68, September 2004. Abstract: Although the fusion proteins EWS-ETS are uniquely associated with Ewing's sarcoma and have been shown to have transformational properties, they are not the only determinants of oncogenesis. Therefore, before molecular-based therapy can be initiated, a better understanding of the molecular network specific to Ewing's sarcoma is mandatory. Specimens from 31 patients with Ewing's sarcoma were analyzed immunhistochemically. We found that human telomerase reverse transcriptase was expressed highly (78%) in Ewing's sarcoma. The mean followup was 7 years (range, 1-21 years), and human telomerase reverse transcriptase expression was correlated with outcome. Because we did not find an association between expression pattern and survival, human telomerase reverse transcriptase may not serve as a tumor marker in Ewing's sarcoma. However, the human telomerase reverse transcriptase promoter is shown to be activated by the fusion proteins. Therefore, transcriptional regulation via EWS-ETS may account for the high human telomerase reverse transcriptase expression in Ewing's sarcoma.

Long-Term Effects of Connective Tissue Cancer Treatment

Written by H. Mankin, J. Gunnoe, Y. Farid, F. Hornicek, M. Gebhardt, this article appeared in Clinical Orthopaedics & Related Research. 1(426) pp 74-86, September 2004. Abstract: In 1999, we began a study to assess the long-term effect of connective tissue cancer treatment on clinical, social, and psychologic aspects of the lives of surviving patients. A specially designed computer program generated an 85-item questionnaire, which was sent to more than 2000 patients with malignant bone and soft tissue neoplasms. Twelve hundred forty-four patients responded. The data were entered into a computer system and were correlated with the clinical information already contained in the system for the individual patients. Although there are many possible uses for these data, we chose to do a study comparing the lifestyle and physical and sociologic problems for 144 patients treated with chemotherapy and surgery for high-grade osteosarcoma against a control population consisting of 61 patients treated surgically for benign giant cell tumors of bone. The data show a remarkable degree of compensation on the part of the patients with the malignant tumors in terms of some problems but some significant differences particularly in physical status and functional limitations.

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