Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG).

BACKGROUND: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. PATIENTS AND METHODS: In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. RESULTS: Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. CONCLUSION: Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

Radiotherapy for rhabdomyosarcoma: indications and outcome.

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Improvements in the clinical outcomes of rhabdomyosarcoma have been secondary to the intensification and refinement of treatment investigated by the Intergroup Rhabdomyosarcoma Study Group. Advances in diagnostic imaging techniques have led to improvements in staging and contribute to precision in radiation field design. Radiation treatment has been integrated into the primary treatment of most patients with rhabdomyosarcoma. Each treatment site has special considerations with regards to prognosis, outcomes and potential morbidities that affect the choice of local therapy. Advanced radiotherapy techniques using conformal treatment with intensity-modulated radiotherapy and proton therapy are particularly advantageous for the treatment of sites close to critical structures, such as the head and neck and genitourinary system. Active investigation is underway to develop strategies to reduce the radiation dose and volume in an effort to minimise late toxicity and improve the therapeutic ratio.

Intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) has found widespread use in the treatment of head and neck cancers. This technology allows for conformal dose distributions around a tumor target while a rapid dose fall-off spares surrounding critical structures. The properties of IMRT are particularly suited for treating head and neck cancers due to the close proximity of dose-limiting normal tissues allowing for potential dose escalation. Further studies are ongoing to investigate long-term clinical outcomes and toxicity.

Mechanism of inhibition of the human immunodeficiency virus type 1 reverse transcriptase by d4TTP: an equivalent incorporation efficiency relative to the natural substrate dTTP.

Among the clinically used nucleoside analogue inhibitors that target human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), there is little detailed mechanistic information on the interactions of 2',3'-didehydro-2', 3'-dideoxythymidine-5'-triphosphate (d4TTP) with the enzyme. primer-template complex and how these interactions compare with those of the natural substrate, dTTP. Using a pre-steady-state kinetic analysis, we found that d4TTP was incorporated by HIV-1 RT just as efficiently as dTTP during both DNA- and RNA-dependent DNA synthesis. To our knowledge, these results represent the first observation of a 3'-modified nucleoside triphosphate analogue that has an incorporation efficiency comparable to that observed for the natural substrate during DNA synthesis by HIV-1 RT. This information provides a mechanistic basis for understanding the inhibition of HIV-1 RT by d4TTP as well as insight into the clinically observed lack of d4T resistance mutations in HIV-1 RT isolated from AIDS patients.