Radiation oncology investigations最新文献

Paraaortic nodal irradiation (PAI) was thought to be useful in the treatment of cervical cancer, but its clinical application has been limited by a relatively high morbidity. To reduce this morbidity, we routinely applied the four-field technique in PAI. To clarify its efficacy, clinical data were retrospectively analyzed. Ninety-seven patients with cervical cancer, who received a minimum 40 Gy of paraaortic irradiation between 1976 and 1994, were enrolled in the analysis. The patients were prescribed PAI using four-field portals with 10 MV photons (mean 50.4 Gy, range 40-70 Gy). The 5-year cause-specific survival rate was 32.2%. As for sequelae determined using the French-Italian glossary, G1a/G2a of stomach and duodenum developed in 26.8/1.0%, G2b of small bowel in 3.1%, G1b of nonspecific abdominal symptoms and/or signs in 12.4%, and G2 of bone in 3.1%. The operative history group had a slightly larger incidence of gastrointestinal complications than those without operative history, but the difference was not statistically significant. Application of four-field portals in PAI was useful, with acceptably low toxicity and successful compliance for moderate-to-high dose irradiation. This suggests that PAI may greatly contribute to the improvement of the therapeutic outcome of cervical carcinoma.

The purpose of this study was to evaluate the outcome of treatment for patients with newly diagnosed nonsmall-cell lung cancer (NSCLC) with an isolated, single, synchronous brain metastasis. A retrospective review was performed evaluating any patient diagnosed between 1982 and 1996 at the Cleveland Clinic Foundation with NSCLC metastatic only to the brain. Patients with multiple brain metastases or with systemic metastases to any other organ were excluded. Survival was measured from the date of the first treatment for malignancy. All hospital records were thoroughly reviewed in a retrospective manner. Thirty-three patients were identified who met the study criteria. Twelve patients had primary disease limited to the lung and hilar nodes, and 21 had more advanced primary disease with involvement of the mediastinum. Treatment of the chest was considered aggressive in 13 patients and palliative in 15. The primary tumor was observed in 5 patients. The management of the brain metastasis was as follows: 21 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT), 5 underwent stereotactic radiosurgery (SRS) and WBRT, 3 had resection alone, 2 had SRS alone, and 2 underwent WBRT alone. The median overall and disease-free survival for all patients was 6.9 months and 3.3 months, respectively. Overall survival was markedly improved with the addition of WBRT (P = 0.002) and with the aggressive management of the primary tumor (P = 0.005). A total of 9 patients experienced CNS failure, including both patients receiving WBRT alone. CNS failures were divided as follows: 3 local, 5 distant, and 1 local and distant. Two of the 4 patients with a local failure were salvaged, and ultimate local control of the original brain metastasis was achieved in 93.6% of cases. Survival remains poor for patients with Stage IV NSCLC even when metastatic disease is limited to a single site within the brain; however, aggressive therapy of both the lung primary and the brain metastasis may provide a survival advantage. Excellent local control of single brain metastases was achieved with a combination of WBRT with either surgical resection or SRS.

Nitric oxide (NO) has been implicated both in regression and progression of tumors due to its production by both tumor cells and infiltrating leukocytes. Ionizing radiation causes the regression of tumors, and can augment the production of NO by macrophages in vitro. We examined the cellular and systemic production of NO in mice in which radiation-resistant RIF-1 fibrosarcoma cells were implanted subcutaneously and were then either irradiated or sham-treated at the tumor site. Ten days following implantation of the tumors, CD45- tumor cells and CD45+ leukocytes were derived from resected tumors immediately after irradiation with 60 Gy, a dose previously reported to reduce tumor growth. Leukocytes from tumors of irradiated hosts produced spontaneously up to four-fold more NO than did either leukocytes from unirradiated mice or CD45- tumor cells from either unirradiated or irradiated mice. Between days 10-14 following tumor implantation, serum NO2-/NO3- increased in both irradiated and unirradiated mice to an equal extent, culminating in levels higher than those of non-tumor-bearing mice. Though NO production is elevated in macrophages treated with 1-10 Gy of radiation in vitro, higher doses may be required by tumor-infiltrating macrophages in vivo and thus may indicate that tumor-infiltrating macrophages are deactivated.

Recent reports have suggested that pretreatment hemoglobin level (Hgb) is significantly associated with local control (LC) and overall survival (OS) in patients with T1 and T2 squamous cell carcinoma of the glottic larynx. To further evaluate the association of pretreatment Hgb level and other factors with outcome, we performed a retrospective review limited to patients with T1 squamous cell carcinoma of the glottic larynx treated with external beam radiation therapy. One-hundred thirty-nine patients with T1 squamous cell carcinoma of the glottic larynx were analyzed. Median follow-up was 5 years (range 2-22). Median pretreatment Hgb was 14.4 gm/dl (range 8.2-17.2). The following parameters were analyzed for their impact on LC, OS, and disease specific survival (DSS): age; gender; pretreatment Hgb; tumor grade; anterior commissure involvement; field size; total dose; dose per fraction; and overall treatment time. Five-year actuarial LC was 84%. Pretreatment Hgb was not a significant predictor for LC when assessed as a continuous variable (P = 0.38), nor as a dichotomous variable with a cutoff at 13 gm/dl. Local control was 82% for patients with Hgb >13 vs. 92% for Hgb < or = 13 (P= 0.13). No other factor was significant for LC. Five-year actuarial OS was 74%. Univariate analysis revealed that, pretreatment Hgb, total dose, and patient age were significant factors for OS. Overall survival was 78% for patients with pretreatment Hgb > 13 gm/dl vs. 68% for patients with Hgb < or = 13 gm/dl (P = 0.004). Overall survival was 77% for patients treated with > 66 Gy vs. 67% for those treated with < or =66 Gy (P = 0.0013), and 80% for patients < or =61 years as opposed to 69% for patients older than 61 years (P = 0.017). Multivariate analysis revealed that only age (P = 0.014) and Hgb concentration (P = 0.001) retained significance. Five-year actuarial DSS was 92%. Pretreatment Hgb was not a prognostic factor for DSS, nor were any other analyzed factors. Pretreatment Hgb is not a significant prognostic factor for LC in patients with T1 squamous cell carcinoma of the glottic larynx, but it does predict for a poorer OS without affecting DSS. This suggests that patients with lower pretreatment Hgb may have confounding medical problems that detract from their overall survival.

The extent of positivity of the final excision margin in relationship to other relevant factors was evaluated as a predictor for local recurrence after breast conservation therapy (BCT). As part of an institutional practice policy for BCT in 509 stage I/II breast carcinomas, 105 cases had a final excision margin, which was positive. The median age for this cohort was 58 years and the median follow-up was 86 months. All positive margin patients received whole breast irradiation to 50 Gy-50.4 Gy followed by a boost to the tumor bed for an additional 20 Gy. The extent of positivity (EOP) of the excision margin was graded according to a four-point scale: focal, minimal, moderate, extensive. Cases were then analyzed for local failure according to EOP grade, histology, age, tumor size, total excision volume, re-excision, tamoxifen therapy, and chemotherapy. A focal or minimal EOP grade was found in 70% of specimens while an additional 26% were moderate or extensive. The incidence of invasive carcinoma with prominently associated DCIS was significantly greater in cases with an EOP grade of moderate/extensive. There were nine ipsilateral breast recurrences, eight of which could be evaluated for EOP grade. All recurrences were in or near the previous biopsy cavity. A Kaplan-Meier plot of freedom from local failure showed a significant (P = 0.008) difference between cases grouped by EOP grade of focal/minimal as compared to moderate/extensive. A Cox proportional hazards regression model found that the only variable significantly related at the P < or = 0.05 level to local failure was an EOP grade of moderate/extensive. For breast excision specimens with a positive final margin, an EOP grade of moderate/extensive is a predictor for local recurrence after BCT, which may be independent of other variables such as age or histology.

Using a series of human bladder cancer cell lines and an immortalised normal ureteral cell line, radiosensitivities measured by three different methods after a single dose of X-radiation are compared. Clear differences between cell survival curves obtained using the clonogenic, microtetrazoline (MTT) and sulforhodamine B (SRB) assays are shown. The most sensitive of the assays investigated was the clonogenic assay. The MTT and SRB assays were found to be relatively insensitive especially at lower radiation levels, suggesting that these assays may not be suitable for predicting therapeutic dose schedules in vivo, but will be important for investigating radio-sensitivity in cell lines with very low plating efficiencies. Each assay discriminated between a range of sensitivities in the cell lines examined, and with some minor differences, the ordering of sensitivities using the three assays was similar. Possible explanations for the differences between results obtained with the three assays are discussed.

Intermediate grade non-Hodgkin's lymphoma (IGNHL) is generally considered a radiosensitive tumor that can be controlled with moderate radiation doses. Cell-survival curves of cell lines derived from IGNHL have been typically described to exhibit small or no shoulder, implying inability to accumulate or repair sublethal radiation damage. We characterize in this report the clonogenic radiation survival curves of two human IGNHL cell lines, WSU-DLCL2 and SK-DHL2B, established from patients who expired after having exhibited chemotherapy resistance of their tumors. The cells were irradiated with 60Co radiation at a dose rate of 85-100 cGy/min and cell survival data were analyzed according to the linear quadratic model. The alpha/beta values for WSU-DLCL2 and SK-DHL2B cells are 2 and 8.6, respectively. The corresponding SF2 are 0.42 and 0.35, respectively. Both cell lines are able to repair radiation-induced sublethal damage. These data indicate that these cells are only moderately radiosensitive.

The central nervous system injury that can result after radiotherapy has been suggested to involve induced gene expression and cytokine production. We have previously shown that irradiation of primary cultures of rat astrocytes results in the activation of NF kappa B. To determine whether such an effect also occurs in vivo, NF kappa B activity was analyzed in the cerebral cortex of the rat brain after whole body irradiation. After a single dose of 15 Gy, NF kappa B activity was increased by 2 h postirradiation, returning to unirradiated levels by 8 hours. The increase was dose-dependent beginning at 2 Gy and continuing to at least 22.5 Gy. NF kappa B activity in the irradiated cortex was not accompanied by I kappa B alpha degradation. When 7.5 Gy was delivered 24 h before the 15 Gy, the increase in NF kappa B activity after 15 Gy was significantly reduced. These results suggest that an initial exposure to radiation induced a refractory period in the brain during which the susceptibility of NF kappa B to activation by subsequent irradiation was significantly reduced. This period of reduced sensitivity to radiation was also apparent for the induction of the NF kappa B-regulated cytokines IL-1 beta, IL-6, and TNF alpha.

Malignant gliomas remain refractory to intensive radiotherapy and cellular hypoxia enhances clinical radioresistance. Under hypoxic conditions, the benzotriazine di-N-oxide (3-amino-1,2,4-benzotriazine 1,4-dioxide) (tirapazamine) is reduced to yield a free-radical intermediate that results in DNA damage and cellular death. For extracranial xenografts, tirapazamine treatments have shown promise. We therefore incorporated tirapazamine into the synthetic, biodegradable polymer, measured the release, and tested the efficacy both alone and in combination with external beam radiotherapy in the treatment of experimental intracranial human malignant glioma xenografts. The [(poly(bis(p-carboxyphenoxy)-propane) (PCPP):sebacic acid (SA) (PCPP:SA ratio 20:80)] polymer was synthesized. The PCPP:SA polymer and solid tirapazamine were combined to yield proportions of 20% or 30% (wt/wt). Polymer discs (3 x 2 mm) (10 mg) were incubated (PBS, 37 degrees C), and the proportion of the drug released vs. time was recorded. Male nu/nu nude mice were anesthetized and received intracranial injections of 2 x 10(5) U251 human malignant glioma cells. For single intraperitoneal (i.p.) drug and/or external radiation treatments, groups of mice had i.p. 0.3 mmol/kg tirapazamine, 5 Gy cranial irradiation, or combined treatments on day 8 after inoculation. For fractionated drug and radiation treatments, mice had i.p. 0.15 mmol/kg tirapazamine, 5 Gy radiation, or combined treatments on days 8 and 9 after inoculation. For intracranial (i.c.) polymer treatments, mice had craniectomies and intracranial placement of polymer discs at the site of cellular inoculation. The maximally tolerated percentage loading of tirapazamine in the polymer.disc was determined. On day 7 after inoculation, groups of mice had i.c. empty or 3% tirapazamine alone or combined with radiation (5 Gy x 2 doses) or combined with i.p. drug (0.15 mmol/kg x 2 doses on days 8 and 9). Survival was recorded. Polymers showed controlled, protracted in vitro release for over 100 days. The 5 Gy x 1 treatment resulted in improved survival; 28.5 +/- 3.7 days (P = 0.01 vs. controls), while the single i.p. 0.3 mmol/kg tirapazamine treatment, 17.5 +/- 1.9 days (P = NS) and combined treatments; 21.5 +/- 5.0 days (P = NS) were not different. The fractionated treatments: 5 Gy x 2, i.p. 0.15 mmol/kg tirapazamine x 2 and the combined treatments resulted in improved survival: 44.5 +/- 3.9 (P < 0.001), 24.5 +/- 2.3 (P = 0.05) and 50.0 +/- 6.0 (P < 0.001), respectively. Survival after intracranial empty polymer was 16.5 +/- 3.0 days and increased to 31.0 +/- 3.0 (P = 0.003) days when combined with the 5 Gy x 2 treatment. The survival after the polymer bearing 3% tirapazamine alone vs. combined with radiation was not different. The combined 3% tirapazamine polymer, i.p. tirapazamine, and radiation treatments resulted in both early deaths and the highest long-term survivorship. The basis for potential toxicity is discussed. We conc