摘要:

AbstractThe incidence of malignant melanoma (MM) has one of the fastest growth rates in the world and external beam radiation therapy (RT) is an important component in the total therapeutic management of MM. The radiobiology of MM provides a fascinating example of the complexities of radiation tumor biology. Both the multitarget model and the linear quadratic model predict that high dose per fraction (HDPF: 400 cGy or more) RT may be more efficacious than low dose per fraction (LDPF: 180–300 cGy) RT for some MM. However, other radiobiological factors such as repair of potentially lethal damage, reoxygenation, and repopulation appear to support the use of LDPF RT. Therefore, the MM radiobiological data predict a diverse response to a wide spectrum of HDPF and LDPF time‐dose prescriptions. The clinical data for MM are consistent with these radiobiological predictions. MM exhibits a high response rate to both HDPF and LDPF time‐dose prescriptions. RT is an effective therapy for MM in many clinical settings: 1) RT is the single most effective local therapy for metastatic disease with complete response rates of 23–72% and long‐term local tumor control rates of 48–82%; 2) heavy ion RT is the primary treatment for many ocular MM with 5‐year eye retention rates of 89% and 5‐year local tumor control rates of 96%; 3) RT is the treatment of choice for mucosal non‐cutaneous, non‐ocular MM with results that are equal or superior to radical surgery; and 4) recent reports suggest an important role for adjuvant RT in postoperative patients who are at high risk for local‐regional recurrence. The current roles for RT in MM should be reevaluated since it is likely that RT is being underutilized in the overall clinical management of MM.

ISSN:1065-7541    

DOI:10.1002/roi.2970010502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have compared the effectiveness of three short‐term proliferative assays [3(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction, methylene blue staining, and [3H]‐thymidine incorporation]in predicting the results of clonogenic assay of radiosensitivity in five mammalian cell lines (SCCVII, AA8, V3, FME, and MM‐96). Cells were cultured in 96‐well microculture plates and a lead wedge was employed to provide a range of radiation doses (60Co source) up to 10 Gy. Radiation dosimetry was determined by a novel modification of the Fricke/thiocyanate dosimetry technique to allow direct determination in 96‐well plates. Cells were cultured following irradiation to determine clonogenic survival curves and to calculate the survival at 2 Gy (SF2), the initial slope of the fitted linear quadratic function (α), and the mean inactivation dose (D). A broad range of radiosensitivity was obtained (SF2= 0.14–0.92) with the clonogenic assay. All three proliferation assays provided measures of radiosensitivity which correlated with clonogenicity at low radiation dose. The thymidine incorporation assay, which provided excellent linear correlation (r = 0.98) with clonogenicity for SF2and D, used semiautomated methods for harvesting and scintillation counting to give sample processing times comparable to the colorimetric methods. It offered the advantages of superior assay linearity and dynamic range, and reduced interference by non‐proliferating cells at high radiation dose

ISSN:1065-7541    

DOI:10.1002/roi.2970010503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to evaluate whether a “vascular steal” mechanism (preferential arteriolar vasodilation in normal vs. tumor tissue concomitant with a reduction in blood pressure) is responsible for tumor blood flow reduction after hydralazine administration. Fischer‐344 rats, fitted with dorsal flap window chambers that allowed visualization of tumor and normal healing subcutaneous tissue vasculature, were the experimental subjects. Intravital microscopy of tumor and normal microvasculature was used to measure microvessel diameters and red cell velocities before and after hydralazine (0.4 mg/kg, i.v.) administration. Hydralazine caused an average drop in mean arterial pressure of 32 mmHg and a concomitant 70% drop in capillary and venous blood flow in central tumor regions in both 9‐ and 14‐day‐old tumors. Intermittent blood flow frequency increased in capillaries and veins from 3% prior to drug to 46% after drug administration. In contrast, capillary and venous flow increased in adjacent normal tissues by 30%. Normal and tumor arterioles showed no significant change in diameter after hydralazine administration. Since the reductions in tumor blood flow were not accompanied by preferential arteriolar dilation in normal arterioles, the hypothesis that a vascular steal phenomenon was responsible for the observed reduction in tumor blood flow in this model system was disproved. A more likely explanation is that the reduction in tumor vessel diameter and concomitant flow reduction are a passive effect related to the relative difference between intravascular pressure and interstitial fluid pressure and/or tissue pressures, the latter of which are known to be increased in tumors. The results suggest that reduction in tumor blood flow might be expected following blood pressure reduction, even when the tumor resides in normal tissue beds that are not actively vasodilated by an antihypertensive agent. © 1994 Wil

ISSN:1065-7541    

DOI:10.1002/roi.2970010504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThis study was undertaken to determine if nonhuman primates are suitable models for the veno‐occlusive disease (VOD) that characterizes radiation hepatopathy in man. Adult rhesus monkeys had near total liver irradiation to 36 Gy in 8 fractions (Group 1, n = 5) or to 50 Gy in 20 fractions (Group II, n = 5). All had normal liver function and no lesions in liver biopsies 9 months after irradiation. A monkey from each group was given either doxorubicin, cyclophosphamide, cisplatin, or methotrexate over a 15‐week period. The one given 36 Gy in 8 fractions and doxorubicin died of congestive heart failure 1 month after the last course. The remainder of Group 1 animals had normal liver function and morphology 2 to 3 years after therapy. Group II animals given methotrexate or cisplatin had the liver retreated with 30 Gy in 30 fractions at 2 years after receiving 50 Gy in 20 fractions. Within 1 month, the animal given methotrexate developed massive hepatic necrosis. The other given a cumulative liver dose of 80 Gy remained clinically normal. This animal and the others in Group II underwent left hepatic lobectomy 2 years after the first radiation course. All had normal liver function and no VOD when they were sacrificed 1 year later. A monkey given methotrexate followed by liver irradiation (50 Gy in 20 fractions) developed hepatic necrosis 10 months later. Another given cyclophosphamide and 50 Gy in 20 fractions was normal for 2 years after treatment.In summary, none of the monkeys developed classical VOD, and they apparently were resistant to induction of significant hepatic injury by radiation alone. Occult radiation injury was not exacerbated by either chemotherapy or partial hepatectomy.Hepatic necrosis in this model was induced by methotrexate administration followed by liver irradiation. The reason for the difference in radiosensitivity of the monkey liver and human liver is unknown. © 1994 Wiley‐Lis

ISSN:1065-7541    

DOI:10.1002/roi.2970010505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTumor hypoxia contributes to the response to radiotherapy and to chemotherapy. The oxygenation status of normal tissues and tumors was evaluated using the KIMOC‐6650 histograph in 35 patients with head and neck tumors, 13 patients with metastatic malignant melanoma (MMM), and 6 patients with uterine cervical carcinoma. Patient compliance was good. The pO2values measured in tumors were in general lower than those measured in normal tissues of the same patient. The pO2in the tumors varied along the track and from one track to another. Important pO2variability was also detected from one tumor to another. Patients with head and neck tumors had a median pO2of 6.76 kPa (52 mmHg) in normal tissues (subcutaneous) and 1.33 kPa (10 mmHg) in tumors with 25% of the values below 0.26 kPa (2 mmHg). Patients with MMM had a median pO2of 3.64 kPa (28 mmHg) in normal tissues (subcutaneous tissues and muscles) and pO2was 0.91 kPa (7 mmHg) in tumors with 18% of the values below 0.26 kPa. Patients with uterine cervical carcinoma had a median pO2of 6.37 kPa (49 mmHg) in normal tissues (vagina) and 2.73 kPa (21 mmHg) in tumors with 16% of the values below 0.26 kPa. The data for N2 and N3 head and neck nodes showed significantly more values below 0.26 kPa (2 mmHg) as nodal size increased (P<0.001 by chi‐square test). The best parameters to describe tissue oxygenation are discussed. © 1994 Wiley‐Lis

ISSN:1065-7541    

DOI:10.1002/roi.2970010506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractNicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to date no clinical studies have substantiated this effect. Twenty‐nine patients with brain metastases were randomized to receive NAM and external radiation therapy (RT) (n = 14) or irradiation alone (n = 15). NAM was started on day 1 at 3 g/day and continued until radiation was completed. The RT dose to the whole brain was 30 Gy in 10 fractions in 12–14 days. To evaluate response, a computed tomographic (CT) scan of the head was repeated 1 month post‐treatment. Toxicity was graded from the skin, liver, and gastrointestinal tract. There were no toxicities observed at 39.0 g total dose of NAM. Median survival for the 29 patients, calculated by the Kaplan‐Meier method, was 3.5 months for the NAM + RT group (14 patients) and 3.9 months for the RT alone group (15 patients). Eighteen patients were evaluable for 1 month tumor response by CT scan. Response rates were compared with Fisher's exact two‐tailed test. There was no difference in complete response (CR) (P= 0.62) or CR + partial response (PR) (P= 1.000) between the two groups. Adjuvant NAM, given in doses of 3.0 g/day (39.0 g total dose) in the treatment of brain metastases, has shown no benefit in survival or response in this preliminary Study. © 1994 Wiley

ISSN:1065-7541    

DOI:10.1002/roi.2970010507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractPurpose: A phase I toxicity trial aimed at defining an appropriate dose of the bioreductive alkylating agent porfiromycin to be used in conjunction with radiation therapy in patients with squamous cell carcinoma of the head and neck.Methods and Materials: A total of 21 patients were entered into this phase I clinical trial. All patients had locally advanced squamous cell carcinoma of the head and neck and were treated with radiation therapy with or without surgical intervention. Porfiromycin was administered on days 5 and 47 of the course of radiation therapy. The initial dose of the drug was 50 mg/M2, but due to hematological toxicity the dose was lowered to 40 mg/M2. The final 12 of the 21 patients in this phase I clinical trial was treated at the dose of 40 mg/M2. Radiation therapy was directed at the primary site and regional lymph nodes as clinically indicated with conventional fractionations of 200 cGy/day to total doses in excess of 6,000 cGy.Results: Five patients were treated at the initial dose of 50 mg/M2, but due to excessive hematologic toxicity the dose was reduced to 45 mg/M2for 4 patients and lowered again to 40 mg/M2for the final 12 patients of the study. As expected, the major toxicity was hematological with thrombocytopenias and neutropenias. There were no clinically evident bleeding episodes secondary to thrombocytopenia and no neutropenic deaths during the course of the study. Of the 21 patients treated in the series, 10 remain alive no evidence of disease (NED) with a median follow‐up of 18.5 months. Four of the alive NED patients have been followed for over 2 years.Conclusions: The bioreductive alkylating agent porfiromycin may be safely administered at a dose of 40 mg/M2to patients undergoing radiation therapy for squamous cell carcinoma of the head and neck. Based on the results of this phase I trial, we have now mounted a phase III clinical trial in patients with all stages of squamous cell carcinoma of the head and neck, comparing radiation therapy with porfiromycin to radiation therapy with mitomycin C. There is no radiation therapy without drug in this phase III clinical report. © 1994 Wiley‐Liss,

ISSN:1065-7541    

DOI:10.1002/roi.2970010508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:1065-7541    

DOI:10.1002/roi.2970010501

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY