The effect of recovery from potentially lethal damage on the determination of reoxygenation in a murine tumour.

The pattern of reoxygenation in the murine anaplastic MT tumour was investigated using the established method of determining the hypoxic fraction, at intervals after a priming X-ray dose, from test doses given either to unclamped or clamped-off tumours. Little reoxygenation was apparent whilst the tumour was increasing in size for 12--72 hours after a single dose of 20.3 Gy, but extensive reoxygenation was evident whilst the tumour was shrinking at nine days after a dose of 50 Gy. However, the degree of reoxygenation may have been underestimated, especially after the smaller priming dose. This is because only the chronically hypoxic cells in this tumour have the ability to recover from potentially lethal damage (PLD) and so are more radioresistant than cells rendered acutely hypoxic by clamping. Because of this, even when tumours are clamped off during irradiation, the resulting survival curve is biphasic and the apparent effect of the clamp becomes a function of the X-ray dose used. The larger the dose, the smaller the observed effect of the clamp, so the greater the apparent hypoxic fraction and hence the smaller the apparent degree of reoxygenation.     

碳离子调强放射治疗复发性局部晚期鼻咽癌的近期疗效及不良反应

目的 分析局部复发性鼻咽癌患者再程调强碳离子放射治疗（IMCT）和调强X射线放射治疗（IMXT）后的近期疗效及不良反应。方法 收集本院2015年5月至9月收治的14例确诊为局部复发性鼻咽癌的患者,经再程IMCT治疗后,观察其治疗相关不良反应及近期疗效,并与2012年5月至2014年5月接受再程IMXT挽救性治疗的47例患者进行比较分析。复发肿瘤体积的IMCT和IMXT的处方剂量分别为50～60 GyE（2.0～2.5 GyE/次）和54～66 Gy/27～33次（2.0～2.1 Gy/次）。结果 两组患者在性别、年龄、初诊分期、初诊治疗策略、复发距首次IMXT时间间隔、复发T、N分期差异均无统计学意义（P>0.05）。两组患者放疗后3个月的完全缓解率（64.3%和78.7%）差异无统计学意义（P>0.05）,且在6个月内均无局部肿瘤进展,但IMXT组有2例死亡,其中1例死于鼻咽坏死大出血。IMCT组治疗中的急性中重度黏膜炎的发生率为0,明显低于IMXT组的31.9%（P<0.05）。IMXT治疗后6个月内黏膜坏死的发生率为29.8%,明显高于IMCT组的0（P<0.05）;IMXT组有2例（4.3%）伴症状的颞叶坏死,IMCT组无颞叶坏死;两组均无颅神经损伤发生。结论 同再程IMXT挽救治疗相比,复发性局部晚期鼻咽癌再程IMCT后近期疗效类似,且未出现2级或以上的近期不良反应,但IMCT的远期疗效尚需更长时间的观察。     

Accelerated hematopoietic recovery with angiotensin-(1–7) after total body radiation

Purpose: Angiotensin (1–7) [A(1–7)] is a component of the renin angiotensin system (RAS) that stimulates hematopoietic recovery after myelosuppression. In a Phase I/IIa clinical trial, thrombocytopenia after chemotherapy was reduced by A(1–7). In this study, the ability of A(1–7) to improve recovery after total body irradiation (TBI) is shown with specific attention to radiation-induced hematopoietic injury.

Materials and methods: Mice were exposed to TBI (doses of 2–7 Gray [Gy]) of cesium 137 gamma rays, followed by treatment with A(1–7), typical doses were 100–1000 μg/kg given once or once daily for a specified number of days depending on the study. Animals are injected subcutaneously via the nape of the neck with 0.1 ml drug in saline. The recovery of blood and bone marrow cells was determined. Effects of TBI and A(1–7) on survival and bleeding time was also evaluated.

Results: Daily administration of A(1–7) after radiation exposure improved survival (from 60% to 92–97%) and reduced bleeding time at day 30 after TBI. Further, A(1–7) increased early mixed progenitors (3- to 5-fold), megakaryocyte (2- to 3-fold), myeloid (3- to 6-fold) and erythroid (2- to 5-fold) progenitors in the bone marrow and reduced radiation-induced thrombocytopenia (RIT) (up to 2-fold). Reduction in the number of treatments to 3 per week also improved bone marrow recovery and reduced RIT. As emergency responder and healthcare systems in case of nuclear accident or/and terrorist attack may be overwhelmed, the consequence of delayed initiation of treatment was ascertained. Treatment with A(1–7) can be delayed up to 5 days and still be effective in the reduction of RIT or acceleration of bone marrow recovery.

Conclusions: The data presented in this paper indicate that A(1–7) reduces the consequences of critical radiation exposure and can be initiated well after initial exposure with maximal effects on early responding hematopoietic progenitors when treatment is initiated 2 days after exposure and 5 days after exposure for the later responding progenitors and reduced thrombocytopenia. There was some effect of A(1–7) even when given days after radiation exposure.     

急性放射性脑损伤鼠模型的建立

目的 建立急性放射性脑损伤动物模型。方法 SD大鼠头部接受^60Coγ射线照射后。每日观察大鼠摄食、饮水量，自主活动情况及神经系统症状与体征；每周检查照射区皮肤情况及体重变化，末次照射结束后第3，7，14，30天断头取脑行病理组织学检查。结果 放射疗程中及结束后均未出现异常神经系统体征；两组的自主活动、每日摄食、饮水量及体重均无统计学差异；末次照射后约2周时出现照射野轻度脱毛；照射后出现脑组织神经元变性坏死。结论 该模型制作方法能较好地模拟放射性脑损伤的过程，可用于放射性脑损伤的实验研究。     

Lymphangiographic changes after radiation therapy.

Lymphangiographic appearance following radiotherapy is described in 21 patients with pre- and posttherapy lymphangiograms. Following radiotherapy to normal lymphatics, decrease in nodal size and lymph vessel caliber is noted uniformly after 12 months. Before 12 months the development of these changes is variable and may not be seen, especially during the first several months. Following irradiation of abnormal lymph nodes, dilatation of the lymph vessels distal to the abnormal nodes may occur. These lymphangiographic findings can be related to histologic changes seen in lymph nodes after radiation therapy.     

Enhancement of biological effectiveness of carbon-ion beams by applying a longitudinal magnetic field

Abstract

Purpose: A magnetic field longitudinal to an ion beam will potentially affect the biological effectiveness of the radiation. The purpose of this study is to experimentally verify the significance of such effects.

Methods and materials: Human cancer and normal cell lines were exposed to low (12?keV/μm) and high (50?keV/μm) linear energy transfer (LET) carbon-ion beams under the longitudinal magnetic fields of B_// = 0, 0.1, 0.2, 0.3, or 0.6 T generated by a solenoid magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in a survival fraction of 10% (D₁₀s) were determined for each cell line and magnetic field.

Results: For cancer cells exposed to the low (high)-LET beams, D₁₀ decreased from 5.2 (3.1) Gy at 0 T to 4.3 (2.4) Gy at 0.1 T, while no further decrease in D₁₀ was observed for higher magnetic fields. For normal cells, decreases in D₁₀ of comparable magnitudes were observed by applying the magnetic fields.

Conclusions: Significant decreases in D₁₀, i.e. significant enhancements of the biological effectiveness, were observed in both cancer and normal cells by applying longitudinal magnetic fields of B_// ≥?0.1 T. These effects were enhanced with LET. Further studies are required to figure out the mechanism underlying the observed results.     

Accelerated fast neutron therapy: a pilot study.

The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.     

Tumor induction in mice after local irradiation with single doses of either carbon-ion beams or gamma rays

Abstract

Purpose: To determine the dose-dependent relative biological effectiveness (RBE) for tumor prevalence in mice receiving single localized doses to their right leg of either carbon ions (15, 45 or 75 keV/μm) or 137Cs gamma rays.

Methods and materials: A total of 1647 female C3H mice were irradiated to their hind legs with a localized dose of either reference gamma rays or 15, 45 or 75 keV/μm carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during their three-year life span, and the dimensions of any tumors found were measured with a caliper. The tumor induction frequency was calculated by Kaplan-Meier analysis.

Results: The incidence of tumors from 50 Gy of 45 keV/μm carbon ions was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15 keV/μm carbon ions induced significantly fewer tumors than did gamma rays. RBE values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were calculated for 15, 45 or 75 keV/μm carbon-ion beams, respectively. Fibrosarcoma predominated, with no Linear Energy Transfer (LET)-dependent differences in the tumor histology. Experiments measuring the late effect of leg skin shrinkage suggested that the carcinogenic damage of 15 keV/μm carbon ions would be less than that of gamma rays.

Conclusions: We conclude that patients receiving radiation doses to their normal tissues would face less risk of secondary tumor induction by carbon ions of intermediate LET values compared to equivalent doses of photons.     

Haematologic evaluation after radiation therapy in Hodgkin's disease.

Haematologic evaluation of 30 patients 2 to 7 years after radiation therapy for Hodgkin's disease was made. A complete general recovery of haematopoiesis occurred as concluded from the normal or even supranormal blood cell values. However, in only 5 of 28 patients was a complete local regeneration of haematopoiesis observed in the sternal marrow biopsies after 38 to 48 Gy. In the other cases, haematopoiesis was numerically or morphologically abnormal or totally absent.