The sequence of histological changes in mouse lungs after single doses of X-rays

Histological changes in mouse lungs have been quantified up to one year after irradiation of both lungs with a range of single X-ray doses. Three lesions characteristic of the acute, intermediate, or late phase of lung response were scored separately according to the area of the miscroscopic section involved. An “average score” was obtained for each lesion and plotted against time. Clearly separated peak response times were found for the acute phase (18 weeks) and intermediate phase (36 weeks). The peak response times of these 2 phases were independent of dose. Fibrosis was just detectable histologically at 36 weeks after 14 Gy and 13 Gy. The severity of each phase was dose related. The mice that died did so mostly between 14 and 24 weeks (98 and 168 days), the normal time over which death occurs in lung LD₅₀ studies. The histological data indicated that the lung LD₅₀ assay is related to acute radiation pneumonitis rather than to late fibrosis.     

Cobalt-60 therapy unit for large field irradiation

A cobalt-60 therapy unit designed and constructed by The Ontario Cancer Institute is described. This unit is capable of treating large fields up to 50 × 160 cm² at a conventional source to surface distance of 90 cm by using large collimator openings. Three selectable filters were incorporated. They all act as electron filters to improve the build-up characteristics of these beams. Two of the three filters also act as beam flatteners. The longitudinal collimators are individually driven so that it is possible to produce a vertical beam edge by closing one of the collimators completely. This condition is very useful for matching adjacent fields. The output of this unit, at its operating distance, ranges from 100–200 rad/min depending on which of the filters is chosen, which makes the treatment time shorter than most known facilities for very large field irradiation. This unit has been in routine use since 1977.     

Dosimetry of single fraction high dose total body irradiation as measured by thermoluminescent dosimeters

Eighty-five patients with acute myelogenous or acute lymphoblastic leukemia were treated at the City of Hope National Medicine Center with chemotherapy, total body irradiation, and bone marrow transplant. The average mid-line dose to these patients was 1002 rad with a uniformity of 8%.     

Radiation induced sarcomas of bone following therapeutic radiation

Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed.     

Malignant transformation of mouse bone marrow cells induced in vitro by 60Co gamma-ray irradiation

Mouse bone marrow cells were irradiated in vitro with 300, 200 and 100 rad of 60Co gamma-ray. Morphological transformation ensued from day 42 after exposure, but only in cells receiving 300 rad. Malignant transformation appeared in the 2nd generation in the subcultures. Some biological characteristics of malignant transformation were observed as follows: The attaching rate was 40.0%. Malignant transformation rate was 0.10-0.45%; Some colonies and clusters were formed in the semi-solid agar medium; There was no cell proliferation or colony formation in anti-ouabain inhibition test which implies that no mutation took place in the malignant transformation cells; Cytochalasin B rendered the cells to form a large number of multinuclear cells; Obvious chromosome aberration in number and structure was observed; Subsequent induction of fibrosarcomas in sites of subcutaneous inoculation of the malignant transformed cells in immunosuppressed mice. The results show that mouse bone marrow mesenchymal cells can undergo malignant transformation by large dose of gamma-ray irradiation in vitro. Criteria of malignant transformation: some clusters of cells formed in the semi-solid agar medium, multinuclear cell formation by action of cytochalasin B, and tumor mass induced in the location of inoculation.     

Comparative 60Co total body irradiation (220 cm SAD) and 25 MV total body irradiation (370 cm SAD) dosimetry

Adults with acute leukemia and malignant lymphoma in relapse after conventional therapy are treated with cyclophosphamide and total body irradiation (TBI) followed by autologous bone marrow transplants. For cobalt TBI, patients seated in a stand angled 45° above the floor are treated in a single fraction with sequential right and left lateral 87 cm ×87 cm fields at 220 cm source-axis distance (SAD) using a 5000 Ci cobalt unit. Typical lateral diameters, mid-plane dose rates, mid-plane doses, and maximum doses are: Hips, 34 cm, 8 rad/min, 900 rad, and 1050 rad; and shoulders, 38 cm, 7.7 rad/min, 800 rad, 1080 rad. The estimated lung dose is 1000 to 1100 rad. A compensator limits the dose to the head to 1000 rad. Estimated organ doses are: small intestine, liver and kidneys-1100 rad, and heart-1200 rad. Phantom dosimetry and dosimetry on patients treated reveals that these doses are delivered within 5 % accuracy. Patient tolerance of treatment, and some biological considerations of low dose rate therapy are reviewed. Certain dosimetry features of an alternate treatment at 370 cm SAD, using 25 MV photons are also presented.     

Tolerance of autologous and allogeneic bone grafts to therapeutic radiation in humans

Purpose: To examine the effect of perioperative irradiation on bone graft healing and functional integrity.

Methods and Materials: Fifty-five bone grafts (10 autologus and 45 allogeneic) performed between 1978 and 1995 were evaluated retrospectively. Sixteen received preoperative radiation, 11 received postoperative, and 13 were treated with a combination of pre- and postoperative radiation. Fifteen nonirradiated grafts were randomly selected to serve as controls. Twenty-three of the grafts were placed in patients who received chemotherapy in the perioperative period. Functional graft survival and radiographic healing quality were evaluated.

Results: Overall rates of graft survival at 1 year were 89% for autografts and 79% for allografts. Graft survival rates were 86% and 68% at 1 and 5 years for the irradiated group, and 67% and 58% for the control group. No significant difference was seen in the Kaplan-Meier graft survival curves of the two groups. There was a nonsignificant trend toward improved radiographic healing quality in the control group. No significant differences in outcome based on treatment chronology were found with survival rates of 88% for preoperative treatment and 100% for postoperative treatment. No relation between outcome and bone dose (preoperative + postoperative dose), graft dose (postoperative dose), or mean dose/day was found. There was a trend (p = 0.0525) toward worse outcome seen in the Kaplan-Meier curves of patients who received chemotherapy. This difference, however, was not seen in the 1-year survival rates or healing quality. Tobacco use tended toward predicting failure, with 63% graft survival compared to 85% in nonsmokers (p = 0.09). Healing quality was significantly lower in the smoking group.

Conclusion: The low failure rate of grafts in irradiated sites, overall and compared to controls from this study and relevant literature, as well as the lack of dose and time effects, does not support significant deviation from the indicated treatment regimen for patients who have received or are expected to receive a graft. The trend toward decreased quality of radiographic bone healing, and data published in relevant literature indicating improved healing when radiation is withheld until 3–4 weeks postoperatively suggest this delay should be attempted when not expected to otherwise compromise patient outcome. A nonsignificant trend only for the effect of chemotherapy on bone grafts was seen, thus we do not recommend changes in its use as appropriate for disease management other than a preference against use during the immediate perioperative period.     

Functional and morphological changes in pig skin after single or fractionated doses of X rays

The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days ($\text{6}\text{f}\text{18}$ days; 3780 cGy) or 30 fractions in 39 days ($\text{30}\text{f}\text{39}$ days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the $\text{30}\text{f}\text{39}$ days treatment group. The second wave (10–16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the $\text{30}\text{f}\text{39}$ days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after $\text{6}\text{f}\text{18}$ days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation ($\text{30}\text{f}\text{39}$ days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the $\text{30}\text{f}\text{39}$ days group than in the other treatment groups. Isotope clearance was similar to that in normal skin, as was the vascular density of the dermis. The return of these parameters to normal was correlated with the development of dermal atrophy.     

Continuing evidence for poorer treatment outcomes for single male patients: retreatment data from RTOG 97-14

PURPOSE: The specific aim of this study was to evaluate outcome differences by gender and partner status for patients treated on Radiation Therapy Oncology Group (RTOG) protocol 97-14. METHODS AND MATERIALS: RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Retreatment rates and overall survival were made based upon gender, marital status, and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate retreatment time at 36 months from enrollment, and Gray's test was used to test for treatment differences within the same groupings. Marital status, gender, KPS, and treatment were variables tested in a univariate Cox model evaluating the time to retreatment. RESULTS: Married men and women and single women receiving 30 Gy had significantly longer time to retreatment, p = 0.0067, p = 0.0052, and p = 0.0009 respectively. We failed to show a difference in retreatment rates over time in single men receiving either 30 Gy or 8 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive retreatment, p < 0.0001, with a trend toward single patients less likely to be re-treated, p = 0.07. CONCLUSION: Non-disease-related variables, such as social support, might influence the results of clinical trials with subjective endpoints such as retreatment rates. The statistically nonsignificant difference in the 36-month retreatment rates observed in single male patients receiving 8 Gy may be a result of inadequate social support systems in place to facilitate additional care. Patients receiving 8 Gy in a single fraction had significantly higher retreatment rates compared with patients receiving 30 Gy in 10 fractions.     

The dosimetry of 60Co total body irradiation.

The dosimetry characteristics of a single source ⁶⁰Co total body irradiation (TBI) facility have been studied. The dose distribution for AP-PA irradiation in an adult size and an infant size phantom was measured in detail using thermoluminescent dosimeters. A 10% homogeneity relative to the midline dose was found over most of the body. An increase of 10% relative to midline dose was noted in the thoracic region because of lower density lung tissue. A relative decrease of more than 10% was found in the head region because of the reduced beam intensity away from the central axis and reduced scatter volume. Dose in the abdomen was homogeneous to ± 5%.     

Dose-response relationship for radiation therapy of recurrent, residual, and primarily inoperable colorectal cancer

One hundred and thirteen patients with advanced locoregional recurrent (77), residual (18) or primarily inoperable (18) colorectal carcinoma were treated with radiotherapy. Eighty-five patients had locoregional disease only and 28 had both local disease and distant metastases. The treatment was given with varying dose levels (23-73 Gy) in daily fractions of approximately 2 Gy in 3-8 weeks. This dose variation allowed an evaluation of the dose-response relationship for radiation treatment of this tumour. A good subjective response was obtained in 63%. This effect showed no dose-response relationship except for doses greater than or equal to 56 Gy, where all patients received relief of symptoms. Eighty-two per cent of evaluable patients achieved an objective response (PR 53%, CR 29%). The frequency and duration of the complete responses showed a marked dose-response relationship. Thus, at doses greater than or equal to 56 Gy, a 2-year actuarial complete response rate of 40% was found compared with 7, 4 and 0% at doses of 46-55 Gy, 36-45 Gy and less than or equal to 35 Gy, respectively. The dose-response relationship for local control also influenced the survival rate, although a number of patients died from distant metastases even when local control was obtained. However, with regard to locoregional disease, the 2-year survival was 53% for patients with complete tumour regression but only 8% for patients without complete tumour regression.     

抑制ATM表达对60Co照射下宫颈癌细胞损伤修复机制的影响

目的：探讨抑制毛细血管扩张-共济失调突变基因（ataxia-telangiectasia mutated，ATM）表达对人宫颈癌细胞株HeLa在^60Co照射下细胞损伤修复机制的影响。方法：电穿孔法将人ATM基因siRNA的重组真核表达质粒pSup．ATM转染宫颈癌HeLa细胞；G418筛选建立稳定转染株；RT-PCR、Western-blot、免疫荧光法检测ATM基因表达的抑制情况；Western-blot法检测^60Co照射前后各组细胞ATM、p53Ser15磷酸化、CHK2Thr 68磷酸化、p53、CHK2蛋白的表达水平；流式细胞术检测^60Co照射后各组的细胞周期变化。结果：ATM基因在HeLa^ATM细胞中表达明显低于在HeLa、HeLa^ms细胞中的表达水平，成功地建立了ATM低表达的宫颈癌细胞模型。HeLa^ATM细胞在^60Co照射后p53^Ser15磷酸化、CHK2^Thr68磷酸化、p53蛋白表达均显著降低，细胞周期呈现为G2期延长，G1／G2倒置。结论：抑制ATM基因表达可显著抑制宫颈癌细胞对^60Co辐射损伤的修复。这一机制可能与HeLa^ATM细胞中ATM蛋白表达缺失，ATM依赖性的细胞损伤修复通路受阻有关。     

Overall response rates to radiation therapy for patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment

Introduction

Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment.

Objective

To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment.

Methods

Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment.

Results

In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment.

Conclusions

Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment.     

Single-dose half-body irradiation for the palliation of multiple bone metastases from solid tumors: a preliminary report

The on-going protocol of the Radiation Therapy Oncology group RTOG #78-10, which tests escalating single doses of half-body irradiation (HBI) for the palliation of multiple!,bone metastases, has accrued 108 patients as of August 1980. Of these, 91 patients are evaluable at this time. Low r half-body irradiation (LHBI) was given to 52 patients and another 12 patients received mid-body irradiation (MBI) both LHBI and MBI were targeted to receive escalating doses of 800 rod (27 patients), 900 rod (25 patients), and 1000 rod (12 patients). The latter test dose still required another 13 patients for completion. The remaining 27 patients received upper half-body irradiation (UHBI) with single doses of 600 rod (24 patients), 700 rod (3 patients) and 800 rod (no patients). The 700 rod test dose just opened for accrual and patients will not enter the 800 rodtegory until the lower dose closes with approximately 25 patients. Of the 91 evaluable patients, 36 96 bad breast,596 prostate, and 18% lung primary tumors. Seventy patients (77 96) bad pain relief after HBI, 21% actually had complete subjective responses. Of all relieved patients, 50% achieved pain relief within two days after HBI and aft r a week, almost 80% bad achieved relief. The duration of pain relief was substantial and persisted for 70% of the patient's remaining life. The technique has been well tolerated with mininal toxicity and no treatment-related fatalities were reported in the doses employed. Increasing the dose from 600 rod to 800 rod was beneficial, but 800 rad on (to 900 red or 1000 rod) has not produced better symptomatic responses and may result in increased toxicity. HBI appears to be highly effective in achieving results similar to conventional (2–3 week) radiation with localized fields     

肿瘤型假体置换术后再手术的原因与策略

目的 分析肿瘤型假体置换术后再手术的原因，探讨再手术的策略。方法 复习10年间再手术的21例患者。男13例，女8例。再手术时平均年龄37．3岁。再手术时间2周。20年。再手术的原因：肿瘤复发8例，假体松动5例，切口不愈合4例，关节脱位3例，假体断裂1例。行截肢术和肿瘤假体返修术各6例，肿瘤扩大切除术3例，病灶清除腓肠肌内侧头肌瓣转移术4例，切开复位术和关节旷置术各1例。结果 18例获得平均3年4个月的随访，死亡4例，余14例无异常。再手术后保留肢体功能满意率为84．6％，肢体功能优良率为53．9％。结论 肿瘤假体置换术后。再手术应根据不同的原因采取相应的治疗策略，在不违犯保肢手术的原则下，仍然可行保留肢体的手术，并可获得满意的治疗效果。     

Toxicity of WR-2721 administered in single and multiple doses

Two hundred forty-three patients have received WR-2721 in Phase I-II studies. Separate studies were conducted in which patients with advanced malignancies received WR-2721 before single or multiple doses of radiotherapy or in single doses prior to cyclophosphamide, nitrogen mustard or cis-platinum. Single doses were escalated from 25 to 1330 mg/m2. An Acceptable Tolerated Dose (ATD) of 740 mg/m2 infused in 15 minutes has been established and is currently used in Phase II studies. Significant persistent hypotension (greater than 20 torr systolic) as a dose-limiting toxicity has occurred in 5% of patients in the single dose study. Fifty-five patients have been entered in the multiple dose trial. Dose levels of 340 mg/m2, four times a week for three weeks, and 250 mg/m2, four times a week for six weeks have been reached. There were five idiosynchratic reactions (fever, chills, rash, hypotension), one of which was severe. Some patients withdrew from the multiple dose study because of vomiting after each injection, or fear. No deaths nor any long-term untoward effects were observed. There is no suggestion of tumor protection.     

同种异体骨移植重建骨肿瘤切除术后骨缺损

目的评价同种异体骨移植修复骨肿瘤切除后骨缺损的重建方法、疗效、并发症及防治。方法18例骨肿瘤患者年龄15～48岁，平均23岁；其中骨肉瘤10例，软骨肉瘤3例，尤文肉瘤3例，骨巨细胞瘤2例，应用交锁髓内钉、重建钢板、解剖钢板等内固定器材结合同种异体骨关节或骨段移植治疗。随访时间12～50个月，平均36个月。结果14例植骨愈合，3例骨不愈合（其中1例因内固定断裂而行更换），1例异体骨骨折，发生局部免疫反应9例，无肿瘤局部复发。功能结果按Mankin标准评定，优9例，良5例，中4例，优良率77．7％。结论同种异体骨是治疗良恶性骨肿瘤切除术后骨缺损的有效方法，异体骨不愈合、骨折、感染、免疫反应等为常见的并发症，选择合适患者、恰当的内固定、做好术前计划可减少此类并发症的发生。