Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer

PurposeTo investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT).Methods and MaterialsWithin a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie—European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center.ResultsAt 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V₆₀ were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V₆₀ <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4–11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control.ConclusionsThis multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V₆₀ for IR-CTV was identified as an important predictive factor for local control.     

Curiethérapie du cancer de l’œsophage

The main indication of oesophageal brachytherapy is palliative: it can improve dysphagia in patients with a tumor not suitable for surgery or chemoradiotherapy. A randomized clinical trial showed that survival without dysphagia and quality of life was improved by endoluminal brachytherapy in comparison to self-expansible metallic stents. It also increases the duration of palliation after laser deobstruction. Its role as a curative treatment of locally advanced tumors is still discussed: in combination with external beam radiotherapy, it seems that brachytherapy increased the rate of severe toxicity (haemorrhages, fistula, stenosis). In superficial lesions, brachytherapy with or without external beam radiotherapy seems logical but large prospective studies are missing in this setting.     

Cancer risks in a population with prolonged low dose-rate γ-radiation exposure in radiocontaminated buildings, 1983 – 2002

Purpose: To assess cancer risks in a population that received prolonged low dose-rate γ-irradiation for about 10 years as a result of occupying buildings containing ⁶⁰Co-contaminated steel in Taiwan.

Materials and methods: The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis.

Result: A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range < 1 – 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 – 7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0 – 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age.

Conclusions: The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.     

Ex Vivo Evaluation of Residual Activity and Infusion Dynamics in a Commercially Available Yttrium-90 Resin Microsphere Administration System

PurposeTo evaluate the infusion dynamics and residual yttrium-90 activity during and after resin microsphere radioembolization with different injection techniques and initial activities. To assess the distribution of residual activity in the administration systems to allow optimization of the procedure and the equipment.Materials and MethodsIn a setup similar to that in standard clinical practice, radioembolization procedures were performed ex vivo. The influence of different injection techniques was assessed by comparing pulsatile and continuous injections. The influence of the absolute amount of activity to the residual activity was assessed by comparing pulsatile 0.5-GBq- with 1.0-GBq-procedures. Continuous dose rate measurements were performed. Activity distribution was determined by positron-emission tomography (PET)/CT.ResultsFifteen procedures were performed: 5 pulsatile 0.5-GBq-, 5 continuous 0.5-GBq-, and 5 pulsatile 1.0-GBq-procedures. Mean residual activity was 4.0% ± 1.7% (range 1.2%–6.6%), without statistically significant differences between injection techniques (P = .841) or between prescribed activities (P = .222). Dose-rate measurements revealed an exponential decrease of the activities in the vials with high variability. Activity fell rapidly to 32% ± 7.9% (range 23%–55%) after injection of 4 of 20 mL 5% dextrose solution. Residual activity accumulations were identified at the 3-way stopcock (100% of procedures), in the C-line (80%), at the microcatheter connector (20%), and in the A-line (6.7%), but not in the vials.ConclusionsResidual activity in a commercial administration system for resin microsphere radioembolization is variable and does not systematically depend on initial yttrium-90 activity or on injection technique. Predilection sites for residual activity were identified, which should receive special attention when performing resin transarterial radioembolization procedures, and for further administration system developments.     

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase Ⅱ study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m 2 , infused at 10 mg/m 2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reducti     

Sensitivity of drosophila melanogaster to low concentrations of gaseous mutagens: III. Dose-rate effects

Sex-linked recessive lethal mutations were induced in D melanogaster males by chronic as well as acute treatments of gaseous 1, 2-dibromoethane ranging from 2.3 to 31 ppm.hr. Acute treatments corresponding to each chronic treatment were made by increasing chemical concentration approximately 30 times with a concomittant decrease in exposure period. Germ cell stages sampled, in order of decreasing sensitivity, were spermatocytes, spermatids, and spermatozoa. The most significant finding is that no consistent pattern of difference is observed between acute and chronic exposure for three of the four exposure levels. Only at the highest exposure level (30–31 ppm.hr) was any consistent difference observed between chronic and acute exposure levels. At the higher exposure level in all three germ cell stages the acute exposure showed a significant increase in mutation frequency over the chronic exposure. The greater acute vs chronic mutation frequency for spermatozoa, a metabolically inactive cell stage, leads to the conclusion that the exposure rate effect at high exposure levels is due to systemic factors such as metabolic deactivation or elimination rather than repair of premutational damage in the target cells. The significance of these observations in risk assessment for environmental pollutants is discussed.     

低剂量率辐射生物效应的研究进展

辐射的剂量率能显著影响放射治疗的生物效应,降低剂量率就降低了生物效应。然而,当剂量率降低到一定阈值以下,DNA损伤不能激活细胞的探测器——共济失调毛细血管扩张症突变(ATM)基因以及ATM基因介导的损伤修复途径,因而出现细胞高的致死性,即"反剂量率效应"。在持续低剂量率照射下,主要有两条修复途径参与双链断裂(DSB)的修复,即非同源末端连接(NHEJ)修复和同源重组(HR)修复。这些修复系统在亚致死性损伤和产生剂量率效应中起重要作用,如果损伤得以完整和精确的修复,细胞的辐射敏感性就会发生改变;如果损伤不能被修复,则会诱导细胞凋亡。p53基因在低剂量率辐射引起的细胞周期阻滞和诱导细胞凋亡过程中起关键作用。     

脉冲式低剂量率放疗治疗胃癌腹膜后淋巴结转移1例报道并文献复习

目的:本文通过病例报道及文献复习探讨脉冲式低剂量率放疗(pulsed reduced dose-rate radiotherapy,PRDR)治疗胃癌腹膜后淋巴结转移灶的可行性。方法:对1例胃癌术后腹膜后淋巴结转移致腰背部疼痛的病例应用脉冲式低剂量率放射治疗,结合临床资料,随访观察治疗效果并复习国内外相关文献。结果:该患者治疗前腰背部疼痛严重影响生活质量,影像学提示腹膜后巨大淋巴结肿大影。采用脉冲式低剂量率放疗治疗后靶区转移灶体积缩小90%以上,腰背部疼痛消失,复查CT疗效评价达到部分缓解。放疗后无进展生存期（progression-free survival,PFS）达11个月。结论:胃癌腹膜后淋巴结转移灶因解剖位置特殊导致无法耐受常规放疗的毒性,而应用脉冲式低剂量率放疗可以在降低不良反应的同时提高疗效,延长生存期,提高生存质量。因此脉冲式低剂量率放疗可作为胃癌腹膜后淋巴结转移患者的一个治疗选择。     

Enhanced transplantability of a cell line from a murine ovary granulosa cell tumour in syngeneic B6C3F1 mice continuously irradiated with low dose-rate gamma-rays

Purpose:?To understand the mechanisms of life-shortening due to early neoplastic death caused by chronic low dose-rate (LDR; 20 mGy/22 h/day) radiation which accumulates to a high dose (HD; 8 Gy) (LDR/HD) as reported previously.

Materials and methods:?Female B6C3F₁ mice were continuously exposed to LDR/HD gamma-rays under specific-pathogen-free (SPF) conditions for 400 days. OV3121 cells, which were derived from an ovarian granulosa cell tumour that arose in irradiated B6C3F₁ mice, were inoculated into LDR/HD irradiated and age-matched non-irradiated control mice. The transplantability of tumour cells as well as T cell subsets and the proliferative activities of T cells were compared between irradiated and non-irradiated mice.

Results:?We found that tumour formation of subcutaneously inoculated tumour cells occurred earlier in irradiated mice than in non-irradiated mice. Proliferative activity of draining lymph node lymphocytes against transplanted tumour cells as well as allogeneic mixed lymphocyte reactions were significantly reduced in irradiated mice compared to non-irradiated mice.

Conclusions:?These results suggest that decreased tumour-specific immune response due to LDR/HD irradiation may enhance tumorigenesis resulting in life-shortening of mice after chronic LDR/HD irradiation.