Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice.

PURPOSE: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. METHODS AND MATERIALS: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD(50)) were determined and compared to controls (carrier without PTK787/ZK222584). RESULTS: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD(50) values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. CONCLUSIONS: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584.

Evaluation of dose-volume histograms after prostate seed implantation. 4-year experience.

BACKGROUND AND PURPOSE: Permanent interstitial brachytherapy by seed implantation is a treatment alternative for low-volume low-risk prostate cancer and a complex interdisciplinary treatment with a learning curve. Dose-volume histograms are used to assess postimplant quality. The authors evaluated their learning curve based on dose-volume histograms and analyzed factors influencing implantation quality. PATIENTS AND METHODS: Since 1999, 38 patients with a minimum follow-up of 6 months were treated at the authors' institution with seed implantation using palladium-103 or iodine-125, initially using the preplan method and later real-time planning. Postimplant CT was performed after 4 weeks. The dose-volume indices D90, V100, V150, the Dmax of pre- and postplans, and the size and position of the volume receiving the prescribed dose (high-dose volume) of the postplans were evaluated. In six patients, postplan imaging both by CT and MRI was used and prostate volumes were compared with preimplant transrectal ultrasound volumes. The first five patients were treated under external supervision. RESULTS: Patients were divided into three consecutive groups for analysis of the learning curve (group 1: n = 5 patients treated under external supervision; group 2: n = 13 patients; group 3: n = 20 patients). D90post for the three groups were 79.3%, 74.2%, and 99.9%, the V100post were 78.6%, 73.5%, and 88.2%, respectively. The relationship between high-dose volume and prostate volume showed a similar increase as the D90, while the relationship between high-dose volume lying outside the prostate and prostate volume remained constant. The ratio between prostate volumes from transrectal ultrasound and CT imaging decreased with increasing D90post, while the preplanning D90 and V100 remained constant. The different isotopes used, the method of planning, and the implanted activity per prostate volume did not influence results. CONCLUSION: A learning curve characterized by an increase in the D90post can be observed and results in a stable technique after 18 patients. An important factor influencing the learning curve in addition to the precision of seed positioning is organ volume definition on postimplant imaging.

Clonogenic survival of human keratinocytes and rodent fibroblasts after irradiation with 25 kV x-rays.

Low energy x-rays (E(ph)

Induction of micronuclei in human fibroblasts and keratinocytes by 25 kV x-rays.

A relative biological effectiveness (RBE) not much larger than unity is usually assumed for soft x-rays (up to approximately 50 keV) that are applied in diagnostic radiology such as mammography, in conventional radiotherapy and in novel radiotherapy approaches such as x-ray phototherapy. On the other hand, there have been recent claims of an RBE of more than 3 for mammography and respective conventional x-rays. Detailed data on the RBE of soft x-rays, however, are scarce. The aim of the present study was to determine the effect of low-energy x-rays on chromosomal damage in vitro, in terms of micronucleus induction. Experiments were performed with 25 kV x-rays and a 200 kV x-ray reference source. The studies were carried out on primary human epidermal keratinocytes (HEKn), human fibroblasts (HFIB) and NIH/3T3 mouse fibroblasts. Micronucleus (MN) induction was assayed after in vitro irradiation with doses ranging from 1 to 5.2 Gy. Compared to the effect of 200 kV x-rays, 25 kV x-rays resulted in moderately increased chromosomal damage in all cell lines studied. This increase was observed for the percentage of binucleated (BN) cells with micronuclei as well as for the number of micronuclei per BN cell. Moreover, the increased number of micronuclei per micronucleated BN cell in human keratinocytes and 3T3 mouse fibroblasts suggests that soft x-rays induce a different quality of damage. For all cell lines studied the analysis of micronucleus induction by 25 kV soft x-rays compared to 200 kV x-rays resulted in an RBE value of about 1.3. This indicates a somewhat enhanced potential of soft x-rays for induction of genetic effects.

Report of a study on IMRT planning strategies for ethmoid sinus cancer.

AIM: This communication reviews the planning strategies and dose statistics of nine IMRT plans generated for a complex head and neck case. PATIENT AND METHOD: An ethmoid sinus cancer case was sent as an IMRT planning task to all participants of the ESTRO course on "IMRT and Other Conformal Techniques in Practice", held in Amsterdam in June 2001. RESULTS: Nine IMRT plans were generated for the case, the majority of the plans generated with commercial planning systems. The number of beam incidences ranged between four and eleven, while five of the nine beam setups were coplanar. The planning target volume dose homogeneity was inversely correlated with the degree of sparing of the surrounding organs at risk. CONCLUSION: IMRT strategies for complex head and neck cases, such as ethmoid sinus cancer, can be strikingly different in various aspects, such as beam setup, total number of segments, PTV dose coverage and dose statistics for organs at risks.