Long term outcome of adolescent and adult patients with pineal parenchymal tumors treated with fractionated radiotherapy between 1982 and 2003 -- a single institution's experience

Background: To evaluate the effectivity of fractionated radiotherapy in adolescent and adult patients with pineal parenchymal tumors (PPT). Methods: Between 1982 and 2003, 14 patients with PPTs were treated with fractionated radiotherapy. 4 patients had a pineocytoma (PC), one a PPT with intermediate differentiation (PPTID) and 9 patients a pineoblastoma (PB), 2 of which were recurrences. All patients underwent radiotherapy to the primary tumor site with a median total dose of 54 Gy. In 9 patients with primary PB treatment included whole brain irradiation (3 patients) or irradiation of the craniospinal axis (6 patients) with a median total dose of 35 Gy. Results: Median follow-up was 123 months in the PC patients and 109 months in the patients with primary PB. 7 patients were free from relapse at the end of follow-up. One PC patient died from spinal seeding. Among 5 PB patients treated with radiotherapy without chemotherapy, 3 developed local or spinal tumor recurrence. Both patients treated for PB recurrences died. The patient with PPTID is free of disease 7 years after radiotherapy. Conclusion: Local radiotherapy seems to be effective in patients with PC and some PPTIDs. Diagnosis and treatment of patients with more aggressive variants of PPTIDs as well as treatment of PB need to be further improved, since local and spinal failure even despite craniospinal irradiation (CSI) is common. As PPT are very rare tumors, treatment within multi-institutional trials remains necessary

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

<p>Abstract</p> <p>Background</p> <p>To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer.</p> <p>Methods</p> <p>125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes.</p> <p>Results</p> <p>The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment.</p> <p>Conclusion</p> <p>Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.</p

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

Rad51 Inhibits Translocation Formation by Non-Conservative Homologous Recombination in Saccharomyces cerevisiae

Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in mammalian cells also reduce DSB repair by conservative gene conversion and stimulate non-conservative repair by SSA, this mechanism may also operate in humans and, perhaps contribute to the genome instability that propels the development of cancer

Computational Identification of Transcriptional Regulators in Human Endotoxemia

One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically ‘coregulated’ genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes