Non-closure of peritoneum after abdominal hysterectomy for uterine carcinoma does not increase late intestinal radiation morbidity

Background/AimTo evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity.Materials and methodsA total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed.ResultsVisceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm³ (range 200–840 cm³, median 469 cm³); mean volume of bowels irradiated in patients without peritonealization was 456 cm³ (range 254–869 cm³, median 428 cm³). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34).ConclusionNon-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.     

Long-term follow-up in adult patients with low-grade glioma (WHO II) postoperatively irradiated. Analysis of prognostic factors

AimTo report the long-term follow-up of a cohort of adult patients with LGG post-operatively irradiated in one institution, and to identify prognostic factors for progression free survival.BackgroundThere is little consensus about the optimal treatment for low-grade glioma (LGG), and the clinical management of LGG is one of the most controversial areas in neurooncology. Radiation therapy is one option for treatment of patients with LGG, whereas other options include postoperative observation.Materials and methodsBetween 1975 and 2005, 180 patients with LGG (WHO II) received postoperative irradiation after non radical (subtotal or partial) excision. Patients had to be 18 years of age or older, and have histologic proof of supratentorial fibrillary (FA), protoplasmic (PA) or gemistocytic astrocytoma (GA). Radiotherapy was given within 3–10 weeks after surgery. Treatment fields were localized and included the preoperative tumor volume, with a 1–2 cm margin, treated to a total dose of 50–60 Gy in 25–30 fractions over 5–6 weeks.ResultsActuarial ten-year progression free survival (APFS) in the whole group was 19%. The worse prognosis was observed in patients with GA. Ten-year APFS rates for GA, PA and FA were 10%, 18% and 22%, respectively.ConclusionThe findings from our long-term cohort of 180 patients with LGG confirmed by uni- and multivariate analysis demonstrated that only astrocytoma histology significantly determined the prognosis. The best survival was observed in patients with the fibrillary variant, and the worst for the gemistocytic one.     

Investment in radiotherapy infrastructure positively affected the economic status of an oncology hospital

BackgroundRadiotherapy is among the most efficient treatment methods of cancer. However, a radiotherapy base needs a substantial financial investment, especially before the beginning of its operation, and in some cases, in developing countries such a huge investment may cause some financial disturbances for a hospital concerned.AimTo assess the influence of investments modernizing the radiotherapy base in the period between 2000 and 2007 on the financial condition of the oncology hospital in the region with population of about 3 million.Material and methodsFinancial reports and medical statistics for the period between 2000 and 2007 from the studied oncology hospital and a recognized staffing model, as well as data on epidemiological situation of the region have been used to calculate the economic effects of financial investment in the radiotherapy base.ResultsThe growth of RT therapeutic potential has been driven by two cost-effective investment programmes. The total amount invested in both programmes was PLN 127,191,000.The number of radiotherapy patients treated in the hospital increased from 2301 in 2000 to 4799 in 2007 with a the same number of five therapeutic machines, although all five of them were replaced over that period. Investments modernizing the radiotherapy base lead to a significant increase in depreciation and operating costs, which adversely affects financial results of the hospital.ConclusionLong term trends showed that investments had positive influence on hospital performance shown both in increased income and larger number of patients treated.     

Concomitant chemo-radiotherapy for unresectable oesophageal cancer: A mono-institutional study on 40 patients

Background/AimTo analyse clinical response, overall (OS) and disease free survival (DFS) and toxicity in patients with unresectable oesophageal cancer treated by concomitant chemo-radiotherapy (CRT).Materials and methodsForty patients with stage IIa–IVa biopsy proven oesophageal carcinoma were treated with CRT. All patients were studied with endoscopy and CT and judged unresectable after multidisciplinary discussion. CRT consisted of 3 cycles of cisplatin 100 mg/m² or carboplatin 300 mg/m² on day 1 and 5-fluorouracil 1000 mg/m² as a continuous infusion of 96 h associated with concurrent 3D-conformal RT. By using 15 MeV X-rays, a total dose of 60–66 Gy was delivered with daily fractions of 1.8–2.0 Gy.ResultsComplete response (CR), partial response (PR) and no response (NR) were observed in 50%, 20% and 20% of cases, respectively. Of the 20 patients with CR, 15 developed loco-regional recurrent disease. OS and DFS rates at 3 and 5 years were 38%, 8%, 49% and 10%, respectively. Total radiation dose ≥60 Gy improved loco-regional control and complete response (CR vs. PR + NR; p = 0.004) influenced both DFS and loco-regional control. Grade 3 gastrointestinal and haematological acute toxicity occurred in 3/40 patients (7.5%). One patient developed grade 4 renal failure. Late toxicity was reported in 2/40 patients (5.0%), consisting of grade 3 radiation pneumonitis.ConclusionsConcomitant CRT for unresectable oesophageal cancer can result in an acceptable loco-regional control with limited toxicity. Response after treatment and total radiation dose influenced the outcome.     

Quality of life and radiotherapy in brain metastasis patients

AimThe primary objective of this study was to assess whether there was an improvement in QoL for patients with brain metastases after radiotherapy treatments.BackgroundAssessment of quality of life (QoL) in brain metastasis patients has become increasingly recognized as an important outcome.Materials and methodsPatients treated for brain metastasis in our department during 2010 were included in our prospective study. QoL assessments were conducted at baseline, 1 month, and 3 months after completion of whole-brain radiotherapy (WBRT). Wilcoxon test for multiple comparisons was calculated to detect significant differences in global QoL scores.ResultsThirty-nine patients with brain metastases completed the EORTC QLQ-C30/BN-20 questionnaire independently. Median age was 59.9 years (from 37 to 81 years). Our results report differences between the baseline and 3 months in worsening of a global health status (p = 0.034) and cognitive function (p = 0.004), as well as drowsiness (p = 0.001), appetite loss (p = 0.031) and hair loss (p = 0.005). There is a tendency for deterioration of physical function (p = 0.004), communication deficit (p = 0.012), and weakness of legs (p = 0.024), between the baseline and 1 month evaluation. There was no difference in a global cognitive status between different evaluations. Median survival time was 3 months (CI 95% 1.85; 4.15).ConclusionsOur findings indicate a small deterioration for a global QoL status, and large deterioration for cognitive function after radiation treatments, as well as worsening of brain metastasis related symptom items. Further research is necessary to refine treatment selection for patients with brain metastases, since it may at least contribute to the stabilization of their QoL status.     

In vivo ionizing irradiations produce deletions in the hprt gene of human T-lymphocytes

The hprt T-lymphocyte cloning assay, which detects mutations occurring in vivo in humans, has been used to examine mutants induced in patients receiving radioimmunoglobulin therapy (RIT) for cancer. Samples from 13 patients before treatment (controls) and 15 samples from 12 patients after treatment were studied for both mutant frequencies and molecular changes in the hprt mutant T-cell clones. Patients were studied up to 48 months after treatment. Post-RIT patients showed increased mutant frequencies as compared to pre-treatment values. T-cell receptor (TCR) gene analysis of mutant T-cell clones demonstrated that 84% arose independently, both pre- and post-treatment, which is the same proportion as seen in normal individuals. However, several individuals did show large sets of mutants with the same TCR gene rearrangement patterns. Molecular analysis of mutants demonstrated a greater proportion of mutations with hprt gene changes on Southern blots after RIT treatment than before (40% versus 20%). RIT increases the proportion of mutations with total rather than partial gene deletions or other gross structural changes compared to normal individuals or pre-treatment patients. These studies are defining the spectrum for radiation-induced hprt gene mutations in vivo in human T-lymphocytes.     

Combination of integrin siRNA and irradiation for breast cancer therapy

Up-regulation of integrin alpha(v)beta(3) has been shown to play a key role in tumor angiogenesis and metastasis. In this study, we evaluated the role of integrin alpha(v)beta(3) in breast cancer cell resistance to ionizing irradiation (IR) and tested the anti-tumor efficacy of combining integrin alpha(v) siRNA and IR. Colonogenic survival assay, cell proliferation, apoptosis, and cell cycle analysis were carried out to determine the treatment effect of siRNA, IR, or combination of both on MDA-MB-435 cells (integrin alpha(v)beta(3)-positive). Integrin alpha(v)beta(3)-negative MCF-7 cells exert more radiosensitivity than MDA-MB-435 cells. IR up-regulates integrin alpha(v)beta(3) expression in MDA-MB-435 cells and integrin alpha(v) siRNA can effectively reduce both alpha(v) and alpha(v)beta(3) integrin expression, leading to increased radiosensitivity. Integrin alpha(v) siRNA also promotes IR-induced apoptosis and enhances IR-induced G2/M arrest in cell cycle progression. This study, with further optimization, may provide a simple and highly efficient treatment strategy for breast cancer as well as other integrin alpha(v)beta(3)-positive cancer types.     

Mathematical modelling of radiotherapy strategies for early breast cancer

Targeted intraoperative radiotherapy (Targit) is a new concept of partial breast irradiation where single fraction radiotherapy is delivered directly to the tumour bed. Apart from logistic advantages, this strategy minimizes the risk of missing the tumour bed and avoids delay between surgery and radiotherapy. It is presently being compared with the standard fractionated external beam radiotherapy (EBRT) in randomized trials. In this paper we present a mathematical model for the growth and invasion of a solid tumour into a domain of tissue (in this case breast tissue), and then a model for surgery and radiation treatment of this tumour. We use the established linear-quadratic (LQ) model to compute the survival probabilities for both tumour cells and irradiated breast tissue and then simulate the effects of conventional EBRT and Targit. True local recurrence of the tumour could arise either from stray tumour cells, or the tumour bed that harbours morphologically normal cells having a predisposition to genetic changes, such as a loss of heterozygosity (LOH) in genes that are crucial for tumourigenesis, e.g. tumour suppressor genes (TSGs). Our mathematical model predicts that the single high dose of radiotherapy delivered by Targit would result in eliminating all these sources of recurrence, whereas the fractionated EBRT would eliminate stray tumour cells, but allow (by virtue of its very schedule) the cells with LOH in TSGs or cell-cycle checkpoint genes to pass on low-dose radiation-induced DNA damage and consequently mutations that may favour the development of a new tumour. The mathematical model presented here is an initial attempt to model a biologically complex phenomenon that has until now received little attention in the literature and provides a 'proof of principle' that it is possible to produce clinically testable hypotheses on the effects of different approaches of radiotherapy for breast cancer.     

Analysis of survival data with cross-effects of survival functions

We present a model and semiparametric estimation procedures for analysis of survival data with cross-effects (CE) of survival functions. Finite sample properties of the estimators are analyzed by simulation. A goodness-of-fit test for the proportional hazards model against the CE model is proposed. The well known data concerning effects of chemotherapy and radiotherapy on the survival times of gastric cancer patients is analyzed as an example.     

光量子加血卟啉疗法对大鼠肿瘤放射增敏作用的对比研究

本文应用透射电子显微镜技术观察了应用血卟啉加光量子疗法后,再施以放射治疗,大鼠皮下移植性肿瘤Ｗ２５６细胞超微结构的变化,结果表明,与单纯充氧放疗组的肿瘤细胞相比,经过血卟啉,光量子疗法及同时应用血卟啉和光量子疗法后再施放疗组大鼠组织周围有明显增多的炎性细胞浸润及淋巴细胞浸润;肿瘤细胞可见有不同程度的核改变及粗面内质脱颗闰,扩张：线粒体肿胀,嵴及膜的断裂,基质丢失,应用血卟啉及血卟啉加光量子同时应用