P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Preliminary results of preoperative radiotherapy in carcinoma of the rectum (author's transl)

Preliminary results were evaluated in patients with carcinoma of the rectum of whom 33 had preoperative radiotherapy and 23 were treated by operation only. The tumour stage was T2-4 NX MO in all patients. There was no significant difference between the groups as to postoperative mortality, would healing, and postoperative admission time. However, the recurrence rate was significantly lower in pre-irradiated patients than in those treated by operation only. The combination of radiotherapy and radical operation appears to be a possible means of significantly improving the survival rate of patients with carcinoma of the rectum.     

Internal radiotherapy in prostatic carcinoma; disappointing long-term results of retropubic Iodine-125 implantation

OBJECTIVE: To evaluate the results of retropubic implantation of 1-125 seeds in patients with carcinoma of the prostate. DESIGN: Retrospective study of records. SETTING: Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHOD: A retrospective study of records provided follow-up data on 75 patients treated in the period 1981-1990 with implantation of 1-125 seeds by a retropubic approach, preceded by pelvic lymph node dissection. Criteria for the treatment were: To, T1 or T2 carcinoma of the prostate, prostatic volume < 40 ml, no contraindications to surgery. RESULTS: The median follow-up was 103 (60-157) months. Four patients died of complications (5%). Major postoperative complications occurred in 23% (17/75) of the cases. Residual carcinoma or distant metastasization was encountered in 43 of the 71 patients (61%). Sixteen patients died from the consequences of the prostatic carcinoma. The 5- and 10-year survival rates amounted to 74% and 42%, respectively, the cancer-specific 5- and 10-year survival rates to 85% and 67%, respectively. At the latest check-up, 18 patients were alive with tumour, 16 of them under hormonal treatment, while 21 patients were alive without indications of active prostatic carcinoma. CONCLUSION: Treatment of carcinoma of the prostate with retropubic implantation of 1-125 seeds resulted in a high incidence of local therapeutic failure and numerous postoperative complications. These results are poorer than those of total prostatectomy and external radiotherapy.     

Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study

To ascertain whether preoperative short-term radiotherapy can improve local tumor control and the long-term survival of patients with operable rectal cancer, a prospective randomised trial was performed from 1988 to 1993. Ninety-three patients with rectal cancer were either directly treated with surgery (n = 46) or underwent preoperative radiotherapy with 5 x 3.3 Gy irradiation and operation within 48 h (n = 47). If indicated (T4, UICC stage III) patients also received postoperative irradiation. Comparison of the methods of operation (abdominoperineal amputation versus anterior resection) revealed no significant difference in 5-year survival rate (P = 0.393). Local control of R0-resected tumors was improved after preoperative irradiation (P = 0.08). The 5-year survival rate was significantly higher after preoperative short-term radiotherapy (P = 0.027). Preoperative radiotherapy is not an independent factor according to overall survival (P = 0.078) and local recurrence (P = 0.07). In agreement with the results of other authors the present study indicates improved local tumor control of rectal cancer after preoperative radiation therapy. The 5-year survival rate was significantly better after preoperative radiotherapy than after surgery alone.     

The results of radiotherapy managements in Hodgkin's disease (author's transl)

We reported the results of radiotherapy managements in Hodgkin's disease about 185 patients. From this study, it seems to appear possible to confirm or to note some particular facts: the real good prognosis of the forms begining in the right sus-clavicular fossa; the special staging of the long time survival patients (II Aa, type II); the small value in survival of chemotherapy done before and/or after radiotherapy in the I and II stages; in the other side, the true amelioration comming from chemotherapy in the III and IV stages; the value of irradiation by expanded fields; the particular interest of the total mode irradiation done at the beginning or during the course of the illness; the optimal dose of larger than or equal to 4 000 rads with a weekly dose of larger than or equal to 1 000 rads; the good tolerance of the radiotherapy. From this prelimary study, we hope dowing well in further with a greater number of patients.     

Clinical and radiobiologic evaluation of radiation dosage in radiotherapy of vaginal cancer

In line with the dramatic revolution in healthcare delivery within the last decade, the role of the infection control nurse (ICN) as first described by Brendan Moore (1959) must change to meet today's expectations. This article suggests that ICNs should function as clinical nurse specialists (CNS). The author shows how this change in role can be used to implement research-based practice by using the example of changing ventilator tubing change times.     

Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.     

Intraepithelial neoplasia and carcinoma in the vaginal vault

An 11-year biopsy material from the vagina is presented. The indication for taking the 370 vaginal biopsies was abnormal cytology, polyps, or suspicion of tumor tissue. The material was found to include 10 cases of intraepithelial neoplasia, viz. 4 primary, 6 secondary, and 2 late cases of secondary invasive carcinoma. The interval between the primary and secondary diagnosis ranged from 7 months to 19 years. It is concluded that the risk of secondary changes in the vaginal mucosa is slight, but cytological follow-up is recommended.     

The results of radiotherapy for ependymomas: the Mayo Clinic experience

It is known that exogenous 11-cis-retinol inhibits the recovery of photosensitivity of bleached rod outer segments (ROS) and 11-cis-retinol exists in the interphotorecepter matrix. We examined the conversion of 11-cis-retinol with bovine ROS. ROS was incubated with 11-cis-retinol under dim red light. Retinoids were extracted from the reaction mixture with hexane and analyzed by HPLC coupled with a fluorescence spectrophotometer. Isomerization of 11-cis-retinol to all-trans-retinol was observed in the presence of ROS. This isomerization was not suppressed by heat treatment and did not have stereospecificity. In addition, we incubated purified rhodopsin and phospholipids extracted from ROS with 11-cis-retinol. Rhodopsin was found to isomerize 11-cis-retinol to all-trans-retinol as well as ROS, but phospholipids did not. In contrast, the phospholipids inhibited the isomerization of 11-cis-retinol to all-trans-retinol by the purified rhodopsin. Commercially available phospholipids, especially phosphatidylserine, also inhibited the isomerization. Our results suggest that rhodopsin has activity for the isomerization of 11-cis-retinol to all-trans-retinol and may play an important role in the detoxification of 11-cis-retinol in the ROS.     

Intraoperative radiotherapy of unresectable pancreatic carcinoma

During the period from 1986 to 1991, 33 patients with unresectable carcinoma of the pancreas received intraoperative radiotherapy (IORT). Abdominal and back pain which tormented all patients before IORT totally disappeared in 18 patients (54%) and was allevrited in 13 patients (40%). The average survival time of 6.5 months for patients treated with IORT was not statistically different from that of 30 patients with resectable pancreatic cancers undergoing resection. IORT hence is a good palliative therapy for unresectable carcinoma of the pancreas.     

Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy

BACKGROUND: Radiotherapy is used in the treatment of laryngeal carcinoma. The search for biologic parameters that could be used to identify patients who will respond to radiotherapy is crucial. The aim of this study was to determine whether the Ki-67 and p53 indices and the pretreatment apoptotic index would be useful in predicting local control and survival for a group of laryngeal carcinoma patients given postoperative radiotherapy. METHODS: Fifty-seven patients with laryngeal carcinoma treated between 1988 and 1993 were included in this study. Postoperative radiotherapy was given to a mean dose of 57.7 gray (Gy) (range, 50-68; median, 60) in 2-Gy daily fractions. Ki-67 and p53 immunostaining were performed on paraffin-embedded tissue. Cells were evaluated for apoptosis using hematoxylin and eosin-stained slides. Clinicopathologic tumor characteristics were studied in relation to Ki-67, p53, and apoptotic indices, and as prognostic factors for local control and survival in both univariate and multivariate analysis. RESULTS: The Ki-67, p53, and pretreatment apoptotic indices were not related to any clinicopathologic tumor characteristics. Five-year actuarial local control for the whole group was 47%. Patients with tumors that had low Ki-67 proliferation had better long term local control (P < 0.01). and survival (P < 0.03). p53 expression was not predictive of local control or survival in this study. Patients with tumors that had low pretreatment apoptotic indices had better local control (P < 0.049) and survival (P < 0.056) than patients with highly apoptotic tumors. Tumor extension and the pretreatment apoptotic index were significant predictive factors for local control and survival in multivariate analysis. CONCLUSIONS: Ki-67 proliferation measurement and the pretreatment apoptotic index are useful in predicting the clinical outcome of laryngeal carcinoma patients referred for radiotherapy. The role of p53 oncoprotein determination in predicting these outcomes is unclear. Assessment of biologic tumor characteristics could aid in the selection of patients for different treatment strategies.     

The remineralization of the vertebral metastases of breast carcinoma after radiotherapy

BACKGROUND: The early detection of effects caused by radiotherapy on bone mineralisation has influence on clinical treatment. Usually the follow-up is done by conventional X-rays, presenting a loss of calcification of at least 30%. Quantitative CT-measurements are much more sensitive. PATIENTS AND METHODS: In a prospective study we evaluated the CT-scans of 14 patients with multiple vertebral metastases of mamma carcinoma. Our patients underwent SEQCT (one 10 mm slice in each affected vertebral body, 80 kV, 250 mAs) before and immediately after radiation therapy (total dose 30 Gy to 36 Gy) followed by further examinations 6 weeks and 3 months later. RESULTS: While there is no significant change in increased BMD (bone mineral density) of osteosclerotic and decreased BMD of osteolytic metastases just after therapy, the following examinations present an increase of BMD in osteolytic metastases 6 weeks after therapy more distinct 3 months after. Osteosclerotic metastases show a decline in bone density. In mixed metastases is no significant change while normal bone lying in the irradiation field demineralizes. Additive chemotherapy is very important especially for mineralisation of lytic metastases. Referring to mixed metastasis in one vertebral body we suggest a separate evaluation of the left and right side. CONCLUSION: Mineralizing effects of radiation therapy depend on the characteristics of the metastases. Supported by QCT histopathological change can be documented and exactly demonstrated to the clinician.     

Clinical evaluation of the effectiveness of radiotherapy in vaginal metastases of uterine cancer]

AIMS/BACKGROUND: To describe a bilateral, mid peripheral, ring-shaped corneal opacity, not resembling any known corneal degeneration, dystrophy, or other disorder, and occurring without ocular or systemic disease. METHODS: Ophthalmic examination, haematological screening, and ultrasound biomicroscopy. RESULTS: A 25 year old man showed grey-white, granular opacities in both corneas, with an 8 mm diameter ring configuration, and a V-shaped distribution in the anterior stroma. The surrounding corneal stroma was clear, and the tear film, the epithelium and its basement membrane, Descemet's membrane, and the endothelium were normal. Evidence of systemic disease was not found. Family members did not show corneal abnormalities. CONCLUSION: A bilateral corneal ring opacity may occur in healthy, asymptomatic, young people. These corneal rings may result from depositions of unknown origin, or possibly a rare corneal dystrophy.     

Hematometra after radiotherapy for cervical carcinoma

The development of a hematometra after radiotherapy for cervical carcinoma is often related to recurrent disease. We present two cases in which a hematometra developed during the use of estrogen replacement therapy. This development was related to regained endometrial activity in combination with fibrosis and obliteration of the upper vagina and/or cervix. In one patient a dilatation and curettage could be performed; in the other a hysterectomy was necessary in order to exclude recurrent disease. These two cases show once more that endometrium can regain its proliferative activity after radiotherapy for cervical cancer. Estrogen replacement therapy in these patients should include the use of a progestagen agent in order to avoid continuous unopposed endometrial stimulation. In the absence of progesterone withdrawal bleeding the uterine cavity should be routinely examined for the development of a hematometra.     

Preliminary results of primary chemotherapy in retinoblastoma

Transcranial duplex real time sonography (TCCS) is a non-invasive imaging modality that allows repetitive examinations of central nervous system vascular and parenchymal anatomy; a broad spectrum of cerebral pathology may be disclosed: vascular changes include ischemic and hemorrhagic stroke, arteriosclerotic vascular degeneration, arteno-venous malformations and aneurysms, as well as neoplastic and degenerative parenchymal disorders. Imaging was performed with a duplex ultrasound system, employing a 2.25 resp. 2.0 MHz phased-array transducer. Imaging was achieved through the acoustic bone window of the temporal bone and through the foramen magnum. For three-dimensional image reconstruction a mechanical position sensor and online video grabbing was applied. To evaluate the potential of a transpulmonary stable ultrasound contrast enhancing agent we used galactose-based SH U 508 A (Levovist, Schering, Berlin) with 1 to 6 i.v. injections per patient in a phase 2/3 clinical protocol. The signal to noise ratio is significantly improved; the Doppler signal intensity is increased by approx. 25 dB. Levovist was well tolerated and no adverse events occurred, approx. 30% of patients had a sensation of heat and slight pain at the injection site during and shortly after the injection. With the increase in signal intensity, the complete circle of Willis, the peripheral arterial branches, the vertebro-basilar system and the basal venous system may be depicted. In addition, tumour parenchyma vascularisation may be detected, as well as improved delineation of arteriovenous malformations and aneurysms. Three dimensional image reconstruction may represent a novel option in contrast enhanced transcranial duplex imaging including additional information about 3D structure and continuity.     

Multivariate analysis results of radiotherapy for laryngeal cancer

We assess the impact of radiotherapy in the treatment of laryngeal cancer and evaluate the value of the standard dose (linear quadratic plus time model) and other variables to predict tumor control and survival. Between 1972 and 1989, 80 patients with laryngeal cancer received comprehensive radiotherapy. Patients with stage I laryngeal glottic cancer (T1-N0-M0) were excluded from this study. Mean follow-up was 15 months (range 4 to 181). The mean age was 64.8 years (range 40 to 92). Standard dose varied from 32.65 to 81.81 Gy (mean 66.78). The 5-year overall survival and tumor-specific survival rates were 44.9 +/- 5.8% and 51.4 +/- 5.9%, respectively. Five-year local control and locoregional control rates were 66.4 +/- 5.7% and 61.9 +/- 5.8%, respectively. Multivariate analysis showed that local control was significantly predicted by T stage (p = .032), but not by standard dose (p = .906). Independently significant factors predicting tumor-specific survival included stage (p = .006), site (p = .019), and age (p = .001). Local control and survival were significantly predicted by the TNM-staging classification. The standard dose did not predict local recurrence or survival.     

Target volume and indications of radiotherapy in breast carcinoma

Breast-conserving surgery is now commonly used to treat breast cancer. While mastectomy has been the traditional treatment for ductal carcinoma in situ, it is felt to be excessive in most cases. A great effort has been made to identify pathobiological characteristics of DCIS that can be used to identify patients best suited for wide local excision vs. wide local excision and breast irradiation. Mastectomy and conservative surgery plus irradiation offer a similar outcome in patients with early stage invasive breast cancer. Radiotherapy has not been shown to improve survival but is able to reduce significantly the rate of local recurrence, which is regarded as a very undesirable outcome. There is still controversy concerning the necessity of irradiation of the breast in all patients. Analysis of predictors of outcome cannot identify a subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy. In premenopausal, node-positive breast cancer patients XRT has a beneficial effect not only on locoregional but also on systemic recurrences. Radiotherapy has to be integrated for a pre- or postoperative consolidation in new treatment concepts for locally advanced breast cancer which use primary chemotherapy and immediate or subsequent breast radiation. Radiation of internal mammary chain and supraclavicular fossa after conservative surgery does not lead to an increase in clinically important skin or pulmonary complications. Its role is being evaluated in current multicentre studies.