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Frieze patterns follow a set of tiling instructions including reflection, rotation, and translation, and tile the infinite strip. Many metamaterials function due to the underlying symmetry, and its strategic breaking, of their constituent sub-structures that allow tailoring of the dispersion of modes supported by the structure. We design, simulate, and experimentally characterize seven one-dimensional acoustic metasurfaces whose unit cells each belong to one of the distinct Frieze groups. [ABSTRACT FROM AUTHOR]

For layered metamaterial devices, the reflection and transmission coefficients at an interface typically depend on the properties of the coupling between different layers. In this paper, we set out to engineer the reflection/transmission behaviour at boundaries to obtain desirable properties such as achieving total reflection and transmission. Based on the quantum graph formulation for modelling metamaterials developed in Sci. Rep. 12 (1), 18006 (2022), we tailor the interface reflection and transmission coefficients by patterning the boundary with resonant elements at each interface vertex. By tuning the internal lengths of the resonant elements, we demonstrate both minimization and maximization of the reflection coefficient via a scattering formulation. In addition, we present an interface set-up incorporating beyond-nearest-neighbour connections, which yields narrow-band transmission for certain angles only, creating an angular filtering interface. [ABSTRACT FROM AUTHOR]

The phenomenon of selective diffraction is extended to in-plane elastic waves, and we design surface corrugated periodic laminates that incorporate crystal momentum transfer, which, due to the rich physics embedded within the vector elastic system, results in frequency, angle, and wave-type selective diffraction. The resulting devices are elastic grating couplers, with additional capabilities as compared to analogous scalar electromagnetic couplers, in that the elastic couplers possess the ability to split and independently redirect, through selective negative refraction, the two body waves present in the vector elastic system: P- (compressional) and SV- (shear-vertical) elastic waves. The design paradigm, and interpretation, is aided by obtaining isofrequency contours via a non-dimensionalized transfer matrix method. [ABSTRACT FROM AUTHOR]

A potential weakness of topological waveguides is that they act on a fixed narrow band of frequencies. However, by 3D printing samples from a photo-responsive polymer, we can obtain a device whose operating frequency can be fine-tuned dynamically using laser excitation. This greatly enhances existing static tunability strategies, typically based on modifying the geometry. We use a version of the classical Su–Schrieffer–Heeger model to demonstrate our approach. [ABSTRACT FROM AUTHOR]

We design, simulate and experimentally characterize a multi-scale bullseye antenna for the broadband manipulation of microwaves. The device achieves far-field beam-forming via tailored diffraction at the interface between two concentric bullseye geometries, with near-field energy concentration resulting from the overlap of the diffracted beams. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'. [ABSTRACT FROM AUTHOR]

Important distinctions are made between two related wave control mechanisms that act to spatially separate frequency components; these so-called rainbow mechanisms either slow or reverse guided waves propagating along a graded line array. We demonstrate an important nuance distinguishing rainbow reflection from genuine rainbow trapping and show the implications of this distinction for energy harvesting designs, through inspection of the interaction time between slowed zero group velocity waves and the array. The difference between these related mechanisms is highlighted using a design methodology, applied to flexural waves on mass loaded thin Kirchhoff–Love elastic plates, and emphasised through simulations for energy harvesting in the setting of elasticity, by elastic metasurfaces of graded line arrays of resonant rods atop a beam. The delineation of these two effects, reflection and trapping, allows us to characterise the behaviour of forced line array systems and predict their capabilities for trapping, conversion and focussing of energy. [ABSTRACT FROM AUTHOR]

We identify that flexural guided elastic waves in elastic pipes carry a well-defined orbital angular momentum associated with the compressional dilatational potential. This enables the transfer of elastic orbital angular momentum, that we numerically demonstrate, through the coupling of the compressional potential in a pipe to the acoustic pressure field in a surrounding fluid in contact with the pipe. [ABSTRACT FROM AUTHOR]

Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan–Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival.British Journal of Cancer (2008) 98, 217–224. doi:10.1038/sj.bjc.6604163 www.bjcancer.com Published online 8 January 2008 [ABSTRACT FROM AUTHOR]

We analysed the S-year relative survival among 4473 breast cancer cases diagnosed in 1990- 1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, `special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the S-year relative survival ranged from 66% (95% CI 61 -71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriforrn, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis. [ABSTRACT FROM AUTHOR]

In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available. [ABSTRACT FROM AUTHOR]

The rainbow trapping phenomenon of graded metamaterials can be combined with the fractal spectra of quasiperiodic waveguides to give a metamaterial that performs fractal rainbow trapping. This is achieved through a graded cut-and-project algorithm that yields a geometry for which the effective projection angle is graded along its length. As a result, the fractal structure of local band gaps varies with position, leading to broadband "fractal" rainbow trapping. We demonstrate this principle by designing an acoustic waveguide, which is characterised using theory, simulation and experiments.

Strategically combining four structured domains creates the first ever three-way topological energy-splitter; remarkably, this is only possible using a square, or rectangular, lattice, and not the graphene-like structures more commonly used in valleytronics. To achieve this effect, the two mirror symmetries, present within all fully-symmetric square structures, are broken; this leads to two nondistinct interfaces upon which valley-Hall states reside. These interfaces are related to each other via the time-reversal operator and it is this subtlety that allows us to ignite the third outgoing lead. The geometrical construction of our structured medium allows for the three-way splitter to be adiabatically converted into a wave steerer around sharp bends. Due to the tunability of the energies directionality by geometry, our results have far-reaching implications for applications such as beam-splitters, switches and filters across wave physics.

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis.

Unlabelled: The aim of our study was to evaluate and compare in thyroid cancer patients the predictive value for disease progression of thyroglobulin (Tg) levels measured under thyroid-stimulating hormone (TSH) stimulation, in the postoperative period just before (131)I ablative therapy and at the time of control 6-12 mo later., Methods: Two-hundred twelve consecutive patients treated for a well-differentiated thyroid carcinoma (184 papillary, 28 follicular) with no initial distant metastases were retrospectively studied. All patients had a total or near-total thyroidectomy followed by ablation with 3.7 GBq (131)I. Tg levels were determined just before ablative therapy (Tg1) and 6-12 mo later (Tg2). Thresholds of 30 and 10 ng/mL were used for Tg1 and Tg2, respectively. Univariate and multivariate analyses were performed to assess the predictive value for disease progression of the 2 Tg determinations., Results: Thirty patients had a Tg1 level > 30 ng/mL. Six to 12 mo later, 30 patients had a Tg2 level > 10 ng/mL, 19 of whom had initially a Tg1 level > 30 ng/mL. Disease progression was reported in 20 patients (9%). Progression-free survival rates were significantly lower in patients with a low Tg1 or Tg2 level but the difference was more important with Tg2. With univariate analysis, 5 variables were significantly associated with disease progression: Tg2, Tg1, node invasion, extrathyroidal extension, and tumor size. With multivariate analysis, only Tg2 (odds ratio [OR] = 16.4; 95% confidence interval [95% CI] = 5.7-47.4; P < 0.001) and node invasion (OR = 2.7; 95% CI = 1.0-7.2; P = 0.04) had an independent prognostic value. When only initial parameters were considered, Tg1 and node invasion were the 2 independent prognostic factors. The OR decreased for Tg1 (OR = 10.1; 95% CI = 4.0-25.7; P < 0.001) but increased for node invasion (OR = 4.4; 95% CI = 1.7-11.2; P = 0.002)., Conclusion: Among all clinical and tumoral variables, lymph node invasion and serum Tg level are 2 important parameters to define the risk of disease progression. Although Tg2 appears more significant than Tg1, both Tg levels measured under TSH stimulation, in the postoperative period and a few months after ablative therapy, have a predictive value. In clinical practice, patients at risk can be selected as soon as the initial lymph node status and Tg1 level are known.

Background: Breast carcinoma survival rates were found to be higher in the U.S. than in Europe., Methods: Multiple regression analysis of breast carcinoma survival rates among women diagnosed between 1990 and 1992 was performed using clinical data from population-based case series from the Surveillance, Epidemiogy, and End Results (SEER) program (13,172 women) and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project (4478 women)., Results: Early-stage tumors (T1N0M0) were more frequent in the SEER data (41% of cases) than in the EUROCARE data (29%). In the SEER data, early tumors were more frequent in women age > or = 65 years (43%) than in younger women (38%), whereas the reverse was true in the European data (25% vs. 31%). In both case series, > 90% of women underwent surgery and 81-82% underwent lymphadenectomy, but the number of axillary lymph nodes evaluated was higher in the SEER data than in the EUROCARE data. The 5-year survival rate was higher in the U.S. case series (89%) than in the European series (79%). This differential was observed for each stage category evaluated: early (T1N0M0), large lymph node-negative (T2-3N0M0), lymph node-positive (T1-3N+M0), locally advanced (T4M0), and metastatic (M1) tumors. The overall relative excess risk (RER) of death was significantly higher (RER, 1.37; 95% confidence interval [95% CI], 1.25-1.50) among European women compared with U.S. women (referent group). Adjustment for stage, age, surgery, and the number of lymph nodes evaluated explained most of the excess risk (RER, 1.07; 95% CI, 0.98-1.17)., Conclusions: Transatlantic differences in the 5-year survival rates for women diagnosed with breast carcinoma between 1990 and 1992 were attributable mainly to differences in stage of disease. Resources should be invested to achieve earlier diagnosis of breast carcinoma in Europe, especially for elderly women., (Copyright 2003 American Cancer Society.)

Our objectives were to evaluate the effectiveness of cervical cancer screening outside organized programs in the prevention of cervical carcinoma in situ (CIS) and to enhance the way in which case control studies avoid some common biases. In our case-control study, we assessed all incident, histologically verified cases of CIS registered from 1987 to 1997 in the population-based cancer registry of C te-d'Or, France (N = 104) and 208 controls randomly selected from the screened population and matched for age, date of last screening, residence, and pathology laboratory results. We considered as appropriate for controls screened women who had had at least one Papanicolaou smear in the 3 years preceding the diagnosis or similar period. Screening for controls was higher (67.8%) than for cases (41.4%; P < .001), with a relative protection against CIS of 3.09 (95% confidence interval, 1.83-5.22) and a prevented fraction in the screened population of 45% to 50%. These findings suggest a protective advantage for CIS even in the absence of organized screening. The methodologic approach has advantages as compared to previous types of case-control studies. Although further refinements still are warranted, learning about the protective effect of screening for CIS provides information that may be useful in assessing the impact of a screening policy on women actually at risk of invasive cervical cancer.

Purpose: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors., Patients and Methods: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d'Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area., Results: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P <.0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses >/= 13 mg/m(2)., Conclusion: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.

Purpose: The aim of the study was to determine the predictive factors of complications, to evaluate the impact of customized treatment planning on late normal tissue effects per stage, and to report disease-free survival (DFS) and local control (LC) rates., Methods and Materials: From 1970 to 1994, 642 patients were treated with radiotherapy alone for carcinoma of the intact uterine cervix. According to the International Federation of Gynecology and Obstetrics (FIGO) substaging, 34% were Stage I, 39% Stage II, and 27% Stage III. The analysis was divided into three periods: 1970-1978 (use of standard prescriptions),1979-1984 (implementation of individual adjustments), 1985-1994 (systematic individual adjustments). Five-year DFS, LC, and complications rates were calculated using the Kaplan-Meier method. Predictive factors of complications were determined by univariate analysis using frequency tables and nonparametric t-tests. Multivariate analysis consisted of a polychotomous stepwise regression., Results: The comparison of the three time periods showed a significant reduction of the external radiation dose (dose above 40 Gy in 47% of patients before 1979 vs. 36% after 1984), of the use of parametrial boost (55% vs. 39%), of the use of vaginal cylinder (28% vs. 11.5%), and of the HWT volume (combined intracavitary and external irradiation) (842 cc vs. 503 cc on average). The total sequelae/complications rate, all toxicity grades, all stages, all organs was 51%. Five-year actuarial rate per toxicity grade was: G1, 42%; G2, 23.5%; G3, 10%; G4, 3%. The three main predictive factors for rectal and bladder sequelae/complications (all toxicity grades) taking into account time period were: the increase of external radiation dose, the high dose rate at reference points, and the whole vagina brachytherapy. No G4 occurred in the third period. The rate of G3 complications dropped from 16% to 6% over time: from 5% during the first period to 0% during the third period in Stage I, from 8% to 6% in Stage II, and from 23% to 12% in Stage III. G3 currently describes a variety of clinical situations with a different impact on quality of life which justifies further refinements of definitions of late effects. In our experience the severity of G3 markedly decreased: less than one-third of G3 had a real impact on quality of life in the last period compared to more than two-thirds in the first period. Meanwhile, 5-year LC rates remained stable in Stages I and II, 91% and 85% respectively. Conversely they fell from 75% to 55% in Stage III, thus raising the problem of underdosage and/or more accurate staging with time., Conclusions: Customized treatment planning eradicated lethal complications and provided a significant decrease of G3 in all stages while maintaining high cure rates in early stages. Dose reduction should be considered with caution in Stage III.

In France, as in several other European countries, prevalence has to be estimated from the modelling of 2 of the 3 basic epidemiological measures of incidence, mortality, and survival. Since, in these countries, follow-up of cancer patients is only made in a few registries, we explored the feasibility of estimating prevalence in the absence of follow-up data. The method, which used only incidence and mortality, was validated on Danish data and applied to France. For this latter country, the estimation procedure is based on the recorded mortality data and an estimate of incidence for the entire country. It is applied to selected sites of cancer, which account for 80% of the estimated incidence. In 1992, the prevalence of patients who had such a diagnosis amounts to 538,000 women and 424, 000 men. The most frequent cancer sites are head and neck, breast, and large bowel. Most of the cancer sites present an increase in prevalence proportion between 1987 and 1992. The larger increases concern breast and prostate cancer., (Copyright 2000 Wiley-Liss, Inc.)

Using the 2,208 non metastatic breast cancer diagnosed women who underwent breast surgery from the 2,432 first breast cancers recorded by the French département of Côte-d'Or cancer registry from 1982 to 1992, we described in this well-defined population, the trend in breast-cancer adjuvant treatment, and related practices with recommendations according to risk groups. Adjuvant treatment was received by 44.1% of the 2,208 women. Inflammatory tumors were systematically treated with chemotherapy. For the non-inflammatory M0 breast-cancer (2,167 women), the adjuvant treatment probability was mainly determined by the nodal involvement. After adjustment on the tumor- and host-characteristics, time period was associated with increased probability of adjuvant treatment in the whole group of patients and within each pN subgroup. In the group without nodal involvement, this increase was also associated with the SBR histologic grade. There was strong evidence of large changes in breast-cancer adjuvant treatment. Clinical practices in the Côte-d'Or region have paralleled the NIH recommendations. For node-negative breast cancers, these trends appeared despite persistent uncertainty in the definition of subgroups to treat. Over time, the SBR histologic grade became an apparent factor of treatment. This use as a treatment indicator was done without validation in any adjuvant treatment trial. The simultaneous recommendation to treat with the absence of guidelines could lead to the treating of an increasingly large group by extending the "high-risk" definition. This could be a non-optimal management of risk while putting strain on health care resources.

Objectives: To conduct a survey of the angiosarcomas developing after breast conservation for carcinoma in the French Cancer Centers, to study the evolution of these cases in detail, and to review literature in an attempt to propose an optimal treatment scheme., Material and Methods: Eleven of the 20 French Cancer Centers agreed to research and retrospectively analyze all angiosarcomas discovered in patients previously treated by conservative treatment. The majority of the patients were node negative, T1N0M0. The mean age of the patients at the time of primary breast cancer treatment was 62.5 years, and 69 years at the diagnosis of the angiosarcoma., Results: During the last two decades, nearly 20,000 patients have been treated conservatively in these 11 centers, and only 9 cases of angiosarcoma were found. The median latency period between the treatment of the breast carcinoma and the diagnosis of the breast angiosarcoma was approximately 74 months, with a range of 57-108 months. Mastectomy was performed as the main treatment of this angiosarcoma. All recurrences after mastectomy for the angiosarcoma appeared within 16 months after the mastectomy. A median time of recurrence was found to be 7.5 months, regardless of the treatment. The angiosarcomas appeared to be very aggressive, and chemotherapy, radiotherapy, and sometimes hyperthermia could only palliate the condition for a short time. After the diagnosis of angiosarcoma, the median survival was 15.5 months, showing a particularly poor prognosis. Only 1 patient of 9 is alive without progressive disease at 32 months after salvage mastectomy for the recurrence of the angiosarcoma. Precise data obtained from 11 centers show that, of 18115 breast carcinomas treated conservatively, only 9 breast angiosarcomas are reported, which represents a prevalence of 5 cases of angiosarcoma per 10,000, which is the same prevalence for primary breast angiosarcomas occurring in healthy breasts., Conclusion: Angiosarcoma developing after breast conserving therapy for carcinoma is a rare event, and induction of it by treatment is controversial. However, early diagnosis is essential and it appears that radical mastectomy gives the highest chance of cure and the best long-term survival.

Purpose: The aim of this study was to describe the implication of the different health care structures in the treatment of breast cancer., Methods: In Côte-d'Or, from 1982 to 1992, there were 2432 cases of breast cancer. Surgery came first as treatment for 93% of the patients, radiotherapy came second (77%). The department is subdivided in several geographic areas (ZPIU):--Dijon, equipped with university hospital (UH) and with private hospitals (PH),--cities with general hospitals (GH)--and areas without hospitals. Demographic, geographic and clinical variables were studied in order to explain the patient distribution between the various hospitals., Results: 52% of the cases were operated in PH, 37% in UH and 11% in GH. The main users of the GH were women who lived nearby. Age over 75 was associated with a treatment in GH. Women with clinical signs of severity were twice as often operated in UH rather than PH. Post-operative radiotherapy was done in 95% of the cases in the same structure where surgery was done., Conclusion: No matter how popular university and private hospitals were in our regional capital, general hospitals played a proximity role.

The aim of the study was to assess the incident number of female breast and genital tract cancers for the whole of France. The study focused on the 1983-1987 period and on 9.1% of the French population. The incident number of female breast and genital tract cancers was estimated for each site and for each of eight French administrative regions covered by a cancer registry qualified through the National Committee of Registries (Calvados, Côte-d'Or, Doubs, Hérault, Isère, Bas-Rhin, Somme, Tarn). Information on mortality rates was available at a regional level as well as at a nationwide level. The method estimated the national incidence rate modelizing the regional age-specific incidence rate as a function of corresponding mortality rate. Breast cancer was the leading site with 25,277 new cases per year while female genital tract cancers affected about 13,856 women. The cancer risk, estimated in using cumulative rate 0-74 years, was assessed at 7.1% for breast and at 1.2%, 1.4% and 1.1% for cervix uteri, corpus uteri and ovary respectively. Breast and genital tract cancers constituted 49% of the whole of cancers in women. Observed breast incidence rate was stable through French regions. There were pronounced contrasts in cervix uteri cancer risk, and some french regions displayed a high risk close to the observed European maxima. Interregional contrasts in risk of the other genital tract cancers were less striking. This study emphasized the importance of female breast and genital tract cancers for public health in France. The main aim of the French Cancer Registries Network is to provide a comprehensive description of cancer risk in France and to produce pertinent projection to 2005 horizon, combining the present data and the already accumulated 1988-1992 data.

TP53 abnormalities have been reported as an early event in the process of cellular transformation of human breast cancers, and involved in mammary-tumor evolution, from in situ to invasive disease. In this study, node-negative (N-) tumors were examined for TP53 allelic loss in relation to different genetic instability events, including allelic loss at chromosome 17p13.3 and c-H-ras-1 loci, as well as alteration of the c-myc and c-erbB-2/neu oncogenes. TP53 allelic loss was analyzed to determine whether such an abnormality was the more important, among other genetic events, in the N- tumors, whether it appeared independently of these genetic events, and whether accumulation of genetic events arises in this group of breast tumors. Clinicopathological parameters were also examined. Loss of heterozygosity (LOH) at the TP53 gene appears the most frequent alteration detected (26% vs. 13%, 8%, 9% and 3% for LOH at D17S30 and c-H-ras-1 loci, and amplification of c-myc and c-erbB-2/neu respectively). There was no association between LOH at the TP53 locus and other genetic events. Among clinicopathological parameters, significant associations were observed only with estrogen-receptor-negative tumors (p = 0.05). Our results demonstrate that LOH at TP53 arises more frequently in the N- breast cancer, thus supporting earlier findings suggesting that TP53 abnormality has a role early in the pathogenesis of breast lesions. Moreover, the data indicate that accumulation of many genetic events occurs at a low level in N- breast tumors, and that TP53 abnormality occurs independently of these genetic events.

From 1970 to 1994, 642 patients with carcinomas of intact uterine cervix were treated with radiotherapy alone Univariate and multivariate analysis was carried out of predictive factors for: 1) pelvic control and survival rates; 2) complications using French-Italian Syllabus, combined with an evaluation of the impact of customized treatment planning policy (CTP) on G3-G4. According to Figo substaging 30% of patients were stage I, 42% stage II and 28% stage III/IV. Diameter of cervical disease was 3-5 cm in 38% of cases and > 5 cm in 15%. Nodal involvement from lymphangiogram was 21%. The distribution of sequelae and complications was: G1 23%, G2 18%, G3 6%, G4 2.5%. The distribution of G3-G4 per organ was: genitalia 6% (no G4), rectum 4%, colon 1.5%, bladder 1.2%, soft tissues 1%, small bowel 0.5%. Stage (RR ranging from 1.5 for stage IIb to 5 for stage III/IV), tumor size (RR = 1.5), nodal involvement (RR = 2) were significant predictive factors for survival and pelvic control rates (p < 0.0001). In univariate analysis the main factors influencing the risk of G3-G4 complications were: Figo substaging, external radiation dose over 40 Gy (ED), parametrium boost (PB), use of brachytherapy vaginal cylinders applicator (CA), high HWT and mean rectal dose rate for rectal complications. In multivariate analysis, CA remained the only predictive factor for G3-G4 bladder events (odds ratio OR = 10.8) while the increase of mean dose rate (OR = 1.1), use of CA (OR = 4.2) and ED > 40 Gy (OR = 4.4) were predictive of severe rectal sequelae. Prevention of complications based upon individual changes of treatment planning according to dosimetry parameters led to a sharp decrease in severe complications with time. No G4 occurred after 1983. G3 rates dropped from 5% before 1978 to 0% after 1983 in stage I, from 10% to 6% in stage II and from 23% to 12% in stages III/IV. Meanwhile 5-year LC rates remained stable in early stages, about 91% in stage I and 85% in stage II, conversely they fell from 75% to 55% in stages III/IV, thus raising the problem of underdosage and/or more reliable staging with time. It is concluded that radiotherapy prescriptions based upon tumor diameter per stage and delivered using CTP led to an eradication of lethal complications and provided significant decrease of G3 in all cases while maintaining high cure rates in early stages. Dose reduction should be considered with caution in stages III/IV.

Purpose: Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patients who are complete responders. To clarify the treatment policies, a retrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival., Methods and Materials: Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50-65 Gy according to nodal involvement and surgical margins status., Results: The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients still alive with no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival., Conclusions: Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systematic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.

From 1981 to 1985, 428 patients presenting with an epidermoid carcinoma of the hypopharynx and/or larynx were treated with a curative intent by surgical resection and postoperative irradiation. Two-thirds of the tumours were T3 and 60% of patients presented with a clinical node involvement. The rates of local failure were 8%, 18% and 13%, respectively, for cancers of the larynx, of the piriform sinus and of the posterior wall; the rates of regional failure were 8%, 23% and 13%, respectively. There is no head and neck site with either a high or low risk of recurrence after resection, but the capsular rupture remains a factor of poor prognosis. The survival rate at 5 years of the whole series is 38%, for laryngeal localisation it reaches 62%. The risk of metastases is related to the node involvement and the interval between surgery and irradiation.

In the search for changing medical practices, this population-based study dealt with the breakdown of adjuvant systemic breast cancer treatments from 1982 to 1990. The 1,760 women recorded by the cancer registry of the French Côte d'Or region (241,020 women in 1990) during 1982-1990, who were found to have both a non metastatic breast invasive carcinoma and a no perceptible residual disease after locoregional treatment completion were the subjects of this analysis. Forty percent of the patients received adjuvant treatment: 17% only had chemotherapy, 7% had chemotherapy associated with hormonal therapy and 16% only had hormonal therapy. Chemotherapy was the only adjuvant treatment for the patients under 35 years of age. Hormonal therapy was the main treatment for the patients over 74. For patients from 35 to 74 with a non-inflammatory tumour, the determination of adjuvant treatment was multifactorial. For each modality of adjuvant treatment, the logistic regression model provided an assessment of the contribution of each independant variable to the risk of being treated. This method has focused on period effect after adjustment on the tumor and patient characteristics. Adjuvant treatments were more widely used in the late 1980s than in the early 1980s (OR = 1.9; p = 0.006). On the one hand, the use of chemotherapy-hormonal therapy association remained stable and the use of chemotherapy decreased with a boundary significance (OR = 0.6; p = 0.056); on the other hand, the use of hormonal therapy dramatically increased and was 3.5 times as high for the period 1988-1990 as for the period 1982-1984 (OR = 3.5, p < 0.0001). Comprehensive study of survival trends after breast cancer should take into account the adjuvant systemic treatments and the conditions of their indications to separate their potential beneficial effects from the effects of lead time bias. Necessity of treatment indicator quality control was emphasised.

Purpose: Thymoma is a rare disease. The treatment of patients with invasive thymoma remains controversial. The prognosis of such patients is poor, even with the use of postoperative radiation therapy and chemotherapy. We retrospectively reviewed the outcome and prognostic factors in a series of 90 patients presenting with an invasive thymoma treated by partial resection or biopsy and radiation therapy., Methods and Materials: From 1979-1990, 163 patients with the diagnosis of lymphoepithelial thymoma were treated in 10 French cancer centers. Patients were staged using the postoperative "GETT" classification derived from that of Masaoka. Ninety patients who presented with an invasive thymoma, 58 Stage III (21 IIIA: partial resection and 37 IIIB: biopsy) and 32 Stage IVA (intrathoracic thymoma spread), are the subject of this report. Treatment combined surgery and radiation therapy (+/- chemotherapy), with curative intent. Surgery consisted of partial resection in 31 patients (21 Stage III), and biopsy in 55 patients (37 Stage III). The median radiation dose to the tumor was 50 Gy (30-70 Gy). Supraclavicular radiation was performed in 59 patients (median dose 40 Gy). Chemotherapy, combined with radiation in 59 patients, consisted of multidrug regimens, mainly platinum based., Results: The median follow-up is 105 months (20-165 months). The 5- and 10-year overall survival rates are 51 and 39%, respectively. There is a great impact of the extent of surgery on survival: the 5- and 10-year survival rates were 64% and 43%, respectively, after partial resection, compared to 39% and 31% after biopsy (p < 0.02). Local control at 8.5 years was obtained in 59 of 90 patients (66%): 40 Stage III, 19 Stage IVA. There is a significant relationship between the extent of surgery and the local control (16% of relapse after partial resection vs. 45% after biopsy, p < 0.05). Seven patients developed significant (grades 3-4 WHO grading system) treatment-induced side effects. Stage, histologic type, and chemotherapy were not prognostic factors., Conclusion: In this large multicentric retrospective study of invasive thymomas (Stage III-IVA) treated by surgery and radiation, results show the importance of loco-regional treatments, such as surgery and radiation therapy. There is also a great impact of radiation on local control. However, the rate of local recurrence (34%) justifies recommending a higher dose of radiation (> 50 Gy) than doses used in this study, for incompletely resected patients. The role of chemotherapy needs to be further assessed.

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.

Thymomas is a rare disease. Staging systems and surgical adjuvant treatments remain controversial. We retrospectively reviewed the outcome and the prognostic factors in a series of 149 patients with non metastatic thymomas treated in ten French cancer centers between 1979 and 1990. Patients were staged according to the "GETT" classification derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IV. Surgery consisted of complete resection in 63 patients, partial resection in 31 patients and biopsy alone in 55 patients. All patients received postoperative radiation therapy and 74 were given postoperative chemotherapy. Median follow-up was 7.7 years. Local control was obtained in 117 patients (78.5%) and was influenced by the extent of surgery (p < 0.0001). Metastases occurred in 26 patients. Seven patients developed grade 3-4 pulmonary and heart complications. One patient developed a malignant lymphoma after 24 cycles of chemotherapy. Disease-free survival (DFS) rates were of five years 92%, 75%, 60%, 39% and 48% in stage I, II, IIIA, IIIB and IVA patients, respectively. After complete resection, partial resection and biopsy alone, these rates were 74%, 60% and 38%, respectively. With a multivariate analysis, DFS rates were influenced by the extent of surgery (p < 0.001) and by chemotherapy (p < 0.001). Three other factors could predict a worse DFS: young age (p < 0.006), stages III-IV (p < 0.04) and mediastinal symptoms (p < 0.001), "GETT" staging correlated well with local control and survival. After complete resection, a 50 Gy postoperative radiation therapy can be recommended in patients with invasive thymomas. Despite a 65% local control rate after partial resection or biopsy alone in this series, a higher dose of radiation (> 60 Gy) must be evaluated. Despite the benefit of the chemotherapy in this retrospective and multicentric study, the role of this treatment remains to be assessed.

Between January 1980 to December 1985, 248 patients with advanced squamous cell carcinoma of the pyriform sinus were retrospectively analysed. Criteria for inclusion in the study were the following: no previous treatment and treatment combining total pharyngolaryngectomy and postoperative radiotherapy. Mean follow up was 5 years with a minimum of 3 years. Seventy-one patients had a local regional recurrence (27.4%). Clinical staging at presentation and residual tumor at the primary site after surgery were factors significantly associated with higher local failure rates. The 5 year survival rate was 33% and the median survival time was 32 months (plateau was reached after the 6th year). The most frequent severe complication observed was pharyngeal stenosis occurring in 6% of the cases. This study confirms the poor prognosis of squamous cell carcinoma of the pyriform sinus, in spite of the combination of radical surgery and high dose postoperative radiotherapy.

In the French administrative "departement" of Côte-d'Or, between 1982 and 1990, the crude incidence rate and the age-adjusted world standardised incidence rate (ASR) for corpus uteri cancer were respectively 16.0 +/- 0.8 and 10.7 +/- 0.6 per 100,000 women per year. The incidence increased after 50 years of age, reaching a maximum of 66.7 per 100,000 women per year at the age of 70-74 and thereafter declined. Ninety-six percent of the patients were older than 50. The 5- and 10-year crude survival rates (all histologic types) were 66 +/- 3% and 61 +/- 4%. The 5- and 10-year relative survival rates were 76%. Histologic types were specified in 99.7% of cases, categorized as follows: 92.7% carcinomas (333 cases), 6.7% sarcomas (24 cases) and 0.3% lymphoma (one case). Carcinomas were clinically evaluated according to FIGO staging: stage I: 61.4% (205 cases); stage II: 7.7% (59 cases); stage III: 7.8% (26 cases); stage IV: 6.6% (22 cases) and unspecified stage: 6.6% (22 cases). The ASR by stage, were 6.4 +/- 0.5 (stage I); 0.8 +/- 0.2 (stage II); 1.3 +/- 0.2 (stages III and IV); 0.6 +/- 0.2 (unspecified stage). The 5-year relative survival rates related to FIGO stage were 90% (stage I); 85% (stage II); 25% (stage III) and 0% (stage IV). Elderly patients (> 75) had significantly lower survival rates. With respect to localized disease (stages I and II) the relative risk of death associated with age older than 75 was 4.9. The 5-year relative survival rate of patients with sarcoma was 37%.

The aim of this study is to check, for a defined period and within a geographic area, whether the increased use of breast conserving treatment was related to changes in tumor characteristics, or whether changes in therapeutical practice persisted after adjustment on patients and tumor characteristics. From 1982 to 1990, 1,952 women with invasive carcinomas were registered in the French "departement" of Côte-d'Or. Seventeen hundred and seven non metastatic patients were treated by loco-regional surgery. A breast conserving surgery was performed in 60% of cases. The incidence of this treatment raised from 32% in 1982 to 73% in 1987. In univariate analysis, factors determining the type of tumor excision were: age, hormonal status, tumor size, tumor location, "clinical seriousness", nodal status, multiple tumors, inflammatory tumors, neoadjuvant treatments and year of diagnosis. Age and tumoral factors remained significant in a logistic regression analysis. Other factors being constant, the odds ratios of mastectomy was 12.9 times lower in 1987-1990 than in 1982, and 2.1 times lower than in 1985-1986, showing a "period effect". Ninety four percent of patients treated by breast conserving surgery were irradiated post operatively, showing that the clinical research recommendations were well transferred to the clinical practice in this department.

Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy (55/59), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoral bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases.