Dosimetry comparison between volumetric modulated arc therapy with RapidArc and fixed field dynamic IMRT for local-regionally advanced nasopharyngeal carcinoma

Objective: A dosimetric study was performed to evaluate the performance of volumetric modulated arc radiotherapy with RapidArc on locally advanced nasopharyngeal carcinoma (NPC). Methods: The CT scan data sets of 20 patients of locally advanced NPC were selected randomly. The plans were managed using volumetric modulated arc with RapidArc and fixed nine-field coplanar dynamic intensity-modulated radiotherapy (IMRT) for these patients. The dosimetry of the planning target volumes (PTV), the organs at risk (O...     

Effects of dosimetric inadequacy on local control and toxicities in the patients with T4 nasopharyngeal carcinoma extending into the intracranial space and treated with intensity-modulated radiotherapy plus chemotherapy

Background:To protect neurological tissues,underdosing occurs in most cases ofT4 nasopharyngeal carcinoma (NPC) with intracranial extension.In this study,we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy.Methods:We prospectively enrolled patients who had non-metastatic T4 NPC with intracranial extension treated between January 2009 and November 2013.The prescribed dose was 66.0-70.4 Gy to the primary planning target volume (primary gross tumor volume [GTVp;i.e.,the nasopharyngeal tumor] + 5.0 mm).Dose-volume histogram parameters were calculated,including minimum point dose (Dmin) and dose to 95％ of the target volume (D9s).All patients received chemotherapy with the cisplatin,5-fluorouracil,and docetaxel regimen.Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test.Results:In total,41 patients were enrolled.The local partial response rate was 87.8％ after induction chemotherapy.With a median follow-up of 51 months,7 patients experienced failure in the nasopharynx;the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4％ and 90.2％,respectively.The actual mean Dmin to the GTVp was 55.2 Gy (range 48.3-67.3 Gy),and D9s was 61.6 Gy (range 52.6-69.0 Gy).All doses received by neurological organs remained well within their dose constraints.No patients developed temporal lobe necrosis or other neurological dysfunctions.Conclusions:With relative underdosed IMRT plus effective chemotherapy,the patients achieved satisfactory local control with few late toxicities of the central nervous system.Determining the acceptable extent of dosimetric inadequacy requires further exploration.     

局部晚期宫颈癌调强和适形放疗的剂量学对比研究(英文)

Objective:This study was to compare 5 field conformal technique to the intensity modulated radiotherapy (IMRT) 8 fields technique in boosting locally advanced cancer cervix cases after external beam radiotherapy with respect to target volume coverage and dose to normal tissues. Methods:We conducted a single institutional comparative dosimetric analysis of 10 patients with cancer cervix who was presented to radiotherapy department in National Cancer Institute, Cairo in period between June 2012 to September 2012 and received a CRT boost in the place of planned brachytherapy after large field pelvic radiotherapy (PRT) with concurrent chemotherapy were retrospectively identified. All tumors were situated in the low central pelvis. Two plans were done for every patient; one using the 8 fields IMRT and the second one using 5 fields’ 3DCRT the two techniques were then compared using dose volume histogram (DVH) analysis for the PTV, bladder, rectum and both femoral heads. Results:Comparing different DVHs, it was found that the planning target volume (PTV) was adequately covered in both plans while it was demonstrates that the 8 fields IMRT technique carried less doses reaching OARs (rectum, bladder, both femoral heads). Conclusion:From the present study, it is concluded that IMRT technique spared more efficiently OARs than CRT technique but both techniques covered the PTV adequately so whenever possible IMRT technique should be used.     

Dosimetric analysis of tomotherapy-based intensity-modulated radiotherapy with and without bone marrow sparing for the treatment of cervical cancer

Objective The aim of the study was to compare tomotherapy-based bone marrow-sparing intensity-modulated radiotherapy(BMS-IMRT) with intensity-modulated radiotherapy(IMRT) without entering the pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods BMS-IMRT and IMRT plans were designed for a cohort of nine patients. The prescribed dose was 45 Gy in 1.8 Gy daily fractions, and 95% of the planned target volume received this dose. The doses were computed using a commercially available treatment planning system with the convolution/superposition algorithm. Plans were compared according to dose-volume histogram analysis in terms of planning target volume homogeneity and conformity indices(HI and CI) as well as organ at risk dose and volume parameters. Results BMS-IMRT had advantages over IMRT in terms of CI, but was equivalent to the latter in HI. V5, V10, V20, V30, and V40 of pelvic bone marrow in BMS-IMRT decreased by 0.06%, 17.33%, 22.19%, 13.85%, and 16.46%, respectively, compared with IMRT. Except for V30 of the small bowel and V30 and V40 of the bladder, no statistically significant differences were found between BMS-IMRT and IMRT in the small bowel, bladder, and rectum. Conclusion For cervical cancer patients receiving tomotherapy-based radiotherapy after hysterectomy, BMS-IMRT reduced pelvic bone marrow volume receiving low-dose radiation, and it may be conducive to preventing acute hematologic toxicity.     

儿科患者的同时整和加量调强放射治疗:对两个商业治疗计划系统的评价(英文)

Objective: The aim of the work was to compare the dosimetric results that were obtained by using two treatment planning systems (TPS) Siemens KonRad version 2.2.23, Elekta XiO version 4.4 to perform a simultaneous integrated boost (SIB) for head and neck and central nervous system (CNS) cases in paediatric patients. Methods: The CT scan data for five paediatric patients, with head and neck and CNS tumors, were transferred into both of the TPSs. Clinical step-and-shoot intensity-modulated radiotherapy (IMRT) treatment plans were designed using 6 MV photon beam for delivery on a Siemens Oncor Accelerator with multileaf collimator MLC (82 leaf). Plans were optimized to achieve the same clinical objectives using the same beam energy, number and direction of beams. The analysis was based on isodose distributions, the dose volume histogram (DVH) for planning target volume (PTV) and the relevant organs at risk (OARs) as well as volume receiving 2 Gy and 5 Gy, also total number of segments, MU/segment, and the number of MU/cGy had been investigated. Treatment delivery time and conformation number were two other parameters in this study. Results: The segmentation using KonRad was more efficient, resulting in fewer segments (reduction between 13.2% and 48.3%), fewer MUs (reduction between 10.7% and 33%) and that reflected on treatment delivery times to be shorter by up to 8 min or 46%. In most of the cases KonRad had the highest volume receiving in excess of 2 and 5 Gy, and XiO showed the lowest. Also KonRad achieved slightly better conformality (0.76±0.054) than XiO (0.73±0.05) while XiO presented a higher modulation factor value (3.3 MU/cGy) than KonRad (2.4 MU/cGy). Conclusion: The KonRad treatment planning system was found to be superior to the XiO treatment planning system. This is true for the possible increase of radiation-induced secondary malignancies as well as for the local control.     

Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment

The volumetric modulated arc therapy(VMAT)technique,in the form of RapidArc,is widely used to treat prostate cancer.The full-single arc(f-SA)technique in RapidArc planning for prostate cancer treatment provides efficient treatment,but it also delivers a higher radiation dose to the rectum.This study aimed to compare the dosimetric results from the new partial-single arc(p-SA)technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment.In this study,10 patients with lowrisk prostate cancer were selected.For each patient,two sets of RapidArc plans(f-SA and p-SA)were created in the Eclipse treatment planning system.The f-SA plan was created using one full arc,and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors.Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters.The f-SA and p-SA plans showed an average difference of±1%for the doses to the planning target volume(PTV),and there were no clear differences in dose homogeneity or plan conformity.In comparison to the f-SA technique,the p-SA technique reduced the doses to the rectum by approximately 6.1%to 21.2%,to the bladder by approximately 10.3%to 29.5%,and to the penile bulb by approximately 2.2%.In contrast,the dose to the femoral heads,the integral dose,and the number of monitor units were higher in the p-SA plans by approximately 34.4%,7.7%,and 9.2%,respectively.In conclusion,it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment.For the same PTV coverage and identical plan optimization parameters,the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.     

图像引导鼻咽癌调强放疗位置误差导致剂量差异分析

Objective To discuss the set-up isocenter error based on kilovolt cone beam computed tomography (KVCBCT) and to investigate dose deviation led to set-up isocenter error. Methods 21 cases of nasopharyngeal carcinoma ( NPC ) treated with image guided intensity modulated radiotherapy (IG-IMRT)were investigated. The online KVCBCT scan, rigid image registration, set-up error was gained for 376 sets before radiotherapy. We sampled ten and fifteen setup isocenter error in the 376 sets randomly. Without changing beam angle,fields size and leaf sequences and dose weight et al. , we only replaced new isocenter and accumulated the new plan for ten or fifteen plans. We compared the percentage deviation between ten,fifteen times accumulated plans and normal ten , fifteen times plans. Results All 376 sets of KVCBCT image were analyzed for 21 cases. Under the condition of non-correction, the setup isocenter errors are 0. 75mm ± 1.13 mm, 0. 92 mm ±2. 15 mm,0. 82 mm ± 1.24 mm in left-right, superior-inferior and anteriorposterior directions respectively. So, we developed the margins which were 4 mm,6 mm、4 mm in three directions respectively from clinical tumor volume to planning tumor volume (PTV) calculated by two parameters model. In the fifteen accumulated plan, the deviation in the dose of 95% PTV (D95) was -7. 5% - - 11.9%, and the deviation in the D50 was -5. 1% - -8. 2%. Conclusions It is possible of small effects to normal organs and targets because of small error of patient displacement in one fraction.However, many small errors can led to considerable dose difference in targets and normal tissue in thirty fractions of all treatments period. So, according to two parameters model, PTV margin can be designed new planning and depended on IG-IMRT technique, which it will be significantly reduced these dose differences.     

乳腺癌保乳术后常规、三维适形及两种调强放疗技术剂量学评估(英文)

Objective: The purpose of this study was to compare the dose distribution and dose volume histogram (DVH) of the planning target volume (PTV) and organs at risk (OARs) among conventional radiation therapy (CR), three-dimensional conformal radiation therapy (3DCRT), two-step intensity-modulated radiation therapy (TS-IMRT) and direct machine parameter optimization intensity-modulated radiation therapy (DMPO-IMRT) after breast-conserving surgery. Methods: For each of 20 randomly chosen patients, 4 plans were designed using 4 irradiation techniques. The prescribed dose was 50 Gy/2 Gy/25 f, 95% of the planning target volume received this dose. The cumulated DVHs and 3D dose distributions of CR, 3DCRT, TS-IMRT and DMPO-IMRT plans were compared. Results: For the homogeneity indices, no statistically significant difference was observed among CR, 3DCRT, TS-IMRT and DMPO-IMRT while the difference of the conformality indices were statistically significant. With regard to the organs at risk, IMRT and 3DCRT showed a significantly fewer exposure dose to the ipsilateral lung than CR in the high-dose area while in the low-dose area, IMRT demonstrated a significant increase of exposure dose to ipsilateral lung, heart and contralateral breast compared with 3DCRT and CR. In addition, the monitor units (MUs) for DMPO-IMRT were approximately 26% more than those of TS-IMRT and the segments of the former were approximately 24% less than those of the latter. Conclusion: Compared with CR, 3DCRT and IMRT improved the homogeneity and conformity of PTV, reduced the irradiated volume of OARs in high dose area but IMRT increased the irradiated volume of OARs in low dose area. DMPO-IMRT plan has fewer delivery time but more MUs than TS-IMRT.     

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma:a feasibility study

There is increasing interest in the clinical use of flattening filter-free(FFF) beams.In this study,we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy(VMAT) with FFF beams for nasopharyngeal carcinoma(NPC).Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams(RA-FFF) or conventional beams(RA-C).The doses to the planning target volumes(PTVs),organs at risk(OARs),and normal tissues were compared.The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams.Both techniques delivered adequate doses to PTVs.For PTVs,RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF.Both techniques provided similar maximum doses to the optic nerves and lenses.For the brain stem,spinal cord,larynx,parotid glands,oral cavity,and skin,RA-FFF showed significant dose increases compared to RA-C.The dose to normal tissue was lower in RA-FFF.The monitor units(MUs) were(536 ± 46) MU for RA-FFF and(501± 25) MU for RA-C.The treatment duration did not significantly differbetween plans.Although both treatment plans could meet clinical needs,RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Résumé: Lefficacité optimale des fluoropyrimidines nécessite des concentrations élevées en 5-10 méthylènetétrahydrofolate (CH₂FH₄), contrôlées par la méthylènetétrahydrofolate réductase (MTHFR) qui convertit irréversiblement le CH₂FH₄ en 5-méthyltétrahydrofolate (CH₃FH₄). Les polymorphismes 677CT et 1298AC du gène MTHFR sont associés à une baisse dactivité de lenzyme. Les tumeurs «MTHFR mutées» devraient donc être plus sensibles aux fluoropyrimidines que les tumeurs «MTHFR sauvages». Les études expérimentales et cliniques publiées à ce jour tendent à montrer une plus grande sensibilité au 5-FU (associé ou non à lacide folinique) dans les tumeurs MTHFR mutées par rapport aux tumeurs sauvages. Ces résultats montrent la nécessité de poursuivre ces recherches afin de confirmer limpact de ces polymorphismes sur lefficacité des fluoropyrimidines.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

PSA-Test zur Früherkennung des Prostatakarzinoms

Zusammenfassung Prostatakrebs ist hierzulande seit einigen Jahren die häufigste Krebserkrankung bei Männern. Da über die Ätiologie wenig gesichertes Wissen vorliegt und daher kaum Möglichkeiten zur primären Prävention bestehen, konzentrieren sich die Anstrengungen auf die Suche nach wirksamen Verfahren zur sekundären Prävention. Hierbei gilt die Verwendung des PSA-Tests zur Früherkennung des Prostatakarzinoms als derzeit aussichtsreichstes Verfahren. Bevor ein neues Früherkennungsverfahren zur breiten Anwendung empfohlen oder in das gesetzliche Früherkennungsprogramm aufgenommen wird, muss jedoch seine Wirksamkeit in hierfür geeigneten wissenschaftlichen Untersuchungen nachgewiesen werden. Bis jetzt gibt es bereits eine ganze Reihe epidemiologischer Studien zur Effektivität des PSA-Screenings, doch konnte ein Wirksamkeitsnachweis bisher nicht erbracht werden. Zwei große randomisierte Studien in Europa und den USA lassen für die Jahre 2005–08 erste Ergebnisse erwarten. Da epidemiologische Arbeiten belegen, dass durch PSA-Screening eine nicht unerhebliche Überdiagnostik und Übertherapie eintritt, d. h. Schaden angerichtet werden kann, ist das Ergebnis der genannten randomisierten Studien vor weitergehenden Entscheidungen unbedingt abzuwarten. Bis dahin sollte von der Anwendung des PSA-Tests zur Prostatakrebsfrüherkennung unmissverständlich abgeraten werden. Da für den Test bereits ausgiebig Werbung betrieben wurde, kommt einer gründlichen ärztlichen Aufklärung von an dem Test interessierten Personen eine Schlüsselrolle zu.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?