Magnetic resonance imaging of the prostate at 1.5 versus 3.0T: A prospective comparison study of image quality.

OBJECTIVES: This study prospectively evaluates objective image quality (IQ), subjective IQ, and PI-RADS scoring of prostate MRI at 3.0T (3T) and 1.5T (1.5T) within the same patients. METHODS: Sixty-three consecutive patients (64±9years) were prospectively included in this non-inferiority trial, powered at 80% to demonstrate a ≤10% difference in signal-to-noise (SNR) and contrast-to-noise ratio (CNR) of T2-weighted and diffusion-weighted imaging (T2WI, DWI) at 1.5T compared to 3T. Secondary endpoints were analysis of subjective IQ and PI-RADS v2 scoring. RESULTS: All patients received multi-parametric prostate MRI on a 3T (T2WI, DWI, DCE) and bi-parametric MRI (T2WI, DWI) on a 1.5T scanner using body coils, respectively. SNR and CNR of T2WI were similar at 1.5T and 3T (p=0.7-1), but of DWI significantly lower at 1.5T (p<0.01). Subjective IQ was significantly better at 3T for both, T2WI and DWI (p<0.01). PI-RADS scores were comparable for both field strengths (p=0.05-1). Inter-reader agreement was excellent for subjective IQ assessment and PI-RADS scoring (k=0.9-1). CONCLUSION: Prostate MRI at 1.5T can reveal comparable objective image quality in T2WI, but is inferior to 3T in DWI and subjective IQ. However, similar PI-RADS scoring and thus diagnostic performance seems feasible independent of the field strength even without an endorectal coil.

Targeted MRI-guided prostate biopsy: are two biopsy cores per MRI-lesion required?

PURPOSE: This study evaluates the feasibility of performing less than two core biopsies per MRI-lesion when performing targeted MR-guided in-bore prostate biopsy. METHODS: Retrospectively evaluated were 1545 biopsy cores of 774 intraprostatic lesions (two cores per lesion) in 290 patients (66 ± 7.8 years; median PSA 8.2 ng/ml) regarding prostate cancer (PCa) detection, Gleason score, and tumor infiltration of the first (FBC) compared to the second biopsy core (SBC). Biopsies were acquired under in-bore MR-guidance. RESULTS: For the biopsy cores, 491 were PCa positive, 239 of 774 (31 %) were FBC and 252 of 771 (33 %) were SBC (p = 0.4). Patient PCa detection rate based on the FBC vs. SBC were 46 % vs. 48 % (p = 0.6). For clinically significant PCa (Gleason score ≥4 + 3 = 7) the detection rate was 18 % for both, FBC and SBC (p = 0.9). Six hundred and eighty-seven SBC (89 %) showed no histologic difference. On the lesion level, 40 SBC detected PCa with negative FBC (7.5 %). Twenty SBC showed a Gleason upgrade from 3 + 3 = 6 to ≥3 + 4 = 7 (2.6 %) and 4 to ≥4 + 3 = 7 (0.5 %). CONCLUSION: The benefit of a second targeted biopsy core per suspicious MRI-lesion is likely minor, especially regarding PCa detection rate and significant Gleason upgrading. Therefore, a further reduction of biopsy cores is reasonable when performing a targeted MR-guided in-bore prostate biopsy. KEY POINTS: • Higher PI-RADS overall score (IV-V) correlated well with PCa detection rate • In more than 80 % SBC was concordant regarding overall PCa detection • In almost 90 % there was no Gleason upgrading by the SBC • Only 2/54 (3.7 %) csPCa was missed when the SBC was omitted • For IB-GB a further reduction of biopsy cores is reasonable.

Basic principles in hyperthermic tumor therapy.

Literature on hyperthermic tumor therapy in the past 10 years has grown exponentially. Since 1975 three international symposia on cancer therapy by hyperthermia have been held. Hyperthermia is of clinical interest in the temperature range of 40 degrees-43 degrees C. Higher temperatures of 44 degrees-46 degrees C are not clinically realizable. With local heat application a higher elevation of tissue temperature is possible. Whole-body hyperthermia in men is limited physiologically, as the rate of complications increases exponentially above 42 degrees C. The heat dose normally is defined by temperature degree and time of temperature elevation. Hyperthermia has several effects on tumor cells. It influences proliferation activity; within the mitotic cycle, preferentially the M-phase cells and S-phase cells are thermosensitive. It is possible to synchronize tumor proliferation by heat. Hyperthermia inactivates tumor cells in hypoxic condition as well. This was demonstrated in vitro with tumor cells under varying oxygenation and with spheroid experimental tumors. Experiments with solid tumors in animals had the same effect. Hyperthermia enhances the effect of radiation on tumors. In solid human tumors only 3%-5% of cells are in growth fraction; 95% of tumor cells are hypoxic or prenecrobiotic. Only well-oxygenated cells are sensitive to a sparsely ionizing radiation and can be killed. This selective radiosensitivity is the reason why other radiation qualities for radiotherapy, which are also effective on hypoxic cells, are examined. Neutrons and heavy ions are densely ionizing radiations, which inactivate hypoxic radioresistant cells. Hyperthermia in combination with sparsely ionizing radiations--e.g., X-rays or gamma rays--could be an alternative to neutrons or heavy ions. The main problem with heat application in clinical radiotherapy is the lack of heating methods which are able to heat the entire volume of a large solid tumor homogeneously. In small experimental animals there is a TER of about 1.5-2.0. The therapeutic gain of additional heat in radiotherapy is greatly dependent on localization of the tumor (skin, extremities) and on cooling of the skin. Hyperthermia enhances cytostatic drugs. Many investigations have been done on the interaction of heat and cytostatics; in vitro experiments evaluated three types. First, the activity of many drugs increases slightly with temperature; no special effects are observed above 42 degrees C. Examples of drugs of that pattern are the hypoxic sensitizer Ro-07-0582 and the alkylating agents thio-TEPA and CCNU. A second type of mechanism is seen with cytostatic drugs which exhibit greatly increased effectiveness at temperatures above 42 degrees C; adriamycin and bleomycin belong to this type.(ABSTRACT TRUNCATED AT 400 WORDS)

Further progress with oncolysis due to apathogenic clostridia.

Cl. onc. apathogenic for human beings and small animals is not able to cure tumor-bearing hosts. Combined treatments with local X-irradiation and local HFH have decreased the death rate of Harding-Passey-Melanoma-bearing mice. A cure rate of ca. 20% has resulted for the first time in such experiments. The survival time has increased significantly, however relapses occured on the sites of transplantation which finally killed the animals. Therefore it was tried to repeat the threefold-combined treatment. The animals with a relapse tolerated such a second and third series well. After the second series of treatment some animals became free of relapse and some after the third series. That means, if repeating treatment with local HFH, local X-irradiation, and i.v. spore-application of Cl. onc., it is possible to cure the Harding-Passey-Melanoma of the mouse at a high percentage.

[Cell loss after combined thermo-radiotherapy. Determination in vivo of the cell-loss rate of euoxic and hypoxic cells of experimental tumors (author's transl)]. / Der Zellverlust nach kombinierter Thermo-Radio-Therapie--Bestimmung der Zellverlustrate bei euoxischen und hypoxischen Tumorzellen an Experimentaltumoren in vivo.

Solid Ehrlich cancers with a volume of one millilitre, situated on the necks of mice, were treated with X-rays (150 kV), a low dose of hyperthermia (high frequency), a high dose of hyperthermia and a combined therapy of mild hyperthermia and X-ray irradiation. As labeling method, the technique of 125-I-deoxyuridine was employed. At the time of the therapy, there uas either a majority of hypoxic tumor cells or a majority of euoxic tumor cells, both in labeled form. The loss of cells was measured externally as a decrease of activity between the 96th and the 192th hour after the injection of 125-I. Xray irradiation tends above all to destroy euoxic cells while hypoxic cells are preponderantly destroyed by high doses of hyperthermia. Mild hyperthermia does not influence the cell loss in a significant manner. Mild hyperthermia in combination with X-ray irradiation, however, increases the loss of hypoxic cells up to the rate of euoxic cells.

[Local high-frequency hyperthermia of the Brown-Pearce carcinoma in the urinary bladder of rabbits (author's transl)]. / Lokale Hochfrequenz-Hyperthermie des Brown-Pearce-Karzinoms der Harnblase des Kaninchens.

The effect of a conductive high-frequency hyperthermia on a model tumor in the urinary bladder of rabbits (Brown-Pearce Carcinoma) was studied at a temperature of 43 degrees C, and with an application time of 30 min. The frequency used was 500 kHz, wattage 30-300 and wavelength 600 m. This resulted in the homogeneous warming of the urinary bladder tissue, in contrast to the results obtained when warm water was injected. Essential test results included: (1) a temperature gradient of max. 6.7 degrees C from the tumor center to the lumen of the urinary bladder, the tumor favoring the higher temperatures; (2) a prolongation of the survival time for animals with heat-treated tumors as opposed to the control animals. After transplantation heat-treated tumors evolved to receptor animals considerably less often than did untreated tumors.

[Intensification of the oncolysis by clostridia by means of radio-frequency hyperthermy in experiments on animals--dependence on dosage and on intervals (author's transl)]. / Verstärkung der Clostridienonkolyse durch Hochfrequenzhyperthermie im Tierversuch--Dosisabhängigkeit und Intervallabhängigkeit

The effect of a local pretreatment by radio-frequency hyperthermy upon the capability of germination and, hence, upon the oncolysis by intravenously given spores of oncolytic clostridia (M55) was tested with 2305 NMRI-mice carrying neck tumors. Using two different experimental tumors (Ehrlich adenocarcinoma and Harding-Passey-melanoma) it is possible to show the dependence of the intensification on the thermic dose. Additionally, there is a distinct dependence of the extent of oncolysis on the time interval between the hyperthermy treatment and the administration of clostridia. The intensification effect in both the tumors is mostly marked twelve hours after hyperthermy. The rapidly growing Ehrlich adenocarcinoma regenerates more quickly than the slowly growing Harding-Passey-melanoma. A period of 12 hours between hyperthermy and injection of clostridia represents a favourable interval for the timing of slowly as well as of rapidly growing tumors.

[Tumor hyperthermia using high frequency for increase of oncolysis by clostridium butyricum (M 55)]. / Tumorhyperthermie mit Hochfrequenz zur Verstärkung der Onkolyse durch Clostridium Butyricum (Stamm M55)

In solid experimental tumors hypoxic cells preferably are inactivated by means of a short-termed radio-frequency treatment with eddy-current fields. Hence follows an increase of the necro-biotic areas. The presence of anoxic-necrobiotic areas is indispensable for the termination of certain anaerobic spores such as Clostridium butyricum s. oncolyticum (M 55). Local tumor hyperthermy is tested as a technique in altogether 861 mice bearing neck tumors, in order to enhance the germination of oncolytic Clostridia in tumors differing by their mode of formation and rate of growth. In all the three test systems used (Ehrlich solid carcinoma, Harding-Pasey-melanoma, fibrosarcoma induced by methylcholanthrene), the oncolysis being brought about by Clostridia can be intensified significantly by means of a short-termed warming of the tumor up to temperatures of 42 to 44 degress C using radio-frequency.

Microwaves in radiotherapy of tumors - alternative to heavy particles?

An increase of the radiosensitivity can be obtained by means of microwave use in combination with sparsely ionizing radiation. Comparing the therapeutic effect on the model of an euoxic tumor (mice testicles) with a tumor that contains important parts of hypoxic cells (solid tumor of Ehrlich) it appears that the sensitization evidentely is seen in the hypoxic tumor first of all. No sensitization can be obtained on the euoxic profileration tissue on the testicles. The temperature enhancement ratio (equal TER) does not increase linearly with increasing temperature, but is the greatest within the scope of 41 degrees C. The mere heat effect appears in the foreground with high temperatures (43 degrees C and more). The high frequency application lets hope a solution of the oxygen problem in radiotherapy and could substitute the use of heavy particles (high LET) in the combination with sparsely ionizing radiation as far as a concentration of high frequency and heat on the tumor succeeds in.

[The influence of high-frequency hyperthermia on Ehrlich-ascites carcinoma in the mouse]. / Der Einfluss einer Hochfrequenz-Hyperthermie auf den Verlauf des Ehrlich-Aszites-Karzinoms der Maus

On 988 NMRI-mice the influence of a single high-frequency hyperthermia of differing intensity in the decimeter-wave field was investigated regarding the course of the Ehrlich's-ascites carcinoma. The application of high frequency (461,04 MHz) was made with an electrode on an induction field of 3,8 cm diameter, and covers the whole peritoneal cavity. No significant prolongation of the survival time was achieved, neither by increasing the intensity up to the final rectal temperature of 40 degrees-43 degrees C, nor by selecting different therapeutic periods during the growth of the tumor (1, 3, 6, and 10 days after inoculation). In contrast to local tumors which can be cured solely by high frequency treatment in the chosen model of a generalized tumor (in which the tumor tissue cannot be separated), no significant therapeutic effect can be reached by sole thermotherapy--not even with the risk of extremous therapy-induced complication rates. An interesting field for research seems to exist as to what extent tumor proliferation kinetics can be influenced by high frequency.