The transmission color value: a novel egg quality measure for recording shell color used for monitoring the stress and health status of a brown layer flock.

Stress and diseases have the potential to influence the deposition of eggshell pigmentation during egg formation. Therefore, defining the shell color of eggs on a daily basis could be a representative method for monitoring stress or health status of a flock and maintaining good performance. A novel way of measuring eggshell color based on visible-near infrared transmission spectroscopy transmission spectra was defined: the transmission color value (TCV). The TCV was calculated as the ratio between the transmission at 643 nm (maximum absorbance of the pigmentation molecule protoporphyrin IX) and the transmission at 610 nm (a reference wavelength). Experiments were carried out to investigate the relevance of TCV for monitoring flock stress and health or even anticipating any factors unfavorable to performance. In 2 small experimental flocks, deliberate heat stress challenges were applied. A medium-scale experimental flock in an aviary was monitored on a daily basis during the whole productive period. From the deliberate heat stress challenges, it was seen that stress had a significant effect on eggshell pigmentation. This observation was confirmed in a daily monitored flock, in which, for example, an infectious bronchitis infection occurred. These stress situations were quickly reflected by an increased TCV value: more transmission due to less pigmentation and hence less absorbance at the pigmentation wavelength. Furthermore, for the observed problems in the daily monitoring, the TCV value signaled the problem earlier (4 d) than the average egg weight or even signaled when the other parameters did not signal anything. Measuring the TCV of all eggs produced on a daily basis provides relevant information on the stress or health status of a flock of brown layers. This could be used as an early detection of stress situations or emerging diseases, even before important quality and health damage can occur.

Whole-body hyperthermia in the scope of von Ardenne's systemic cancer multistep therapy (sCMT) combined with chemotherapy in patients with metastatic colorectal cancer: a phase I/II study.

This phase I/II study evaluated the feasibility, toxicity and response rates of von Ardenne's systemic cancer multistep therapy (sCMT) when applied as an adjunct to cytostatic therapy in patients with metastatic colorectal cancer. sCMT consists of whole-body hyperthermia (WBH) at 41.8-42.1 degrees C, hyperglycaemia and hyperoxaemia. All patients who entered the trial first received three monthly courses of chemotherapy (folinic acid, 50 mg, days 1-5; 5-fluorouracil, 425 mg/m2, days 1-5; mitomycin 8 mg/m2, day 1), followed by response evaluation according World Health Organization (WHO) criteria. Responders (partial/complete remission) were assigned to three further courses of chemotherapy, whereas non-responders (stable/progressive disease) were allocated to additional sCMT on day 1 of every subsequent chemotherapy course. The WBH procedure was administered under general anaesthesia employing the Iratherm-2000 radiant heat device. Of 28 patients enrolled, 19 received more than three treatment courses. Eight of these 19 patients had responded to chemotherapy (PR) and thus obtained three further courses of chemotherapy alone. In 10 of 19 patients who had not responded (SD, PD), three additional courses of chemotherapy were combined with sCMT (with 25 sCMT applications). One patient who did not respond to initial treatment declined sCMT and was continued with chemotherapy alone. It was found that sCMT was feasible, but associated with a specific spectrum of grade III/IV toxicity (skin 20%, pain 16%, peripheral nerves 8% of treatment courses). The fact that three patients who did not respond to initial chemotherapy achieved a PR after additional sCMT suggests that sCMT may enhance the effect of chemotherapy in patients with colorectal cancer.

Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial.

Therapeutic vaccination of tumor patients with cytokine gene-transfected tumor cells leads to tumor regression in animal models but has so far not resulted in significant clinical benefit. We and others demonstrated that tumor cells transfected to mediate overexpression of a cytokine gene activate immunologic effector cells for an improved proliferation rate and significantly higher antitumoral cytotoxic activity. Here, we performed a pilot study of therapeutic vaccination in patients with metastatic disease. Autologous tumor cells were simultaneously transfected with novel minimalistic, immunogenically defined, gene expression constructs (MIDGE) for overexpression of the two cytokines interleukin 7 (IL-7) and GM-CSF and newly designed double stem-loop immunomodulating oligodeoxyribonucleotides (d-SLIM) as a Th1-promoting and NK cell-stimulating adjuvant. Transfection was performed ex vivo by ballistomagnetic gene transfer. Patients received four subcutaneous injections of at least 1 x 10(6) of their expression-modulated and immunomodified autologous tumor cells. Ten patients have been enrolled in the study protocol. In all patients no adverse effects could be detected. IL-7 and interferon gamma levels were elevated in the serum of the patients after treatment. Interestingly, cytotoxicity of patient-derived PBLs increased significantly during treatment. All 10 patients had progressive disease when entering our protocol. One complete, one partial, and one mixed response with progression of abdominal metastases and regression of lung metastases were observed. Two patients showed a stable disease after treatment and five patients remained in progressive disease. Our observations confirm the capability of autologous expression-modified and immunomodulated tumor cell vaccines to stimulate a strong immune response in patients with metastatic cancer even in the presence of a large tumor burden.

Feasibility and analysis of thermal parameters for the whole-body-hyperthermia system IRATHERM-2000.

The infrared system IRATHERM-2000, with water-filtered infrared A wavelength underwent 20 treatments of whole body hyperthermia in conjunction with chemotherapy. In all the sessions, the aimed systemic temperature (41.8 degrees C, maximum 42.0 degrees C) could be achieved and maintained for 60 min. Due to increasing clinical experience, the unnegligible local toxicity, exhibited as heat-induced superficial lesions, and neurotoxicity, could be reduced during the course of the study. Data from three other series accomplished at the von Ardenne Clinic, totalling 120 heat sessions, were available and included for a comparative analysis. Analysis of the toxicity shows that a correlation exists between thermal side-effects and heat-up periods (until steady-state), maximum temperatures, and superficial thermal doses. The time needed to reach the plateau seems to correlate with fluid loss, which, thus, indirectly influences toxicity, and most importantly the initial power level. The typical heat-up time in such a standard set-up amounts to 100-150 min, for a temperature rise from 37.5 to 42.0 degrees C. Evaluation of the energy balance reveals a highly patient-specific range for the reactive evaporation in the IRATHERM system, resulting in a power (heat) loss of up to 1400 W via sweat production of approximately 2 l/h. In order to counterbalance this effect, an accordingly high infrared power, ranging from 1200-1500 W, needs to be delivered, resulting in a significant thermal skin exposition. Concepts used to reduce the heat loss by reactive evaporation include prevention of convection by appropriate sealing of the heating chamber and increasing the humidity by a nebulizer. For the more trained user, the heat-up time can be considerably shortened, particularly, in the introductory phase of the heating process, by employing higher, but still tolerable, patient-specific power levels. However, such a strategy requires, due to higher risks, close monitoring of skin temperatures together with a considerable amount of clinical experience. The results of the IRATHERM pilot study were compared, not only with previous groups where the IRATHERM was applied, but also with results of various other investigators where the Enthermics Radiant Heat Device was employed. In the authors' opinion, improved understanding of the mechanisms and crucial parameters underlying whole body hyperthermia, will enable a controllable and tolerable therapy through proficient contribution to equipment and methods.

Whole body hyperthermia: a secure procedure for patients with various malignancies?

OBJECTIVE: To establish the safety of systemic Cancer Multistep Therapy (sCMT) including whole body hyperthermia, by means of hemodynamic, laboratory and clinical investigations. DESIGN: Prospective study. SETTING: University clinic. PATIENTS: 12 patients with various cancers (with sCMT), a second group of 20 patients with colorectal carcinoma treated with chemotherapy (without sCMT). INTERVENTIONS: 25 treatments with sCMT for 60 min at 41.8 degrees C (including chemotherapy) were given in addition to induced hyperoxemia and hyperglycemia under general anesthesia. MEASUREMENTS AND RESULTS: Invasive monitoring of systemic and pulmonary hemodynamics as well as pulmonary gas exchange was used at 37 degrees C, 40 degrees C, 41.8 degrees C and 39 degrees C. In addition, laboratory parameters were measured before and within 4 days of therapy. At 41.8 degrees C, invasive monitoring showed characteristic signs of hyperdynamic circulation. In addition, right-to-left shunt, oxygen consumption, oxygen delivery and lactate levels were significantly different from pretreatment values. At the end of therapy, lactate levels and the extravascular lung water index increased, whereas all other parameters showed a clear tendency to return to initial values. Within the first day after sCMT, we measured a slight but significant reversible increase in serum creatinine compared to pretreatment values, but found no significant alterations of other chemical parameters. Between the sCMT group and controls, there was only a temporary significant difference in aspartate aminotransferase levels 2 days after therapy. CONCLUSIONS: sCMT, including whole body hyperthermia, accompanied by suitable anesthesiological management and monitoring, does not lead to any serious or sustained organ dysfunction and can therefore be regarded as a safe therapy.

[Phase II study on preoperative radio-chemo-thermotherapy in locally advanced rectal carcinoma]. / Phase-II-Studie zur präoperativen Radio-Chemo-Thermo-Therapie beim lokal fortgeschrittenen Rektum-Karzinom.

BACKGROUND: Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas. PATIENTS AND METHODS: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. RESULTS: Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too. CONCLUSIONS: Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.

Radiochemotherapy and hyperthermia in the treatment of rectal cancer.

We evaluated the use of regional hyperthermia with radio-chemotherapy in a phase I/II study on locally advanced rectal carcinomas. Thirty-four patients with primary advanced (stage T3/T4) rectal carcinomas (24 patients) or recurring rectal carcinomas (6 patients) were treated using preoperative radiochemo-thermotherapy. Initial tumour staging was carried out clinically (degree of fixation) and using endorectal ultrasonography and CT. Radiotherapy was carried out with the patient prone (on a belly board) at 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300-500 mg/m2) was administered with low-dose leucovorin (50 mg) on days 1-5 and 22-26. Patients were treated with regional hyperthermia each week prior to radiotherapy, using the Sigma-60 ring of the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded via endocavitary catheters (tumour contact, bladder, vagina). Following endosonographic and clinical restaging, the operation was carried out 4-6 weeks after the end of preoperative therapy. In cases where tumours were unresectable, a boost of up to 60 Gy was given. Twenty-three of the 34 patients (68%) proved to be curatively resectable. Of these patients, 70% were downstaged endosonographically during preoperative therapy. The actuarial survival rates among these patients were 85% (primary rectal cancer) and 60% (recurrences) at 30 months. All in all, the preoperative multimodal therapy was well tolerated, and premature termination was necessary in only two cases. The quality of temperature distribution (T90, cum min T90 > 40.5 degrees C) depends on the power level and relative power density. The response (particularly downstaging) correlates significantly with the quality parameters of the temperature distributions. This regimen proved practical and effective, with encouraging downstaging rates and local control rates.

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma.

We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 microg/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 x 10(3) WBC/microl (6.8-46.9), 3.5 x 10(3) MNC/microl (1.1-8.8), 122 x 10(3) platelets/microl (72-293) and 30.7 CD34+ cells/microl (6.7-207.8). Cumulative harvests resulted in medians of 4.6 x 10(8) MNC/kg (3.0-6.4), 2.9 x 10(6) CD34+ cells/kg (1.1-11.1) and 12.0 x 10(4) CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC >0.5 x 10(3)/microl and 14 days (8-27) for platelets >20 x 10(3)/microl. One patient, who received 1.6 x 10(6) CD34+ cells/kg, exhibited delayed ANC recovery on day +37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT.

Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial.

OBJECTIVE: A prospective phase II study was performed to determine the feasibility and efficacy in terms of response rate, resectability, and morbidity in patients with locally advanced rectal cancer who received preoperative regional hyperthermia combined with radiochemotherapy (HRCT). SUMMARY BACKGROUND DATA: Recent studies suggest that preoperative radiochemotherapy in locally advanced rectal cancer can induce downstaging, but after resection the incidence of local recurrences remains high. Hyperthermia (HT) may add tumoricidal effects and improve the efficacy of radiochemotherapy in a trimodal approach. PATIENTS AND METHODS: Thirty-seven patients with histologically proven rectal cancer and T3 or T4 lesions, as determined by endorectal ultrasound and computed tomography, entered the trial. 5-Fluorouracil (300-350 mg/m2) and leucovorin (50 mg) were administered on days 1 to 5 and 22 to 26. Regional HT using the SIGMA 60 applicator (BSD-2000) was given once a week before radiotherapy (45 Gy with 1.8-Gy fractions for 5 weeks). Surgery followed 4 to 6 weeks after completion of HRCT. RESULTS: Preoperative treatment was generally well tolerated, with 16% of patients developing grade III toxicity. No grade IV complications were observed. The overall resectability rate was 32 of 36 patients (89%), and 31 resection specimens had negative margins (R0). One patient refused surgery. In 5 patients (14%), the histopathologic report confirmed no evidence of residual tumor (pCR). A partial remission (PR) was observed in 17 patients (46%). The survival rate after 38 months was 86%. In none of the patients was local recurrence detected after R0(L), but five patients developed distant metastases. CONCLUSION: Preoperative HRCT is feasible and effective and may contribute to locoregional tumor control of advanced rectal cancer, which is to be proven in an ongoing phase III trial.

[A phase-I/II study on the local hyperthermia of cervical N2/N3 lymph node metastases]. / Phase-I/II-Studie zur lokalen Hyperthermie zervikaler N2/N3-Lymphknotenmetastasen.

BACKGROUND: Patients with advanced lymph node metastases from head and neck tumors at stage N2/N3 (i.e. UICC IV) present a difficult therapeutic problem. Despite combined radio-chemotherapy and hyperfractionated and/or accelerated fractionation regimens, local control of these tumors remains unsatisfactory. For this reason, the value of local radio wave/microwave hyperthermia was examined for this patient group in a phase I/II study.

Local hyperthermia of N2/N3 cervical lymph node metastases: correlationof technical/thermal parameters and response.

PURPOSE: Patients with advanced head and neck carcinomas, primarily nonresectable as well as recurrent cases, were treated in multimodality regimens with radiotherapy, chemotherapy, and local hyperthermia. Commercially available microwave and radiowave applicators were used in 50 patients with N2/N3 cervical lymph node metastases during more than 250 heat treatments. To assess technical suitability, the achieved power densities and thermal parameters were tested for correlation with anatomical and geometrical factors. To assess effectiveness, the response was compared with derived parameters of the achieved temperature distributions. METHODS AND MATERIALS: The temperature measurement points (in thermometry catheters) documented by computerized tomography are labeled according to tissue depth, shielding by osseous structures, and location in relation to the external applicators. Relative and absolute specific absorption rates (SAR) and cooling coefficients are extracted from the temperature-time curves. Time-averaged temperature-position curves are evaluated to obtain index temperatures (T90, T50, T20), minimum/maximum tumor temperatures, cumulative minutes T90 > or = 43 degrees C, and 43 degrees C-equivalent min T90. Radiation dose, treatment time, and chemotherapy regiment are also considered. A response parameter is defined using the pre- and posttherapeutic tumor volumes. A multivariate variance analysis is performed for the dependent variables power density, thermal parameters, and response. RESULTS: A significant correlation exists between power density and absorption, presence of a fat layer, and applicator illumination. The maximum depth is 5 cm, where SAR of >= 10 mW/g are registered. Achieved temperatures at individual measurement points are dependent on the SAR, and to a lesser extent, the perfusion-dependent cooling coefficients, but the index temperature T90 is only significantly related to intratumorally achieved SAR. The thermal gradient (T20-T50) and temperature peak (T20) are significantly influenced by the tumor volume. The response is directly related to the index temperature T90, equivalent minute T90 43 degrees C, and cumulative minutes T90 > or = 40.5 degrees C, and inversely related to the tumor volume. CONCLUSIONS: Local hyperthermia using microwave and radiowave applicators in the head and neck region is a tolerable and clinically practical supplementary therapy used as part of multimodal regimens, and has already been proven to be effective. However, the analyses also demonstrated the limits of currently available technology, and confirm the need for continued methodical research.

Hyperthermia in the multimodal therapy of advanced rectal carcinomas.

The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were R0-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.

Chemotherapy for patients with adenocarcinoma of the pancreas.

Adenocarcinomas of the pancreas are diagnosed at an advanced, non-curable stage in most patients. In addition to local relapse or progression, distant metastases determine the poor prognosis, resulting in a median survival of less than 6 months in most studies of patients with locally advanced or metastatic pancreatic cancer. None of the cytotoxic drugs available show impressive activity in treatment of this disease. Therefore, chemotherapy is not recommended in pancreatic cancer. In selected cases, 5-fluorouracil-based therapy - with or without simultaneous radiation - may result in tumor responses. With a once-a-week outpatient protocol of folinic acid and 5-fluorouracil, we observed a progression-free period from 15 to 42 weeks in nine of 19 patients treated without any serious adverse effects, confirming reports of the weak, but well-tolerated activity of this combination. To alter the prognosis for patients with advanced adenocarcinomas of the pancreas, new drugs with more activity have to be developed and tested in well-designed trials.

[The use of an early postoperative interstitial-hyperthermia combination therapy in malignant gliomas]. / Einsatz einer früh postoperativen interstitiellen Hyperthermiekombinationstherapie bei malignen Gliomen.

BACKGROUND: The survival of people suffering from malignant gliomas (WHO level III and IV) is predominantly limited by local progress in the primary tumor region. Interstitial hyperthermia combined with radiotherapy or chemotherapy is one approach for the intensification of local therapy. It is possible to combine (partial) tumor resection with hyperthermia as well as with brachytherapy by implanting catheters intraoperatively. PATIENTS AND METHODS: A pilot study was performed to examine practicality, tolerability, effectiveness and scope for improvement in early postoperative hyperthermia treatment following catheter implantation as part of (partial) tumor resection. Each CT data set was transferred into a VAX 3100 workstation for retrospective analysis of the hyperthermia treatment. The implanted catheters were segmented and the distributions of power density and temperature were simulated. We sought to achieve the best possible temperature distributions by optimising the catheter arrangement in the planning calculations. The corresponding Ir-192-source brachytherapy treatments were simulated in a similar way using the implanted, as well as optimised catheter arrays. RESULTS: Intraoperative catheter implantation in 4 patients was problem-free. Postoperative complications were not observed, neither were infections. Interstitial microwave hyperthermia in combination with percutaneous irradiation or chemotherapy a few days after the operation was also tolerated well by all patients. Effective temperatures (of at least 42 degrees C) were regularly achieved at measurement points, but the temperature distributions were unsatisfactory, with T90 values (the temperature reached in at least 90% of the target volume) of under 38 degrees C. Measured temperature/position curves showed qualitative correlation with the simulated calculations. The catheter positions determined by optimisation varied significantly from the positions clinically used. CONCLUSIONS: Early postoperative combination therapy using hyperthermia for the treatment of malignant gliomas is a very practical approach. The optimisation strategies described should be used preoperatively to plan catheter arrays for interstitial hyperthermia and brachytherapy, and these arrays should be implanted using stereotaxic surgery.

A pilot study of a new therapeutic approach in the treatment of locally advanced stages of rectal cancer: neoadjuvant radiation, chemotherapy and regional hyperthermia.

The synergistic effects of hyperthermia (temperatures > or = 41 degrees C) when combined with radiotherapy or cytotoxic drugs, as well as a modulation of tumour-related immunological phenomena have been demonstrated preclinically. Local or regional hyperthermia in combination with radiation or chemotherapy has been studied in patients during recent years, and has convincingly demonstrated that hyperthermia is feasible and tolerated by patients. Furthermore, there is strong evidence that hyperthermia may provide an improvement in local control as compared with radiotherapy or chemotherapy alone. Systems based on radiowave irradiation allow sufficiently tolerable and effective regional hyperthermic therapy in patients with rectal carcinomas. Used as part of curative pre-operative and postoperative multimodal therapeutic strategies in high-risk patients with locally advanced rectal carcinomas, hyperthermia may result in improved local control and a higher rate of sphincter-sparing procedures. 20 patients with non-resectable, locally advanced primary or recurring rectal carcinoma T3/4 entered a phase I/II study of pre-operative radiochemothermotherapy with folinic acid and 5-fluorouracil, radiation (45 Gy HD), as well as regional hyperthermia once a week followed by chemotherapy after surgery. The regimen proved to be sufficiently tolerable. Acute grade III or IV toxicities did not occur after hyperthermia. Tumour resections were performed on 14 of the 20 patients, with 13 being complete. In 9 of the carcinomas, downstaging compared with the pretherapeutic stage was achieved. In 3 of 6 patients with persistent non-resectable tumours, local control has now been maintained for more than 12 months. One patient progressed locally during neoadjuvant combination therapy. These results prompted the initiation of a prospective randomised study to evaluate the relative importance of regional hyperthermia in this setting.

Clinical, physiological and anatomical determinants for radiofrequency hyperthermia.

Temperature/time curves and corresponding CT scans of > 200 regional heat treatments with the hyperthermia system BSD-2000 in 43 patients have been analysed. In vivo variables and treatment parameters such as local specific absorption rate SAR, local relative SAR parallel SAR parallel, total power P, local cooling coefficients wb, and local steady-state temperature elevations delta Tss (above systemic temperature) have been determined. For determination of wb the well-known and accepted steady-state approach has been used, which was slightly modified for the purposes of this study. Specifically, comparison of cooling coefficients at the beginning and end of heat treatments were performed in tumours and normal tissues. Other variables are anatomical descriptors from CT scans, score of side effects plim, and various clinical factors. A variance analysis of the dependent variables, specifically delta Tss and parallel SAR parallel, is performed with respect to factors which were estimated as predictive. The intratumoral steady-state temperature elevations are determined by the perfusion-related cooling coefficients and local SAR to almost the same extent. Increase of cooling coefficients in tumours during the heat treatment characterizing the thermoregulatory potential have a slight but less important influence with respect to the achieved temperature elevations. SAR is influenced by several anatomical factors which determine the relative SAR distribution and clinical factors which limit the total power P. However, options for controlling present RHT systems in order to optimize the relative SAR distribution or to avoid hot spot phenomena appear limited. Three-dimensional modelling calculations show that the spatial arrangement of electrical interfaces emerging from bone and fat structures limits SAR control in available RHT technology and is mainly responsible for local power-dependent discomfort (Wust et al. 1994b). Some conclusions are drawn, about how technological development of hyperthermia technology can contribute towards overcoming this problem.