Daniel Den Hoed Cancer Center Research Articles

Comments and controversies

Department of Surgical Oncology, Erasmus University Medical Center – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands Correspondence to Alexander C.J. van Akkooi, MD, PhD, Department of Surgical Oncology, Erasmus University Medical Center – Daniel den Hoed Cancer Center, Groene Hilledijk 301 – Kamer A1-41, 3075EA Rotterdam, The Netherlands Tel: +31 10 7041223; fax: +31 10 7041011; e-mail: [email protected] Received December 17, 2012 Accepted January 18, 2013

Interview: Improving outcome for brain tumor patients.

Martin J van den Bent is trained as a neurologist. Since 1992, he has worked at the Neuro-Oncology Unit of Erasmus MC – Daniel den Hoed Cancer Center in Rotterdam, The Netherlands. In 2002 he became the head of the Neuro-Oncology Unit, which is focused on the treatment of primary brain tumors and on neurological complications of cancer and its treatment. He is currently Professor of Neuro-Oncology at Erasmus University, Rotterdam. He has been the principle investigator of a large number of international multicenter trials on both high- and low-grade glial tumors, most of which were conducted through the European Organisation for Research and Treatment of Cancer Brain Tumor Group. Many of these trials included translational research projects, focusing on the identification of prognostic and predictive molecular parameters of outcomes of treatment. He was Secretary of the European Organisation for Research and Treatment of Cancer Brain Tumor Group from 1996 to 2002 and from 2002 to 2009 he was Chair of this internationally recognized group. He has served as Chairman of the CNS section of the 14th European Cancer Conference and of the Dutch Neuro-Oncology Working Group. He has published widely, not only on the treatment of primary brain tumors, but also on neurological complications of systemic cancers. He has chaired and lectured at numerous national and international educational symposia and scientific meetings on neuro-oncology and serves on the editorial board of several oncology journals, including CNS Oncology. He has written chapters in many textbooks on neuro-oncology and is active in the Response Assessment in Neuro-Oncology Group revising the end points and response criteria of trials in neuro-oncology.

Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p= 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, Tstage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade ≥2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in view of the pattern of failures observed in this study, the role of adjuvant systemic or targeted therapy in patients at high risk of DM should be investigated in prospective trials.

The incidence of pseudo-progression in a cohort of malignant glioma patients treated with chemo-radiation with temozolomide

2009 Background: Radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is now the standard of care for newly diagnosed glioblastoma. The occurrence of pseudo-progression at the end of RT is an often-mentioned phenomenon, but the actual incidence is unknown. It is also unclear if this is only a radiological phenomenon or is accompanied by clinical signs and symptoms. We retrospectively assessed this phenomenon in a cohort of patients treated with chemo-irradiation with temozolomide (RT/TMZ). Methods: The pre- and post-chemo-radiotherapy brain CT’s and MRI’s from all patients treated with RT/TMZ for a malignant glioma in the Daniel den Hoed Cancer Center between 2000 and 2005 were reviewed. Treatment consisted of 60 Gy RT in 6 weeks combined with daily TMZ (75mg/m2/day), followed after 4 weeks by 6 cycles of TMZ (150–200 mg/m2/day 1–5 every 4 weeks). Scans were made prior to the start of RT, four weeks after the end of RT and thereafter every three months. Macdonald’s criteria were used to assess the response. In addition information was collected on clinical signs and symptoms, dexamethasone dose, histology, and survival. Results: Sixty-five patients were identified; 54 had been diagnosed with a GBM. Mean age was 48 years and 42 were male. In 23 patients the first follow-up scan 4 weeks after the end of RT showed progression as compared to the pre-RT imaging. This was accompanied by clinical deterioration in12 patients. All patients continued with adjuvant TMZ. In 12 of these 23 patients the MRI and clinical signs and symptoms stabilized or improved in the months thereafter. In 8 of these 12 patients a response was observed without additional treatment other than TMZ. In none of these cases changes in dexamethasone dose could explain the observed MRI changes. Conclusions: In up to 50% of high grade glioma patients treated with chemo-irradiation with TMZ and a progressive MRI lesion immediately after RT suffer from pseudo-progression; this was observed in 12 out of 65 patients. These data support the notion to continue TMZ in case of progressive lesions immediately after RT/TMZ. Studies on recurrent gliomas that accept patients with progressive lesions directly after chemo-radiation will lead to an overestimation of the results. No significant financial relationships to disclose.

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer

Aims To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. Methods In the period 1994–2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. Results Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p = 0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. Conclusion TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Total pelvic exenteration for primary locally advanced and recurrent rectal cancer

Aims: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. Methods: In the period 1994e2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. Results: Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p ¼ 0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. Conclusion: TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival. 2006 Elsevier Ltd. All rights reserved.

CO2-laser treatment of recurrent glottic carcinoma.

Evaluation of the results of CO2 laser treatment of recurrent glottic carcinoma after radiotherapy. Records of all patients treated in the University Hospital Rotterdam and the Dr. Daniel den Hoed Cancer Center between 1980 and 1996 by CO2 laser for recurrent glottic carcinoma were studied. Forty patients were treated by laser surgery. Average follow-up was 77 months. Twenty-three patients (58%) had another recurrence develop after laser surgery. Three were cured by a second laser procedure. Therefore, 20 patients (50%) were successfully treated with laser surgery. In 23 patients the recurrence did not extend into the anterior commissure; in 57% a total laryngectomy could be avoided. In 17 patients the recurrence did extend into the anterior commissure; in 41% a total laryngectomy was avoided. Most patients with recurrent carcinoma of the larynx after radiotherapy can be cured by laser surgery if the tumor does not extend into the anterior commissure.

Development and evaluation of a 27 MHz multielectrode current‐source interstitial hyperthermia system

Hyperthermia is a cancer therapy, which is mostly applied in combination with radiotherapy. The aim of hyperthermia is to increase tumor temperatures to 40 °C−45 °C. One of the heating techniques that has been developed to be combined with afterloading interstitial radiotherapy (IRT) is 27 MHz current‐source interstitial hyperthermia (IHT). A four‐channel version of a current‐source IHT system had been developed to study the effectiveness of interstitial hyperthermia in combination with IRT in tumors growing in the flank of a rat. Temperatures up to 46 °C at the edges of various solid tumors with volumes in the range 1500–2000 are easily reached within 4–10 min. Furthermore, in a collaboration between the University Hospital Utrecht and the Daniel den Hoed Cancer Center in Rotterdam, a multielectrode current‐source (MECS) IHT‐system for clinical use has been developed. Basically, this system consists of three units. First, the actual heating system, including a 27 MHz electromagnetic power unit and multielectrode applicators. Second, a 196‐channel thermometry system with manganin–constantan thermcouple thermometers. Third, a computer plus treatment control software that provides the connection between the first two units and the operator. The power unit has 2 groups of 32 channels with opposite phase. The power can be controlled separately for each channel. Temperatures are measured with seven‐point thermocouple probes inside applicators or inside extra nonheating catheters. The performance of the MECS‐IHT system was examined, focusing on the efficiency of the power deposition in tissue, the homogeneity of the temperature distribution, and on thermometry accuracy.

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients

Purpose: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials.Materials and Methods: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports.Results: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic factors in our material, although with lesser importance. In patients with lung primaries, sex was found to have significant impact on survival. In patients with breast primaries, interval between primary tumor and development of brain metastases appeared to be a statistically significant prognostic factor. Histology in patients with lung primaries and distribution of brain metastases were not found to be statistically significant in multivariate analysis.Conclusions: In this large database, the value of established prognostic factors was confirmed and, furthermore, some less well-recognized parameters such as response to steroid treatment, serum lactate dehydrogenase, age, sex in lung primaries, and site of primary tumor were established. From the three strongest prognostic factors—performance status, response to steroids, and evidence of systemic disease—simple identification of favorable and unfavorable subgroups of patients with brain metastases can be constructed.

High-precision prostate cancer irradiation by clinical application of an offline patient setup verification procedure, using portal imaging

Purpose : To investigate in three institutions, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis [AvL]), Dr. Daniel den Hoed Cancer Center (DDHC), and Dr, Bernard Verbeeten Institute (BVI). how much the patient setup accuracy for irradiation of prostate cancer can be improved by an offline setup verification and correction procedure, using portal imaging. Methods and Materials : The verification procedure consisted of two stages. During the first stage, setup deviation were measured during a number ( max) of consecutive initial treatment sessions. The length of the average three dimensional (3D) setup deviation vector was compared with an action level for corrections, which shrunk with the number of setup measurements. After a correction was applied, N max measurements had to be performed again. Each institution chose different values for the initial action level (6, 9, and 10 mm) and N max (2 and 4). The choice of these parameters was based on a simlation of the procedure, using as input preestimated values of random and systematic deviations in each institution. During the second stage of the procedure, with weekly setup measurements, the AvL used a different criterion (“outlier detection”) for corrective actions than the DDHC and the BVI (“sliding average”). After each correction the first stage of the procedure was restarted. The procedure was tested for 151 patients (62 in AvL, 47 in DDHC, and 42 in BVI) treated for prostate carcinoma. Treatment techniques and portal image acquisition and analysis were different in each institution. Results : The actual distribution of random and systemic deviations without corrections were estimated by eliminating the effect of the corrections. The percentage of mean (systematic) 3D deviations larger than 5mm was 26% for the AvL and the DDHC, and 36% for the BVI. The setup accuracy after application of the procedure was considerably improved (percentage of mean 3D deviations larger than 5 mm was 1.6% in the AvL and 0% in the DDHC and BVI), in agreement with the results of the simulation. The number of corrections (about 0.7 on the average per patient) was not larger than predicted. Conclusion : The verification procedure appeared to be feasible in the three institutions and enable a significance reduction of mean 3D setup deviations. The computer simulation of the procedure proved to be a useful tool, because it enable an accurate prediction of the setup accuracy and the required number of corrections.

Pulsed dose rate and fractionated high dose rate brachytherapy: Choice of brachytherapy schedules to replace low dose rate treatments

Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of "pulses," i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term "PDR brachytherapy" is used for treatment schedules with a large number of fractions (at least four per day), while the term "fractionated high dose rate (HDR) brachytherapy" is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both alpha/beta values and the half time for repair of sublethal damage (T 1/2), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of alpha/beta and T 1/2. The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears to be less need for strong fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (slightly) adapted, PDR schedules can be designed using longer pulse intervals of up to 3 h. Schedules with sufficiently long intervals have significant logistic advantages in terms of patient care and treatment tolerance. However, in general, PDR schedules that apply more fractionation have a lower risk of overdosing normal tissues in comparison to fractionated HDR schedules. Applying probable ranges for the values of alpha/beta and T 1/2, the model calculations indicate that the differences in effects between the proposed fractionated HDR and PDR schedules could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. Pulsed dose rate treatment schedules with longer intervals of up to 3 h appear adequate to replace LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment schedules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical studies.

Cytogenetic evidence for cell fusion during tumor progression of a nonseminomatous germ cell tumor of the testis: [formula omitted], J. van Echten, A. Dam, J.W. Oosterhuis, B. de Jong, Department of Medical Genetics and Pathology, State University of Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, and Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Cytogenetic evidence for cell fusion during tumor progression of a nonseminomatous germ cell tumor of the testis: [formula omitted], J. van Echten, A. Dam, J.W. Oosterhuis, B. de Jong, Department of Medical Genetics and Pathology, State University of Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, and Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

A comparative study of late radiation damage assessment methods as part of a dose-fractionation study in inoperable bronchial carcinoma patients : P.A. Helle, W.L.J. van Putten, D.T.K. Gouw, M. Pillay, S.L. Tjiam, M. Oudkerk. Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

A comparative study of late radiation damage assessment methods as part of a dose-fractionation study in inoperable bronchial carcinoma patients : P.A. Helle, W.L.J. van Putten, D.T.K. Gouw, M. Pillay, S.L. Tjiam, M. Oudkerk. Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Second cancer risk following Hodgkin's disease: a 20-year follow-up study.

To determine risk factors for the development of second primary cancers during long-term follow-up of patients with Hodgkin's disease (HD). We assessed the risk of second cancers (SCs) in 1939 HD patients, who were admitted to the Netherlands Cancer Institute (NKI; Amsterdam) or the Dr Daniel den Hoed Cancer Center (DDHK; Rotterdam) between 1966 and 1986. For 97% of the cohort, we obtained a medical status up to at least January 1989. The median follow-up duration of the patients was 9.2 years; for 17% of the patients, follow-up was longer than 15 years. For more than 98% of all second tumors, the diagnosis was confirmed through a pathology report. In all, 146 patients developed a SC, compared with 41.9 cases expected on the basis of incidence rates in the general population (relative risk [RR], 3.5; 95% confidence interval [CI], 2.9 to 4.1). The mean 20-year actuarial risk of all SCs was 20% (95% CI, 17% to 24%). Significantly increased RRs were observed for leukemia (RR, 34.7; 95% CI, 23.6 to 49.3), non-Hodgkin's lymphoma (NHL) (RR, 20.6; 95% CI, 13.1 to 30.9), lung cancer (RR, 3.7; 95% CI, 2.5 to 5.3), all gastrointestinal cancers combined (RR, 2.0; 95% CI, 1.2 to 3.1), all urogenital cancers combined (RR, 2.4; 95% CI, 1.4 to 3.7), melanoma (RR, 4.9; 95% CI, 1.6 to 11.3), and soft tissue sarcoma (RR, 8.8; 95% CI, 1.8 to 25.8). As compared with the general population, the cohort experienced an excess of 63 cancer cases per 10,000 person-years. Cox-model analysis indicated the following as significant risk factors for developing leukemia: first-year treatment with chemotherapy (CT), follow-up treatment with CT, age at diagnosis of HD greater than 40 years, splenectomy, and advanced stage. Patients treated with CT in the 1980s had a substantially lower risk of leukemia than patients treated in the 1970s (10-year actuarial risks of 2.1% and 6.4%, respectively; P = .07). Significant risk factors for NHL were older age, male sex, and combined modality treatment as compared with either modality alone. Risk of lung cancer was strongly related to radiotherapy (RT), while an additional role of CT could not be demonstrated. After more than 15 years of follow-up, women treated with mantle-field irradiation before age 20 years had a greater than forty-fold increased risk of breast cancer (P < .001). While the long-term consequences of HD treatment as administered in the 1960s and 1970s are still evolving, it is promising that patients who received the new treatment regimens introduced in the 1980s have a much lower leukemia risk than patients treated in earlier years. Beginning 10 years after initial RT, the follow-up program of women who received mantle-field irradiation before age 30 years should routinely include breast palpation and yearly mammography.

Possible leakage radiation during malfunctioning of a sagittaire accelerator

A non-fatal accident with a CGR-Sagittaire accelerator in the Dr Daniel den Hoed Cancer Center (DDHCC) in Rotterdam in 1988 is described. In a period with frequently occurring technical problems, a patient, undergoing fractionated treatment at this accelerator for prostatic cancer, developed severe skin reactions on the right half ventral part of thorax, head and upper arm. The skin reactions suggested an irradiation with a dose of up to 10–20 Gy, so it was likely that a radiation accident had occurred caused by leakage radiation. A number of experiments were performed in attempting to explain the estimated large dose rates of leakage radiation. Under rather extreme malfunctioning conditions, a high leakage dose rate (4 Gy/min) could be obtained during therapy use. This condition might have occurred during this period of technical difficulty.

Possible leakage radiation during malfunctioning of a Sagittaire accelerator

A non-fatal accident with a CGR-Sagittaire accelerator in the Dr Daniel den Hoed Cancer Center (DDHCC) in Rotterdam in 1988 is described. In a period with frequently occurring technical problems, a patient, undergoing fractionated treatment at this accelerator for prostatic cancer, developed severe skin reactions on the right half ventral part of thorax, head and upper arm. The skin reactions suggested an irradiation with a dose of up to 10–20 Gy, so it was likely that a radiation accident had occurred caused by leakage radiation. A number of experiments were performed in attempting to explain the estimated large dose rates of leakage radiation. Under rather extreme malfunctioning conditions, a high leakage dose rate (4 Gy/min) could be obtained during therapy use. This condition might have occurred during this period of technical difficulty.

Recurrent endometrial adenocarcinoma after surgery alone: prognostic factors and treatment

Twenty-six patients with a local and/or regional relapse of a previously surgically treated adenocarcinoma of the endometrium were referred to the Dr. Daniel den Hoed Cancer Center (DDHCC) in Rotterdam, The Netherlands between 1965 and 1985 for external radiotherapy (ERT) and/or brachytherapy (BT). The 5-year overall survival was 44%. Tumour volume seemed to be an important prognostic factor in locoregional control; 1 out of 17 patients with tumour sizes smaller than or equal to 4 cm relapsed locoregionally, while in 3 out of 9 patients with tumour sizes of more than 4 cm a locoregional recurrence developed. Another important finding is the impact of RT on treatment outcome: none of the 16 patients treated with a combination of ERT and BT failed locoregionally, while 4 out of 10 patients treated with either ERT or BT relapsed.

Anaplastic carcinoma of the thyroid gland treated by radiation therapy

Purpose : A retrospective review was performed to investigate the potential role of external beam radiation therapy with or without chemotherapy in anaplastic carcinoma of the thyroid. Methods and Materials : Fifty-one patients with a histologically or cytologically proven anaplastic thyroid carcinoma, treated by external beam radiation therapy between January 1970 and December 1986 in the Dr. Daniel den Hoed Cancer Center are the subject of this report. The overall survival, local control rate and pattern of metastasis were analyzed. Results : It was found that the impact of lung metastases and local relapse on survival was appreciable. Patients with metastases but locally free of tumor achieved a median survival of 7.5 months. In patients with local regional residual disease after therapy, an actuarial risk of death of 100% at 8 months and a median survival of 1.6 months was observed. For patients without disease at the end of radiation therapy, an actuarial median survival of 8 months was observed. Conclusion : This retrospective analysis supports the data from the literature that local control is indispensable for achieving a higher short-term survival rate, whereas even with local regional control patients might still die soon after the completion of their treatment because of distant metastases, predominantly in the lungs. A potentially new way of treatment, that is the combination of low dose Adriamycin with hyperfactionated external beam radiation therapy to the primary tumor and prophylactic irradiation to the lung, in order to obtain higher locoregional control and diminishing of distant metastases is briefly discussed.

Experimental assessment of electrical impedance imaging for hyperthermia monitoring.

Two experimental studies are presented that attempt to assess the use of electrical impedance tomography (EIT) to map thermal changes deep in the body. The first was a joint study between our group in Sheffield and the Daniel den Hoed Cancer Center in Rotterdam, funded by the COMAC-BME Hyperthermia project. Phantom and in vivo experiments were conducted with a deep heating ring-capacitive hyperthermia device; the results highlighted some of the inherent problems (electromagnetic interference, nonuniform sensitivity) that remain to be solved for this application. The second experimental study involved heating the stomachs of volunteers by pumping known quantities of liquid (a salt/glucose solution, conductivity 5 mS) at controlled temperatures (25, 37 and 47 degrees C) in and out of the stomach via a nasogastric tube. Results indicated that the level of thermal change induced by these liquids could be reproducibly measured by impedance imaging. Both studies were a further step in assessing the capabilities of EIT for noninvasive monitoring of deep body hyperthermia. The results are encouraging and indicate the value of continued development of EIT for non-invasive thermometry.

Numerical chromosome 1, 12 and 15 distributions in invasive germ cell tumor components and adjacent carcinoma in situ of the human adult testis. A study based on the simultaneous application of interphase cytogenetics and immuno-histochemistry on tissue sections: L.H.J. Looijenga, A.J.M. Gillis, W.L.J. van Putten, [formula omitted]. Laboratory of Experimental Patho-Oncology, Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Numerical chromosome 1, 12 and 15 distributions in invasive germ cell tumor components and adjacent carcinoma in situ of the human adult testis. A study based on the simultaneous application of interphase cytogenetics and immuno-histochemistry on tissue sections: L.H.J. Looijenga, A.J.M. Gillis, W.L.J. van Putten, [formula omitted]. Laboratory of Experimental Patho-Oncology, Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands