Bone metastases: assessment of therapeutic response through radiological and nuclear medicine imaging modalities.

Radiological and nuclear medicine imaging modalities used for assessing bone metastases treatment response include plain and digitalised radiography (XR), skeletal scintigraphy (SS), dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), magnetic resonance imaging (MRI), [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) and PET/CT. Here we discuss the advantages and disadvantages of these assessment modalities as evident through different clinical trials. Additionally, we present the more established response criteria of the International Union Against Cancer and the World Health Organization and compare them with newer MD Anderson criteria. Even though serial XR and SS have been used to assess the therapeutic response for decades, several months are required before changes are evident. Newer techniques, such as MRI or PET, may allow an earlier evaluation of response that may be quantified through monitoring changes in signal intensity and standard uptake value, respectively. Moreover, the application of PET/CT, which can follow both morphological and metabolic changes, has yielded interesting and promising results that give a new insight into the natural history of metastatic bone disease. However, only a few studies have investigated the application of these newer techniques and further clinical trials are needed to corroborate their promising results and establish the most suitable imaging parameters and evaluation time points. Last, but not least, there is an absolute need to adopt uniform response criteria for bone metastases through an international consensus in order to better assess treatment response in terms of accuracy and objectivity.

Tumor volumetry as predictive and prognostic factor in the management of ovarian cancer.

BACKGROUND: The usefulness of tumor volumetry in ovarian epithelial cancer has never been intensively investigated. The aim of the present study was to determine the value of quantitative analysis of tumor volume as a predictive method for response to treatment and as a prognostic method for disease outcome. MATERIALS AND METHODS: Seventy-five women with advanced ovarian cancer who presented with measurable disease on CT scan prior to chemotherapy were retrospectively studied. The patients were treated with platinum-based chemotherapy. The median follow-up was 113.36 weeks. An independent radiologist identified and delineated tumor contours in each slice of sequential CT scans before and after therapy. Volumetry was measured with a three-dimensional approach by utilizing a digitizer and a specific algorithm on a software computed program. RESULTS: Data were analyzed according to initial and to residual tumor volumes. Patients with low initial volume of <52 cm3 exhibited higher responses (p<0.01), while patients with medium (52-165 cm3) or high (>165 CM3) initial tumor volume had a shorter time to progression (p<0.01). Patients without or with low residual volume of <35 cm3 were found to have a longer time to progression (p<0.05) and longer survival (p<0.01 and p<0.05). In addition, serum CA 125 levels followed precisely tumor volumetry for both initial and residual disease. CONCLUSION: Tumor volumetry in advanced ovarian cancer was found to have predictive value for response to platinum-based chemotherapy. Initial tumor volume has prognostic significance only for the time to progression, whereas residual tumor volume has for both time to progression and survival.

Palliative radiotherapy in recurrent head-and-neck tumors by a percutaneous superfractionated treatment schedule.

PURPOSE: A frequent problem in treatment of patients with head-and-neck tumors is recurrence in pre-irradiated areas, thus limiting dose for another full-course radiotherapy. We present our experience with a percutaneous superfractionated short-term radiotherapy regimen that may be useful for palliative irradiation. METHODS AND MATERIALS: Twenty-three patients with head-and-neck tumor recurrence after radiotherapy or extensive tumor growth have been treated by a superfractionated regimen. At each of two subsequent days, eight fractions of 1 Gy were applied with an interfraction interval of 1 h, resulting in a total dose of 16 Gy. Time between the last fraction of the first day and the first fraction of the second day was 17 h. RESULTS: In 16 of 23 patients (70%), our irradiation schedule could achieve a palliative effect such as tumor necrosis or reduction of swelling or pain. Seven patients showed erythema (WHO I) at the end of the second day. Neither mucositis nor late effects of treatment were observed. CONCLUSIONS: Our superfractionated schedule is feasible without severe acute side reactions and can achieve a palliative effect in advanced or recurrent head-and-neck cancer.

Intraoperative radiotherapy for pre-irradiated head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy of recurrent head and neck tumours is limited in dose due to pre-treatment up to normal tissue tolerance doses. Surgery alone is limited by the problems related to pre-surgery, post-radiation fibrosis, and infiltration of tumours into nerves and vessels too closely to be completely removed. Our aim was to evaluate the possible role of intraoperative radiotherapy (IORT) in such tumours treated with palliative intent. METHODS: In the last 10 years, we performed 113 intraoperative irradiations in a total of 84 pre-irradiated patients with head and neck cancer. The patient data were evaluated with regard to palliative effect, complications of treatment, recurrence and survival after IORT. RESULTS: Palliation of symptoms, as assessed by clinical evaluation, was achieved in 88% of symptomatic patients, often just by removal of large exophytic or exulcerating tumours, with IORT preventing their immediate recurrence after surgery. The complication rate did not exceed that expected after surgery alone. The median survival after IORT was 6.8 months, with a median time to local tumour recurrence or progression of 3.7 months. CONCLUSION: Intraoperative irradiation can be used as a palliative treatment option in pre-treated head and neck tumours with satisfactory results. With large and infiltrating tumours, however, recurrences or tumour progression occur close to the IORT portals, thus rendering this method unsuitable for achieving long-term control in such extended tumours.

Radioimmunodetection of residual, recurrent or metastatic germ cell tumors using technetium-99 anti-(alpha-fetoprotein) Fab' fragment.

PURPOSE: The majority of patients with germ cell tumors are cured by multimodality therapy that consists of cisplatin-based chemotherapy and/or surgical resection. Serum tumor markers and conventional radiographs are utilized to stratify patients into treatment categories. Efforts to individualize chemotherapy or minimize surgical interventions without compromising outcome are important. Immunomedics (Morris Plains, New Jersey) developed an anti-(alpha-fetoprotein) (anti-AFP) monoclonal antibody IMMU-30 labeled with 15-20 mCi technetium-99, and the purpose of this study is to determine the sensitivity and specificity of radioimmunoscintigraphy using 99mTc anti-AFP antibody for the diagnosis of active germ cell tumors. METHODS: A group of patients with germ cell tumors were enrolled in a non-prospective fashion and 48 AFP scans using 99Tc anti-AFP Fab' fragment were obtained. At the time of the AFP scan, serum AFP was elevated in 40 measurements with a median level of 21 ng/ml (1.6-66, 210.0 ng/ml). AFP scans were obtained at the initial staging, during treatment, at relapse or at long-term follow-up and compared with conventional radiographs done within 4 weeks of the AFP scans. RESULTS: An overall diagnostic sensitivity of 89% and specificity of 58% were obtained. CONCLUSIONS: AFP scanning appears useful and to be sufficiently sensitive to justify prospective studies comparing the procedure with conventional imaging.

Radioprotection of human endothelial cells with amifostine.

MATERIALS AND METHODS: We studied the effect of amifostine on radiation sensitivity of human endothelial cells and several tumor cell lines (HeLa, MIA PaCa-2 and BxPC-3). The cells were incubated in medium with a concentration of 1 microgram/microliter amifostine and after 1 hour irradiated with 10 or 20 Gy single dose. Proliferation index was measured by BrdU assay after another 8 and 24 hours. RESULTS: The results show a higher proliferation rate of endothelial cells following radiation plus amifostine, compared with radiation alone. Amifostine induced an increase of proliferation in the control/non-irradiated human endothelial cells. After irradiation with 10 Gy single dose the proliferation of amifostine treated human endothelial cells was still higher. Amifostine exerts no apparent proliferative effect on the tumor cells. CONCLUSIONS: The results presented indicate that amifostine acts as an activation of proliferation of the human endothelial cells in a simple in-vitro system and indicate that amifostine supplementation prior to radiation therapy might exert a radioprotective effect to healthy tissue without spurring tumor growth.

[Radioprotection of human endothelial cells by sodium selenite]. / Radioprotektion humaner Endothelzellen durch Natriumselenit.

BACKGROUND: Sodium selenite is applied in tumor patients during chemo- or radiotherapy due to its cytoprotective effects. Aim of our study was to evaluate the effect of exposure with sodium selenite on proliferation of human endothelial and tumor cells after irradiation. MATERIALS AND METHODS: We studied the proliferative activity of human umbilical vein endothelial cells in comparison to tumor cells of the HeLa, MIA Paca-2 and SiHa cell line after single-dose irradiation with 2 or 10 Gy and controls without irradiation. All cells had been exposed to different concentrations of sodium selenite prior to irradiation. Evaluation was done by BrdU-ELISA. RESULTS: Exposure of human endothelial cells with sodium selenite concentrations > or = 100 micrograms/l led to an increase of BrdU proliferation index. This effect was markedly weaker in HeLa cells and not found in SiHa and MIA Paca-2. CONCLUSIONS: High concentrations of sodium selenite can counteract the decrease of proliferative activity caused by irradiation in human endothelial cells and thus exert a radioprotective effect on these cells. This effect was observed by far stronger in endothelial cells than in tumor cells, implying the possible clinical use of sodium selenite as a protective agent for normal tissue in radiotherapy.

[Combined treatment of localized prostate cancer with HDR-Iridium 192 remote brachytherapy and external beam irradiation]. / Die kombinierte Behandlung des lokal begrenzten Prostatakarzinoms mit HDR-Iridium-192-Nachlade-Brachytherapie und perkutaner Bestrahlung.

BACKGROUND: The localized prostate cancer can be treated curatively by radiation therapy. The combined treatment of external beam irradiation and HDR-Iridium 192 remote brachytherapy allows higher radiation doses within the tumor without increasing radiation sequelae. PATIENTS AND METHODS: Patients of our clinic have been treated with this combined procedure since 1991. Between 1991 and 1994 15 patients received 2 x 9 Gy of high-dose-rate brachytherapy, followed by 36 Gy external beam irradiation (group A). Because of the frequent local failures in group A, the reference dose of external beam irradiation was increased to 50.4 Gy after brachytherapy between 1994 and 1996. RESULTS: Seven of 15 patients (47%) in group A developed a local recurrence after a median of 17 (13 to 30) months. In group B (20 patients) local failure occurred in 3 patients (15%) after 11, 16 and 32 months. CONCLUSION: The combined radiation therapy of localized prostate cancer cannot substitute radical prostatectomy completely, but it is a promising alternative in the curative treatment in selected patients.

A new method for the placement of brachytherapy probes in paranasal sinus and nasopharynx neoplasms.

PURPOSE: In afterloading therapy, the exact placement of the applicator is crucial for the result of radiotherapy. A deviation of few millimeters from the target leads to a significant reduction of radiation energy to the tumor. METHODS AND MATERIALS: We present a new method using a computer-assisted device for three-dimensional placing of afterloading probes based on CT scans that allows for the exact placement. RESULTS: Target points have been reached with an accuracy of 0.6 mm. Since 1991 we have used this technique for 24 clinical applications in 11 patients with recurrent neoplasms in the region of the paranasal sinuses and nasopharynx for palliative treatment. CONCLUSIONS: The presented method is a reliable and precise procedure for the positioning of afterloading probes, avoiding the inaccuracy of the traditional methods.

99mTc-labelled diphytanoylphosphatidylcholine liposomes: in vitro and in vivo studies.

The uniquely structured diphytanoylphosphatidylcholine (DphPC) forms liposomes more stable than conventional straight chain phospholipids. In this study DphPC and pegylated DphPC (DphPC-PEG) liposomes were radiolabelled and evaluated in vitro and in vivo. 99mTc-DphPC liposomes were found to be nontoxic to human white blood cells in vitro. In addition 99mTc labelled DphPC-PEG liposomes were evaluated as a nonspecific infection imaging agent in a mouse model. Infection sites were imaged within 30 min postinjection, and the radiopharmaceutical exhibited a remarkable in vivo stability. As their biodistribution and pharmacokinetic patterns can be size-modulated, DphPC-based lipsomes are excellent candidates for diagnostic and therapeutic applications.

Intra-operative radiotherapy--5 years of experience in the palliative treatment of recurrent and advanced head and neck cancers.

Recurrent and advanced cancer in the head and neck region is usually associated with limited therapeutic concepts and a dismal prognosis. Efforts mainly focus on palliative treatment in order to improve the patient's quality of life. From May 1989 to December 1994, a total of 120 intra-operative radiotherapy (IORT) procedures with high-energy electron beams (mean energy: 7 MeV: mean dose: 20 Gy) were performed in 95 patients. Therapy was usually performed under endotracheal anaesthesia (84%). There were 91 cases (75.8%) of recurrence in the lymph nodes of the neck and 14 cases (11.7%) of local recurrence. 15 patients (12.5%) received IORT as part of the initial treatment. Considering the palliative nature of IORT in these patients, only an R2 resection (gross residual tumour) was achieved in 71.7%. Local tumour control was nonetheless possible in 17% (R2 resection) to 64% (complete R0 resection), with a mean 11-month follow-up period for survivors (mean for deceased patients: 8 months). Regarding palliative criteria, IORT proved to be feasible since patients profited from short hospitalisation (median: 10 days), a low complication rate (27 instances; e.g. tracheostomy: 11; necrosis: 8, or fistula: 3) and, in part, a substantial reduction of pain (73.8%). Most of them regained physical and psychic integrity for weeks to months and were able to take part in social life during the final stage of their disease.

[Palliative intraoperative irradiation of recurrent neck lymph node metastases in the head and neck area]. / Die palliative intraoperative Bestrahlung (IORT) rezidivierender Hals-Lymphknotenmetastasen in der Kopf-Halsregion.

BACKGROUND: In the course of a malignant tumor disease, metastases in the regional lymph nodes commonly are linked with poor prognosis. Especially in cases of recurrence after surgery and radiation therapy, curative management of the disease can rarely be achieved. Therefore several palliative treatment modalities have been developed. Intraoperative radiation therapy represents one of them it allows a single high-dose irradiation of a region which, in light of the global tumor disorder, cannot be cured by surgical intervention. METHODS/ PATIENTS: Between 1989 and 1994, 70 patients with recurrent metastases in the head and neck lymph nodes were treated with IORT in the ENT Department of the University Hospital Aachen in collaboration with the Radiation Department. Since some patients were irradiated up to four times, 91 operations (77 under general anesthesia and 14 under local anesthesia) and irradiations were performed. During the procedure each, patient had to be transported twice from the standard operating suite to the radiation unit and back. RESULTS: Regarding the palliative intention of IORT in these cases, we mainly evaluated parameters which had an influence on quality of life of the patients: duration of hospitalization, pain treatment, removal of necrotic tumor mass, and safety of treatment. Depending on the general condition, the patients stayed in the hospital for 3-56 days (median: 10 days). In almost every case, mental and to some extent physical integrity was restored for some time after the disfiguring tumor on the neck had been removed. In nearly 90%, pain treatment could be reduced (e.g., discontinuation of opiate treatment) or further progression could be avoided (74%). Despite the transportation only few complications occurred, which primarily involved healing disturbances (n = 8), fistulas (n = 3), and edemas of the arm (n = 2; after primary treatment of breast cancer). There was no serious infection observed under prophylactic antibiotic treatment in 74% of the cases. Local tumor control (LTC), which only was of minor interest in this treatment group, was possible depending on the extent of tumor resection that could be achieved during the surgical approach: R0 resection = > 50% LTC/R1 resection = > 40% LTC/R2 resection (72.5% of the cases) = > 24.8% LTC. Follow-up of the surviving patients lasted 6-26 months (mean: 14.4 months) but generally did not allow an exact assessment of the time of tumor control. CONCLUSIONS: IORT of recurrent metastases in the head and neck region in our opinion represents an effective alternative for palliative treatment. Important aspects of the patients' quality of life could be improved, and patients were then able to take part in social life again for some time. On the other hand tumor control was not to be expected since in most of the cases only an incomplete tumor resection was achieved. However, the extent of resection substantially affects local tumor control in the head and neck region.

Intraoperative radiotherapy for pancreatic carcinoma.

Intraoperative radiotherapy (IORT) with an electron beam is a therapeutic modality employed predominantly in tumours with a high risk of local recurrence. In this department 35 patients with proven adenocarcinoma of the pancreas underwent surgery and IORT, while 41 patients underwent surgery only. Irradiated patients suffered more serious postoperative complications (21 per cent versus 7 per cent), spent more time in hospital (32 days versus 26 days) and did not show a survival advantage (median of 326 days versus 366 days for two patients with curative resection). Anastomotic breakdown (twp patients), abscess formation (two patients) and pancreatitis in the pancreatic remnant (one patient) occurred only in this group. It is concluded that IORT may increase the risk of postoperative complications. As, on the basis of experimental data, an additional serious long-term risk is to be expected, application of IORT should be limited to well controlled study conditions.

Computed tomography and histologic results in the early stages of endotoxin-injured pig lungs as a model for adult respiratory distress syndrome.

RATIONALE AND OBJECTIVES: To determine early radiographic changes in diffuse alveolar injury, the authors correlated computed tomography (CT) and histopathology in pigs with recurrent endotoxinemia. METHODS: Five pigs received recurrent endotoxin over a 17-hour period. Three pigs received physiologic saline and served as controls. Hemodynamic and blood-gas data were analyzed. CT was performed immediately before killing the animals. The lungs were cut into 5-mm-thick slices in the same axis as the CT scans and were investigated by light and electron microscopy. RESULTS: Hemodynamic data, blood-gas analysis, and morphologic changes closely simulated the clinical situation of septic shock in the five pigs that had received endotoxin. Results of histologic examination depicted changes similar to those associated with adult respiratory distress syndrome (ARDS). CT clearly demonstrated both interstitial, and to a minor degree, intra-alveolar lesions in the endotoxin-injected group, which correlated well with dilated lymph vessels, thickened interstitium, and areas of dystelectasis on histologic examination. Although there was a rather uniform clinical picture, CT and histologic findings showed different degrees of involvement. CONCLUSIONS: CT clearly depicts changes in endotoxin-injured pig lungs in an early clinical state, which are similar to changes associated with ARDS on histologic examination.