Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose.

PURPOSE: Dose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions. MATERIALS AND METHODS: This was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3â€¯× 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided. RESULTS: In all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found. CONCLUSIONS: This planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Time management in radiation oncology: evaluation of time, attendance of medical staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO trial.

PURPOSE: In order to evaluate resource requirements, the German Society of Radiation Oncology (DEGRO) recorded the times needed for core procedures in the radio-oncological treatment of various cancer types within the scope of its QUIRO trial. The present study investigated the personnel and infrastructural resources required in radiotherapy of prostate cancer. METHODS: The investigation was carried out in the setting of definitive radiotherapy of prostate cancer patients between July and October 2008 at two radiotherapy centers, both with well-trained staff and modern technical facilities at their disposal. Personnel attendance times and room occupancy times required for core procedures (modules) were each measured prospectively by two independently trained observers using time measurements differentiated on the basis of professional group (physician, physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated radiotherapy (IMRT). RESULTS: Total time requirements of 983 min for 3D-cRT and 1485 min for step-and-shoot IMRT were measured for the technician (in terms of professional group) in all modules recorded and over the entire course of radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was significant, although variations in time spans occurred primarily as a result of various problems during patient treatment. CONCLUSION: This investigation has permitted, for the first time, a realistic estimation of average personnel and infrastructural requirements for core procedures in quality-assured definitive radiotherapy of prostate cancer. The increased time needed for IMRT applies to the step-and-shoot procedure with verification measurements for each irradiation planning.

Phylogeny and biogeography of Hydra (Cnidaria: Hydridae) using mitochondrial and nuclear DNA sequences.

The polyp hydra is ubiquitous in freshwater and is highly variable, with many species names assigned to different strains. Types of hydra do fall into four morphologically recognizable groups but many of the species determinations are confusing. To assess the diversity of hydra we collected 101 strains from six continents and built a phylogeny using three genetic markers. Each of the four well-defined groups of species represents a clade in our phylogeny. The green hydra group diverged first, followed by the braueri group and finally the sister groups vulgaris and oligactis. Each of eight species easily definable by morphological criteria represents a distinct clade in our phylogeny. Hydra of two clades, the green and the vulgaris hydra, are found on all continents (except Antarctica) and many islands, whereas hydra of the other two groups (braueri and oligactis) are restricted to the Northern Hemisphere. Our best estimate of the time of origin of hydra is about 60 Ma, long after the breakage of Pangea into northern and southern landmasses. Hydra appear to have diversified in the Northern Hemisphere, and their current diversity is greatest here. Two species were then able to disperse to the Southern Hemisphere, perhaps due to their thermal tolerance.

Antepartum percutaneous renal biopsy.

OBJECTIVE: To assess the value and adverse effects of an ultrasound-guided renal biopsy technique in women with normal and pathologic pregnancies. METHOD: Biopsy samples were taken from 36 women with hypertensive disease (28 with pre-eclampsia) and 18 healthy pregnant women using a thin needle and an ultrasound-guided biopsy device. RESULTS: Glomerular endotheliosis, a structural change typical of pre-eclampsia, was found in all hypertensive women, but it was more pronounced in the 28 pre-eclamptic women than in the 8 women with nonproteinuric hypertension. A similar change, however, was seen in 11 of the 18 controls. One serious adverse event occurred, retroperitoneal hematoma, in the woman with the most severe pre-eclampsia. CONCLUSION: Glomerular endotheliosis is not to be considered pathognomonic for pre-eclampsia. Few complications followed renal biopsy in this study, but complications arose in the sickest patient. It is probably not advisable to perform antepartum renal biopsies in pregnant women with a rapidly deteriorating renal function and swollen kidneys. In these women, the biopsy does not facilitate diagnosis and is hazardous.

Long-term follow-up of corneal graft survival following bone marrow transplantation in the Maroteaux-Lamy syndrome.

PURPOSE: To present a case of Maroteaux-Lamy syndrome (MLS, mucopolysaccharidosis [MPS] type VI) who underwent bone marrow transplantation (BMT) for gene transfer at the age of 13, and penetrating keratoplasty at the age of 17, and maintained clear corneal grafts bilaterally for 13 years. To our knowledge, this is the longest follow-up reported on corneal graft survival in a patient with MLS and BMT. METHODS: In 1982, BMT was successfully performed on a 13-year-old girl with MLS with growth retardation, typical facial features, skeletal and joint deformities, hepatosplenomegaly, cardiopulmonary dysfunction, and corneal clouding. Corneal transplantation was done on the left eye in 1986, and on the right eye in 1987 (6 months later) without difficulty or complication. RESULTS: Thirteen years postoperatively, the patient was systemically well, and both eyes retained clear corneal grafts. CONCLUSION: BMT retarded further dysfunction from MLS, and the corneal transplants retained clarity. Further controlled studies with longer follow-up are required to establish the efficacy of BMT in ocular manifestations of MPS or MLS.

Soft X-ray therapy of recurrent pterygium--an alternative to 90Sr eye applicators.

BACKGROUND: Analysis of effectiveness of perioperative 20 kV soft X-ray irradiation in recurrent pterygium as an alternative to postoperative 90Sr beta irradiation. PATIENTS AND METHODS: Between 1987 and 2000 a total of 65 patients with 81 pterygia were treated with 20 kV X-ray therapy in the course of surgical treatment of recurrent pterygium. Until 1995 simple excision (bare sclera technique) followed by postoperative irradiation (generally four fractions of 5 Gy) was applied, with radiation starting on mean 4 days following surgery (34 cases, mean follow-up 52 months). Since 1995 we have changed our policy to a perioperative regimen starting with a single dose of 7 Gy prior to microsurgical excision with conjunctival autograft and proceeding within 24 hours with 5 Gy single dose to the surgical bed and then every other day to a total dose of 27 Gy (47 cases, mean follow-up 31 months). Recurrence rate was calculated by Kaplan Meier method. A multivariate Cox regression analysis of prognostic factors for recurrence was performed. RESULTS: A total of 19 recurrences were observed, 15 in the historical postoperative group and four in the perioperative group. Actuarial 2- and 5-year recurrence rate is 9% in the "new treatment group" compared to 34% and 56% in the historical group (p = 0.001). Only one of the four recurrences among the pre- and postoperatively irradiated group required a new surgical procedure. In this case radiation had been terminated at 17 Gy. Actuarial rate of surgical reintervention was only 2% at 2 and 5 years compared to 28% and 36% in the historical group. In multivariate Cox regression analysis only the new treatment strategy was found to influence control rate significantly. Until now no case of severe side effects like scleral necrosis or thinning, symble-pharon, radiation-induced cataract or glaucoma were observed in both groups. CONCLUSION: The combination of pre- and postoperative 20 kV X-ray therapy and microsurgical excision combined with conjunctival autograft is a highly effective treatment to prevent recurrence in the high-risk group of recurrent pterygia and can be recommended as an alternative to postoperative 90Sr beta irradiation.

Sequential chemo-radiotherapy in non-small cell lung cancer.

Locally advanced non-small cell lung cancer (NSCLC) stage IIIA/IIIB represents approximately 30% of NSCLC and still has a poor prognosis. In this article we give a short review on several randomized phase III trials that showed a slight but significant survival benefit for sequential chemo-radiotherapy in the treatment of locally advanced NSCLC.

[Carcinoma of the external ear canal and middle ear as interdisciplinary challenge for ear surgery and radiotherapy]. / Das Karzinom des äusseren Gehörgangs und des Mittelohres als interdisziplinäre Herausforderung für Otochirurgie und Strahlentherapie.

BACKGROUND: Carcinoma of the external auditory canal are tumours considered to have a poor prognosis. Improvement of the survival rate by surgical means alone is not possible. Individual therapy modalities as a result of an interdisciplinary approach between otosurgeon and radiotherapist are necessary. PATIENTS AND METHODS: A series of 30 patients (3 patients pretreated at other institutions) with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions was analysed with particular reference to tumour size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques. Clinical endpoints were freedom from local failure, overall survival, disease-free survival. The mean follow-up was 4.7 years (range: 0.1 to 18.8 years), median 3 years. RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 51%. According to Pittsburgh classification the 5-year survival rate for early disease (T1- and T2-tumours) was 89%, for stage III 67% and for stage IV 39%. Most important prognostic factors were dural infiltration (all patients with dural invasion died within 2.2 years) and the infiltration of surgical margins (the 5-year survival rate of patients with complete tumour resection was 100%, but 54% in patients with tumour beyond surgical margins). 192-iridium HDR afterloading brachytherapy based on 3D CT-treatment planning is an effective tool in the management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSIONS: Surgical resection followed by radiotherapy adapted to the stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Sequential chemo- and radiochemotherapy with weekly paclitaxel (Taxol) and 3D-conformal radiotherapy of stage III inoperable non-small cell lung cancer. Results of a dose escalation study.

The purpose of this study was the determination of the maximum tolerable dose (MTD) of weekly paclitaxel (PX) in combination with 3D-conformal radiotherapy in non-small cell lung cancer (NSCLC) and the evaluation of side effects, patient outcome and tumor response. Thirty-eight patients with inoperable NSCLC, UICC-stage IIIA (n=14)/IIIB (n=24) received two cycles of induction chemotherapy with PX/carboplatin followed by combined radiochemotherapy (60 Gy/6 weeks) with weekly PX which was escalated in cohorts of four patients until dose limiting toxicity (DLT) was reached. Starting level was 40 mg/m(2). 3D-conformal radiotherapy was applied in all patients. Toxicity was determined by WHO criteria. Patients were followed-up 3-monthly. Thirty eight patients have entered the study, 34 patients are evaluable. DLT was esophagitis III degrees, requiring interruption of radiotherapy and was reached at the PX 70 mg/m(2). Two hypersensitivity reactions (50 mg/m(2)) and one leucopenia III degrees (60 mg/m(2)) were observed. Only one patient (60 mg/m(2), 50 Gy) completely aborted treatment. The pneumonitis rate was between 21 and 36% but showed no clear correlation with PX dose. Tumor response (PR and CR) defined by CT-scan 6 weeks following radiotherapy was 88% (30/34). The 1- and 2-year survival rate is 73% and 34%. We conclude that the MTD of weekly PX with 60 Gy normofractionated radiotherapy is 60 mg/m(2). The DLT is esophagitis. Response and survival data of this sequential/combined approach are promising. A minor increase of pulmonary toxicity of irradiation is suspected.

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract.

PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS: In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

The postoperative adjuvant radiation therapy and radiochemotherapy for UICC stage II and III rectal cancer. A retrospective analysis.

AIM: This analysis was undertaken to review the outcome and toxicity of postoperative adjuvant therapy for Stage II and III rectal cancer. PATIENTS AND METHODS: We reviewed 112 patients treated with radiotherapy (44 patients) and radiochemotherapy (68 patients) after potentially curative (R0) surgery for rectal cancer (UICC Stages II and III), between 1983 and 1994 at the University Clinic of Würzburg. Median radiation dose was 56 Gy (range: 45 to 66 Gy). Chemotherapy consisted of 4 to 6 courses of 5-fluorouracil (5-FU) (420 mg/m2/d) and leucovorin (200 mg/m2/d). Median follow-up was 37 months. RESULTS: The overall survival was 84% for patients with UICC Stage II and 45% for patients with UICC Stage III disease (p = 0.0045). There were no statistically significant differences between patients treated with radiochemotherapy vs radiotherapy in terms of 5-year survival (63% after radiochemotherapy vs 53% after radiotherapy, p = 0.16), relapse-free survival (52% vs 50%) and locoregional control (69% vs 67%). UICC Stage III disease was associated with high failure rates (40% pelvic recurrences and 53% distant metastases). There was a statistically significant difference in terms of the incidence of distant metastases between the 2 treatment modalities for patients with Stage III disease (49% 5-year probability for developing distant metastases after radiochemotherapy vs 66% after radiotherapy, p = 0.047). In a multivariate analysis, the addition of chemotherapy, lymph node stage and grading were independent prognostic factors for survival. Severe late toxicity was documented in 5% of treated patients. CONCLUSIONS: Prognosis of patients with UICC Stage III rectal cancer remains poor after "standard" surgery followed by postoperative adjuvant treatment (pelvic radiotherapy and bolus intravenous injection of 5-FU and leucovorin). Major efforts should be made in order to improve prognosis for these patients, including optimization of surgical treatment and systemic treatment. More effective multimodality treatment strategies should be investigated in prospective randomized trials.

Systematics in lymphatic tumor spread of carcinomas of the upper aerodigestive tract--a clinical study based on embryologic data.

BACKGROUND: The aim of this study was to assess the incidence and pattern of cervical lymph node (LN) metastases in carcinomas of the upper aerodigestive tract in relation to primary tumor (PT) invasion of the equivalents of pharyngeal arches (PhA) and occipital and cervical somites (OCS) in adults. METHODS: The pretherapeutic computed tomography scans and clinical findings in 729 patients with histologically proven carcinoma of the upper aerodigestive tract (112 nasopharyngeal, 289 oropharyngeal, 252 laryngo-hypopharyngeal, and 76 oral cavity carcinomas, with LN involvement in 70% of the total) were analyzed in relation to PT invasion of equivalents of PhA and OCS. Tumors were recorded according to the infiltration of these equivalents. The metastatic involvement of the different cervical LN groups was analyzed and correlated to the pattern of PT invasion of equivalents of PhA and OCS by the chi-square test. RESULTS: The findings show that the pattern of cervical LN involvement depends on the location and extension of the PT and its invasion of equivalents of the PhA and OCS. Jugular LN metastases were found in tumors invading the equivalents of PhA 2-6. Submandibular LN metastases were evident in tumors invading tissues arising from the first PhA and the tongue. Retropharyngeal, spinal accessory and transversa colli LN metastases were found in tumors invading tissues arising from OCS. The frequency of LN metastases in the different LN chains decreased in the cranio-caudal direction. Each neck hemisphere showed separate lymphatic drainage. CONCLUSIONS: Analysis of PT extension in relation to PhA and OCS equivalents allows patterns of LN involvement to be predicted.

[Combined radiochemotherapy of non-small-cell bronchial carcinoma with taxol]. / Kombinierte Radiochemotherapie des nichtkleinzelligen Bronchialkarzinoms mit Taxol.

BACKGROUND: In the last few years platin-based radiochemotherapy has become standard treatment for patients with advanced, surgically unresectable non-small-cell lung cancer (NSCLC). More recently new chemotherapeutic agents have shown superior activity. Among them paclitaxel (Taxol) is one of the most extensively investigated. RADIOTHERAPY: Despite of promising initial results, locally uncontrolled tumor and distant metastases continue to be the most serious problem of this disease. Improvement of local control can be achieved by escalating radiation dose, by shortening of treatment time with accelerated fractionation or by additional use of radiosensitizing agents. Concerning local control a tumor volume-dose relationship has been described. Three-dimensional conformal treatment planning eventually with intensity modulated fields, combined with biological TCP/NTCP calculation models allows risk-adapted escalation and intensification of irradiation. TAXOL: A radiosensitizing effect of Taxol by means of G2/M block has been reported. However, radiobiological data are contradictory and suggest a radiosensitizing effect even without cell-cycle arrest. For simultaneous paclitaxel and 60 Gy normally fractionated radiotherapy several prospective dose escalation studies have confirmed a maximum weekly Taxol dose of 60 mg/m2. Changes in paclitaxel application (e.g. daily, twice weekly or biweekly) or in radiotherapy fractionation require a corresponding adaption of Taxol dose. Dose limiting toxicity of this simultaneous treatment is esophagitis. With respect to the high rate of distant metastases sequential application of combined chemotherapeutic regimens (e.g. Taxol 200 mg/m2/Carboplat AUC 6) is generally recommended.

[Autocrine activation of fibroblasts following irradiation]. / Autokrine Aktivierung von Fibroblasten nach Bestrahlung.

BACKGROUND: The most important limitation of thoracic radiotherapy is radio-toxicity of the normal lung. We distinguish the pneumonitis with acute clinical onset, histologically characterised by infiltration of inflammatory cells to alveoli and interstitium, from fibrosis, which is slowly progressive and characterised by fibroblast proliferation and collagen deposition in the interstitium. Radiogenetic fibrosis can occur without evidence of alveolitis, an active role of mesenchymal lung cells in the pathogenesis of this special disorder is assumed. METHODS: Human lung fibrobasts were irradiated in vitro with single doses of 4, 7 and 10 Gy and afterwards observed or incubated together with non-irradiated cells in a co-culture system. After 3, 6, 9, and 12 days cells were counted, and TGF beta 1 and fibronectin was measured in supernatants. RESULTS: Cell growth of irradiated fibroblasts was inhibited as expected. In contrast, we observed a significant stimulation of cell growth of the non-irradiated fibroblasts, which were incubated together with the irradiated cells. This effect was obvious from day 1 until day 9 following irradiation and was dose dependent. In irradiated cells TBF beta 1 was increased in culture supernatants up to five-fold compared to sham-irradiated cells from day 6 until day 12. Fibronectin was elevated in dose dependent manner. CONCLUSION: Irradiation of fibroblasts in vitro induces synthesis of substances which stimulate cell growth. TGF beta 1 and fibronectin may be involved in this act of "self-activation".

Carcinoma of the external auditory canal and middle ear.

PURPOSE: To evaluate therapeutic modalities used at our institutions regarding local control, disease-free survival and actuarial survival in carcinoma of the external auditory canal and middle ear, in an attempt to provide guidelines for therapy. METHODS AND MATERIALS: A series of 27 patients with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions were analyzed with particular reference to tumor size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques employed. Clinical endpoints were freedom from local failure, overall survival, and disease-free survival. The median follow-up was 2.7 years (range 0.1-17.9 years). RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 61%. According to the Pittsburgh classification, the actuarial 5-year survival rate for early disease (T1 and T2 tumors) was 86%, for T3 tumors 50%, and T4 stages 41%. Patients with tumors limited to the external auditory canal had a 5-year survival rate of 100%, patients with tumor invasion of the temporal bone 63%, and patients with tumor infiltration beyond the temporal bone 38%. The rate of freedom from local recurrence was 50% at 5 years. Unresectability by dural and cerebral infiltration, and treatment factors such as complete resection or resection with tumor beyond surgical margins are of prognostic relevance. All patients with dural invasion died within 2.2 years. The actuarial 5-year survival rate of patients with complete tumor resection was 100%, but 66% in patients with tumor beyond surgical margins. 192Iridium high-dose-rate (HDR) afterloading brachytherapy based on three-dimensional computed tomography (3D CT)-treatment planning was an effective tool in management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSION: Surgical resection followed by radiotherapy adapted to stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Tumor volume and local control in primary radiotherapy of nasopharyngeal carcinoma.

An investigation of the effect of tumor volume and total dose on local control following primary radiotherapy for nasopharyngeal carcinoma was carried out in order to estimate the radiation dose necessary to control a specific tumor volume. Between 1983 and 1996 a total of 104 patients underwent radiation therapy for nasopharyngeal carcinoma at the Department of Radiation Oncology of the University of Wuerzburg. Total doses of between 8 and 80 Gy (5 fractions per week) were administered. Complete CT-data on primary tumor size, total tumor dose (calculated by 3D- or quasi 3D-CT-based radiation planning computer) and on local control status in the follow-up period were available for 63 patients. Lymph node metastases were present in 38 of these patients and they were also entered into the study. Thus this study is based on a total of 101 tumor regions. A Poisson probability-based model was used for calculating the dose-response relationship. Assuming a correlation between tumor volume and the total dose necessary to obtain local control, the individual tumor volumes were rescaled to a 1 ml volume by introducing a volume-dependent modification factor for the applied dose, in order to eliminate the influence of different individual tumor volumes. All dose values given are based on a fractionation scheme of 2 Gy single dose, 5 fractions per week. Nineteen tumors and 11 lymph nodes were considered locally uncontrolled or recurrent. Without dose-volume modification, a weak dose-response correlation was found and a typical shallow dose-response curve was calculated with a 50% response dose (RD50) of 60.2 Gy and a normalized dose-response gradient (gamma50) of 3.2+/-0.62. After dose-volume modification and rescaling to a 1 ml tumor volume, a steep dose-response curve with an RD50 of 40.9 Gy and gamma50 of 8.2. was found. Tumor volume is a very important factor influencing local control in nasopharyngeal carcinoma. The rescaling procedure to a reference volume of 1 ml used in this study revealed a very steep dose-response relationship. This result suggests that the clinically observed smooth dose-response relationships may be explained by interindividual tumor volume heterogeneity. The additional dose necessary to control a tumor of the double volume is close to 5 Gy. With a total dose of 72 Gy (5x2 Gy/week), tumor volumes larger than 64 ml are unlikely to be controlled.

Long-term survival following postmastectomy locoregional recurrence of breast cancer.

Only a few reports describe long-term survivors following locoregional recurrence of breast cancer after mastectomy. We analyzed 145 patients who were treated for an isolated postmastectomy breast cancer recurrence at our department between 1979 and 1992. All patients were free from distant metastases at the time of recurrence. Nineteen of these patients remained free from distant metastases after a follow-up of more than 10 years following recurrence. Clinical and histopathological characteristics of these 19 patients were analyzed. Primary tumors were small with almost all being T1 or T2 primaries. The majority of survivors had negative axillary node status (16/19 [84%]). Locoregional recurrences were mainly chest wall recurrences (16/19 [84%]) and all recurrences were smaller than 5 cm (19/19). Only 7 patients showed a typical scar recurrence. Sixteen patients had a single recurrent nodule. Early recurrences (<1 year after mastectomy) were rare (n=2). Treatment of recurrence consisted of tumor excision in all cases followed by radiotherapy in 16 patients (including 6 patients who had undergone elective irradiation following mastectomy), hormonal therapy in 6 and chemotherapy in 1 case. In all patients local control at the recurrence site was achieved. Cure after postmastectomy recurrence seems possible in a subgroup of patients (small primary tumor with negative axilla, small and solitary chest wall recurrence) provided adequate therapy is prescribed. Treatment of these patients should not be regarded as palliative therapy.