Search

Purpose: To define the patterns of failure and outcome of patients presenting supraclavicular lymph node involvement and the prognostic significance of supraclavicular lymph node involvement. Methods and Materials: We reviewed the history of 795 breast cancer patients treated at the Department of Radiation Therapy, University of Wurzburg between 1978 and 1988. The clinical and pathologic features of 21 patients who had ipsilateral supraclavicular lymph node metastases at primary diagnosis and 38 patients who presented supraclavicular lymph node recurrence during the course of disease were reviewed. These were compared with the features of 20 patients who initially had M 1 status at primary diagnosis and 278 patients who had developed distant metastases in the follow-up period. Survival rates were calculated starting from the time of diagnosis of supraclavicular involvement respective of distant metastases. Results: Survival from appearance of supraclavicular lymph node metastases at primary diagnosis or as a recurrence is not different from survival of patients presenting with a primary M 1 stage or presenting distant metastases during the course of disease. Two and 5-year survival rates of patients with supraclavicular lymph node involvement at primary diagnosis were 52% and 34% compared to 50% and 16% 2- and 5-year survival rate of patients with supraclavicular lymph node involvement as a recurrence. Patients who presented a primary M 1 -status had 2- and 5-year survival rates of 56% and 24%. Survival of patients with distant metastases calculated from the onset of metastatic disease was similar to that of the other three groups with a 46% and 16% survival rate at 2 and 5 years. There was no difference in survival rates between the four groups. Conclusion: The prognostic significance of suproclavicular lymph node involvement at primary diagnosis or as a relapse is similar, both have the same significance as the first distant relapse and are characterized by a poor prognosis.

Sixty-two breast cancer patients with central nervous system (CNS) metastases were reviewed. The CNS was the first site of metastatic involvement in 38 cases (61%). The median survival from the primary diagnosis was 3.0 years; from the diagnosis of the CNS metastasis, 6 months. The interval between primary diagnosis and CNS metastasis had a median value of 2.0 years; between the initial extra-cranial metastasis and CNS metastasis this was 0.9 years. Prognostic factors for the appearance of CNS metastasis could not be identified. Subsequent to CNS metastasis appearing, the well-known prognostic factors for the survival time and the metastasis-free interval lose their importance. Brain metastases occur, above all, in patients aged between 50 and 55 years, very often in the first 2.5 years after the first distant metastasis and not later than 10 years from the primary diagnosis.

Follicle centre lymphoma grade I, II (REAL) or centroblastic-centrocytic lymphoma (Kiel classification) present a well defined clinical entity from a clinical point of view. These lymphomas are not curable by chemotherapy in early or advanced stages. They are treated by radiation therapy in early stages, but up to now the curative potency of radiotherapy has not been confirmed by prospective clinical trials.Between January 1986 and August 1993 117 adults with follicle centre lymphoma were recruited from 24 institutions to enter the multicentric prospective, not randomised clinical trial. Patients with histologically proven nodal follicle centre lymphoma of stages I, II and limited III were included. They were treated by a standardised radiotherapy regimen, in stage I by extended field and in stages II and III by total nodal irradiation. Dose per fraction was 1.8 to 2.0 Gy, in the abdominal bath 1.5 Gy up to a total dose of 26 Gy in adjuvant situation and 36 Gy to enlarged lymphoma.All patients developed a complete remission at the end of radiotherapy. Median follow-up is 68 months. Overall survival of all patients in 86 +/- 3% at 5 and 8 years. Stage adjusted survival at 5 and 8 years was 89% for stage I, 86% for stage II and 81% for III. Patients in stages I and II60 years had survival rates of 94% at 5 and 8 years, patients60 years 63% (p0.0001). Recurrence free survival of all patients is 70% at 5 and 60 +/- 5% at 8 years. The number of recurrences is high with 29% at 5 and 41% at 8 years. All recurrences were seen within 7 years. The probability of localised nodal in-field recurrences is 11% and 22% at 5 and 8 years, respectively. Adverse prognostic factors were identified by multivariate analysis: age60 years, treatment breaksor = 7 days and dose deviations20% from prescribed doses. Acute side effects of extended field irradiation were moderate.On the basis of these results radiotherapy is a potentially curative therapeutic approach in stages I, II and limited III of follicle centre lymphoma. The optimal technique is total lymphoid irradiation with doses of 30 Gy in the adjuvant situation and 40 to 44 Gy in enlarged lymphomas. The number of local recurrences leads to the assumption, that the extension of radiotherapy to the total lymphoid system might reduce their frequency.

To show treatment results and to define prognostic subgroups in patients undergoing radiotherapy for brain metastases from malignant melanoma.Between 1985 and 1993 30 patients underwent radiation therapy for brain metastases from malignant melanoma. In 9 patients they had been surgically resected. All except 1 patient received whole brain irradiation with a total dose of 20 to 46 Gy/2 to 5 weeks using daily fractions of 2.0 to 4.0 Gy. In 5 patients a local boost of 20 to 25 Gy/2 weeks was administered. Survival rates were compared using the Cox-method. Univariate and multivariate analyses were performed to define prognostic subgroups.In 6/30 patients (20%) brain metastases were diagnosed at the time of primary manifestation of melanoma. In 83% of patients brain metastases developed during the first 5 years following primary diagnosis. Late manifestation was observed (18 years). Overall survival rate of the whole group was 39% at 6 months and 23% at 1 year. Univariate analysis revealed that age at diagnosis of brain metastases, time to manifestation, number of intracranial metastases and existence of extracerebral distant metastases had significant influence on survival. Sex was not found to influence survival rate. Multivariate analysis identified the existence of extracerebral distant metastases at the time of diagnosis of brain metastases as the most important prognostic factor for survival, followed by age and surgical resection. The role of fractionation was studied separately in a subgroup of patients receiving whole brain irradiation to a total dose of 39 to 42 Gy. Survival rates deteriorated when overall treatment time exceeded 3 weeks.Prognosis following brain metastases from malignant melanoma is very unfavourable. The described prognostic factors can be helpful to choose the adequate therapeutic modality for the patient, especially for selection of patients for radiosurgery. Whole brain irradiation with 13 x 3 Gy/3 weeks seems a safe and well tolerated treatment schedule either in palliative care or following surgical resection or preceding radiosurgical treatment.

Treatment results were reviewed in a retrospective analysis and compared with literature data. Prognostic factors for freedom from relapse and overall survival were identified.We analyzed the history of 183 patients treated for Hodgkin's disease between 1977 and 1989 at the Department of Radiation Therapy at the University of Würzburg. There were 100 males and 83 females between 16 and 86 years of age. 70.5% of patients presented with early stage Hodgkin's disease (23.5% stage I and 47.0% stage II) and 29.5% had advanced stages (25.1% stage III and 4.4% stage IV). All patients were treated initially with radiotherapy, 114 had radiotherapy alone and 69 patients received combined modality treatment.Hundred and sixty-one patients (88.0%) reached a complete remission. Freedom from relapse was 73.7% at 5 years and 70.3% at 10 years for these patients, overall survival was 74.3% and 62.8% at 5 and 10 years for all patients. Prognostic factors for freedom from relapse were stage IV, B symptoms, age greater than 35 years and more than 3 involved lymph node regions. These factors also were relevant for overall survival, in addition mixed cellularity or lymphocyte depleted subtype, high erythrocyte sedimentation rate, failure to achieve a complete remission following initial treatment and relapse of Hodgkin's disease were identified as negative prognostic factors. Laparotomy staged patients who received radiotherapy only for stage I and II Hodgkin's disease had better outcome than clinically staged patients. Our data suggest that adequate therapy is able to reduce the impact of unfavourable prognostic factors. The outcome for patients with bulky mediastinal disease was similar to that in patients without a mediastinal mass.The optimal choice of treatment for patients with early stage Hodgkin's disease--combined modality treatment/radiotherapy alone/chemotherapy alone?--and for patients with advanced stages--consolidation radiotherapy?--remains an unresolved issue and needs further testing in large randomized trials considering acute and late complications. Staging laparotomy may be used only for a small group of patients who would receive radiotherapy alone as definitive treatment. Modifications of therapy clearly reduce the impact of negative prognostic factors.

Using the pre-therapy CT scans of 266 node positive non-small cell lung cancer patients, we analysed the lymphatic pathways and the incidence of lymph node metastases in regional lymph nodes (as described by CT criteria corresponding to the modified mapping scheme of the American Thoracic Society), in order to develop the target volume for curative irradiation treatment. Among the 105 patients with node positive left sided primaries, the incidence of involvement of the ipsilateral supraclavicular lymph nodes was 9.5%, and the incidence of involvement of the contralateral lymph nodes was 3.8%. The incidence of involvement of the contralateral hilar lymph nodes was 4.8%. Among the 161 patients with nodal positive right sided primaries, the incidence of involvement of the ipsilateral supraclavicular lymph nodes was 8.7% and the incidence of involvement of the contralateral lymph nodes was 1.8%. For this group of patients, the incidence of involvement of the contralateral hilar lymph nodes was 3.7%. All patients with involvement of the contralateral hilar lymph nodes died within 2.5 years of diagnosis. In the cases where there was involvement of the supraclavicular lymph nodes, the patients died within 1.6 years. Involvement of the ipsilateral and/or contralateral supraclavicular lymph nodes, and/or the contralateral hilar lymph nodes, is defined as N3 disease, and is included in Stage IIIb. No curative surgery is indicated for these patients. Why therefore should this group of patients be treated with curative intent by irradiation of the primary, ipsilateral and contralateral hilar lymph nodes, as well as mediastinal, ipsilateral and contralateral supraclavicular lymph nodes? The curative radiation treatment volume for lung cancer has to include the primary tumor and the ipsilateral hilar, and the low and high mediastinal lymph nodes, as is indicated for Stage I, II and IIIa disease.

Examination of the influence of total tumor dose, additional therapy and age on the development of radiation pneumonitis and lung fibrosis.Two hundred and sixteen patients with squamous cell carcinoma of the lung were examined retrospectively. Hundred and eighty-three of them received a percutaneous radiation therapy of the primary tumor and the mediastinal and ipsilateral hilar lymph nodes. The majority of 130 patients was given radiotherapy as only treatment, 27 were irradiated after resection and 26 received chemo- and radiotherapy. Treatment volume was determined by three-dimensional planning using chest CT-scan. The irradiation was administered in a first series of 56 Gy and a following boost to the primary and involved lymph nodes to a total dose of 70 Gy. There was one daily irradiation with 2 Gy 5 days a week. Post-resectional radiation encompassed the bronchus stump and the mediastinum with a total dose of about 60 Gy.Sixty-eight of the 183 irradiated patients developed a pneumonitis (37.2%) and 60 a lung fibrosis (32.8%). The most important factor was the administered total irradiation dose (p0.001). There was no pneumonitis documented below 36 Gy and no fibrosis below 40 Gy. An additional chemotherapy did not increase the incidence (pneumonitis after radiotherapy 35.4%, after radio- and chemotherapy 34.6%; fibrosis after radiotherapy 33.9%, after radio- and chemotherapy 38.5%). Particularly high was the incidence of pneumonitis when radiotherapy followed resection (48.2%) while the rate of fibrosis in this group of patients was relatively low (22.2%). Age of patients did not affect the frequency of pneumonitis while fibrosis significantly occurred more often with increasing age (p = 0.037).The total dose affecting the normal lung tissue is the most important factor for the development of radiation pneumonitis and lung fibrosis. It is recommended to keep the treatment volume appropriate to the individual extend of tumor. Good results are achieved with a computer supported CT-planning which helps to gain minimal burdening of normal tissue.

Prognostic factors in breast cancer have been frequently discussed in the oncologic literature. We reviewed our data of 795 patients who were referred to the Department of Radiation Oncology of the University of Wuerzburg between 1978 and 1988 in order to find out, whether the well known and proven prognostic factors in breast cancer were sufficiently in use in clinical routine, even out of university oncologic centres. We found, that beside of determination of the histological tumor-type the assessment of tumor size (= pT-status) and axillary (= pN-)status is performed nowadays in all patients. In contrary, the determination of the hormonal receptor status (HRS) had a slow beginning. From 1980 the rate of determinated HRS arose from 5% to 80% nowadays. The demand of removal and examination of at least 12 axillary lymph nodes in axillary dissection in order to determine correctly the axillary status is not yet part of the oncological routine. In 1988 in only 40% of the referred patients axillary diagnosis was done in a manner corresponding to international rules.

Local-regional recurrence following mastectomy is not always a sign of poor prognosis. In an attempt to determine these subgroups of patients we analysed 149 patients of our radiation oncology clinic treated between 1978 and 1988 with local or regional recurrence (LR) following mastectomy. Average follow up was 66 months, 47% of these patients developed their recurrence in the first two years, 78% in five years, 90% of the local-regional recurrence appeared in the first ten years. Prognostic features which predicted a poor prognosis in combination with locoregional recurrence after mastectomy were identified; early local recurrence (less than two years from mastectomy) (p less than 0.001), large tumor size T3 and T4 primary) (p less than 0.001), less than five involved axillary lymph nodes (p less than 0.001), negative hormone receptor status, histological grading 3 and 4, lymphangiosis carcinomatosa in the tumor site (p less than 0.05), the presence of tumor-necrosis in the primary tumor (p less than 0.001) and appearance despite of postoperative irradiation (p less than 0.05). Prognosis of patients with more than five involved axillary lymph nodes did not change by local-regional recurrence. The local recurrence did not influence survival in: late local recurrence (more than two years from mastectomy), small tumor size (T1 and T2), negative axillary status, positive hormonal status, histologic grading 1 and 2 and absence of tumor-necrosis or lymphangiosis carcinomatosa in the primary tumor. We conclude that local-regional recurrence is in fact under the above defined circumstances not a sign of systemic disease. With insufficient local therapy it can under these conditions be cause of progressive tumor spread. Thus we strongly support intensive local therapy for local-regional recurrence.

Primary non-Hodgkin's lymphoma occurs quite seldom in the nasopharynx, therefore reports on this topic are rare in medical literature. The treatment results of 30 irradiated patients (40 to 60 Gy) are presented. The period of the study ranges from 1960 to 1985. 13 patients with low grade lymphoma and 17 patients with high grade lymphoma according to the Kiel classification form the basis of this study. The overall actuarial 5-year survival rate is 24%. This also applies for the subgroups of low grade and high grade lymphomas with a 5-year survival rate of 24%, respectively. The evaluation of the patients without generalization in the course of disease shows that the prognosis of stage IE patients with 43% was superior to the one of stage IIE patients with 25% (p less than 0.001). Only patients with lymphoma limited to the nasopharynx survived longer than five years (46%), but none of the patients with simultaneous spread to the nasal cavity, the oropharynx and/or the base of the skull. Local and regional recurrences were rare. However, a generalization of the disease occurred more often (20%), mainly due to insufficient staging in former years. Long-term sequelae of the radiation therapy like rhinitis or pharyngitis sicca were registered occasionally. At present, locoregional radiation therapy is recommended for stage IE and IIE low grade lymphomas and stage IE high grade lymphomas of the nasopharynx.

Based on the postoperative data evaluated in September 1989, the results of a regional prospective treatment study conducted by the DOSAK on preoperative radio-chemotherapy and radical surgery for carcinomas of the oral cavity and the oropharynx are presented. In the univariate analysis the histologic lymph node findings after pretreatment, the histologic grading, and the TPI correlated well with the survival rates. The multivariate analysis confirmed that the histologic demonstration of vital tumor cells in the neck lymph nodes after the end of pretreatment is of grat prognostic relevance. The histologic degree of differentiation, the demonstration of vital tumor cells in the primary tumor area after pretreatment and the length of time between radiotherapy and surgery were of secondary importance.

434 CT examinations of 133 patients with histologically proven bronchogenic carcinoma (22 out of 133 with small cell lung cancer) were analysed before and after radiotherapy. The study evaluates the use of CT for determining target volume, tumour volume and remission rate: 1. Concerning determination of target volume conventional roentgen diagnostic simulator methods are much inferior to CT aided planning: as for our patients changes of the target volume were necessary in 50%, in 22% the changes were crucial. This happened more often in non-small cell lung cancer than in small cell carcinomas. 2. The response rate (CR + PR) after radiotherapy (based on the calculated tumour volumes by CT) was 70 to 80%. The rate of CR of the primary was 45% (non-small cell carcinoma) and 67% (small cell carcinoma). 3. The crucial point for the evaluation of tumour remission after radiotherapy is the point of time. One to three months and four to nine months after irradiation we found complete remissions in 19% and 62%, respectively. Hence, the evaluation of treatment results earlier than three months after radiotherapy may be incorrect. We deem it indispensable to use CT for determination of target, calculation of dose distribution and accurate evaluation of tumour remission and side effects during and after irradiation of patients with bronchogenic carcinoma.

From 1960 through 1972, altogether 418 patients with laryngeal carcinoma have been treated at Würzburg, 333 = 82% of these by primary radiation therapy with Co-60 gamma-rays. The results are reported and analyzed in dependence on prognostic factors as tumor site and extension, formation of metastases and age of the patient. Five-year survival of primarily irradiated cases from 1960 to 1967; Glottic T1 = 90%, T2 = 70%, T3 -31%. Supraglottic T2 = 51%, T3 =20%, T4 = 16%. Quota of cases with posterior surgical treatment: Glottic = 8% supraglottic = 28%. The attempt to preserve the larnyx function by means of radiation therapy as an initial measure does not bring along any risk for the patient. The incidence of recurrences with secondary surgical treatment is not smaller than with irradiation only.

The skip-technique may be used either for screening or lessening the radiation load to sensitive sound organs or for an adjusted formation of the isodoses or for both. To show the possibilities of application of this elegant and quite practicable method, some examples are reported concerning spondylous processes, para-aortic lymph nodes and tumors in the small pelvis. The loss of radiation dose because of the additional opening and closing procedure of the diaphragm demands a correction of the duration of irradiation.

Small glomus jugulare tumors can be operated on successfully. The intraoperative risk of bleeding may be reduced by preoperative irradiation or angiographic embolisation. Patients with advanced tumors (bone destruction, paralysis or cranial nerves and/or invasion of brain) are at high risk if they are operated on. In these cases radiotherapy is an effective alternative with a fairly low complication rate. Prerequisites for successful irradiation are assessment of treatment volume and treatment planning by CT, sophisticated stereotactic irradiation techniques, application of high energy photons and reliable immobilisation measures. Furthermore it is possible to deliver higher doses, leading to regression of the tumor and its symptoms. The technique is illustrated by two characteristic cases. Although irradiation alone can achieve tumor remission the long term prognosis remains doubtful.

The object of this survey concerning 710 patients in Berlin and 418 patients in Wuerzburg/FRG with carcinoma of the larynx is to determine the prognostic factors which are important for the results and the choice of the treatment.

Computed tomography plays an important role in radiotherapy, especially in case of local recurrences after surgical treatment of a carcinoma of the rectum: it is important for the pretherapeutic diagnosis of the tumor, for the localization diagnosis, when the irradiation plan is established, and for checking-up the therapy effect. During the last two years, 37 patients with presacral recurrences were irradiated with high doses and examined before and after treatment. There was no difficulty to discern the foreign tissue presenting the density of soft tissue and to differentiate between recurrences and postoperative fibroses if the patients showed the typical pains. Normally a very good clinical result, but only few regressions of the tumor are achieved by a dose of 80 Gy within the rotation axis.

Glomus jugulare tumors are difficult to manage therapeutically due to their localisation. Operation may be successful in small tumors but can be hazardous in larger lesions mainly because of bleeding and palsy of cranial nerves. In these cases there should be used radiation therapy under the condition that it is planned by use of computed tomography. Moreover reproducibility of radiation treatment set-up is vital. In this way tumor regression may be achieved. Four own illustrative cases are demonstrated. According to the stage of disease a modified treatment strategy is presented which integrates surgical procedures, angiographic embolization and radiotherapy.

In the course of the previous six years, nine osteogenic and three juxtacortical sarcomas have been irradiated for the single purpose of local tumor sanitation and final cure of the patient. Of nine cases with osteosarcomas, six are still alive. Two are surviving without recurrences these five years, three without metastasition. The 3-year survival amounts to 3/5. Radiation effects from high-dosage treatment are remarkably small. The cure rate after radiation therapy seems not to be inferior to the results after surgery.