Tissue water content and nuclear magnetic resonance in normal and tumor tissues.

Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant tissues. When the tissue water content varied from 80 to 93%, the tumors exhibited spin-lattice relaxation times (T1) from 0.9 to 1.8 sec. We report also the results obtained on 9-day-old embryos and on liver, brain, and heart from 2-day-old rats. A good correlation between the spin-lattice (T1) and spin-spin (T2) relaxation times and the tissue water content was found for all tissues studied. The relaxation times T1 and T2 and water content in Walker 256 carcinoma and its lymph node metastasis were quite similar.

Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis.

PURPOSE: The outcome of patients with local-regional breast cancer recurrence after mastectomy often is described as fatal. However, certain subgroups with favorable prognoses are thought to exist. To determine these favorable subgroups, we analyzed prognostic factors for their influence on postrecurrence survival by univariate and multivariate analysis. METHODS AND MATERIALS: Between 1979 and 1992, 145 patients with their first isolated locoregional recurrence of breast cancer following modified radical mastectomy without evidence of distant metastases were treated at the Department of Radiation Oncology of the University of Wurzburg. Thirty-nine percent of patients (n = 67) had had postmastectomy radiotherapy, representing 7% of patients who had received routine postmastectomy irradiation at our institution. Systemic adjuvant hormonal therapy had been applied in 24% and systemic chemotherapy in 19% of patients. Several combinations were used. Treatment of recurrences consisted of surgical tumor excision in 74%, megavoltage irradiation in 83%, additional hormonal therapy in 41%, and chemotherapy in 12% of patients, employing different combinations. Local control in the recurrent site was achieved in 86%. Median follow-up for patients alive at the time of analysis was 8.9 years after recurrence. We tested different prognostic factors, including prior treatment and treatment of recurrence, for their influence on postrecurrence survival, using univariate and multivariate analysis. RESULTS: Eighty-two of the 145 patients (57%) developed distant metastases within the follow-up period. Metastases-free rate was 42% at 2 years and 36% at 10 years following recurrence. With development of distant metastases, the survival rate deteriorated. Recurrences appeared within the first 2 years from primary surgery in 56% of patients, and in 89% within 5 years. Overall, 2-year and 5-year survival rates following local-regional recurrence were 67% and 42%, respectively. Univariate analysis revealed statistically significant worsening of survival rates for pT3 + 4 primary tumors, primary axillary lymph node involvement, tumor grading 3 + 4, lymphatic vessel invasion, blood vessel invasion, tumor necrosis, negative estrogen (ER) and progesterone (PR) hormonal receptor status, postmastectomy chemotherapy and hormonal therapy, short time to recurrence (< 1 year), combined recurrences and supraclavicular site of recurrence, non-scar recurrence, size of the largest recurrent nodule > 5 cm, multiple recurrent nodules, no surgical excision of recurrence, small target volume of irradiation, chemotherapy for recurrence, and no local control within the recurrence site. The 2-year and 5-year survival rates ranged from 68% to 94%, and from 33% to 65%, respectively, in the favorable subgroups compared to 2-year and 5-year survival rates ranging from 20% to 59% and 0% to 35%, respectively, in the unfavorable subgroups. Multivariate analysis showed that site of recurrence and number of recurrent nodules have the strongest influence on postrecurrence survival, but time to recurrence, age at time of recurrence, local control in recurrent site as well as primary pT and axillary status, and the presence of tumor necrosis in the primary tumor specimen showed additional independent influences on survival. Thus, we identified a highly favorable subgroup of patients with a single chest wall or axillary recurrent nodule (in a patient aged > 50 years), a disease-free interval of > or = 1 year, pT1-2N0 primary tumor, and without tumor necrosis, and whose recurrence is locally controlled. This group (12 patients) had 5- and 10-year survival rates of 100% and 69%, respectively. CONCLUSION: We conclude that locoregional recurrence of breast cancer following mastectomy is not always a sign of systemic disease. Our data support previous findings, that subgroups with favorable prognosis exist and they still have a chance for cure, demanding comprehensive local treatment. (ABSTR

Omission of the pelvic irradiation in stage I testicular seminoma: a study of postorchiectomy paraaortic radiotherapy.

PURPOSE: To review the survival, cure rate, and pattern of relapse or progression of patients with histologically confirmed Stage I testicular seminoma who underwent orchiectomy and radiation therapy to paraaortic lymphatics only. The pelvic ipsilateral lymph nodes were not irradiated. METHODS AND MATERIALS: Between 1978 and 1992, 150 patients with Stages I or II testicular seminoma received treatment at the Department of Radiation Oncology of the University of Wuerzburg. The distribution by stage was Stage I, 117 patients of which 93 were pT1 N0 M0 and 24 were pT2 N0 M0. Four patients were staged as Stage II (pT3 N0 M0), and in 29 patients the T Stage was not specified. Eighty-six patients from the 117 Stage I (pT1-pT2, N0 M0 according to the TNM classification) seminoma received postorchiectomy irradiation, and are analyzed for outcome in this article. The distribution of the Stage I patients by pT Stage was 71 pT1 and 15 pT2 patients. All these 86 patients had their paraaortic nodes (the biological target volume extending from top of L1 to the bottom of L5) irradiated with four field technique. Tumor dose was specified at normalization point along the central axis. The median tumor dose was 30 Gy given in 1.8-2.0 Gy fractions. Elective irradiation to the ipsilateral hemipelvis (iliac nodes) was totally abandoned. RESULTS: The 10-year disease-free survival and overall survival were 95.3 and 100%. No recurrence in the irradiated field was noted. Four patients (4.7%) experienced relapse of disease outside the treated volume. The most common site of solitary failure was the ipsilateral hemipelvis (one iliacal and one inguinal). One patient developed metastatic disease to the lung. One patient developed a mediastinal recurrence with superior vena cava syndrome and was successfully salvaged by mediastinal irradiation and chemotherapy. CONCLUSIONS: Recommendation for the future management of Stage I seminoma include: reduced biological target volume to the paraaortal lymph nodes (from lumbar vertebra L1 to L5). Complete elimination of irradiation to the pelvic nodes is warranted. Radiation dose should not exceed 30 Gy.

The prognostic significance of the supraclavicular lymph node metastases in breast cancer patients.

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 Würzburg 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 M1 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 M1 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 M1-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 supraclavicular 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.

Pitfalls in the actual tnm system for lung-cancer and their implications for curative radiotherapy (review).

The knowledge of lymphatic pathways of lung cancer as well as the prognostic significance of the involvement of each lymph node site is of paramount importance for diagnosis, staging and proper treatment indications. A modified TNM classification for lung cancer is proposed considering available data on: (i) survival of patients according to the actual TNM system; (ii) lymphatic drainage pattern; (iii) embryological development of the lymphatics in the thorax. Actual data on survival rate for N3 disease and stage IIIB are critically discussed. The involvement of the supraclavicular and/or contralateral hilar lymph nodes as well as the involvement of the contralateral mediastinal lymph nodes for the right situated lung cancer should be described as M1 (lymph) disease and thus classified as stage IV. The implications for curative irradiation are presented.

The lymphatic pathways of non-small cell lung cancer and their implication in curative irradiation treatment.

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.

Central nervous system metastases in breast cancer.

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.

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.

Pitfalls of the tnm classification of head and neck tumors.

Any TNM system has to be a reproducible description for the anatomic extent of the tumor. In addition, the TNM should reflect the biology of the disease in a specific site in cancer patients at a specific time in the Life history of the cancer. A modified TNM classification for the head and neck cancers is proposed considering available data on: (i) survival rate vs level of involvement; (ii) lymphatic drainage patterns; (iii) embryological development of the neck lymphatics. The modified TNM definitions contain the old 'T','M' and new 'N1', 'N2', 'N3' and 'M1(lymph)' descriptions. The involvement of the supraclaviclar lymph nodes is described by 'M1(lymph)' since the biological significance is that of a distant metastases.

The clinical relevance of lymphatic and blood-vessel invasion in breast-cancer patients.

We reviewed 795 patients treated between 1978 and 1988 at the Department of Radiation Oncology of the University of Wuerzburg to study the influence of lymphatic vessel (LVI), blood vessel (BVI) invasion within the primary tumor on distant recurrence and survival following mastectomy or conservative treatment. Among them there were 140 patients with LVI and 18 patients with BVI. In the LVI positive group 75% of patients had axillary lymph nodes involved. In the BVI positive group 94% were nodal positive. The mean number of involved axillary nodes was higher in the group with LVI (4.6) as well as in the group with BVI (9.6) in comparison to the groups with absence of LVI (1.2) or BVI (1.7). LVI and BVI have a distinct impact on survival (P<0.001, P<0.01 respectively) and metastatic-free interval (P<0.001, P<0.01 respectively). The 2- and 5-year survival rates were 78% and 42% for the LVI group compared to 89% and 71% respectively for the LVI negative group. The corresponding 2- and 4.5-year survival rates for the BVI positive group were 68% and 40% compared to 87% and 70% respectively for the BVI negative group. The 5-year metastatic-free rate was 50% in the LVI group compared to 68% in the group without LVI. In the BVI group 53% were free of distant disease at 5 years compared to 66% in the group without BVI. This study suggests that from the biological point of view, LVI and BVI is a sign of agressive disease with poor prognosis. Patients with intra- or peritumoral LVI or BVI represent high risk groups for distant recurrence.

Supraclavicular lymph-node recurrence of breast-cancer.

To describe prognosis and outcome of patients with a recurrence in the supraclavicular fossa (SCLNR) and to evaluate the role of different therapeutic options for recurrence on the outcome of these patients, clinical and pathological characteristics, treatment and time course of 55 patients with supraclavicular recurrence as their first relapse of disease were analysed. Thirty-nine patients had an isolated recurrence, i.e. no distant metastases were known at the time of supraclavicular recurrence. Median follow-up was 20.4 months from supraclavicular recurrence and 58.8 months from primary diagnosis. For evaluation of treatment only the 39 patients without distant disease before or simultaneous with supraclavicular recurrence were analysed. Mean age of the 55 patients at primary diagnosis and at diagnosis of recurrence was 56.7 and 61.2 years respectively. The majority of patients developing such a recurrence was younger than 60 years at the time of primary diagnosis, Evaluation of patient characteristics showed a high proportion of positive axillary status (65%) at the time of primary diagnosis with a mean number of 7.5 involved nodes. Tumor was located in the medial or central part of the breast in 53% of patients in whom primary tumor location was known. About 80% of patients developed their recurrence in the first 5 years from primary diagnosis of breast cancer. Global survival after SCLNR was poor. Survival rate from recurrence was 65% at 2 years and only 16% at 5 years. Among the 39 patients with an isolated SCLNR 88% developed distant metastases within 5 years from recurrence. The evaluation of different therapeutic options for a SCLNR (radiotherapy, surgery, systemic therapy) revealed no significant influences on survival rates. When local regional control was obtained, a trend towards improved survival was noted. Patients aged younger than 60 years at primary diagnosis, with high positive primary axillary status or tumor of the medial or central part of the breast seem to be at higher risk for developing SCLNR and internal mammary lymphatic route may be a more probable pathway to the supraclavicular nodes besides the common axillary route. SCLNR carries a grave prognosis. Most patients develop distant disease within short time, with only a small section surviving more than 5 years from the onset of recurrence. Survival rate of patients with SCLNR is clearly inferior to patients with local or regional axillary recurrence. From this we conclude that SCLNR should be considered as an indicator of systemic disease despite its lymphogenous genesis and not as regional recurrence. Local therapy of SCLNR is to be defined with palliative intent in most cases. Systemic therapy has to be applied additionally even if no other distant disease is known. Further prospective analyses will have to evaluate the role of systemic treatment for solitary supraclavicular recurrences.

The clinical relevance of metastatic pattern in breast-cancer - the heterogeneity of metastatic disease.

Patients with metastatic breast cancer are considered as a homogeneous group because of the relative rarity of data relating to specific organ metastases. In this study, the clinical course of metastatic breast cancer was documented for 278 female patients registered from 1978 through 1988 at the Clinic for Radiotherapy of the University of Wurzburg. We analysed these 278 patients with metastatic disease to work out the clinical significance of specific organ metastases (SOM). A comparison of the six most frequent specific organ metastatases (SOM), i.e., bone, lung, CNS, liver, lymph node and skin metastases, is presented. Our findings indicate, that the group of patients with metastatic disease is heterogenous relating to age at time of metastatic disease, to metastatic-free intervall and to the influence of specific organ metastases on survival. The heterogeneity in the group of patients with distant metastatic disease has to be taken in consideration, when the results of chemotherapy are reported.

Incomplete axillary dissection in early breast-cancer and the risk of erroneous staging.

Maximum control of local disease in early breast cancer is obtained by breast conserving surgery, minimally invasive surgery of the axilla and consecutive selection for adjuvant therapy based on the number of involved axillary level I nodes. The answer to the question what is a 'node negative' patient? by defining the number of lymph nodes excised at operation exclusively, and the number of involved nodes found by the pathologist is given. Based on the data of Veronesi et al (Eur J Surg Oncol 16: 127-133, 1990) on 1446 complete axillary dissections performed between 1983-1986, the mathematical basis of the incomplete axillary dissection of the axilla in early breast cancer is presented: (i) To achieve a degree of confidence of 90% of the entire axilla being negative, histological examination of 10 level I nodes for a T1 tumor and 11 level I nodes for a T2 primary are necessary. In order to obtain these lymph nodes a total en bloc dissection of level I is indicated. (ii) The axillary status was considered negative if 10 or more lymph nodes for T1 or 11 or more in T2 tumors were found and were negative. (iii) The axillary status was considered positive, if <10 lymph nodes in T1 or <11 nodes in T2 tumors were found, even if they all were negative. If positive lymph nodes are left or estimated in the axilla after incomplete dissection, surgical treatment of the axilla is mandatory.

Differences in uptake of aminoacids by patients with various forms of cancer.

The serum concentrations of alphaaminonitrogen (AAN), lysine, valine and leucines were determined before and within the period of 24 hr after the administration of Trophysan (10% solution of glucose containing a mixture of aminoacids) in 100 patients with cancer (17 with gastrointestinal carcinoma, 34 with uterus carcinoma, stages I to III; 8 with breast carcinoma, stages II and III; 15 with bronchogenic carcinoma, 10 with various localizations and 15 with metastatic cancer) and in 22 patients with benign tumors. A significant decrease in the serum content of AAN, valine and lysine was noted in patients with cancer (stages I to III) at 24 hours after the administration of Trophysan. This effect was absent for the patients with benign tumors. The enhanced uptake of aminoacids found in patients with cancer is probable the result of the negative nitrogen balance associated with the malignant state.

31-P mr spectroscopy of a leg lymphangiosarcoma.

In a 64 year old man with a large, low grade lymphangiosarcoma of the right thigh, we correlated the results of in vivo 31-P-magnetic resonance spectroscopy (MRS), proton magnetic resonance imaging (MRI), and digital subtraction (DSA) with the pathologic specimen and histology. The 31-P MRS spectra of the tumor showed well-resolved peaks as follows: intense PCr (phosphocreatine), PDE (phosphodiester) and Pi (inorganic phosphate), and low PME (phosphomonoester). The Pi peak revealed an intratumor pH of 6.96 compared with 7.16 of normal skeletal muscle. The lower PME signal was consistent with low histopathologic mitotic activity of the tumor.

[Conformal irradiation technique for the peri- and retrobulbar space in endocrine orbitopathy]. / Konformations-Bestrahlungstechnik für den Peri- und Retrobulbärraum bei endokriner Orbitopathie.

The clinical target volume (CTV) for the irradiation of the endocrine orbitopathy (Graves ophthalmopathy) includes the peri- und retrobulbar space with the extraocular muscles. We present here a conformal irradiation technique aimed at optimal coverage of the CTV. The irradiation technique consists of two rotation fields with a central lens block and two lateral fixed fields with dorsal blocking. In each Gantry position, the lenses are faded out through the central lens block. The isocenter of the two rotation fields is located in the lenses. For quality assurance of this irradiation technique, verification of the dose distribution was performed by film dosimetry using the humanoid Aldersone phantom. The use of this irradiation technique yielded a dose distribution with conformal CTV coverage of the peri- and retrobulbar space and of the extraocular muscles. The film dosimetry of the Aldersone phantom showed a maximal deviation of 5% between the measured and the calculated dose distribution. The radiation load to the eye lenses was 25% of the applied total dose.