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.

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.

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

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.

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.

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.

Sentinel node concept in breast cancer.

BACKGROUND/PURPOSE: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. MATERIAL AND METHODS: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin & Eosin (H&E) stained sections and immunohistochemistry. RESULTS: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2 procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a "pN0" patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or lymphatic basins could be spared from unnecessary irradiation. CONCLUSION: The sentinel node concept seems to revolutionize the treatment of early breast cancer. Biopsy of the sentinel node is a highly accurate, minimally invasive method of staging patients and can substantially reduce the morbidity and costs of treatment by avoiding unnecessary complete axillary lymph node dissection. The procedure may lead to a more justifiable approach to adjuvant therapy strategies with low complication rates. The identification of the individual lymphatic flow pattern would permit the irradiation of the individual locoregional lymphatic basin.

Selection and delineation of lymph node target volume for lung cancer conformal radiotherapy. Proposal for standardizing terminology based on surgical experience.

PURPOSE: To select and delineate the target volumes for definitive or postoperative radiotherapy for lung cancer. METHODS AND MATERIALS: The lymphatics of the lung and the dissemination of tumor cells to the intra- and extrathoracic lymph nodes are described. The incidence of involvement of the different lymph node sites in the chest is analyzed. The involvement of the contralateral hilar and/or supraclavicular lymph nodes and the consequences for target volume selection for curative radiotherapy are discussed. CT-based nodal classification and distribution of lymph nodes in the chest in CT-axial slices are presented. The sentinel node concept (SNC) and the preliminary data available for lung cancer are described. RESULTS: A critical review of the current TNM classification for lung cancer and the implications for target volume selection is given. The individual target volume selection and delineation have to be based on clinical and pathological data from large surgical. studies and upon the individual pathological and diagnostic patient data. The selection and delineation of the clinical target volumes for definitive and for postoperative radiotherapy, dependent on the lymph node involvement, are presented. CONCLUSIONS: Criteria for the selection and delineation of the clinical target volumes for definitive and for postoperative conformal radiotherapy in axial CT slices under consideration of site, size and stage of the lung cancer are described. Recommendations for target volume selection for definitive or postoperative radiotherapy are presented.

Lymphangiosarcoma of arm after chronic lymphedema: a rare long-term complication after radical mastectomy in breast cancer patients. Case report and overview.

Lymphangiosarcoma after mastectomy was first described by Stewart and Treves in 1948. Today, this tumor associated with chronic lymphedema has become a rare entity, due to less radical surgery. Chronic lymphedema and lymphangiectasia of limbs preceding lymphangiosarcoma may not only be induced by radical mastectomy. Also post-traumatic, congenital, filarial-associated or spontaneous chronic lymphedema may be associated with lymphangiosarcoma. A time interval of years seems to be required before malignant changes supervene and lymphangiosarcoma develops. This paper describes a case with lethal and arising in an edematous arm years after radical mastectomy and irradiation. Current concepts of etiology, histopathology, immunohistology, diagnostic investigation, treatment and prognosis are presented.