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H Sack

Publications and source records attributed to H Sack.

At least 37 records · Page 2Linked to original sources

[Radiotherapy alone in early stages of low malignancy non-Hodgkin lymphomas].

About 25% of patients with low grade Non-Hodgkin's Lymphomas (NHL) of the B-cell type present in an early stage. They are candidates for radiotherapy alone. Thereby a complete remission can be achieved in the majority of stage I and II patients with centroblastic-centrocytic (cb-cc), centrocytic (cc) and immunocytic (ic) NHL--at least in cb-cc also a relapse-free survival of 50-60%. Standardization of the radiotherapeutic technique is essential to reduce the risk of recurrence. Retrospective analyses of radiotherapeutic studies from the literature are limited by the lack of homogenous irradiation techniques. Relapses occur inside as well outside of radiotherapy ports. It is the aim of current studies to optimize the radiotherapeutic approach with curative intent.

Follow-Up Studies↗

[Boron neutron capture a a new radiotherapy model].

The boron neutron capture therapy is based on the reaction occurring with certain probability, if a thermal neutron meets the boron 10 isotope. The low energy slow neutron is captured by the nucleus and it disintegrates into Li-nucleus and He-nucleus (alpha particle). If this physical reaction occurs in a living cell that will be destroyed. If the boron neutron capture reaction could be achieved selectively in malignant cells of tumor patients, that could be an effective therapeutical modality to treat the locally growing cancers. For boron neutron capture therapy to be successful two basic conditions must be fulfilled, an appropriate neutron source must be available and the sufficient number of 10B must be delivered possibly selectively into the tumor cells by a boron compound. At present both part of this binary system are under intensive investigation, the development of the neutron source, the synthetisation and experimental testing of boron delivery agents. The development of the dosimetry, microdosimetry, the work out of the powerful tools of detection the cellular, subcellular 10B distribution, the continuous improvement of the planning system and the optimization of the boron neutron capture therapy are the main point of the research area on boron neutron capture therapy. Clinical studies and clinical application of boron neutron capture therapy are under way for the treatment of melanoma malignum and for brain tumors, with the two boron compound has been clinically tested up to now, in Japan, at two Centres in USA, and recently has been started in Europe. The authors give an overview about the principles of boron neutron capture therapy, about the result of the research on neutron sources and boron compounds, moreover about the possible application area of this new radiation modality.

Boron↗

[Radiotherapy of follicle center lymphoma. Results of a German multicenter and prospective study. Members of the Study Group "NHL-early stages"].

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 II < 60 years had survival rates of 94% at 5 and 8 years, patients > 60 years 63% (p < 0.0001). 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: age > 60 years, treatment breaks > or = 7 days and dose deviations > 20% from prescribed doses. Acute side effects of extended field irradiation were moderate. CONCLUSIONS: 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.

Adult↗

[Workshop "Radio-oncology and the Law"].

From 25 to 27 Sept 1997, a workshop was organized at the Essen Medical School (Universitätsklinikum Essen), at which radiooncologists and jurists from universities and courts as well as lawyers contributed their views on mutual problems. The following topics were discussed by papers and in round table meetings: "Requirements on the patient's information", "definition of therapeutic guidelines-limits of clinical research and standard treatments", "treatment documentation", "liability of the physician for treatment faults" and "technical standard and preserve of quality". The consensual guidelines to the topics "patient's information", "therapeutic guidelines" and "liability" are presented here.

Documentation↗

[Hyperfractionated accelerated simultaneous radiochemotherapy in advanced hypopharyngeal carcinomas. Survival rate, retained function quality of life in a phase II study].

Forty-one patients with locally advanced hypopharyngeal carcinomas were followed for at least 3 years (median, 60 months) after simultaneous radiochemotherapy. Conventionally fractionated radiotherapy was administered as 5 x 2 Gy/week to a total dose of 30 Gy within 3 weeks. From the fourth week an accelerated hyperfractionated schedule was used as 2 x 1.4 Gy/day five days weekly given exclusively to the first order target volume of macroscopic tumor (adding up to a total dose of 72 Gy in six weeks). The second and third order target volumes received conventional fractionation only to 60 Gy and 50 Gy, respectively. The moderate acceleration of the concomitant boost scheme in the second half was counterbalanced during the first week by the introduction of a 5-fluorouracil bolus of 350 mg/M2 with 200 mg/M2 folinic acid and a subsequent continuous infusion using the same dose each 24 h for 5 days. Additionally, a Mitomycin-C bolus of 10 mg/M2 was infused at the fifth day and on the first day of the sixth week. Six weeks after treatment the patients were restaged. In cases with residual carcinoma salvage surgery was performed (11 patients). Late effects of therapy were analyzed according to the Lent-Soma index and life quality according to the European Organisation for Research and Treatment of Cancer-Module. Late effects of treatment were tolerable and were controlled locally. The 3-year-survival rate was 39%, with a local-regional recurrence-free control rate of 71%. Fifty-two percent of all cases of death were caused by distant metastases, secondary carcinomas or other diseases not related to tumor recurrence. The poor prognosis of hypopharyngeal carcinomas despite acceptable local tumor control may be due to specific biological factors present in affected patients.

Antineoplastic Combined Chemotherapy Protocols↗

Contiguous pattern spreading in patients with Hodgkin's disease.

BACKGROUND: In 1966, Rosenberg and Kaplan hypothesized that Hodgkin's disease (HD) arises at a discrete primary site and subsequently spreads in a predictable manner via functionally contiguous lymph nodes. However, their results were not statistically evident. It was our aim to describe the spreading in the lymphatic system more precisely and to confirm their postulate. METHODS: Between 1971 and 1992, 297 patients underwent pathological staging for HD. Our subsequent evaluation was restricted to the 236 cases with cervical involvement (65 bilateral, 80 dextral and 91 sinistral), those with lymph nodes on the right side (65 + 80 = 145) being analyzed separately from those with tumours on the left (65 + 91 = 156). Spreading via the lymphatic system was assessed by scoring of the number of involved and uninvolved nodes in six regions, which are functionally contiguous in the lymph system but not necessarily anatomically neighboured. The number of 'gaps' (i.e. missed nodes) observed according to a systematic spreading model was compared with that expected (probability model) if a random course had been followed. RESULTS: Of the 156 patients with left cervical HD, 117 (75%) had para-aortic or spleen involvement, 90 (58%) had mediastinal involvement, 65 (42%) had right cervical involvement, 50 (32%) had axillary involvement and 23 (15%) had inguinal involvement. Of the 145 patients with right cervical HD, 112 (77%) had mediastinal involvement, 89 (61%) had para-aortic or spleen involvement, 65 (44%) had left cervical involvement, 44 (30%) had axillary involvement and 16 (11%) had inguinal involvement. In patients with left or right cervical lymph nodes, the proportions observed with gaps in the spreading were 37 and 27% (SE 7%), respectively, whereas the corresponding values of gaps expected in a probability model if a random course of spreading had been followed would have been 84 and 73% (P = 0.0001 and 0.0001, respectively). CONCLUSION: Our data support the concept that HD spreads in a predictable manner via functionally contiguous lymph nodes. In patients with right cervical lymph nodes, HD spreads via the upper mediastinum and pulmonary hila to the upper abdominal nodes and the spleen. In those with left cervical tumours, HD spreads directly to the abdomen (bypassing the mediastinum), then upward again via the pulmonary hila and upper mediastinum to the neck region (bilateral involvement) and from here it proceeds to the axillary nodes. Finally the inguinal nodes are involved.

Adult↗

The effect of combined nicotinamide and carbogen treatments in human tumour xenografts: oxygenation and tumour control studies.

BACKGROUND AND PURPOSE: This was an investigation to study the effect of giving carbogen and nicotinamide (CON) on pO2 and the radiation response of human xenografted tumours. MATERIALS AND METHODS: The human xenografts were two sarcomas (ENE2 and ES3) and a glioblastoma (HTZ17). Nicotinamide (500 mg/ kg, i.p.) was administered 60 min before PO2 measurements and irradiation, while carbogen was given for 5 min before and during these treatments. Tumour pO2 was measured with an Eppendorf electrode and radiation response was assessed by local tumour control following irradiation with 10 daily fractions. RESULTS: All three xenografts were found to be poorly oxygenated (about 80% of all pO2 values were < or =2.5 mmHg). CON treatment improved the oxygenation status in all three tumours such that 65, 52 and 71% of the pO2 values were < or =2.5 mmHg in ENE2, ES3 and HTZ17, respectively. However, only in ES3 was this decrease significant. The TCD50 doses for all tumours were around 52-54 Gy. No significant improvement was seen with CON in ENE2 (TCD50 = 48 Gy) and HTZ17 (TCD50 = 56 Gy), but for the ES3 xenograft a significant decrease to 42 Gy was found. CONCLUSIONS: The three tumours used in this study appeared to show the same level of hypoxia as measured both by pO2 and radiation response. However, only one tumour showed a significant improvement after CON treatment, suggesting that not all hypoxic human tumours might benefit from this type of therapy.

Administration, Inhalation↗

Experimental studies on the possible influence of invasive oxygen measurements on tumour radiosensitivity.

The effects of tissue damage associated with invasive pO2 measurements on radiation sensitivity were investigated using a xenografted squamous cell carcinoma model. For the tumour cure experiments, single dose irradiations were given following different regimens of polarographic pO2 measurements associated with different degrees of mechanical tissue damage. With a dose of 32 Gy, 57% of animals were cured. Following 3 tracks of needle measurements, 73% of tumours were locally controlled, and 75% were cured after 8 needle tracks. The polarographic measurements gave virtually identical oxygenation data for recurrent or cured tumours (both median pO2 1.0 mmHg), respectively. There was thus no evidence of decreased radiosensitivity associated with tissue damage after invasive pO2 measurements. The pre-therapeutic oxygenation status gave no evidence for a prediction of radiation response on an individual basis.

Animals↗

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial.

PURPOSE: To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC). PATIENTS AND METHODS: Following staging, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation. RESULTS: Of 94 consecutive patients (52 stage IIIA [> or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. CONCLUSION: This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls

Adult↗

Extended field and total central lymphatic radiotherapy in the treatment of early stage lymph node centroblastic-centrocytic lymphomas: results of a prospective multicenter study. Study Group NHL-frühe Stadien.

BACKGROUND: A prospective multicenter trial was performed to evaluate survival, patterns of relapse, and toxicity for clinically staged patients with lymph node centroblastic-centrocytic (cb/cc) lymphomas in Stages I-IIIA after large extended field irradiation (EFI) or total central lymphatic irradiation (TCLI). METHODS: Between January 1986 and August 1993, 117 adults with clinical Stage I-IIIA lymph node cb/cc lymphoma (Kiel classification) were recruited. Patients in Stages I or II with mediastinal, hilar, periaortic, iliac, or mesenteric involvement and in Stage IIIA received TCLI, whereas patients with more peripherally located cb/cc lymphomas were treated with EFI. TCLI and EFI were administered to a total dose of 26 gray (Gy) with 2 Gy per daily fraction, with the exception of the whole abdomen, which was irradiated to a total dose of 25.5 Gy with 1.5 Gy per fraction. A boost of 10 Gy with 2 Gy per fraction was administered to enlarged and involved lymph nodes at the start of radiotherapy. RESULTS: Sixty, 40, and 17 patients had Stage I, II, and limited IIIA disease (no bulk and less than 6 involved lymph node regions), respectively. Overall survival was 86% at 5 and 7 years; median follow-up was 68 months. The probabilities of relapse at any site, recurrences in lymph nodes, and in-field lymph node recurrences after TCLI were 17% in Stage I; 56%, 43%, and 40% in Stage II, respectively; and 44%, 35%, and 35% in Stage IIIA, respectively. The risk of disseminated extralymphatic relapses was 9% at 7 years. The most important adverse prognostic factor for in-field lymph node recurrences was a deviation of >20% from the assigned total radiation dose. After EFI, patients in Stage I had a significantly lower risk of recurrences in adjuvant irradiated lymph node regions than in unirradiated lymph node regions. Acute toxicity of EFI and TCLI was moderate. CONCLUSIONS: In-field lymph node recurrences remained the main risk after TCLI, and a deviation of >20% from the assigned radiation dose was the major risk factor for in-field recurrences. From these data, a total dose of 40-44 Gy in conventional fractionation for the treatment of macroscopic cb/cc lymphomas and 30 Gy for the treatment of subclinical disease is recommended. A randomized study comparing TCLI with EFI is now being organized by this group.

Adult↗

Radiotherapy for treatment of localized gastrointestinal non-Hodgkin's lymphoma.

BACKGROUND: The study analyses a standardized, risk-adapted radiotherapy for stage IE-IIE primary extranodal lymphoma of the stomach and bowel. METHODS: Sixty eight patients (31 females, 37 males, median age 56 years) were treated from 1987-1992 in 15 centers. Fifty six patients had gastric and 12 patients had bowel lymphomas. Gastric lymphomas (low or intermediate grade stage I-II: 38 patients/high grade stage I: 18 patients) were treated by whole abdominal irradiation (25/30 Gy), booster dose to involved field (30/40 Gy) and additional boost to macroscopic residual lymphoma (40/50 Gy). Surgery consisted of gastrectomy (19 patients), partial gastric resection (30) or biopsy (7). In 8/18 stage II patients, supradiaphragmal irradiation was added. In 10/12 patients with bowel lymphoma, segment resection was performed, two received biopsy only. Radiation doses equalled those used for gastric lymphoma: RESULTS: In 51/56 patients (91%) with gastric lymphoma, the recommended dose for whole abdominal irradiation was given. A total of 40/56 patients (71%) received the required dose to the upper abdominal region, in 22/56 patients (39%) a booster dose for residual disease was applied. Five-year overall survival was 87%, 5-year disease-free survival 84%. Of nine relapses, two were in the gastric stump of low grade patients after reinfection with Helicobacter pylori. Three infield, intraabdominal relapses were observed in intermediate and high grade lymphoma, all other relapses were outfield. Eleven patients experienced late toxicity (bowel obstruction after laparatomy and irradiation, four patients; chronic gastritis, three patients; asymptomatic left kidney atrophy, two patients; asymptomatic hepathopathia, two patients). In bowel lymphoma, 5-year disease-free survival was 65%. CONCLUSION: This study demonstrates the high efficacy of risk-adapted radiotherapy in gastric lymphoma. In low grade gastric lymphoma, whole abdominal irradiation may be reduced in dose or omitted. Total gastrectomy does not improve results and should therefore be avoided if possible.

Adult↗

Correlation between primary chemo- and radiation sensitivity in a panel of highly malignant human soft tissue sarcoma xenografts.

BACKGROUND AND PURPOSE: Sensitivity to radiation and sensitivity to cytotoxic drugs have been proposed to be independent properties of tumour cells. However, very few clinical or experimental studies have tested this hypothesis. Therefore, we evaluated the response to ionizing radiation and to four cytotoxic drugs in a panel of 12 human soft tissue sarcoma cell lines using the xenograft system. MATERIAL AND METHODS: NMRI-nu/nu nude mice with subcutaneous tumours received at a tumour volume of 120-200 mm3 either single dose, single agent chemotherapy with 350 mg/kg ifosfamide, 200 mg/kg dacarbazine, 10 mg/kg doxorubicin, 6.6 mg/kg cisplatin, or 24 Gy local tumour irradiation under acutely hypoxic conditions from a cobalt-60 source. Tumour response to radiotherapy and chemotherapy was measured as specific growth delay (SGD). RESULTS: A significant correlation was found between SGD after radiotherapy and SGD after decarbazine (P < 0.001) and doxorubicin (P = 0.05), whereas no correlation could be demonstrated for cisplatin. For ifosfamide, the correlation reached borderline significance. The maximal response to any of the four tested chemotherapeutic drugs correlated very well with the response to radiotherapy (P < 0.001). CONCLUSION: The results suggest that radiation sensitivity and chemosensitivity are not independent properties of soft tissue sarcoma cell lines.

Animals↗

Postoperative radiotherapy of spinal and intracranial ependymomas: analysis of prognostic factors.

PURPOSE: Postoperative radiation therapy adds significantly to disease control and survival of patients with ependymoma. However, much controversy exists about the radiation treatment policy. We report the long-term results of a cohort of 56 patients with primary intracranial and spinal ependymomas. Special effort has been taken to define prognostic indicators as a basis for future treatment strategies. PATIENTS AND METHODS: Between November 1963 and May 1995, 56 patients with histological proven ependymoma were referred to our clinic for further treatment following surgery. Thirty patients had a high grading tumor and 26 had low grade tumors. Seventeen patients had supratentorial tumors and 24 had infratentorial tumors. Fifteen patients suffered from localized spinal tumors. RESULTS: The mean survival time for all patients was 77 months. Five- and 10-year survival probabilities were 60 and 51%, respectively. The mean progression free survival (PFS) probability for all patients was 67 months with corresponding 5- and 10-year PFS probabilities of 53 and 39%, respectively. On univariate analysis initial performance status, age and tumor grade were significant for survival probability. Concerning PFS radiation dose was significant with improved survival with doses > 45 Gy. On multivariate analysis, tumor grade and initial performance status proved to be the only independent prognostic factors. CONCLUSIONS: Tumor grade, age, initial performance status and radiation dose are significant factors for the clinical course of patients and have to be taken into account for the urgently needed prospective trials.

Adolescent↗