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Biomedical subjects

H Frommhold

Publications and source records attributed to H Frommhold.

At least 19 recordsLinked to original sources
PubMed2000

[Animal experiment study of anastomosis healing after partial resection of the pre-irradiated thoracic esophagus].

BACKGROUND: Multimodal therapeutic concepts in cases of neoplasms of the intestinal tract entail the risk of undesirable complications with respect to healing of wounds and anastomoses. The separate steps of a combined treatment consisting radiation therapy and partial resection of the thoracic esophagus were performed in animal experiments to study the effect of radiation therapy on the healing of anastomoses. METHOD: Adult non-purebred dogs were irradiated in a defined thoracic field with a Betatron (42 MeV) and subsequently underwent esophagectomy. After resection of a 2 cm segment of the esophagus end-to-end anastomosis was performed. Different methods of irradiation and postoperative observation times resulted in a total of 8 groups of 3 animals each. RESULTS: Fractionated irradiation was definitely better tolerated than irradiation with a high single doses. The temporary delay of the anastomotic healing was documented histologically. Only one case of anastomotic leakage occurred, and impaired wound healing was observed in only one animal. CONCLUSION: The mode of irradiation must be regarded as important for the clinical course. Fractionated preoperative irradiation in the area of the thoracic esophagus does not lead to any relevant disturbance of wound and anastomotic healing with meticulous surgical technique and adequate intensive postoperative care. The basic feasibility of surgical therapy combined with preoperative radiotherapy in tumors of the upper digestive tract was confirmed by our experimental work.

Anastomosis, Surgical↗
PubMed1999

[Second malignancies after the therapy of Hodgkin's disease: the Freiburg collective 1940 to 1991].

AIM: To quantify the risk of second malignancies in patients with Hodgkin's disease treated at the Department of Radiotherapy, University Clinic Freiburg, with the object of comparing this risk with the international experience and as a contribution to the discussion about future treatment. PATIENTS AND METHODS: Second malignancies were reviewed in 1,588 patients treated for Hodgkin's disease between 1940 and 1991. Treatment consisted of involved or extended field radiotherapy as a single modality or in combination with chemotherapy. Before the early 1970's, chemotherapy used (sequential) monodrug regimens. The mean follow-up was 8.3 years. The cumulative risk was calculated using the Kaplan-Meier method and related to the risk of a normal population taken from epidemiological data of the National Cancer Institute. An estimate of radiation dose at the site of origin of the second malignancy was obtained from representative measurements employing an Alderson phantom. RESULTS: After 5, 10, 15 and 20 years the cumulative risk for all malignancies was 1.5%, 4.2%, 9.4% and 21%, respectively; for solid tumors it came to 1.2%, 3.1%, 7.9% and 19%; for non-Hodgkin lymphoma (NHL) the risk amounted to 0.1%, 0.9%, 1.4% and 1.9%; and for leukemia it was 0.1%, 0.3%, 0.6% and 0.6%. For the same time points the relative risk for all malignancies was calculated to be 1.1, 1.4, 1.8 and 2.5; for solid tumors it came to 1.0, 1.1, 1.6 and 2.5; for NHL it amounted to 3.3, 11.8, 9.3 and 8.0; and for leukemia it was 3.3, 3.1, 3.4 and 2.1. For combinations of radiotherapy and chemotherapy the risk for second malignancies was highest in patients receiving ABVD any time during their treatment. 51% of the second malignancies were located infield, 22% at the field border and 27% outfield. In those cases for which the cause of death was known, Hodgkin's disease accounted for 79% followed by second malignancies accounting for 8%. The results obtained in Freiburg fell within the range reported in international publications. CONCLUSION: The increased incidence of second malignancies in cured Hodgkin's patients is along-term risk making regular follow-up mandatory. Although part of the second malignancies are unrelated to therapy, there is a need to carefully collect the data from patients treated according to new protocols in order to detect any changes in the number or kind of second malignancies in due time. This may well lead to a reassessment of therapeutic concepts.

Adult↗
PubMed1999

Erythropoietin for patients undergoing radiotherapy: a pilot study.

BACKGROUND AND PURPOSE: To evaluate the feasibility and efficacy of using recombinant human erythropoietin (rhEPO) to correct decreased hemoglobin levels in patients undergoing radiotherapy and to get an estimate of its influence on the efficacy of radiotherapy. MATERIALS AND METHODS: Fifty patients with cancer of the head and neck and the pelvis were randomized before radiotherapy to different rhEPO treatments (none, 3 x 150 U/kg per week i.v., 3 x 300 U/kg per week i.v. and 3 x 150 U/kg per week s.c.). Hematological parameters were evaluated weekly and the locoregional tumor control rates were determined in 38 patients with head and neck cancer. RESULTS: rhEPO-treated patients showed a significant increase in their hemoglobin values (0.7 g/100 ml per week). The rhEPO response was comparable for patients with cancer of the head and neck and the pelvis. A delayed recovery was seen when iron deficiency or impaired iron mobilization was present. No serious toxicity was observed. Locoregional tumor control was improved, although not statistically significantly, in those head and neck cancer patients who experienced a rapid rise of hemoglobin. CONCLUSIONS: Low hemoglobin levels can be safely and quickly corrected with rhEPO. This may improve the effectiveness of radiotherapy.

Adolescent↗
PubMed1999

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: a mature follow-up report.

BACKGROUND: We conducted a phase I-II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I-IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF STANDARD-DOSE VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. CONCLUSIONS: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR > 2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.

Adult↗
PubMed1999

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 107 patients with non-small-cell lung cancer: a mature follow-up report.

BACKGROUND: We conducted a phase I-II trial to assess the activity of standard-dose (SDC) and high-dose chemotherapy (HDC) with etoposide, ifosfamide, cis/carboplatin, and epirubicin (VIP-E, VIC-E) in 107 patients with limited-stage (LS, stage I-IIIB) and extensive stage (ES, stage IV) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Updated results of a previously published trial are presented. RESULTS: Response rates and survival after VIP-E were comparable to those of other standard-dose combination chemotherapies in NSCLC. Treatment-related mortality (TRM) in SDC was 3% in LS-NSCLC, and 8% in ES-NSCLC. TRM was 4% in patients selected for HDC by response rate and performance score. Five-year survival in LS-NSCLC was 12% after SDC, and 18% after HDC; it was 0% for both treatment protocols in ES-NSCLC. CONCLUSIONS: The activity of VIP-E SDC and VIC-E HDC is not superior to that of established protocols in the treatment of NSCLC. In view of the toxicity and TRM associated with this protocol, less aggressive regimens should be preferred for most patients. Whether selected patients with chemosensitive disease could benefit from VIP-E SDC and/or VIC-E HDC in an adjuvant or neo-adjuvant setting could not be determined within the scope of this study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer.

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.

Adult↗
PubMed1998

The impact of blood hemoglobin content on the outcome of radiotherapy. The Freiburg experience.

BACKGROUND: Numerous publications have reported an impaired radiocurability when anemia is present. Tissue hypoxia and consecutive radioresistance are speculated to be the underlying causes. OWN EXPERIENCE: Our own retrospective data impressively confirm these observations: in an analysis of 889 patients homogeneously irradiated for head and neck cancer for locoregional tumor control and survival, anemia has proven to be a highly significant risk factor. Furthermore, hemoglobin content is an independent and, at least equally powerful predictor for outcome when compared to the known risk factors of site, treatment modality, resection status, T-, and N-stage. TREATMENT: In an attempt to improve therapeutic outcome, 50 anemic patients undergoing radiotherapy were treated with erythropoietin (rhEPO). A weekly increment in hemoglobin content of 0.7 g/dl was documented without any major side effects. Additionally, it seems that patients reacting sufficiently to rhEPO stimulation can expect better locoregional tumor control within the irradiation volume. This, however, awaits confirmation in an ongoing trial.

Anemia↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of combination chemotherapy with etoposide, ifosfamide, cisplatin, and epirubicin in limited-stage (LS, stage I-IIIB) and extensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-points were treatment-related morbidity and mortality, response rate, duration of response, and survival. PATIENTS AND METHODS: Chemotherapy followed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) (VIP-E) to 107 patients with NSCLC. Twenty-five patients with qualifying responses proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantation after etoposide (1500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF CONVENTIONAL-DOSE VIP-E: 35 of 102 (34%) evaluable patients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed no change (NC); the remainder of patients progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration of survival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-year survival was 26% in LS and 2% in ES-NSCLC. RESULTS OF HIGH-DOSE VIC-E: 23 of 24 evaluable patients improved or maintained prior responses (92%), I patient showed NC. Treatment mortality was 4%. Median duration of survival was 17 months in LS-NSCLC and 10 months in ES-NSCLC. Two-year survival was 30% in LS and 8% in ES-NSCLC. CONCLUSION: Response-rates and survival after conventional-dose VIP-E chemotherapy are comparable to other published trials of combination chemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage, but unacceptably high in extensive stage NSCLC. Although better response-rates were achieved in the high-dose arm, they did not translate into improved survival. Most stage IV NSCLC-patients will neither benefit from VIP-E conventional dose, nor from VIC-E high dose chemotherapy. Whether selected LS-patients with partial or complete responses to VIP-E induction chemotherapy could benefit from dose intensification in an adjuvant or neo-adjuvant setting remains to be determined.

Adult↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of VIP-E chemotherapy in small-cell lung cancer. End-points were treatment-related morbidity and mortality, response to treatment. duration of response, and survival. PATIENTS AND METHODS: Two cycles of combination chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) were given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) to 100 consecutive patients with SCLC. Thirty patients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) at a cumulative dose of etoposide 1500 mg/m2, ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2 and epirubicin 150 mg/m2 (VIC-E). Surgical resection of primary tumor was attempted at the earliest feasible point. Thoracic irradiation was given after completion of chemotherapy. RESULTS of conventional-dose VIP-E: 97 patients were evaluable for response. Objective response rate was 81% in LD-SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED-SCLC (18% CR, 58% PR). Treatment mortality was 2%. Median survival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survival was 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: All 30 patients improved on or maintained prior responses. Four patients (13%) died of treatment-related complications. Median survival was 26 months in LD-SCLC and 8 months in ED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. CONCLUSION: VIP-E chemotherapy is an effective induction therapy for SCLC. Compared with traditional protocols such as ACO or carboplatin/etoposide, response rates are slightly improved, while survival is not different. In the LD SCLC subgroup, high-dose chemotherapy improved response rates and survival, especially for patients in surgical CR prior to high-dose therapy. In ED SCLC, however, higher response-rates did not translate into improved survival. Selected LD-SCLC patients with good partial or complete remissions after prior therapy may benefit from HDC and PBSCT.

Adult↗
PubMed1996

[Intraoperative radiotherapy in gastrointestinal tumors].

Intraoperative radiotherapy has proved its worth for curative and palliative treatment of gastrointestinal tumors. IORT indications comprise cancer of the stomach, of the pancreas and colorectal carcinomas. Most authors are cautious to apply it to carcinoma of the esophagus, of the small intestine and of the hepatobiliary system. IORT is applied as adjuvant treatment alone or in combination with postoperative external-beam photon irradiation +/- chemotherapy. There is evidence of an improved local control rate. Pain can be relieved in symptomatic patients by an IORT dose of > or = 20 Gy. Until now, however, there is no evidence of a prolonged relapse-free and overall survival.

Colorectal Neoplasms↗
PubMed1995

Use of high-dose etoposide/ifosfamide/carboplatin/epirubicin and peripheral blood progenitor cell transplantation in limited-disease small cell lung cancer.

Conventional-dose chemotherapy for limited-disease small cell lung cancer has resulted in high response rates, but rarely in a cure. In an ongoing phase I-II trial, limited-disease small cell lung cancer patients received high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation as part of an early intensification strategy after two cycles of induction chemotherapy. Eligible patients (n = 18) were initially treated with two cycles of etoposide (500 mg/m2), ifosfamide (4 g/m2), cisplatin (50 mg/m2), epirubicin (50 mg/m2) and granulocyte colony-stimulating factor to combine an effective, standard-dose chemotherapy regimen with simultaneous mobilization of PBPCs. Patients who were in partial remission or complete remission after two cycles of induction chemotherapy received high-dose intensification chemotherapy with cumulative doses of 1,500 mg/m2 etoposide, 12 g/m2 ifosfamide, 750 mg/m2 carboplatin, and 150 mg/m2 epirubicin, followed by autologous PBPC transplantation and granulocyte colony-stimulating factor. The duration of the complete chemotherapy program was 9 weeks. All patients received chest irradiation posttransplantation (50 Gy), and those in complete remission received additional prophylactic cranial irradiation (30 Gy). To date, 13 patients with a median age of 49 years (age range, 34 to 62 years) have been treated within this combined-modality treatment protocol. At a median follow-up of 14 months (range, 3 to 45 months) after transplantation, 11 patients were alive and nine were still in complete remission. Nonhematologic toxicity was acceptable; World Health Organization grades 2 to 4 oral mucositis was the most frequently observed (85%) adverse event. No toxic deaths were observed, and hematopoietic reconstitution occurred rapidly after PBPC transplantation; platelet transfusion independence (> 20,000 microL) and neutrophil counts greater than 500 microL were observed at study day 12+. The median survival time was not yet reached. These preliminary data demonstrate that early, high-dose chemotherapy and PBPC transplantation followed by local radiotherapy is safe and may lead to prolonged disease-free survival in some patients. Prospective, randomized studies in a larger series of patients will be required to provide definitive proof of the role of early high-dose chemotherapy in the management of limited-disease small cell lung cancer.

Adult↗
PubMed1995

[Indications for percutaneous radiotherapy in carcinoma of the thyroid gland. Freiburg consensus].

At the University of Freiburg, a consensus was arrived at concerning the place of external radiotherapy in the management of thyroid cancer. External irradiation is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended, which should be set up in an interdisciplinary conference regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary thyroid carcinoma, whereas it is always indicated in anaplastic carcinoma.

Adenocarcinoma, Follicular↗
PubMed1994

Quality assurance for non-invasive patient fixation during stereotactic convergent beam irradiation.

Using a non-invasive mask this patient fixation system for stereotactic radiotherapy allows one to perform fractionated irradiation. Measuring the statistical quantities of patient motion and positioning uncertainties and calculating its effect on a spherically symmetric dose distribution showed that there is no severe disadvantage in most cases. Only if small field-size, excentric target volume localisation and extreme proximity to an organ at risk coincides have the statistical effects to be taken into account. The greatest measured standard deviation for positioning uncertainty was 2.3 mm. Its effect on the dose distribution with a field size of 9.1 mm increases the diameter of the 80% isodose to about 115%.

External Fixators↗
PubMed1994

[Radiotherapy of malignant obstructive jaundice].

Brachytherapy using the afterloading technique with iridium 192 and percutaneous irradiation using 16 MV photons are used for the irradiation of malignant obstructive jaundice. Mostly, however, a combination of both methods can be used to advantage. In bile duct tumors and Klatskin tumors, the endoluminal part can be treated using brachytherapy. The extralumenal growth and, if necessary, all affected regional lymph node areas can be treated by a 3D planned, percutaneous, moving field technique. Intraoperative radiotherapy can be used in a few cases as booster irradiation of tumor conglomerates at the porta hepatis. The decision to use irradiation must be made very carefully since solid tumors are usually involved that require a high target dose, the application of which can lead to unacceptable side effects. The radio-oncological spectrum is therefore confined predominantly to palliative therapy.

Bile Duct Neoplasms↗