C.F. Hess

A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: Results of a randomized, controlled, multicenter trial

In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status.

Effect of keratinocyte growth factor on the proliferation, clonogenic capacity and colony size of human epithelial tumour cells in vitro.

Purpose : The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. Materials and methods : Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml −1) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. Results : Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGF-treatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. Conclusion : rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment.

Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis

PurposeTo evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis.Patients and Methods31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale.Results23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively.ConclusionSodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis.ZusammenfassungZielDiese prospektive Untersuchung wurde durchgeführt, um den Effekt von Natriumbutyrat-Einläufen in der Therapie der akuten Proktitis sowie den potentiellen Einfluss auf radiogene rektale Spätreaktionen zu evaluieren.Patienten und Methodik31 Patienten wurden mit Natriumbutyrat-Einläufen bei radiogen induzierter akuter Grad-II-Proktitis behandelt, die im Mittel nach 40 Gy aufgetreten war. Während der Radiotherapie wurde die Toxizität wöchentlich anhand der Common Toxicity Criteria (CTC) und anschließend jährlich anhand der RTOG- und LENT-SOMA-Skalen erhoben.Ergebnisse23 von 31 Patienten (74%) erfuhren eine Abnahme des CTC-Grades innerhalb von 8 Tagen im Median. Dadurch war der Unterschied in der Häufigkeit und Schwere der Proktitis vor Therapiebeginn und 14 Tage später bzw. am Ende der Radiotherapie statistisch signifikant. Der mediane Follow-up lag bei 50 Monaten. 20 Patienten entwickelten keine späte Proktitis. 11 Patienten entwickelten eine Grad-I- und 2 von diesen Patienten ebenfalls eine Grad-II-Toxizität. Es konnte keine signifikante Korrelation zwischen der Effektivität der Natriumbutyrat-Einläufe und Prävention bzw. Entwicklung einer späten Toxizität entdeckt werden.SchlussfolgerungNatriumbutyrat-Einläufe sind effektiv in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom, haben aber keinen Einfluss auf die Häufigkeit und Schwere der späten Proktitis.

Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis. A prospective evaluation.

PurposeTo evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis.Patients and Methods31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale.Results23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively.ConclusionSodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis.ZusammenfassungZielDiese prospektive Untersuchung wurde durchgeführt, um den Effekt von Natriumbutyrat-Einläufen in der Therapie der akuten Proktitis sowie den potentiellen Einfluss auf radiogene rektale Spätreaktionen zu evaluieren.Patienten und Methodik31 Patienten wurden mit Natriumbutyrat-Einläufen bei radiogen induzierter akuter Grad-II-Proktitis behandelt, die im Mittel nach 40 Gy aufgetreten war. Während der Radiotherapie wurde die Toxizität wöchentlich anhand der Common Toxicity Criteria (CTC) und anschließend jährlich anhand der RTOG- und LENT-SOMA-Skalen erhoben.Ergebnisse23 von 31 Patienten (74%) erfuhren eine Abnahme des CTC-Grades innerhalb von 8 Tagen im Median. Dadurch war der Unterschied in der Häufigkeit und Schwere der Proktitis vor Therapiebeginn und 14 Tage später bzw. am Ende der Radiotherapie statistisch signifikant. Der mediane Follow-up lag bei 50 Monaten. 20 Patienten entwickelten keine späte Proktitis. 11 Patienten entwickelten eine Grad-I- und 2 von diesen Patienten ebenfalls eine Grad-II-Toxizität. Es konnte keine signifikante Korrelation zwischen der Effektivität der Natriumbutyrat-Einläufe und Prävention bzw. Entwicklung einer späten Toxizität entdeckt werden.SchlussfolgerungNatriumbutyrat-Einläufe sind effektiv in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom, haben aber keinen Einfluss auf die Häufigkeit und Schwere der späten Proktitis.

Monitoring of therapy in head and neck patients during the radiotherapy by measurement of Cyfra 21-1

PURPOSE Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumour stage and tumour size in patients with cervical cancer. It could be a promising marker in squamous lung cancer. We evaluated this new marker with carcinoembryonic antigen, (CEA) and squamous cell carcinoma antigen (SCC-Ag) in the monitoring of 27 patients with head and neck cancer. PATIENTS AND METHODS The retrospective study group consisted of 27 patients, 17 not suited for surgery and 10 after laser resection. Patients were clinically staged according to the TNM-classification. The mean age of the patients was 53 years (range 37-70 years). Serum levels of each marker were studied in relation to tumour stage and clinical status of the patients during radiotherapy and 6 weeks after the end of the treatment. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour was assessed. RESULTS Pre-treatment serum Cyfra 21-1, CEA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of tumour response. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was not better than the Cyfra 21-1 assays. CONCLUSION We could not conclude from this study that Cyfra 21-1 marker is an additional parameter in identifying patients at risk of residual tumour after treatment, recurrent or progressive disease. An elevation of cyfra 21-1 marker was not detectable in 70% of the cases with macroscopic tumour. Therefore, Cyfra 21-1 is not a reliable parameter for the monitoring of patients with head and neck cancer during radiotherapy.

Lack of interferon beta–induced radiosensitization in four out of five human glioblastoma cell lines

PURPOSE To investigate the potential of interferon beta to enhance the cytotoxic activity of ionizing irradiation against glioma cells, and to elucidate the possible mechanisms responsible for conflicting clinical results. METHODS AND MATERIALS Five glioblastoma cell lines (U87MG, U118MG, U373MG, MO59K, MO59J) with different radiosensitivity and genetic background were used. Experiments were performed in exponentially growing cultures, and cell survival was measured by a colony-forming assay. Cells were incubated with natural interferon beta (n-IFN-beta; 30-3000 IU/mL) for 24 h followed by single dose irradiation with 1 to 6 Gy of gamma-rays. RESULTS Significant differences in n-IFN-beta sensitivity were found. The cell lines also differed in their radiation sensitivity, and there was no correlation between the n-IFN-beta and the radiation sensitivity. In three of five cell lines, the interaction of n-IFN-beta and irradiation was infra-additive; in one cell line, it was additive. For MO59J cells only, which are NHEJ-deficient, supra-additivity was observed. CONCLUSION Our results confirm the remarkable heterogeneity that is characteristic of malignant glioma. The combined effect of n-IFN-beta and radiation was mostly infra-additive or additive; synergistic interaction might occur in tumor cells that already have acquired repair deficiencies because of their genetic instability, as shown for the MO59J cell line.

Chemoradioimmunotherapy with 5-fluorouracil, cisplatin and interferon-α in pancreatic and periampullary cancer: Results of a feasibility study

BACKGROUND Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-alpha (IFN-alpha) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution. PATIENTS AND METHODS Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n=7) or periampullary (n=4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-alpha was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly. RESULTS The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed. CONCLUSION Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-alpha and cisplatin as a possible new treatment of pancreatic cancer in resected patients.

[Radiation-induced mucositis and neutrophil granulocytes in oral mucosa].

Hintergrund:Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir überprüften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten.Patienten und Methoden:Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler Granulozyten in der Mundspülflüssigkeit im Verlauf einer Radiotherapie oder einer Radiochemotherapie (5-FU, Mitomycin) untersucht. Als Referenz wurden an vier freiwilligen, gesunden Probanden gleichartige Untersuchungen vorgenommen. Die Patienten/Probanden spülten den Rachenraum 30 s mit 15 ml steriler physiologischer NaCl-Lösung. Das Sputum wurde zentrifugiert, mit 2 µg/ml Akridin-Orange in 1 ml RPMI resuspendiert und anschließend 15 min bei 37 °C inkubiert. Die Zahl der neutrophilen Granulozyten in der Suspension wurde in einer Zählkammer unter dem Fluoreszenzmikroskop ausgewertet.Ergebnisse:Bei den Patienten wurden starke intra- und interindividuelle Schwankungen der enoralen neutrophilen Granulozytenanzahl in der Mundspülflüssigkeit beobachtet. Tendenziell ließ sich ein Zusammenhang zwischen dem Ausmaß der radiogenen Mukositis und der Anzahl der neutrophilen Granulozyten in der Mundspülflüssigkeit feststellen. Mit zunehmender Mukositis nahm die Anzahl der neutrophilen Granulozyten zu. Die Zunahme wurde durch eine Chemotherapie eher verstärkt, die Behandlungspausen am Wochenende zeigten keinen Einfluss auf die Granulozytenanzahl.Schlussfolgerungen:Zwischen dem Ausmaß der Mukositis und der Anzahl der neutrophilen Granulozyten in der Mundspülflüssigkeit wurde tendenziell ein Zusammenhang beobachtet. Die starken Schwankungen der Messwerte verhindern jedoch die Verwendung dieses Parameters als Surrogat, um die radiogene Mukositis zu quantifizieren. Die Vermutung, dass eine Verminderung der neutrophilen Granulozyten in der Mundschleimhaut für die Entstehung der radiogenen Mukositis von Bedeutung ist, konnte nicht bestätigt werden.Background:Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts.Patients and Methods:Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied.Results:We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts.Conclusions:We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated.

Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC – treatment results after long-term follow-up and literature overview

INTRODUCTION Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). METHODS From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). RESULTS After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.

Sodium butyrate enemas in the treatment of acute radiation-induced proctitis in patients with prostate cancer and the impact on late proctitis@@@Natriumbutyrat-Einläufe in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom und der Einfluss auf eine späte Proktitis. Eine prospektive Untersuchung: A prospective evaluation

PurposeTo evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis.Patients and Methods31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale.Results23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively.ConclusionSodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis.ZusammenfassungZielDiese prospektive Untersuchung wurde durchgeführt, um den Effekt von Natriumbutyrat-Einläufen in der Therapie der akuten Proktitis sowie den potentiellen Einfluss auf radiogene rektale Spätreaktionen zu evaluieren.Patienten und Methodik31 Patienten wurden mit Natriumbutyrat-Einläufen bei radiogen induzierter akuter Grad-II-Proktitis behandelt, die im Mittel nach 40 Gy aufgetreten war. Während der Radiotherapie wurde die Toxizität wöchentlich anhand der Common Toxicity Criteria (CTC) und anschließend jährlich anhand der RTOG- und LENT-SOMA-Skalen erhoben.Ergebnisse23 von 31 Patienten (74%) erfuhren eine Abnahme des CTC-Grades innerhalb von 8 Tagen im Median. Dadurch war der Unterschied in der Häufigkeit und Schwere der Proktitis vor Therapiebeginn und 14 Tage später bzw. am Ende der Radiotherapie statistisch signifikant. Der mediane Follow-up lag bei 50 Monaten. 20 Patienten entwickelten keine späte Proktitis. 11 Patienten entwickelten eine Grad-I- und 2 von diesen Patienten ebenfalls eine Grad-II-Toxizität. Es konnte keine signifikante Korrelation zwischen der Effektivität der Natriumbutyrat-Einläufe und Prävention bzw. Entwicklung einer späten Toxizität entdeckt werden.SchlussfolgerungNatriumbutyrat-Einläufe sind effektiv in der Behandlung der akuten radiotherapieinduzierten Proktitis bei Patienten mit Prostatakarzinom, haben aber keinen Einfluss auf die Häufigkeit und Schwere der späten Proktitis.