Jiri Petera

Epidermal Growth Factor Receptor as a Predictor of Tumor Response to Preoperative Chemoradiation in Locally Advanced Gastric Carcinoma

Purpose:The purpose of our study was a retrospective evaluation whether the intensity of epidermal growth factor receptor (EGFR) expression predicts tumor response to preoperative chemoradiotherapy in patients with locally advanced gastric carcinoma.Patients and Methods:Thirty-six patients with gastric adenocarcinoma (cT2–4 or N+) were studied. Preoperative treatment consisted of 30–45 Gy of gastric irradiation with continuous 5-fluorouracil and weekly cisplatin. Surgical resection was performed 4–6 weeks later. EGFR expression in pretreatment tumor biopsies was assessed by immunohistochemistry. Level of EGFR expression was determined from the intensity and extent of staining. Tumor response was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination.Results:Seventeen patients responded to preoperative chemoradiation – 8 patients (22%) had pathologic complete response, 9 patients (25%) were downstaged. Positive EGFR expression was found in 8 tumors (22%), and represented a significant predictive marker of poor tumor response in multivariate logistic regression analysis (p = 0.015). Response to chemoradiotherapy was found in 60% (16/28) of EGFR negative patients and in 13% (1/8) of EGFR positive patients (p = 0.044). None of the eight EGFR positive patients achieved pathologic complete response in comparison with 8/28 (29%) of patients with EGFR negative staining (p = 0.16).Conclusion:EGFR may represent a molecular marker predictive for poor response to preoperative chemoradiotherapy in locally advanced gastric carcinoma.Ziel:Ziel dieser Studie war eine retrospektive Evaluierung, ob die Expressionsintensität des epidermalen Wachstumsfaktor-Rezeptors (EGFR) die Tumorantwort auf präoperative Chemoradiotherapie vorhersagt bei Patienten mit lokal fortgeschrittenem Magenkrebs.Patienten und Methodik:36 Patienten mit Adenokarzinom des Magens (cT2–4 oder N+) wurden untersucht. Die präoperative Behandlung bestand aus einer Bestrahlung des Magens mit 30–45 Gy mit fortlaufendem 5-Fluorouracil und wöchentlichem Cisplatin. Die operative Resektion wurde 4–6 Wochen später durchgeführt. Die Expression des EGFR in den vorbehandelten Biopsiepräparaten des Tumors wurde mittels Immunhistochemie gemessen. Die Höhe der EGFR-Expression wurde festgelegt nach der Intensität und dem Ausmaß der Färbung. Das Downstaging wurde definiert als eine Reduktion von mindestens einem T-Stadium und/oder einem Befund von Tumorregression in der histopathologischen Untersuchung.Ergebnisse:17 Patienten haben auf die präoperative Chemoradiotherapie angesprochen – 8 Patienten (22%) hatten eine pathologisch komplette Reaktion, 9 Patienten (25%) wurden „downgestaged“. Eine positive EGFR-Expression wurde in 8 Tumoren gefunden (22%), und stellte einen signifikanten Vorhersagefaktor dar für eine geringe Tumorantwort in multivariater logistischer Regressionsanalyse (p = 0,015). Eine Reaktion auf die Chemoradiotherapie wurde bei 60% (16/28) der EGFR-negativen Patienten festgestellt und bei 13% (1/8) der EGFR-positiven Patienten (p = 0,044). Keiner der 8 EGFR-positiven Patienten erreichte eine pathologisch komplette Reaktion im Vergleich zu 8/28 (29%) der Patienten mit EGFR-negativer Färbung (p = 0,16).Schlussfolgerung:Der EGFR stellt einen Vorhersagefaktor für eine geringe Reaktion auf die präoperative Chemoradiotherapie beim lokal fortgeschrittenen Magenkarzinom dar.

Prognostic impact of hemoglobin level prior to radiotherapy on survival in patients with glioblastoma.

Purpose:To evaluate prognostic factors in patients with glioblastoma treated with postoperative or primary radiotherapy.Patients and Methods:From 1989 to 2000, a total of 100 patients underwent irradiation as part of their initial treatment for glioblastoma. All patients had undergone surgery or biopsy followed by conventional external-beam radiotherapy. 85 patients who received the planned dose of irradiation (60 Gy in 30 fractions) were analyzed for the influence of prognostic factors. 73/85 (86%) of patients were given postoperative irradiation, while 12/85 (14%) of patients were primarily treated with radiotherapy after biopsy.Results:The median overall survival was 10.1 months (range, 3.7–49.8 months), the 1- and 2-year survival rates were 41% and 5%, respectively. Univariate analysis revealed age ≤ 55 years (p < 0.001), pre-radiotherapy hemoglobin (Hb) level > 12 g/dl (p = 0.009), and pre-radiotherapy dose of dexamethasone ≤ 2 mg/day (p = 0.005) to be associated with prolonged survival. At multivariate analysis, younger age (p < 0.001), higher Hb level (p = 0.002), lower dose of dexamethasone (p = 0.026), and a hemispheric tumor location (p = 0.019) were identified as independent prognostic factors for longer survival. The median survival for patients with an Hb level > 12 g/dl was 12.1 months compared to 7.9 months for those with a lower Hb level. Contingency-table statistics showed no significant differences for the two Hb groups in the distribution of other prognostic factors.Conclusion:The results indicate that lower Hb level prior to radiotherapy for glioblastoma can adversely influence prognosis. This finding deserves further evaluation.Ziel:Evaluation prognostischer Faktoren bei Patienten mit Glioblastom, die mit postoperativer oder primärer Strahlentherapie behandelt wurden.Patienten und Methodik:Bei 100 Patienten mit Glioblastom wurde in den Jahren 1989–2000 die Strahlentherapie im Rahmen der Primärbehandlung angewandt. Bei allen Patienten wurde eine Operation oder Biopsie mit nachfolgender konventioneller perkutaner Bestrahlung durchgeführt. Der Einfluss der prognostischen Faktoren wurde bei 85 Patienten, die die geplante Strahlendosis (60 Gy in 30 Fraktionen) erhielten, evaluiert. 73/85 Patienten (86%) wurden mit postoperativer Bestrahlung, 12/85 Patienten (14%) mit primärer Strahlentherapie und Biopsie behandelt.Ergebnisse:Die mittlere Überlebenszeit betrug 10,1 (3,7–49,8) Monate, die Überlebenszeit nach 1 und 2 Jahren lag bei 41% bzw. 5%. Mittels der univariaten Analyse stellten sich folgende Faktoren dar, die mit einer längeren Überlebenszeit verbunden sind: ein Alter ≤ 55 Jahre (p < 0,001), eine Hämoglobin-(Hb-)Konzentration zu Beginn der Strahlentherapie > 12 g/dl (p = 0,009) und eine prätherapeutische Dexamethasondosis ≤ 2 mg/Tag (p = 0,005). Die multivariate Analyse ermittelte ein jüngeres Alter (p < 0,001), eine höhere Hb-Konzentration (p = 0,002), eine niedrigere Dexamethasondosis (p = 0,026) und eine hemisphärische Tumorlokalisation (p = 0.019) als unabhängige prognostische Faktoren für eine längere Überlebenszeit. Die mittlere Überlebenszeit bei Patienten mit einer Hb-Konzentration > 12 g/dl betrug 12,1 Monate, bei Patienten mit einem niedrigeren Blut-Hb-Wert dagegen nur 7,9 Monate. Die Kontingenztabellenstatistik zeigte keine signifikanten Unterschiede in der Distribution der anderen prognostischen Faktoren bei beiden Hb-Gruppen.Schlussfolgerung:Die Ergebnisse weisen darauf hin, dass eine niedrigere Hb-Konzentration vor Beginn der Strahlentherapie wegen Glioblastoms einen negativen Einfluss auf die Prognose haben kann. Diese Beobachtung verdient weitere Aufmerksamkeit.

Comparison of rectal dose-volume constraints for IMRT prostate treatment planning

The purpose of this paper is to compare different sets of rectal dose-volume constraints and to develop input criteria for the intensity-modulated radiation therapy (IMRT) of prostate cancer. The IMRI treatment plans were created using Varian planning system (CadPlan with Helios module) for ten patients with localized prostate cancer (isocenter dose 78 Gy). The posterior portion of rectum was contoured as an extra volume (help volume). Three sets of input parameters for rectum with gradually increasing priorities (25-50-75-90) were designed for the inverse treatment planning: 1. dose-volume constraints allowing no more than 50, 40, 20 and 10% of the rectum volume be irradiated to 50, 60, 70, and 75 Gy, respectively-volume-based plans, priorities 25-90 (V25-90 plans); 2. maximum dose constraint of 74.1 Gy for rectum-plans with limited maximum reactal dose, priorities 25-90 (M25-90 plans); 3. maximum dose constraint of 50 Gy for the help volume-plans with limited maximum dose for the help volume, priorities 25-90 (H25-90 plans). Dose homogeneity in the planning target volume (PTV) and the rectal volumes (RV) irradiated to 50, 60, 70, and 75 Gy (RV 50-75 Gy) were recorded. Rectum sparing improved for all the plans with increasing priority. While the M plans had the lowest RV 75 Gy values, the H plans gave the minimum RV 50-70 Gy values. Plans were considered acceptable if at least 98% of the PTV was treated to 95% of the prescribed dose. In particular plan groups, the V75, M75, and H50 plans, together with the V50+M75 and H50+M75 combined plans, satisfied this condition and yielded the lowest rectal doses. The H50+M75 combined plan allowed optimal sparing of rectum (RV 50 Gy 51.6%, RV 60 Gy 38.5%, RV 70 Gy 26.0%, and RV 75 Gy 9.1%, respectively). An optima set of dose-based rectal constraints (maximum rectal dose 74.1 Gy, maximum help volume dose 50 Gy) has been developed for Varian planning software. These parameters will constitute a starting point for the prostate IMRT plan optimization.

Conformal Radiotherapy for Prostate Cancer&Longer Duration of Acute Genitourinary Toxicity in Patients with Prior History of Invasive Urological Procedure

The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer

Background: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi‐weekly chemohormonal regimen consisting of epirubicin, etoposide, and low‐dose dexamethasone (EED) in patients with hormone‐refractory prostate cancer (HRPC).

Utilization of cone‐beam CT for reconstruction of dose distribution delivered in image‐guided radiotherapy of prostate carcinoma — bony landmark setup compared to fiducial markers setup

The purpose of this study was to compare two different styles of prostate IGRT: bony landmark (BL) setup vs. fiducial markers (FM) setup. Twenty‐nine prostate patients were treated with daily BL setup and 30 patients with daily FM setup. Delivered dose distribution was reconstructed on cone‐beam CT (CBCT) acquired once a week immediately after the alignment. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed 1 cm safety margin. Alternative plans assuming smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with initial ones. While the margin reduction in case of BL setup makes the prostate coverage significantly worse (p=0.0003, McNemars test), in case of FM setup with the reduced 7 mm margin, the prostate coverage is even better compared to BL setup with 10 mm margin (p=0.049, Fishers exact test). Moreover, partial volumes of organs at risk irradiated with a specific dose can be significantly lowered (p<0.0001, unpaired t‐test). Reducing of safety margin is not acceptable in case of BL setup, while the margin can be lowered from 10 mm to 7 mm in case of FM setup. PACS numbers: 87.55.dk, 87.55.km, 87.55.tm

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma.

Background Currently, there is no standard treatment of inoperable advanced hepatocellular carcinoma. Study A patient with advanced hepatocellular carcinoma was treated with intravenous infusion of pegylated liposomal doxorubicin (PLD, Caelyx) in combination with ultrasound hyperthermia of the liver. Each cycle consisted of infusion of 60 mg of PLD followed by two fractions of hyperthermia 41°C to 43°C for 45 minutes 1 and 48 hours after infusion, respectively. Results A substantial regression of the tumor was observed on computed tomography scans. No toxicity of combined treatment was noted. Conclusions This may be the first report of the combination of PLD and hyperthermia in the treatment of advanced hepatocellular carcinoma. Our observation suggests that the combination of PLD with hyperthermia is technically feasible, well tolerated, and could have synergistic potential.

Preoperative neoadjuvant chemoradiation for locally advanced gastric adenocarcinoma

Abstract Aims and Background To evaluate toxicity and the radical resection rate in gastric adenocarcinoma treated with preoperative neoadjuvant chemoradiation. Materials & Methods 32 patients, 22 males and 10 females with gastric adenocarcinoma, were treated with chemoradiation and hyperthermia. Results The neoadjuvant regimen was completed as planned in 19/32 (59 %) patients; in the remaining patients the intensity of chemotherapy had to be reduced because of haematological and gastrointestinal toxicity. Surgical stage was as follows: 2 patients pathologically complete response, 3 patients AJCC stage I.A, 5 patients stage I.B, 7 patients stage II, 7 patients stage III.A, 1 patient stage III.B, 7 patients stage IV. R0 resection was achieved in 19/32 (59%) patients, R1 in 2/32 (6%) patients and R2 in 11 (34%) patients. Downstaging after neoadjuvant chemoradiotherapy was achieved in 17/32 (53%) patients. At the date of evaluation (31 March 2009), 4 patients were still alive 58, 81, 86 and 98 months from the date of diagnosis. Median survival was 18 months (95% confidence interval: 13–38 months). One-year survival was 69% (95% confidence interval: 53%–85%). Four-year survival was 19% (95% C.I.: 5%–34%). Conclusions Preoperative neoadjuvant chemoradiotherapy has acceptable toxicity, and can lead to a high rate of R0 resections.

Tamoxifen and arrhythmia

Tamoxifen is an orally active selective estrogen receptor modulator that is used in the treatment of breast cancer and is currently the world’s largest selling drug for that purpose. However, it has some side effects including hot flashes, menstrual irregularity, vaginal discharges, uterine bleeding, uterine endometrial cancer, hypercoagulability, steatosis hepatis, risk of trombembolism. Long-term data from clinical trials have failed to demonstrate a cardioprotective effect and beneficial effects on serum lipid profiles. Arrhythmia secondary to tamoxifen is very rare.

Overview of radiation oncology in the Czech Republic

SUMMARY BACKGROUND: Modern radiotherapy (RT) plays a very important role in both curative and palliative treatment of tumours. There are large variations among the EU countries and even regional variations within countries in the provision of RT. AIM: In this report we present an overview of the current infrastructure, organisation, education and quality programme of radiotherapy in the Czech Republic. MATERIAL AND METHODS: Data from the National Cancer Registry, Institute of Health Information and Statistics of the Czech Republic and from questionnaires and clinical audits of radiotherapy departments were used for evaluation of radiotherapy equipment, numbers of patients treated by radiotherapy and workload of radiotherapy facilities. RESULTS: Radiotherapy of malignant diseases is provided in 28 facilities in the Czech Republic. There are 35 linear accelerators and 16 cobalt units for the population of 10.3 million inhabitants, which represents one megavoltage unit for 200 000 inhabitants. Fourteen departments are equipped for brachytherapy with high dose rate afterloading machines. Forty-three percent of newly reported cancer patients undergo radiotherapy as part of oncological treatment. CONCLUSION: The main problem of radiation oncology in the Czech Republic is insuffi cient centralisation and the persistence of small, under-equipped departments.