Zdenek Zoul

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.

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).

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.