Results of postoperative radiochemotherapy of the patients with resectable gastroesophageal junction adenocarcinoma in Slovenia

Jeromen, Ana; Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; Vidmar, Marija Skoblar; Ratoša, Ivica

doi:10.2478/v10019-012-0049-4

Cited by 2 publications

(3 citation statements)

References 42 publications

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“…Several clinical and genetic factors can have a prognostic value in MPM, but successful treatment remains challenging 2. Most patients with MPM are treated with systemic chemotherapy; usually either pemetrexed (PMX) or gemcitabine combined with a platinum agent, which are often used in different oncological diseases 4–6. Studies have shown that chemotherapy significantly improves survival of patients with MPM.…”

Section: Introductionmentioning

confidence: 99%

“…2 Most patients with MPM are treated with systemic chemotherapy; usually either pemetrexed (PMX) or gemcitabine combined with a platinum agent, which are often used in different oncological diseases. 4 – 6 Studies have shown that chemotherapy significantly improves survival of patients with MPM. Randomized clinical trial has shown that treatment with combination of PMX and cisplatin improves outcome in patients with MPM 7 – 9 and comparable results were obtained for treatment with gemcitabine and cisplatin.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

Goričar

Kovač

Dolžan

2014

Radiology and Oncology

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IntroductionA combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM.MethodsMPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival.ResultsPatients with at least one polymorphic MTHFD1 rs2236225 allele had a significantly lower response rate (p = 0.005; odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03−0.54) and shorter progression-free survival (p = 0.032; hazard ratio [HR] = 3.10; 95% CI = 1.10−8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85), SLCO1B1 rs4149056 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85) and rs11045879 (p = 0.014; OR = 0.18; 95% CI = 0.05−0.71) alleles compared to non-carriers, as well as in patients with SLCO1B1 GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03−0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15−52.85) and ABCC2 CAG haplotype (p = 0.006; OR = 5.67; 95% CI = 1.64−19.66).ConclusionsMTHFD1 polymorphism affected treatment response and survival, while polymorphisms in ABCC2 and SLCO1B1 transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential markers of pemetrexed treatment outcome in patients with MPM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

Goričar

Kovač

Dolžan

2014

Radiology and Oncology

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“…An appropriate interpretation of results from past therapeutic trials also became difficult, as GEJ carcinomas were formerly classified and treated as gastric carcinomas. 4 – 6 …”

Section: Introductionmentioning

confidence: 99%

Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

Ratoša

Oblak

Anderluh

et al. 2015

Radiology and Oncology

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Background.To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution.Patients and methods.Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4–6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival.Results.Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, disease-free survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively.Conclusions.Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achi...

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Results of postoperative radiochemotherapy of the patients with resectable gastroesophageal junction adenocarcinoma in Slovenia

Cited by 2 publications

References 42 publications

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

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