14. Search for improvement of the therapeutic ratio in radiotherapy for non-small cell lung cancer (NSCLC)

There are several approaches under investigation in view of improvement of the therapeutic ratio of NSCLC radiotherapy in our Department:1/ Dose escalation above 70 Gy using conformal radiotherapy techniques, 2/ accelerated radiotherapy with or without induction chemotherapy addressed to III stage tumours, 3/ conformal postoperative radiotherapy to total minimum dose in PTV of 50 Gy addressed to completely resected III stage tumours.Ad 1/ From XI 1998 to XI 2000 43 patients were included in dose escalation study. Doses from 70 to 74 Gy were delivered. Apart from one toxic death, due to radiation pneumonitis, toxicity was acceptable. Since 1999 for NO patients the study of omission of elective irradiation is conducted. By the time being 10 patients were irradiated with omission of elective fields. There was no relapse in non-treated “elective areas”. The actuarial 1-, 2- and 3-year survival were respectively 84-, 64-, and 42%. There were 14 local relapses in 19 progressions observed in the entire group. In spite of encouraging results a high level of local relapses shows the limits of moderate dose escalation using conformal techniques and conventional fractionation in improvement of local control of NSCLC.Ad 2/ From III 1999 two different accelerated radiation therapy schedules are investigated for III stage tumours. Forty patients were enrolled in the study: 26 were irradiated according to accelerated hyperfractionated radiotherapy (57 Gy in 40 fractions [first week: elective fields −1.2 Gy × 2 per day, 3 remaining weeks 1.8 Gy to elective fields and 1.2 Gy boost to tumour] during 26 days), 14 were irradiated according to accelerated conformal radiotherapy with concurrent boost (56.7 Gy in 21 fractions and 26 days: all treatment was conformally planned and delivered: 1,9 Gy per fraction to the limited elective field and 0.8 Gy as a concurrent boost to the GTV). There was no difference on compliance with treatment plan, toxicity and response rate (80- and 72%) in the both investigated groups.Ad 3/ From I 1999 eleven patients were enrolled in the phase II study of postoperative conformal radiotherapy of the region of the highest probability of microscopic invasion by the disease to the minimum dose of 50 Gy in PTV. The study is conducted in view of the future design of randomised study addressing question of the value of postoperative radiotherapy using modern techniques in management of NSCLC

40. Comparison of two accelerated radiotherapy regimens in management of locally advanced non-small cell lung cancer (NSCLC) – hyper-fractionated conventional accelerated radiotherapy (RAHIP) and accelerated conformal radiotherapy with concurrent boost (RT-BOOST)

BackgroundRepopulation during radiation therapy may compromise the results of the treatment of NSCLC. In spite of the data showing an improvement of therapeutic ratio with shortening of the total treatment time, there is no univoa.ue way of doing, it. Current study was conducted to compare two different regimens of accelerated radiotherapy.Material/MethodsFrom March 1999 to November 2000 forty patients with stage III NSCLC were included. Twenty-eight pts. (70%) received 3–4 cycles of induction chemotherapy (cis-platinum, vepeside). Twenty-six p. were treated according to RAHIP schema, 14 pts. according to RT-BOOST schedule. RAHIP consisted in radiotherapy twice-daily delivered: first week: 2×1,20 Gy “elective fields”, the remaining three weeks 1,80 Gy “elective fields” and 1,20 Gy boost on involved areas by oblique fields. Total dose was 57 Gy. Conventional treatment techniques were employed. RT-BOOST technique was conformally planned and delivered, total dose was 56,7 Gy in 21 fractions (per fraction: 1,9 Gy to limited elective areas and concurrent boost of 0,8 Gy to the GTV) and 26 days.ResultsWith a follow-up period ranging from 1 to 19 months, there is no difference in the compliance with the treatment-plan, treatment tolerance and response rate in the two analysed groups. In all but two patients treatment plan was realised. In RT-BOOST group treatment was discontinued in one patient, because of prolonged III° EORTC/RTOG oesophageal toxicity. In RAHIP group in one patient treatment was prolonged by 10 days because of pneumonitis (II° lung toxicity). One case of III° oesophageal toxicity was observed in each group. There was no increase in toxicity among patients receiving chemotherapy before radiotherapy. The response rate was similar in both analysed groups (RAHIP: 73% PR, 7,5%, CR; RT-BOOST: 65% PR, 7% CR). Estimated by Kaplan-Meier actuarial one-year survival rate method was 66% and actuarial one-year progression free-survival rate was 58% for the entire group.ConclusionsPreliminary results of accelerated radiotherapy for locally advanced NSCLC seem promising. Additionally a good compliance with the treatment in both groups allows to work out a phase III study dealing with this problem

14. Search for improvement of the therapeutic ratio in radiotherapy for non-small cell lung cancer (NSCLC)

There are several approaches under investigation in view of improvement of the therapeutic ratio of NSCLC radiotherapy in our Department:1/ Dose escalation above 70 Gy using conformal radiotherapy techniques, 2/ accelerated radiotherapy with or without induction chemotherapy addressed to III stage tumours, 3/ conformal postoperative radiotherapy to total minimum dose in PTV of 50 Gy addressed to completely resected III stage tumours.Ad 1/ From XI 1998 to XI 2000 43 patients were included in dose escalation study. Doses from 70 to 74 Gy were delivered. Apart from one toxic death, due to radiation pneumonitis, toxicity was acceptable. Since 1999 for NO patients the study of omission of elective irradiation is conducted. By the time being 10 patients were irradiated with omission of elective fields. There was no relapse in non-treated “elective areas”. The actuarial 1-, 2- and 3-year survival were respectively 84-, 64-, and 42%. There were 14 local relapses in 19 progressions observed in the entire group. In spite of encouraging results a high level of local relapses shows the limits of moderate dose escalation using conformal techniques and conventional fractionation in improvement of local control of NSCLC.Ad 2/ From III 1999 two different accelerated radiation therapy schedules are investigated for III stage tumours. Forty patients were enrolled in the study: 26 were irradiated according to accelerated hyperfractionated radiotherapy (57 Gy in 40 fractions [first week: elective fields −1.2 Gy × 2 per day, 3 remaining weeks 1.8 Gy to elective fields and 1.2 Gy boost to tumour] during 26 days), 14 were irradiated according to accelerated conformal radiotherapy with concurrent boost (56.7 Gy in 21 fractions and 26 days: all treatment was conformally planned and delivered: 1,9 Gy per fraction to the limited elective field and 0.8 Gy as a concurrent boost to the GTV). There was no difference on compliance with treatment plan, toxicity and response rate (80- and 72%) in the both investigated groups.Ad 3/ From I 1999 eleven patients were enrolled in the phase II study of postoperative conformal radiotherapy of the region of the highest probability of microscopic invasion by the disease to the minimum dose of 50 Gy in PTV. The study is conducted in view of the future design of randomised study addressing question of the value of postoperative radiotherapy using modern techniques in management of NSCLC

Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR

Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n = 11), PBC (n = 19), and control liver tissues (n = 19). PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n = 120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role. © 2015 Ewa Wunsch et al