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The impact of anaemia on treatment outcome in patients with squamous cell carcinoma of anal canal and anal margin
Irena Oblak, Monika Češnjevar, Mitja Anžič, Jasna But-Hadžić, Ajra Šečerov Ermenc, Franc Anderluh, Vaneja Velenik, Ana Jeromen, Peter Korošec, 2016, original scientific article

Abstract: Radiochemotherapy is the main treatment for patients with squamous cell carcinoma of the anal canal. Anaemia is reported to have adverse effect on survival in cancer patients. The aim of the study was to evaluate the influence of anaemia on radiochemotherapy treatment outcome in patients with squamous cell carcinoma of the anal canal. Patients and methods. One hundred consecutive patients with histologically confirmed squamous cell carcinoma of the anal canal were treated radically with 3-dimensional conformal or intensity-modulated radiation therapy followed by brachytherapy or external beam radiotherapy boost and with concurrent mitomycin C and 5-fluorouracil. The influence on survival of pre-treatment, mean on-treatment and end-of-treatment haemoglobin (Hb) concentrations was studied. Results. The 5-year locoregional control, disease free survival, disease specific survival and overall survival rates for all patients were 72%, 71%, 77% and 62%, respectively. In univariate analysis, patients with pre-treatment and end-oftreatment Hb > 120 g/L survived statistically significantly better compared to patients with Hb % 120 g/L. Patients with mean on-treatment Hb > 120 g/L only had statistically significant better locoregional control and overall survival than patients with Hb % 120 g/L. In multivariate analysis, independent prognostic factors were pre-treatment Hb (> 120 g/L vs. % 120 g/L) for overall survival (hazard ratio [HR] = 0.419, 95% confidence interval [CI] = 0.190%0.927, p = 0.032) and stage (I & II vs. III) for disease specific (HR = 3.523, 95% CI = 1.375%9.026, p = 0.009) and overall survival (HR = 2.230, 95% CI = 1.167%4.264, p = 0.015). Conclusions. The pre-treatment, mean on-treatment and end-of-treatment Hb concentration > 120 g/L carried better prognosis for patients for with squamous cell carcinoma of the anal canal treated with radiochemotherapy. The pre-treatment Hb > 120 g/L was an independent prognostic factor for overall survival of patients with anal canal cancer.
Keywords: anaemia, anal canal squamous cell carcinoma, radiochemotherapy
Published in DiRROS: 30.04.2024; Views: 93; Downloads: 56
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Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment
Ana Perpar, Erik Brecelj, Nada Rotovnik-Kozjek, Franc Anderluh, Irena Oblak, Marija Skoblar Vidmar, Vaneja Velenik, 2015, other scientific articles

Abstract: Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home. We present a 73-year-old rectal cancer patient who developed acute arterial mesenteric thrombosis at the beginning of the pre-operative radiochemotherapy. Almost the entire length of his small intestine, except for the proximal 50 cm of it, and the ascending colon had to be resected. After multiorgan failure his condition improved, and he was able to successfully complete radical treatment (preoperative radiotherapy and surgery) for the rectal carcinoma, despite developing short bowel syndrome (SBS) and being dependent upon home-based parenteral nutrition to fully cover his nutritional needs. Mesenteric ischemia and resultant short bowel syndrome are not absolute contraindications for radical oncological treatment since such patients can still achieve long-term remission.
Keywords: acute mesenteric ischemia, capecitabine, multiorgan failure, rectal cancer, short bowel syndrome
Published in DiRROS: 23.04.2024; Views: 77; Downloads: 26
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Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer
Ivica Ratoša, Irena Oblak, Franc Anderluh, Vaneja Velenik, Jasna But-Hadžić, Ajra Šečerov Ermenc, Ana Jeromen, 2015, original scientific article

Abstract: 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. 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. 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). Twentysix (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, diseasefree survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patientsʼ cure.
Keywords: neoadjuvant radiochemotherapy, perioperative chemotherapy, chemotherapy, adenocarcinoma, carcinoma, surgery
Published in DiRROS: 23.04.2024; Views: 78; Downloads: 23
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Capecitabine in adjuvant radiochemotherapy for gastric adenocarcinoma
Irena Oblak, Marija Skoblar Vidmar, Franc Anderluh, Vaneja Velenik, Ana Jeromen, Jasna But-Hadžić, 2014, original scientific article

Abstract: Background. In patients with non-metastatic gastric cancer surgery still remains the treatment of choice. Postoperative radiochemotherapy with 5-fluorouracil and leucovorin significantly improves the treatment outcome. The oral fluoropyrimidines, such as capecitabine, mimic continuous 5-fluorouracil infusion, are at least as effective as 5-fluorouracil, and such treatment is more comfortable for the patients. Patients and methods. In the period from October 2006 to December 2009, 101 patients with gastric cancer in stages Ib-IIIc were treated with postoperative chemoradiation with capecitabine. Distal subtotal resection of the stomach was performed in 46.3%, total resection in 50.5% and multivisceral resection in 3.2% of patients. The main endpoints of this study were loco-regional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). The rates of acute side-effects were also estimated. Results. Seventy-seven percent of patients completed the treatment according to the protocol. The median followup time of all patients was 3.9 years (range: 0.4-6.3 years) and in survivors it was 4.7 years (range: 3.2-6.3 years). No death occurred due to the therapy. Acute toxicity, such as nausea and vomiting, stomatitis, diarrhoea, hand-foot syndrome and infections of grade 3 or 4, occurred in 5%, 1%, 2%, 8.9% and 18.8% of patients, respectively. On the close-out date 63.4% patients were still alive and with no signs of the disease. The 4-years follow-up survey showed that LRC, DFS, DSS and OS were 95.5%, 69.2%, 70.7%, and 66.2%, respectively. Higher pN-stage and splenectomy were found to be independent prognostic factors for all four types of survival and perineural invasion and lower treatment intensity for DFS, DSS and OS.
Keywords: gastric cancer, adjuvant therapy, radiochemotherapy
Published in DiRROS: 11.04.2024; Views: 120; Downloads: 22
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The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperattive radiochemotherapy in patients with rectal cancer
Irena Oblak, Vaneja Velenik, Franc Anderluh, Barbara Možina, Janja Ocvirk, 2013, original scientific article

Abstract: Background. The aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Patients and methods. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I- III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Results. Median follow-up time was 68 months (range: 3-93 months) while in survivors it was 80 months (range: 68-93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22-523 ng/mL) and the mean level (standard deviation) was 192 (87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2-3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Conclusions. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative radiochemotherapy in our cohort of patients with rectal cancer, TIMP-1 levels were recognized as an independent prognostic factor for OS in these patients.
Keywords: rectal cancer, radiochemotherapy, tissue inhibitor of metalloproteinases
Published in DiRROS: 22.03.2024; Views: 110; Downloads: 31
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Cetuximab in preoperative treatment of rectal cancer - term outcome of the XERT trial
Vaneja Velenik, Janja Ocvirk, Irena Oblak, Franc Anderluh, 2012, original scientific article

Abstract: Preoperative capecitabine-based chemoradiotherapy (CRT) is feasible for the treatment of resectable locally advanced rectal cancer (LARC). To try to improve efficacy, we conducted a phase II studz in which the epidermal growth factor receptor-targeting monoclonal antibody cetuximab was added to capecitabine-based CRT. The results for long-term survival and for an analysis investigating the relationship between survival and patient and disease characteristics, including tumour KRAS mutation status, and surgery type, are presented. Patients with resectable LARC received capecitabine (1250mg/m2 twice daily, orally) for 2 weeks followed by cetuximab alone (400 mg/m2 for 1 week) and then with CRT (250 mg/m2/week) comprising capecitabine (825 mg/m2 twice daily) and radiotherapy to the small pelvis (45 Gz in 25 1.8-Gz fractions), five dazs a week for five weeks. Surgery was conducted six weeks following CRT, with post-operative chemotherapy with capecitabine (1250 mg/m2 twice daily for 14 days every 21 days) three weeks later. Forty-seven patients were enrolled and 37 underwent treatment. Twenty-eight of the patients (75.7%) had T3N+ disease. Thirty-six patients were evaluable for efficacy. The median follow-up time was 39.0 months (range 5.0-87.0). The three-year local control, disease-free survival, relapse-free survival and overall survival rates were 96.9% (95% CI 90.0-100), 72.2% (57.5-86.9), 74.3% (95% CI 59.8-88.8) and 68.1% (95% CI 36.7-99.4), respectively. There was no significant association between survival and gender, age, tumour location in the rectum, type of surgery, pathological T or N status, tumour regression grade or tumour KRAS mutation status, although sample sizes were small. Preoperative cetuximab plus capecitabine-based CRT was feasible in patients with resectable LARC and was associated with an impressive three-year local control rate. The use of tumour KRAS mutation status as a biomarker for the efficacy of cetuximab-based regimens in this setting requires further investigation.
Published in DiRROS: 21.03.2024; Views: 125; Downloads: 36
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Long term outcome after combined modality treatment for anal cancer
Irena Oblak, Primož Petrič, Franc Anderluh, Vaneja Velenik, Albert-Peter Fras, 2012, original scientific article

Abstract: Background. The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cellcarcinoma of the anal canal treated at a single institution. Patients and methods. Between 1/2003 and 9/2010, 84 patients were treated with radical radiochemotherapy at the Institute of Oncology Ljubljana, Slovenia. The treatment consisted of 3-dimensional conformal external beam radiotherapy with concurrent chemotherapy (5-fluorouracil and mytomycin C), followed by brachytherapy or external beam boost. The toxicity of therapy and its effectiveness were assessed. Results. The treatment was completed according tothe protocol in 79.8% of patients. The median follow-up time of 55 survivors was 53 months (range: 16-105 months). The 5-year locoregional control(LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates were 71%, 68%, 81%, 67% and 85%, respectively. No treatment-related mortality was observed. The most frequent acute side-effect of the treatment was radiodermatitis (grade 3-4 in 58.2% of patients). LENT-SOMA grade 3-4 late radiation side effects were observed in 15 (18%) patients. In patients with brachytherapy boost a trend of less late side effects was observed compared to patients with external beam boost (P=0.066). On multivariate analysis, complete clinicaldisease response was identified as an independent prognostic factor for LRC, DFS and DSS, the salvage surgery for LRC and DFS, whereas Hb below 120 g/l retained its independent prognostic value for OS. Conclusions. Radiochemotherapy provides an excellent disease control and the survival with preserving anal sphincter function in majority of patients. Surgical salvage with abdominoperineal resection for persistent or recurrent disease has curative potential.
Published in DiRROS: 21.03.2024; Views: 118; Downloads: 40
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Post-treatment surveillance in colorectal cancer
Vaneja Velenik, 2010, review article

Published in DiRROS: 15.03.2024; Views: 133; Downloads: 36
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