Background. Although the preoperative radiochemotherapy and the optimised surgical technique have improved the outcome in patients with rectal cancer, the local recurrence still remains a therapeutic problem. In up to 50% of patients the local recurrence appears without simultaneous distant metastases. This review highlights current treatment options of locally recurrent rectal cancer.
Conclusions. The optimal management of the isolated local recurrence remains a difficult and controversial issue. The radical surgical resection is the mainstay of the curative treatment, but an extended surgery can be associated with significant morbidity and impaired quality of life. The preoperative chemoradiation for turnout down staging increases the chance of resectability and the addition of intraoperative radiotherapy may further improve the local control and survival. Re-irradiation is feasible in patients who already received irradiation as part of the primary rectal cancer treatment.
Background. Though the post treatment surveillance of patients with colorectal cancer (CRC) treated with curative intent is common practice, its value is controversial. In the absence of conclusive clinical data, various modalities for the routine follow-up of patients with CRC have been proposed. In practice, the guidelines across countries and regions differ and are influenced by different health care policies, resource availability and doubts about effectiveness of follow-up.
Conclusions. The results of metaanalyses of available clinical trials demonstrated a survival benefit of intensified monitoring, but the questions regarding the optimal frequency of visits and the examinations to be performed remain unanswered. Furthermore, intensive monitoring of CRC survivors may be difficult to be administrated, causes discomfort and morbidity to the patient and can have serious cost-implications to the healthcare system. However, as it seems from available data, a comprehensive surveillance program does not affect the quality of patients' life. Ongoing large prospective multi-institutional randomised trials might elucidate some of the crucial questions and existing dilemmas to establish adequate surveillance strategy for CRC patients.
Quality of life in patients after combined modality treatment of rectal cancer: Report of a prospective phase II study
Background. The literature reports are unclear whether a permanent stoma reduces the quality of life (QOL) of patients with locally advanced rectal cancer (T3-4 and/or N+). Our aim was to compare the QLQ of patients with abdominoperineal resection and with restorative surgery, treated with preoperative radiochemotherapy in a prospective phase II clinical trial.
Methods. Fifty-seven patients were irradiated to 45 Gy in 25 fractions over 5 weeks to the pelvis concomitantly with oral capecitabine 825 mg/m2, twice a day, including weekends. Surgery was scheduled 4-6 weeks after the completion of the chemoradiotherapy. Four courses of chemotherapy were planned postoperatively. Patients still alive and without recurrence of the disease, with a minimum follow up of 2 years, were surveyed with two self-rating questionnaires developed by the European Organisation for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38).
Results. QLQ was assessed in 28 of 32 patients eligible (87.5%). The median time from surgery to filling in the questionnaires was 35 months. For all scales of EORTC QLQ-C30 and EORTC QLQ-C38, no significant differences in median scores were observed between the two groups of patients.
Conclusions. QOL did not differ in patients with abdominoperineal resection from patients with sphinctersparing surgery.
Postoperative radiochemotherapy for gastric adenocarcinoma: long term results
Background. To analyze the efficacy of postoperative radiochemotherapy with 5-florouracil (5-FU) and leucovorin (LV) applied in the patients with gastric carcinoma treated in a single institution.
Patients and methods. Between 2001 and 2004, 123 patients with resected gastric adenocarcinoma were treated with postoperative concomitant radiochemotherapy with 5-FU and LV. The adjuvant treatment consisted of five cycles of chemotherapy with 5-FU (425mg/m2 IV) and LV (20 mg/m2 IV) and concomitant radiotherapy with the total dose of 45 Gy.
Results. The treatment was completed according to the protocol in 82% of patients. The frequency and severity of early toxic effects induced by radiochemotherapy were manageable. Median follow-up time of 56 survivors was 64.5 months (range: 51.7-96.4 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were 81%, 48.3%, 50.4%, and 48.4%, respectively. The multivariate analysis showed that the tumor involvement of cardia and low intensity of chemotherapy were independent adverse prognostic factors for DSS and OS. More advanced pT-stage and tumors with diffuse growth type according to Lauren were identified as negative independent prognostic factor for OS. They were also on the threshold of statistical significance for DSS.
Conclusions. Postoperative radiochemotherapy for gastric carcinoma has acceptable toxicity, and is effective particularly in regard to LRC. High incidence of distant metastases calls for more effective systemic regimens.
Long term outcome after combined modality treatment for anal cancer
Background. The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cell carcinoma 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 to the 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 clinical disease 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.
Cetuximab in preoperative treatment of rectal cancer - term outcome of the XERT trial
Background. 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 study 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 and methods. Patients with resectable LARC received capecitabine (1250 mg/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 Gy in 25 1.8-Gy fractions), five days 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.
Results. 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.
Conclusions. 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.
Low recurrence rates and long term survival are the main therapeutic goals of rectal cancer surgery. Complete, margin- negative resection confers the greatest chance for a cure. The aim of our study was to determine whether the length of the distal resection margin was associated with local recurrence rate and long- term survival.
Patients and methods
One hundred and nine patients, who underwent sphincter-preserving resection for locally advanced rectal cancer after preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral centres were included in the study. Distal resection margin lengths were measured on formalin-fixed, pinned specimens. Characteristics of patients with distal resection margin < 8 mm (Group I, n = 27), 8–20 mm (Group II, n = 31) and > 20 mm (Group III, n = 51) were retrospectively analysed and compared. Median (range) follow-up time in Group I was 89 (51–111), in Group II 83 (57–111) and in Group III 80 (45–116) months (p = 0.326), respectively.
Univariate survival analysis showed that distal resection margin length was not statistically significantly associated with overall survival or local recurrence rate (p > 0.05). In a multiple Cox regression analysis, after adjusting for pathologic T and N stage (yT, yN), distal resection margin length was still not statistically significantly associated with overall survival.
Our study shows that close distal resection margins can be accepted as oncologically safe for sphincter-preserving rectal resections after preoperative chemoradiotherapy.
The aim of our study was to obtain reference data of the EORTC QLQ-C30 quality of life dimensions for the general Slovenian population. We intend to provide the researchers and clinicians in our country with the expected mean health-related quality of life (HRQL) scores for distinctive socio-demographic population groups.
The EORTC QLQ-C30 questionnaire supplemented by a socio-demographic inquiry was mailed or distributed to 1,685 randomly selected individuals in the Slovenian population aged 18 – 90. Answers from 1,231 subjects representing socio-demographic diversity of the Slovenian population were collected and transformed into EORTC dimensions and symptoms. The impact of socio-demographic features on HRQL scores was assessed by multiple linear regression models.
Gender, age and self-rated social class are the important confounders in the quality of life scores in our population. Men reported better quality of life on the majority of the specific scales and, at the same time, reported fewer symptoms. There was no gender-specific difference in cognitive functioning. The mean scores were consistently lower with age in both sexes.
This is the first study to report the normative EORTC QLQ-C30 scores for one of the south-eastern European populations. The reported expected mean scores allow Slovenian oncologists to estimate what the quality of life in cancer patients would be, had they not been ill. As they are derived by common methodology, our results can easily be included in any further international comparisons or in the calculation of European summarized HRQL scores.
The aim of the study was to investigate the feasibility and safety of experimental fractionation using intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) to shorten the overall treatment time without dose escalation in preoperative radiochemotherapy of locally advanced rectal cancer.
Patients and methods
Between January 2014 and November 2015, a total of 51 patients with operable stage II-III rectal adenocarcinoma were treated. The preoperative treatment with intensity modulated radiation therapy (IMRT) and a pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumour in 22 fractions, with standard concomitant capecitabine, was completed in 50 patients out of whom 47 were operated. The median follow-up was 35 months.
The rate of acute toxicity G ≥ 3 was 2.4%. The total downstaging rate was 89% and radical resection was achieved in 98% of patients. Pathologic complete response (pCR) was observed in 25.5% of patients, with 2-year local control (LC), disease free survival (DFS), and overall survival (OS) of 100% for this patient group. An intention-to-treat analysis revealed pN to be a significant prognostic factor for DFS and OS (P = 0.005 and 0.030, respectively). LC for the entire group was 100%, and 2-year DFS and OS were 90% (95 % CI 98.4–81.6) and 92.2% (95% CI 99.6–84.7), respectively.
The experimental regime in this study resulted in a high rate of pCR with a low acute toxicity profile. Excellent early results translated into encouraging 2-year LC, DFS, and OS.
Differences in plasma TIMP-1 levels between healthy people and patients with rectal cancer stage II or III
Background. The purpose of the study was to analyse whether the levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) are higher in patients with rectal cancer as compared with healthy blood donors.
Patients and methods. Two hundred and seventeen patients (147 male, 70 female) with histologically confirmed non-metastatic rectal cancer (clinical stage II-III) and 45 healthy blood donors (15 male, 30 female) were included in analysis. Patient's mean age was 66 years (range: 34-87 years) and healthy blood donor's mean age was 35 years (range: 18-64 years). Plasma TIMP-1 concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) using commercially available TIMP-1 ELISA kit. Mann-Whitney-test for independent groups was used to assess the differences of plasma TIMP-1 levels and clinicopathological parameters. Two-sided tests were used and the differences at P<0.05 were considered as statistically significant.
Results. Median patients TIMP-1 level was 180 ng/mL (range: 22-538 ng/mL); the mean (±SD) level was 193.7 (79.5) ng/mL. The median healthy blood donors TIMP-1 level was 112 ng/mL (range: 48-211 ng/mL); the mean (±SD) level was 115 (35.7) ng/mL. TIMP-1 levels in patients with rectal cancer were statistically significantly higher than TIMP-1 levels in healthy blood donors (P<0.0001). Significant differences in TIMP-1 levels were not found comparing gender (P=0.43), but in both groups TIMP-1 levels were increased with higher age (P=0.007).
Conclusions. Patients with rectal cancer had statistically significantly higher mean and median TIMP-1 level than healthy blood donors which is in accordance with the results published in other publications. These findings suggest possibility that plasma TIMP-1 levels could be used as new biological markers for early cancer detection.