On the impact of surveillance test strategies: a cost-benefit modelling analysis based upon real-world data from SARS-CoV-2.

OBJECTIVES: Active regular surveillance testing of asymptomatic and symptomatic individuals can reduce infection and onward transmission rates, as demonstrated for SARS-CoV-2. STUDY DESIGN: Cost-benefit analysis based on real-world data. METHODS: Two different surveillance-testing strategies using nucleic acid amplification tests (NAATs) performed in 14,177 hospital employees were compared for their costs and their effectiveness in preventing secondary infections. RESULTS: Compared to not testing, NAAT-based testing twice a week accompanied by contact tracing or testing five times a week without tracing of contacts were more effective in preventing infections through early identification of infected individuals. While expansion of the test frequency from two to five times per week increased the initial costs, importantly, a 49.6 % higher inhibitory effect on infection growth with a 11.1-fold reduction of potentially averted infections and resulting workforce loss was observed, demonstrating a substantial cost-benefit of the 5-tests-per-week strategy. CONCLUSIONS: Adaptation of the test frequency of SARS-CoV-2 and possibly of other pathogens with epidemic potential according to the prevailing incidences and reproduction rates in high-prevalence situations may not only be beneficial in averting potential infections in hospital employees and, subsequently, on a population level but may also represent the most cost-effective method.

Importance of chewing, saliva, and swallowing function in patients with advanced oral cancer undergoing preoperative chemoradiotherapy: a prospective study of quality of life.

The primary objective of this study was to investigate the quality of life (QOL) of patients with oral squamous cell carcinoma (OSCC) undergoing curative neoadjuvant chemoradiotherapy followed by radical tumour resection and simultaneous oral cavity reconstruction, using two validated questionnaires. A secondary objective was to assess clinical variables predicting post-treatment dysfunction in chewing, saliva, and swallowing. Thirty-five patients with locally advanced OSCC who underwent preoperative chemoradiotherapy were recruited prospectively. All patients completed both the University of Washington Quality of Life version 4 questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy-Head & Neck version 4 questionnaire (FACT-H&N). UW-QOL and FACT-H&N items were associated with clinical variables. Nearly three-quarters of OSCC patients perceived good to excellent levels of overall QOL after preoperative chemoradiotherapy. Chewing difficulties, decreased salivary function, and swallowing dysfunction were the most frequent complaints of OSCC patients. Items related to food intake were significantly worse in OSCC patients older than 60 years and those with T4 tumours, as well as those without alcohol intake. Chewing, saliva, and swallowing are the most significant issues in patients with OSCC undergoing preoperative chemoradiotherapy. The results of this study may help guide treatment decisions for OSCC patients based on more accurate expectations of adverse effects of cancer treatment.

Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: A systematic review and meta-analysis.

BACKGROUND: Plasma fibrinogen may be involved in several stages of cancer progression. Clinical studies have demonstrated that pretreatment plasma fibrinogen is associated with poor survival in various cancers. The aim of this meta-analysis was to examine the prognostic effect of circulating fibrinogen in solid tumors. MATERIALS AND METHODS: We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, and meeting proceedings to identify studies assessing the effect of pretreatment plasma fibrinogen on survival of cancer patients. Pooled multivariable-adjusted hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were estimated using random-effects models. RESULTS: Data from 52 observational studies and 15,371 patients were summarized. An elevated baseline plasma fibrinogen was significantly associated with worse OS (pooled HR = 1.69; 95% CI = 1.48­1.92). The highest negative effect of elevated plasma fibrinogen on OS was demonstrated in renal cell carcinoma (pooled HR = 2.22), followed by head and neck cancer (pooled HR = 2.02), and colorectal cancer (pooled HR = 1.89). The adverse prognostic impact of high plasma fibrinogen remained in both non-metastatic and metastatic disease and patients of different ethnicity. Patients with high baseline fibrinogen had a significantly shorter DFS (pooled HR = 1.52) and CSS (pooled HR = 2.50). CONCLUSIONS: An elevated pretreatment plasma fibrinogen significantly correlates with decreased survival in patients with solid tumors. Future clinical trials are warranted to determine whether plasma fibrinogen could be incorporated in cancer staging systems and whether fibrinogen-lowering therapies have a favorable effect on disease recurrence and mortality.

Upregulation of osteoprotegerin expression correlates with bone invasion and predicts poor clinical outcome in oral cancer.

OBJECTIVES: We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan-Meier curves and Cox regression models were used for survival analyses. RESULTS: A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders (p=0.032 and p=0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival (p=0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients. CONCLUSION: Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer.

The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines.

BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. RESULTS: Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. CONCLUSION: Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.

HCRP1 expression status is a significant prognostic marker in oral and oropharyngeal cancer.

OBJECTIVE: The hepatocellular carcinoma-related protein 1 (HCRP1) is a key factor in the degradation of the epidermal growth factor receptor. In this study, we assessed the prognostic significance of HCRP1 expression in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). METHODS: HCRP1 expression was determined by immunohistochemistry on tissue biopsy sections of 111 patients with locally advanced OOSCC undergoing neoadjuvant chemoradiotherapy followed by surgery. The Kaplan-Meier method and Cox regression models were used for survival analyses. RESULTS: Low HCRP1 expression was associated with poor recurrence-free survival (P = 0.046) and overall survival (P = 0.03). Multivariate analysis revealed that low HCRP1 expression remained an independent risk factor for relapse (HR 2.98, 95% CI 1.19-7.49, P = 0.02) and death (HR 3.04, 95% CI 1.19-7.79, P = 0.02). CONCLUSION: Low HCRP1 expression was found to be of adverse prognostic significance in patients with OOSCC who received preoperative chemoradiotherapy.

Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients.

BACKGROUND: Tissue factor (TF) expression by tumors contributes to tumor growth. Release of TF-positive microparticles (MPs) may contribute to venous thromboembolism (VTE). OBJECTIVES: To conduct a prospective cohort study to determine whether elevated MP-associated TF (MP-TF) activity is predictive of VTE and mortality in four cancer types. PATIENTS/METHODS: We determined MP-TF activity in pancreatic, gastric, colorectal and brain cancer patients. We used a chromogenic endpoint assay for all patients and also a chromogenic kinetic assay for patients with pancreatic and brain cancer. RESULTS: During follow-up, 12/60 (20%) pancreatic, 6/43 (14%) gastric, 12/126 (10%) colorectal and 19/119 (16%) brain cancer patients developed VTE; 46/60 (77%), 30/43 (70%), 47/126 (37%) and 67/119 (56%), respectively, died. MP-TF activity levels were highest in pancreatic cancer. We did not find a statistically significant association of MP-TF activity with the risk of VTE in any of the four cancer types by using two statistical methods. An association of MP-TF activity with the risk of mortality was detected in pancreatic cancer with the endpoint assay (hazard ratio [HR] 1.8 and 95% confidence interval [CI] 1.4-2.3 per doubling of activity, P < 0.001) and the kinetic assay (HR 1.2, 95% CI 1.1-1.4, P < 0.001); adjustment for type of treatment was not performed. In pancreatic cancer, MP-TF activity correlated with D-dimer level (endpoint assay, r = 0.51; chromogenic assay, r = 0.48), and a correlation between assays (r = 0.61) was found. CONCLUSION: MP-TF activity was not associated with future VTE in pancreatic, gastric, colorectal and brain cancer. However, we found a strong association of MP-TF activity with mortality in pancreatic cancer. MP-TF activity might be reflective of an aggressive pancreatic cancer phenotype.

Re-irradiation combined with capecitabine in locally recurrent squamous cell carcinoma of the head and neck. A prospective phase II trial.

BACKGROUND: We performed a prospective phase II trial to investigate the safety and efficacy of radiotherapy combined with capecitabine in patients suffering from a recurrence of a squamous cell carcinoma of the head and neck (SCCHN) within a previously irradiated field. PATIENTS AND METHODS: A total of 31 evaluable patients with recurrent SCCHN received re-irradiation with a total dose of 50 Gy (25 fractions over 5 weeks) up to a maximum of 60 Gy combined with 900 mg/m(2)/day capecitabine given on the days of radiotherapy. RESULTS: The median time to relapse after the first course of radiotherapy was 15 months. The overall response rate in our study was 68% including 6 patients with a complete response. The median overall survival was 8.4 months. Grade 3 or 4 mucositis occurred in 4 patients and 1 patient, respectively. No grade 4 hematological toxicities were observed; 1 patient had grade 3 anemia. The cumulative median lifetime dose was 116 Gy. CONCLUSION: Capecitabine combined with re-irradiation is a well-tolerated treatment in patients with recurrent SCCHN. In light of its good tolerability, it appears to be a potential option for patients with a reduced performance status and may also serve as a basis for novel treatment concepts, such as in combination with targeted therapies.

Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC). AIM: To identify prognostic factors in sorafenib-treated HCC patients and to evaluate outcomes with respect to liver function. METHODS: In this retrospective study, 148 HCC patients received sorafenib 400 mg b.d. across 11 Austrian institutions. Seventy-eight HCC patients who received best supportive care (BSC) in the pre-sorafenib era served as a control. RESULTS: In sorafenib-treated patients, low baseline α-fetoprotein, low Child-Pugh (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase (AST) were associated with significantly longer overall survival (OS) on univariate analysis. CP score and baseline AST remained independent prognostic factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP-A patients had a median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010), and CP-B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n = 22]) months (P = 0.021). In the sorafenib group, median OS according to baseline AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (≥100 U/L [n = 15]) months for CP-A patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (≥100 U/L [n = 21]) months for CP-B patients (P = 0.011). There was no survival difference between sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P = 0.116). CONCLUSIONS: Sorafenib was associated with improved survival in both CP-A and CP-B patients. In CP-B patients, baseline AST may be helpful in determining which patients are most likely to benefit from sorafenib.

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck.

BACKGROUND: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. DESIGN: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3) grading. RESULTS: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. CONCLUSIONS: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherapy.

[Early effects of systemic and intravitreal bevacizumab (avastin) therapy for neovascular age-related macular degeneration]. / Frühe Effekte nach systemischer und intravitrealer Bevacizumab (Avastin)-Therapie bei neovaskulärer altersbedingter Makuladegeneration.

PURPOSE: The purpose of this study was to evaluate the early treatment response following systemic and intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: In a prospective cohort study 12 eyes with neovascular AMD were treated with 5 mg/kg systemic bevacizumab, and 13 eyes with 1 mg intravitreal bevacizumab. Systemic therapy was given three times at 2-week intervals, intravitreal therapy up to three times at 4-week intervals. Patients were evaluated according to best corrected visual acuity (VA) and optical coherence tomography (OCT) at baseline as well as at week 1, week 4 and week 12 after therapy. Fluorescein angiography (FA) was performed at baseline and week 12. RESULTS: Systemic and intravitreal bevacizumab therapy showed a treatment response within one week. Visual acuity improved at week 1 by 4.9 letters from baseline in the systemic and by 6.9 letters in the intravitreal treatment group. Central retinal thickness (CRT), as measured by OCT decreased by 51.9 microm and 176.4 microm, respectively. At month 3 a persistent treatment effect was detectable. Mean gain in visual acuity was 11 letters in the systemic and 8.3 letters in the intravitreal group, CRT had decreased by 100 microm and 153.8 microm, respectively. Leakage as evaluated by FA was significantly reduced or absent in all patients. CONCLUSION: The early treatment responses following systemic and intravitreal bevacizumab appear to be similar. Both groups show improvement in VA and decrease in CRT within 1 week and up to 3 months. Long-term follow-up is required to evaluate the safety and treatment durability of both treatment modalities using bevacizumab.

Side effects during chemotherapy predict tumour response in advanced colorectal cancer.

To investigate whether a relationship between chemotherapy-associated adverse events and treatment efficacy exists, we have analysed the toxicity, objective response and survival data of 303 patients with advanced colorectal cancer. Patients were divided into two groups: the first with beneficial effect (I, n = 245), and the second with progressive disease (II, n = 58). Differences in terms of incidence rates, type and severity of ad verse events were analysed with univariate and multivariate models. The median number of side effects in group I was 6 vs 4 in group II (OR=1.342; P= 0.0001). An inverse correlation between disease control and treatment tolerance was confirmed when side effects were analysed according to severity and type of treatment-associated toxicities (haematological: P = 0.0005 vs nonhaematological P = 0.0001). When median survival was analysed according to the number of adverse events, it was 10 (95% CI, 3-7), 16 (14-18), and 18 (16-20) months in case of 0-1, 2-5, and > or =6 adverse events, respectively (P = 0.01). In conclusion, the results of this analysis suggest that occurrence of side effects during chemotherapy in advanced colorectal cancer is an independent and reliable prognostic indicator for response and survival.

Preoperative radiochemotherapy and radical resection for stages II-IV oral and oropharyngeal cancer: outcome of 222 patients.

To analyse survival and locoregional control in patients with advanced oral and oropharyngeal squamous cell carcinoma (SCC) after multimodal therapy with preoperative radiochemotherapy (RCT) and radical surgery. We included in this analysis 222 patients who underwent multimodal therapy between 1990 and 2000. Eligible were patients with UICC disease stages II-IV (T2: 33.3%; T3: 12.6%; T4: 54.1%; N0: 45.9%; N1: 17.6%; N2: 33.3%; N3: 3.2%; stage II: 21.1%; stage III: 14.9%; stage IV: 64%). Patients received preoperative radiochemotherapy consisting of Mitomycin C (15-20 mg/m2, day 1) plus 5-Fluorouracil (750 mg/m2/24 h-infusion, days 1-5) and concomitant radiotherapy for a total dose of 50 Gy. Radical locoregional en bloc-resection according to the pretherapeutic tumour extension was carried out in all patients. After a median surveillance period of 72.3 months (24-152 months), 131 patients (59%) were alive, and 91 (41%) patients died; 12 (5%) of them died postoperatively, 46 (21%) due to tumour recurrence, and 33 (15%) deaths were not directly related to the primary tumour. Overall survival probability was 76% after 2 years, and 62% after 5 years. Two- and 5-year local control probability were 88 and 81%, respectively. Regarding the high percentage of stage IV disease in the reported patients, the multimodal concept is an effective therapy offering excellent survival and local control probability.

Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial.

BACKGROUND: Patients with advanced biliary tract carcinoma face a particularly dismal prognosis, and no standard palliative chemotherapy has yet been defined. Among several different single agents, mitomycin C and, more recently, the oral fluoropyrimidine capecitabine and the nucleoside analogue gemcitabine, have been reported to exert antitumour activity. In view of a potential drug synergy, the present randomised phase II trial was initiated. The aim was to investigate the therapeutic efficacy and tolerance of mitomycin C (MMC) in combination with gemcitabine (GEM) or capecitabine (CAPE) in previously untreated patients with advanced biliary tract cancer. PATIENTS AND METHODS: A total of 51 patients were entered in this study and randomly allocated to treatment with MMC 8 mg/m2 on day 1 in combination with GEM 2000 mg/m2 on days 1 and 15 every 4 weeks, or MMC 8 mg/m2 on day 1 plus CAPE 2000 mg/m2/day on days 1-14, every 4 weeks. In both arms, chemotherapy was administered for a total of 6 months unless progressive disease occurred earlier. RESULTS: Pretreatment characteristics were well balanced between the two treatment arms. The overall independent review committee-confirmed response rate among those treated with MMC + GEM was 20% (five of 25) compared with 31% (eight of 26) among those treated with MMC + CAPE. Similarly, median progression-free survival (PFS; 4.2 versus 5.3 months) and median overall survival (OS; 6.7 versus 9.25 months) tended to be superior in the latter combination arm. Chemotherapy was fairly well tolerated in both arms, with a comparably low rate of only grade 1 and 2 non-haematological adverse reactions. Also, only four (17%) patients in both treatment arms experienced grade 3 leukocytopenia, and three (13%) and four (17%) had grade 3 thrombocytopenia in the MMC + GEM and MMC + CAPE arm, respectively. CONCLUSIONS: The results of this study indicate that both combination regimens are feasible, tolerable and clinically active. The MMC + CAPE arm, however, seems to be superior in terms of response rate, PFS and OS, and should therefore be selected for further clinical investigation in advanced biliary tract cancer.

Carcinoma showing thymic-like elements--a rare malignancy of the thyroid gland.

BACKGROUND: Carcinoma showing thymic-like elements (CASTLE) is a rare tumour of the thyroid of thymic origin. The histological appearance of this tumour may be similar to that of squamous cell carcinoma of the thyroid, but outcome associated with CASTLE is more favourable. METHODS: A systematic literature review was conducted for case reports on CASTLE. A text word search of the Medline database was made with a manual search of the citations from these references. Twenty-two case reports were found. RESULTS: In five patients with tumour-negative lymph nodes no local or distant recurrence was observed. Seventeen patients had unknown or involved lymph nodes. Two patients were excluded from further study: one had no follow-up and one was treated by irradiation only. Of the remaining 15, six had local, three had distant and two had local and distant recurrence. In patients with involved or unknown lymph node status, local recurrence was noted in one of five patients treated by surgery and irradiation, and in seven of ten patients treated by surgery alone. Irradiation or systemic chemotherapy was given to four patients with recurrent tumours, with variable response. CONCLUSION: CASTLE with tumour-negative lymph nodes has a low risk of recurrence and surgery without adjuvant therapy is sufficient. Radiotherapy seems indicated when lymph nodes are tumour positive and can be effective for recurrent tumours. In selected patients surgery for recurrent tumour can improve quality of life and outcome.

Second-line treatment of advanced gastric cancer with oxaliplatin plus raltitrexed.

BACKGROUND: Treatment with oxaliplatin plus raltitrexed has demonstrated an encouraging therapeutic index in patients with advanced colorectal cancer and malignant pleural mesothelioma. The aim of this multi-institutional study was to determine the antitumor potential of this combination in patients with metastatic gastric cancer failing prior palliative first-line chemotherapy, and to reconfirm its favorable toxicity profile. PATIENTS AND METHODS: 21 patients with metastatic gastric cancer, who progressed while on or within 6 months after discontinuing palliative first-line chemotherapy, participated in this study. They received raltitrexed 3,0 mg/m(2) and oxaliplatin 130 mg/m(2) both given intravenously on day 1 every 3 weeks. RESULTS: One patient achieved a partial response, 6 had stable disease, and 14 patients progressed. Median progression-free and overall survival from the onset of salvage chemotherapy was 2.0 and 4.5 months, respectively. Hematologic adverse reactions, specifically neutropenia and anemia were common, though generally mild to moderate with only 3 patients experiencing grade 3/4 toxicity. The most frequent non-hematologic adverse events included nausea/emesis, asthenia, and transient elevation of liver functional parameters, again with grade 3 symptoms occurring only in a minority of patients. CONCLUSION: Despite reproducibility of a favorable toxicity profile of oxaliplatin + raltitrexed, our data suggest that this combination regimen has no substantial antitumor activity in patients with progressive, chemotherapeutically pretreated metastatic gastric cancer.

[Follow-up investigations in colorectal cancer]. / Nachsorge des kolorektalen Karzinoms.

BACKGROUND: In view of improved surgical techniques and other local treatment modalities, i.e. radiofrequency ablation, cryosurgery, and the availability of new active cytotoxic agents, which in the neoadjuvant treatment setting may allow curative resection of liver or lung metastases and locoregional recurrences in up to 30% of cases, the ASCO and ESMO recommendations 2002 should be up-dated. CURRENT RECOMMENDATIONS: According to the ASCO, history, clinical examination and CEA assessments should be performed every 3 months for > or =2 years after initial diagnosis and annually thereafter, whereas the ESMO discourages any routine laboratory examinations. Furthermore, rather in contrast to the ASCO guidelines, which do not recommend proctosigmoidoscopy in patients with rectal cancer (unless postoperative radiochemotherapy has not been effected) the ESMO suggests endoscopic +/- endosonographic evaluations of the rectosigmoid every 6 months for 2 years and colonoscopy only every 5 years. Chest x-ray and abdominal ultrasound are not suggested, except in symptomatic patients and in case of elevated CEA levels. POSSIBLE NEW SURVEILLANCE RECOMMENDATIONS: History, clinical examination and CEA testing should be performed every 3 months for 2 years after diagnosis and annually thereafter. Similarly, liver sonography or CT-scan +/- chest x-ray should be performed every 6 months for 2 years and annually thereafter. Because of significantly improved local control in patients with rectal cancer undergoing total mesorectal excision +/- preoperative radiotherapy, the frequency of rectosigmoidoscopy should be reduced.

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.