A cross-sectional analysis of treatment patterns in small-cell lung cancer in five European countries.

Aim: To investigate changes in treatment patterns in extensive-stage small-cell lung cancer (ES-SCLC) in France, Germany, Italy, Spain and the UK (EU5) between 2018 and 2021. Methods: Cross-sectional data from an oncology database were analyzed retrospectively. Results: Of 5832 eligible patients, 88.4% had stage IV disease at diagnosis. Among patients receiving first-line treatment, 91.8% (1079 /1176) received the platinum-etoposide (PE) combination in 2018 which decreased to 42.3% (509/1203) by 2021. Usage of the PE-atezolizumab combination increased from 0 to 41.2% during the same timeframe. Topotecan monotherapy remained the most widely used second-line treatment regardless of patients' platinum sensitivity. Conclusion: The first-line standard of care for ES-SCLC has evolved in EU5 with the PE-atezolizumab/durvalumab combination gradually superseding PE usage.

Lung cancer is the leading cause of cancer-related deaths. Small-cell lung cancer (SCLC) is fast-growing type of lung cancer. New treatments for SCLC using medicines that stimulate the immune system to kill cancer cells (called immunotherapies) have recently been approved for use in Europe. The purpose of the study was to describe the type of treatments that patients received in five European countries before and after the introduction of these new treatments to determine how quickly these new treatments were adopted in a real-world setting. This study found that most patients treated between 2018 and 2020 still received a platinum-based chemotherapy as their first anticancer therapy, but immunotherapies were used more often in later years and became the most common first treatment in 2021 for patients who had never been treated for their cancer. Topotecan, a type of chemotherapy, was the most used treatment for patients whose cancer came back after treatment. There is still a clear unmet need for new, safe and effective therapies for the treatment of patients with SCLC whose cancer comes back again after treatment.

Patient perception of burden of disease and treatment preferences in non-small cell lung cancer: Results from a European survey.

OBJECTIVES: To understand European non-small cell lung cancer (NSCLC) patients' perceptions of disease burden, treatment, and future expectations of treatment and care. MATERIALS AND METHODS: A 32-item online survey was conducted on a sample of NSCLC patients across Europe. Descriptive statistics were used to analyse the data. Results were presented by disease stage (I-III vs. IV). RESULTS: NSCLC patients (N = 292) from 10 countries responded. Most patients resided in France, Spain, Italy, Germany and UK, with 16 patients from five other countries. Patients' knowledge of biomarker testing was limited (23% of 376 responses indicated no knowledge). Patients reported fear (stage I-III: 40%, stage IV: 27%), anxiety (stage I-III: 44%, stage IV: 33%) and depression (stage I-III: 24%, stage IV: 20%), but also hope (stage I-III: 57%, stage IV: 59%). Professional status was majorly impacted for 43% of stage I-III patients and 58% stage IV patients. Household finances were impacted for âˆ¼70% of all patients. Oral treatment was preferred (60%), and respondents understood dosing schedules (stage I-III: 82%, stage IV: 97%) remembering to take medications (stage I-III: 82%, stage IV: 87%). Most respondents were willing to take more pills, but some indicated that this would be difficult. CONCLUSION: Approximately half of the patients in this survey were aware of clinical trial options, but most lacked information about their molecular tumor profile, making it difficult for patients to engage in discussions about their care. The results also suggest that NSCLC patients have significant information and support needs, especially in the areas of emotional and financial burden. Action is needed to address these burdens associated with NSCLC. Furthermore, patients should be provided with the information needed to actively participate in treatment decisions.

On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma.

Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Approximately one-third of patients with NSCLC have a KRAS mutation. KRASG12C, the most common mutation, is found in ~13% of patients. While KRAS was long considered 'undruggable', several novel direct KRASG12C inhibitors have shown encouraging signs of efficacy in phase I/II trials and one of these (sotorasib) has recently been approved by the US Food and Drug Administration. This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.

The evolving landscape of biomarker testing for non-small cell lung cancer in Europe.

The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small-molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment. Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single-driver mutations have been implemented. Improvements in DNA- and RNA-based next-generation sequencing technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing. Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second- or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.

A Retrospective Chart Review Study of Real-World Use of Talimogene Laherparepvec in Unresectable Stage IIIB-IVM1a Melanoma in Four European Countries.

INTRODUCTION: Talimogene laherparepvec (T-VEC; IMLYGIC®, Amgen Inc.) is an oncolytic immunotherapy approved in Europe for the treatment of unresectable metastatic melanoma (stage IIIB-IVM1a). This study characterised real-world use of T-VEC in four European countries. METHODS: Data on demographics, treatment pattern, safety, and clinical effectiveness were examined in a retrospective chart review of patients with stage IIIB-IVM1a unresectable melanoma treated with T-VEC in surgical (the Netherlands) and medical (Austria, Germany, UK) oncology settings. RESULTS: Overall, 66 patients were included (the Netherlands: n = 31; Austria, Germany, UK: n = 35). The median age was 69 years and 59.1% were female. At the time of T-VEC initiation, 47 patients (71.2%) had stage IIIB/C disease; of these, 30 were from the Netherlands. Although 72.7% patients overall received T-VEC as first-line therapy, this was higher in the Netherlands than the other countries (93.5% vs 54.3%). Of the 47 patients who discontinued T-VEC, 26 (55.3%) had no remaining injectable lesions (potentially indicating complete response); 20/26 of these patients were from the Netherlands. One patient discontinued T-VEC due to toxicity. CONCLUSION: This study is the first comprehensive multinational evaluation of the use of T-VEC to treat unresectable stage IIIB/C-IVM1a melanoma in real-world clinical practice in Europe. The differences between European countries were apparent, with physicians in the Netherlands using T-VEC in patients with earlier advanced disease stage and in the first-line setting compared with other countries.

Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives.

The emergence of human intratumoural immunotherapy (HIT-IT) is a major step forward in the management of unresectable melanoma. The direct injection of treatments into melanoma lesions can cause cell lysis and induce a local immune response, and might be associated with a systemic immune response. Directly injecting immunotherapies into tumours achieves a high local concentration of immunostimulatory agent while minimising systemic exposure and, as such, HIT-IT agents are associated with lower toxicity than systemic immune checkpoint inhibitors (CPIs), enabling their potential use in combination with other therapies. Consequently, multiple HIT-IT agents, including oncolytic viruses, pattern-recognition receptor agonists, injected CPIs, cytokines and immune glycolipids, are under investigation. This review considers the current clinical development status of HIT-IT agents as monotherapy and in combination with systemic CPIs, and the practical aspects of administering and assessing the response to these agents. The future of HIT-IT probably lies in its use in combination with systemic CPIs; data from Phase 2 trials indicate a synergy between HIT-IT and CPIs. Data also suggest that the addition of HIT-IT to a CPI might generate responses in CPI-refractory tumours, thereby overcoming resistance and addressing a current unmet need in unresectable and metastatic melanoma for treatment options following progression after CPI treatment.

Real-world use of talimogene laherparepvec in Germany: a retrospective observational study using a prescription database.

Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3-26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed.

Real-World Use of Talimogene Laherparepvec in German Patients with Stage IIIB to IVM1a Melanoma: A Retrospective Chart Review and Physician Survey.

INTRODUCTION: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany. METHODS: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients. Data on demographics, disease and medical history, and use of talimogene laherparepvec were collected. A survey was also conducted to understand physician treatment decisions. RESULTS: Data for 27 patients who initiated talimogene laherparepvec between June 2016 and July 2017 were analyzed (median age 68; stage IIIB/C disease 56%). All patients had prior surgery, and over half had repeated resections for recurrent disease (median 3). Overall, 48% of patients received at least one prior local treatment, mainly radiation therapy or electrochemotherapy. Talimogene laherparepvec was first-line systemic therapy in 63% of patients. The most frequent prior systemic treatment was immunotherapy (7/27 patients). At end of follow-up, 13 patients were still on talimogene laherparepvec and 14 patients had discontinued treatment. Among those who discontinued, 8 (57%) did not receive subsequent systemic therapy. Only one patient receiving first-line talimogene laherparepvec received a subsequent systemic therapy. Three patients stopped treatment because of no remaining injectable lesions. Median treatment duration was 22.1 weeks overall and 27.9 weeks in stage IIIB/C disease patients. Nearly all cutaneous lesions (93%) were injected with talimogene laherparepvec compared to subcutaneous (83%) and nodal lesions (77%). No new safety signals were reported. The main reasons given in the physician survey for treating with talimogene laherparepvec were good tolerability, overall efficacy, and lack of contraindications. CONCLUSION: Talimogene laherparepvec is now included as a routine treatment option for unresectable early metastatic melanoma in Germany. This study characterizes the first patients treated with talimogene laherparepvec in Europe and confirms the good tolerability observed in clinical trials. TRIAL REGISTRATION: EUPAS registry, EUPAS17410. FUNDING: Amgen Inc.

Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe.

Talimogene laherparepvec, a herpes simplex virus type 1-based intralesional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction of anti-tumour immunity, which is enhanced by the production of granulocyte macrophage colony-stimulating factor. Responses (which occur in >40% of stage IIIB-IVM1a patients) are often durable (>50% last ≥6 months) and occur in injected and uninjected lesions (in stage IIIB-IVM1c patients, 64%/34% of evaluable injected/uninjected non-visceral lesions, respectively, decreased in size by ≥50%). As with other immunotherapies, responses may be delayed or can arise after pseudoprogression. The pattern of treatment-emergent adverse events is distinct, being mostly grade 1/2, easy to manage, and rarely leading to treatment discontinuation. Systemic therapy represents the backbone of care for many metastatic melanoma patients. Nonetheless, the potential for durable locoregional control with a locally injected agent may make talimogene laherparepvec suitable for selected patients with stage IIIB/C disease, for whom surgery is not possible (e.g. with in-transit metastases, multiple melanoma lesions at different body sites, or those relapsing rapidly after repeated rounds of surgery) and slowly progressing disease. Here, we discuss which patients could be suitable for talimogene laherparepvec monotherapy based on the European indication, review the patterns/timing of response, and discuss the incidence/management of adverse events. Its potential use combined with immune checkpoint inhibitors is also discussed.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies. METHODS: As part of a comprehensive pharmacovigilance plan, developed with regulators' input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly established national ONJ databases and adjudicated by the committee that functioned during the XGEVA(®) clinical trials program. CONCLUSION: This study will provide a real world counterpart to the clinical trial-estimated risks for ONJ and serious infections for cancer patients initiating denosumab or zoledronic acid. The establishment of ONJ databases in the three Scandinavian countries will have potential benefits outside this study for the elucidation of ONJ risk factors and the evaluation of ONJ treatment strategies.

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents.

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease.

A combined analysis of mismatch repair status and thymidylate synthase expression in stage II and III colon cancer.

UNLABELLED: This study in 716 colon cancer patients evaluates if a combined instead of a single marker analysis of mismatch repair (MMR) status and thymidylate synthase (TS) expression could individualize the treatment decision. The results indicate that a combined analysis of MMR status and TS expression can improve prediction of response to adjuvant 5-fluorouracil (5-FU)-based chemotherapy in stage III colon cancer. BACKGROUND: Colon cancer with mismatch repair deficiency and low TS expression has been associated with an improved prognosis. Data also indicate that MMR proficient colon cancer with high TS expression has a better response to adjuvant 5-FU-based chemotherapy. This study evaluates if a combined analysis of MMR status and TS expression in colon cancer can add prognostic value and better predict response to adjuvant 5-FU-based chemotherapy. The potential relationship between MMR status and TS expression is also investigated. PATIENTS AND METHODS: This study includes a subgroup of 716 patients with colon cancer out of 2224 stage II and stage III colorectal cancer patients enrolled in Nordic trials randomized to surgery alone or surgery plus adjuvant 5-FU-based chemotherapy. After immunohistochemical analysis of tumor MMR status and TS expression the patients were divided into 4 groups. RESULTS: There was a nonsignificant difference in overall survival between group 1 (patients with deficient MMR tumors with low TS) and group 4 (patients with proficient MMR tumors expressing high TS). When comparing group 1 and group 4 patients treated with surgery alone a trend to better overall survival was found in group 1, P=.06. In group 4, stage III patients had a significantly improved survival when receiving adjuvant 5-FU-based chemotherapy compared with surgery alone, P=.01. No relationship was found between MMR status and TS expression. CONCLUSIONS: A combined instead of a single marker analysis of MMR status and TS expression can improve the prediction of response to 5-FU-based chemotherapy in stage III colon cancer.

Mismatch repair protein expression is an independent prognostic factor in sporadic colorectal cancer.

Abstract Background. Mismatch repair (MMR) status has been reported as a prognostic and predictive factor in sporadic colorectal cancer (CRC). The purpose of this study was to determine the prognostic and predictive value of MMR protein expression in the adjuvant setting. Patients and methods. The MMR status in the primary tumor was retrospectively assessed on paraffin-embedded formalin-fixed samples from 1 006 patients with sporadic CRC (488 stage II and 518 stage III) using immunohistochemical analysis (IHC) of MLH1 and MSH2 expression. The patients were included in adjuvant Nordic trials between 1991 and 1996 randomly assigned to surgery alone or surgery plus adjuvant 5-fluorouracil (5-FU)-based chemotherapy. Data was censored at 120 months after surgery. Results. One hundred fifty-seven patients (15.6%) showed a loss of MMR protein expression (139 MLH1 negative, 15 MSH2 negative and 3 MLH1 and MSH2 negative) and were classified as MMR protein negative. A normal MMR protein expression was found in 849 patients who were defined as MMR protein positive. MMR protein expression was a significant prognostic marker in the entire study group with a better overall survival (OS) among patients with MMR protein negative tumors compared to patients with MMR protein positive tumors (p=0.01). In a multivariate analysis the MMR protein expression was significantly associated with OS, (HR 0.70 [95% CI, 0.40 to 0.99]; p=0.01). The MMR status did not predict survival benefit from adjuvant 5-FU-based chemotherapy. Conclusion. This study reveals that IHC of MLH1 and MSH2 expression can yield important prognostic information but is not a predictive factor for adjuvant 5-FU-based chemotherapy in sporadic CRC.

The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer - a pilot study.

AIM: Cytochrome P450 (CYP) enzymes are important for drug metabolism. A novel cytochrome P450 enzyme, CYP2W1, has recently been identified. This enzyme is mainly found in foetal colon tissue and in tumour tissue. In this pilot study, we have investigated the expression of CYP2W1 in 162 tumours from patients with stages II and III colorectal cancer. METHODS: The expression of CYP2W1 enzyme was immunohistochemically detected using a polyclonal antibody. Staining intensity was defined using a visual grading scale from 0 to 3. Grades 0-2 were classified as low, and grade 3 was classified as high expression of CYP2W1. RESULTS: About 64% of the tumours expressed a low level of CYP2W1-expression, and 36% expressed a high level. CYP2W1-expression was an independent prognostic factor for overall survival (p=0.007), where a high expression was associated with a worse clinical outcome. CONCLUSIONS: Immunohistochemically assessed expression of CYP2W1 is an independent prognostic factor in patients with stages II and III colorectal cancer.

Expression of thymidylate synthase in liver and lung metastases of colorectal cancer and their matched primary tumours.

BACKGROUND: In advanced colorectal cancer (CRC) a low expression of thymidylate synthase (TS) in metastases predicts a higher response to 5-fluorouracil (5-FU). The purpose of this study was to investigate the expression of TS in liver and lung metastases of CRC and their matched primary tumours. PATIENTS AND METHODS: Immunohistochemical analysis of TS expression was performed on tissue samples of 48 CRC metastases (liver n=38, lung n=10) and their matched primary tumours (n=45). RESULTS: There was no significant correlation between TS expression in 33/48 (69%), matched samples of metastases and primary tumours (r=0.02, p=1.0). CONCLUSION: This study indicates that TS expression in liver and lung metastases of CRC does not always reflect the level of TS in their corresponding primary tumours. Therefore, it might not be accurate to solely rely on analyses of TS in the primary tumours to predict the effect of 5-FU-based chemotherapy in metastatic CRC.

The number of analyzed lymph nodes - a prognostic factor in colorectal cancer.

The prognostic significance of the number of lymph nodes examined in surgical specimen of colorectal cancer was determined. One thousand and twenty five patients with colorectal cancer stage II and III were included in the study. These patients underwent surgery from 1991 to 1997 and were enrolled in clinical trials to evaluate the efficacy of adjuvant 5-fluorouracil (5FU) based chemotherapy. The median number of examined lymph nodes was five. Only 13% of the patients had > or = 12 lymph nodes analyzed. The number of examined lymph nodes was an independent prognostic factor for overall survival in the entire group of patients with stage II and III colorectal cancer (p=0.009). Patients with a higher number of lymph nodes examined had a longer overall survival. In stage III colorectal cancer the ratio of the number of metastatic lymph nodes to the number of examined lymph nodes (lymph node ratio, LNR) was an independent prognostic factor for overall survival. A decreasing LNR was correlated with a longer overall survival (p<0.0001). Increasing age was associated with a reduction of lymph node harvest (p=0.04). Patients with rectal cancer treated with preoperative radiotherapy had a lower number of lymph nodes analyzed compared with non-radiated (p<0.001). The number of examined lymph nodes in the surgical specimen is an independent prognostic factor for overall survival in colorectal cancer. The LNR is an independent prognostic factor in stage III colorectal cancer.

Detection of thymidylate synthase expression in lymph node metastases of colorectal cancer can improve the prognostic information.

PURPOSE: The level of thymidylate synthase (TS) in primary colorectal cancer (CRC) has been reported as a prognostic marker. The purpose of this study was to determine whether TS expression in lymph node metastases of Dukes' C CRC is a prognostic marker. PATIENTS AND METHODS: TS expression in the primary tumor and lymph node metastases from 348 patients with Dukes' C CRC was retrospectively assessed using immunohistochemistry and the monoclonal antibody TS 106. The patients had all been enrolled onto our previous study of 862 CRC patients who were included in Nordic trials that randomly assigned the patients to either surgery alone or surgery plus adjuvant chemotherapy. RESULTS: TS expression in lymph node metastases was a distinct prognostic marker in the entire study group for overall survival (OS; P = .02) and disease-free survival (DFS; P = .04). A low TS expression in the lymph node metastases correlated with a better clinical outcome. In the subgroup of patients treated with surgery alone, the expression of TS in lymph node metastases also had a prognostic value for OS (P = .04) and DFS (P = .03), but this was not the case for the other subgroup who received adjuvant fluorouracil-based chemotherapy (OS, P = .5; DFS, P = .2). The expression of TS in the primary tumor only had a significant prognostic value among patients who were treated with surgery alone (OS, P = .03; DFS, P = .03) and not among the entire patient population. CONCLUSION: These data show that TS expression in lymph node metastases is a prognostic marker for patients with Dukes' C CRC.