In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-tolymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p 5 0.001) and recurrence-free survival (HR 0.37, p 5 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.One of the key determinants of prognosis in colorectal cancer (CRC) is pathological staging. For patients with Stage III colon cancer, defined by regional lymph node involvement, there is substantial evidence supporting the role of adjuvant chemotherapy.1 The risk of recurrence in Stage II colon cancer is much lower, and in the absence of convincing evidence of a survival benefit, routine use of adjuvant chemotherapy in Stage II disease is not recommended.
Multistate, project-specific data collection involving large numbers of patients is achievable. Providing invaluable insight into the routine clinical management of metastatic colorectal cancer in the era of targeted therapies, this also creates a significant resource for research, including many questions not being addressed by clinical trials.
CIC
‐rearranged sarcoma is a recently established, ultra‐rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of
CIC
‐rearranged sarcomas and explore clinical management including systemic treatments and outcomes.
Methods
A multi‐centre retrospective cohort study of patients diagnosed between 2014–2019.
Results
Eighteen patients were identified. The median age was 27 years (range 13–56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1‐, 2‐ and 5‐year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing‐based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1–20.1), 1‐year OS was 57%. Median progression‐free survival was 5.8 months (95% CI 4.5–7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (
n
= 1) and pembrolizumab (
n
= 1) were not seen.
Conclusion
In this series,
CIC
‐rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.
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