Adjuvant chemotherapy use and outcomes of patients with high‐risk versus low‐risk stage II colon cancer

Kumar, Aalok; Kennecke, Hagen F.; Renouf, Daniel J.; Lim, Howard John; Gill, Sharlene; Woods, Ryan; Speers, Caroline; Cheung, Winson Y.

doi:10.1002/cncr.29072

Cited by 139 publications

(153 citation statements)

References 33 publications

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“…However, the excellent safety profile is contrasted by an inferior therapeutic efficacy. Nevertheless, basing a bacterial therapy along an adjuvant effect alone might prove unfeasible [87–90]. Symbioflor-2 needs to undergo recombinant strengthening to gain efficiency, either by supplementing the bacteria with additional virulence factors and/ or equipping them with expression and secretion systems that ensure delivery of therapeutic molecules to the target tumor.…”

Section: Discussionmentioning

confidence: 99%

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

et al. 2016

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To date, virulent bacteria remain the basis of most bacteria mediated cancer therapies. For clinical application attenuation is required. However, this might result in a drastically lowered therapeutic capacity. Herein we argue that the E. coli probiotic Symbioflor-2, with a history of safe application may constitute a viable tumor therapeutic candidate. We demonstrate that Symbioflor-2 displays a highly specific tumor targeting ability as determined in murine CT26 and RenCa tumor models. The excellent specificity was ascribed to reduced levels of adverse colonization. A high safety standard was demonstrated in WT and Rag1−/− mice. Thus, Symbioflor-2 may represent an ideal tumor targeting delivery system for therapeutic molecules. Moreover, Symbioflor-2 was capable of inducing CT26 tumor clearance as result of an adjuvant effect on tumor specific CD8+ T cells analogous to the Salmonella variant SL7207. However, lower therapeutic efficacy against RenCa tumors suggested a generally reduced therapeutic potency for probiotics. Interestingly, concurrent depletion of Gr-1+ or Ly6G+ cells installed therapeutic efficacy equal to SL7207, thus highlighting the role of innate effector cells in restraining the anti-tumor effects of Symbioflor-2. Collectively, our findings argue for a strategy of safe strain application and a more sustainable use of bacteria as a delivery system for therapeutic molecules.

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Section: Discussionmentioning

confidence: 99%

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

et al. 2016

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“…There is also little evidence in the literature to suggest that patients with any poor prognostic features are more likely to benefit from chemotherapy (10). For example, in a recent population-based study in 1,697 stage II CC patient, a recurrence-free and overall survival benefit of adjuvant chemotherapy was observed in patients with T4 primary cancers, but not other high risk clinical features (46). …”

Section: Discussionmentioning

confidence: 99%

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair–Proficient Stage II Colon Cancer

Ghosh

Tie

Murányi³

et al. 2016

Clinical Cancer Research

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Purpose Prognostic markers that identify patients with stage II colon cancers (CC) who are at risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. Experimental Design Expression of full-length GIV was evaluated by immunohistochemistry (IHC) using a newly developed monoclonal antibody together with a mismatch repair (MMR)-specific antibody panel in three stage II CC patient cohorts, ie. a training (n=192), test (n=317), and validation (n=181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. Results For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR:2.78, p=0.013; LVI: HR 2.54, p=0.025) and combined test and validation (pooled) cohorts (GIV, HR:1.85, p=0.019; LVI, HR:2.52, p=0.0004). A risk model based on GIV expression and LVI-status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts (Training: 52.3% versus 84.8%; HR:3.74, 95%CI: 1.50–9.32; Test: 85.9% versus 97.9%, HR:7.83, 95%CI:1.03–59.54; Validation: 59.4% versus 84.4%, HR:3.71, 95%CI: 1.24–11.12). Conclusions GIV expression status predicts recurrence risk in patients with T3 pMMR stage II CC. A risk model combining GIV expression and LVI-status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms.

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“…The differences between groups were not statistically significant (p = 0.426). Grande et al 28 found statistically significant differences in favor of the use of chemotherapy in terms of overall survival and of five-year DFS, however Kumar et al 30 found that the use of chemotherapy was associated with worse DFS and DSS.…”

Section: Discussionmentioning

confidence: 97%

Assessment of prognosis in patients with stage II colon cancer

Martins

2015

Journal of Coloproctology

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j coloproctol (rio j). 2 0 1 5;3 5(4):203-211 w w w . j c o l . o r g . b r Journal of Coloproctology Colon cancer High-and low-risk stage II Disease-free survival Disease-specific survival a b s t r a c t Pathologic staging is currently the most important prognostic factor in colon cancer, although individually this procedure does not provide a complete clinical outcome.This study aimed to determine the disease-specific survival of patients with colon cancer treated in the Braga Hospital from January 2005 to December 2013, according to the American Joint Committee on Cancer, 6th edition, and the disease-free survival and diseasespecific survival of high-and low-risk stage II patients, whether in use, or not, of adjuvant chemotherapy.We obtained a total sample of 578 patients, with 145 and 65 high-and low-risk stage II patients, respectively. We observed a 5-year disease-specific survival rate of 93%, 27.4% and 75% for stage IIA, IIB and IIIA patients, respectively, where IIIA and IIB present statistically significant differences (p = 0.001). In high-risk stage II patients, disease-free survival (p = 0.107) and disease-specific survival (p = 0.037) were higher in the group submitted to chemotherapy. In low-risk patients, disease-free survival was higher in the group submitted to chemotherapy (p = 0.494), while disease-specific survival was lower (p = 0.426).The differences observed between stage IIB and IIIA survival can be explained by the consensual use of adjuvant chemotherapy in stage IIIA, and by its controversial use in stage IIB. Adjuvant chemotherapy showed to be effective only in high-risk stage II patients in terms of disease-specific survival.In the future, other markers, namely molecular ones, may be used to stratify the risk of stage II patients and determine who will benefit from adjuvant chemotherapy. Avaliação o prognóstico de pacientes com cancer de colon no estadio IIPalavras-chave: Câncer de cólon Estadio II de alto risco e baixo risco Sobrevivência livre de doença r e s u m o O estadiamento patológico é, atualmente, o fator de prognóstico mais importante do câncer de cólon, embora individualmente não preveja totalmente o resultado clínico. Neste estudo, pretendeu-se determinar a sobrevivência para uma doença específica (SDE) dos pacientes com câncer de cólon tratados no Hospital de Braga entre janeiro de 2005 e 204 j coloproctol (rio j). 2 0 1 5;3 5(4):203-211 Sobrevivência para uma doença específica dezembro de 2013, de acordo com a 6 a edição da American Joint Committee on Cancer e a Sobrevivência Livre de Doença (SLD) e SDE dos doentes em estadio II, classificados em alto e baixo risco, de acordo com a realização ou não de quimioterapia adjuvante.Obtivemos uma amostra total de 578 pacientes, dos quais uma parcela pertencia ao estadio II de alto ou de baixo risco (145 e 65 pacientes, respetivamente). Observamos SDE a 5 anos de: 93%, 27,4% e 75% para os estadios IIA, IIB e IIIA, respetivamente; IIIA e IIB apresentaram diferenças significativas (p = 0,001). SLD (p = 0,107) e SDE (p = 0,037) pa...

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Adjuvant chemotherapy use and outcomes of patients with high‐risk versus low‐risk stage II colon cancer

Cited by 139 publications

References 33 publications

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair–Proficient Stage II Colon Cancer

Assessment of prognosis in patients with stage II colon cancer

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